Complement factor H polymorphisms in Japanese population with age-related macular degeneration.

PubMed

Okamoto, Haru; Umeda, Shinsuke; Obazawa, Minoru; Minami, Masayoshi; Noda, Toru; Mizota, Atsushi; Honda, Miki; Tanaka, Minoru; Koyama, Risa; Takagi, Ikue; Sakamoto, Yoshihiro; Saito, Yoshihiro; Miyake, Yozo; Iwata, Takeshi

2006-03-06

To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD). Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 age-matched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results. Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified. The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective.

The "Sardinian" HLA-A30,B18,DR3,DQw2 haplotype constantly lacks the 21-OHA and C4B genes. Is it an ancestral haplotype without duplication?

PubMed

Contu, L; Carcassi, C; Dausset, J

1989-01-01

The C4 and 21-OH loci of the class III HLA have been studied by specific DNA probes and the restriction enzyme Taq 1 in 24 unrelated Sardinian individuals selected from completely HLA-typed families. All 24 individuals had the HLA extended haplotype A30,Cw5,B18, BfF1,DR3,DRw52,DQw2, named "Sardinian" in the present paper because of its frequency of 15% in the Sardinian population. Eighteen of these were homozygous for the entire haplotype, and six were heterozygous at the A locus and blank (or homozygous) at all the other loci. In all completely homozygous cells and in four heterozygous cells at the A locus, the restriction fragments of the 21-OHA (3.2 kb) and C4B (5.8 kb or 5.4 kb) genes were absent, and the fragments of the C4A (7.0 kb) and 21-OHB (3.7 kb) genes were present. It is suggested that the "Sardinian" haplotype is an ancestral haplotype without duplication of the C4 and 21-OH genes, practically always identical in its structure, also in unrelated individuals. The diversity of this haplotype in the class III region (about 30 kb less) may be at least partially responsible for its misalignment with most haplotypes, which have duplicated C4 and 21-OH genes, and therefore also for its decreased probability to recombine. This can help explain its high stability and frequency in the Sardinian population. The same conclusion can be suggested for the Caucasian extended haplotype A1,B8,DR3 that always seems to lack the C4A and 21-OHA genes.

[Relationship between High-Resolution HLA-A,-B,-DRB1 Alleles and Haplotype Polymorphisms with Myeloid Leukemia of Han People in North China].

PubMed

Qi, Jun; Wang, Tian-Ju; Chen, Li-Ping; Wang, Man-Ni; Wu, Jun-Hua; DU, Dan

2018-02-01

To investigate the potential relationship between the high-resolution HLA-A,-B,-DRB1 alleles and haplotype polymorphism with actute myeloid leukemia (AML) and chronic myeloid leukemia (CML) of Han people in North China. A total of 1241 healthy unrelated Han people's bone marrow donors in North China were used as a control group, 259 patients with myeloid leukemia were genotyped at high-resolution level by means of PCR-SBT, -SSO and -SSP typing methods for HLA-A,-B,-DRB1 loci. The frequencies of HLA allele and haplotype were calculated by software Arleguin 3.5.2. The different distribution of genes and haplotypes was analyzed by case control study, and the odd ratio (OR) of leukemia was also calculated. The structural difference of HLA alleles was analyzed 111by HLA three-dimensional structure modeling and software Swiss-PdbViewer v4.1. χ 2 test and correction showed that an increased frequency of A*02:07 (8.47% vs 5.28%, P' =0.013), A*29:01 (1.85% vs 0.68%, P=0.044), B*07:02 (5.29% vs 3.10%, P=0.029), B*07:05:01G (1.85% vs 0.68%, P=0.044) and B*35:02 (1.06% vs 0.20%, P=0.023) were found in AML patients (n=189) as compared with controls, respectively; whereas A*02:03 was less frequent in AML as compared with controls (0.79% vs 3.10%, P=0.011). The frequency of B*46:01 was lower in CML patients (n=70) as compared with controls (2.86% vs 7.82%, P=0.031). However, the above-mentioned discrepancies were not statistically significant by Bonferroni correction. Through Fisher exact test and Bonferroni correction, the frequency of DRB1*11:28 and its haplotype A*24:02-B*15:01-DRB1*11:28 in CML group were very significantly higher than in controls (1.43% vs 0.00%, Pc=0.015; 1.43% vs 0.00%, P=0.003). Three-dimensional structure modeling of DRB1*11:28 and DRB1*11:01 presented significant structure differentiation (RMSD=0.09 nm) in peptide binding region of the backbone calculated by Swiss-PdbViewer v4.1. The haplotype A*03:01-B*50:01-DRB1*07:01 in AML and A*11:01-B*40:06-DRB1*09:01 in CML patients were significantly higher than that in controls (1.06% vs 0.00%, Pc=0.000; 2.86% vs 0.07%, Pc=0.000), and positively correlated with leukemia (OR=59.66, 95% CI=3.21-1110.39; OR=42.91, 95% CI=7.07-260.32). The relationship of HLA-A,-B,-DRB1 alleles and haplotype polymorphism with leukemia at high-resolution level were obtained and unique in north Chinese Han population. AML and CML patients in Northern Han people carry particular susceptible haplotypes. DRB1*11:28, which might not actively present bcr-abl peptide to CD4 + T cells, and is a susceptibile gene for CML patients of Northern Han people, especially in Shaanxi Province (OR=89.62, 95% CI=4.28-1875.87), as well as correlated with its particular haplotype.

β-globin haplotypes in normal and hemoglobinopathic individuals from Reconcavo Baiano, State of Bahia, Brazil.

PubMed

Dos Santos Silva, Wellington; de Nazaré Klautau-Guimarães, Maria; Grisolia, Cesar Koppe

2010-07-01

Five restriction site polymorphisms in the β-globin gene cluster (HincII-5' ε, HindIII-(G) γ, HindIII-(A) γ, HincII- ψβ1 and HincII-3' ψβ1) were analyzed in three populations (n = 114) from Reconcavo Baiano, State of Bahia, Brazil. The groups included two urban populations from the towns of Cachoeira and Maragojipe and one rural Afro-descendant population, known as the "quilombo community", from Cachoeira municipality. The number of haplotypes found in the populations ranged from 10 to 13, which indicated higher diversity than in the parental populations. The haplotypes 2 (+ - - - -), 3 (- - - - +), 4 (- + - - +) and 6 (- + + - +) on the β(A) chromosomes were the most common, and two haplotypes, 9 (- + + + +) and 14 (+ + - - +), were found exclusively in the Maragojipe population. The other haplotypes (1, 5, 9, 11, 12, 13, 14 and 16) had lower frequencies. Restriction site analysis and the derived haplotypes indicated homogeneity among the populations. Thirty-two individuals with hemoglobinopathies (17 sickle cell disease, 12 HbSC disease and 3 HbCC disease) were also analyzed. The haplotype frequencies of these patients differed significantly from those of the general population. In the sickle cell disease subgroup, the predominant haplotypes were BEN (Benin) and CAR (Central African Republic), with frequencies of 52.9% and 32.4%, respectively. The high frequency of the BEN haplotype agreed with the historical origin of the afro-descendant population in the state of Bahia. However, this frequency differed from that of Salvador, the state capital, where the CAR and BEN haplotypes have similar frequencies, probably as a consequence of domestic slave trade and subsequent internal migrations to other regions of Brazil.

β-globin haplotypes in normal and hemoglobinopathic individuals from Reconcavo Baiano, State of Bahia, Brazil

PubMed Central

2010-01-01

Five restriction site polymorphisms in the β-globin gene cluster (HincII-5‘ ε, HindIII-G γ, HindIII-A γ, HincII- ψβ1 and HincII-3‘ ψβ1) were analyzed in three populations (n = 114) from Reconcavo Baiano, State of Bahia, Brazil. The groups included two urban populations from the towns of Cachoeira and Maragojipe and one rural Afro-descendant population, known as the “quilombo community”, from Cachoeira municipality. The number of haplotypes found in the populations ranged from 10 to 13, which indicated higher diversity than in the parental populations. The haplotypes 2 (+ - - - -), 3 (- - - - +), 4 (- + - - +) and 6 (- + + - +) on the βA chromosomes were the most common, and two haplotypes, 9 (- + + + +) and 14 (+ + - - +), were found exclusively in the Maragojipe population. The other haplotypes (1, 5, 9, 11, 12, 13, 14 and 16) had lower frequencies. Restriction site analysis and the derived haplotypes indicated homogeneity among the populations. Thirty-two individuals with hemoglobinopathies (17 sickle cell disease, 12 HbSC disease and 3 HbCC disease) were also analyzed. The haplotype frequencies of these patients differed significantly from those of the general population. In the sickle cell disease subgroup, the predominant haplotypes were BEN (Benin) and CAR (Central African Republic), with frequencies of 52.9% and 32.4%, respectively. The high frequency of the BEN haplotype agreed with the historical origin of the afro-descendant population in the state of Bahia. However, this frequency differed from that of Salvador, the state capital, where the CAR and BEN haplotypes have similar frequencies, probably as a consequence of domestic slave trade and subsequent internal migrations to other regions of Brazil. PMID:21637405

X-chromosome as a marker for population history: linkage disequilibrium and haplotype study in Eurasian populations

PubMed Central

Laan, Maris; Wiebe, Victor; Khusnutdinova, Elza; Remm, Maido; Pääbo, Svante

2005-01-01

Linkage disequilibrium structure is still unpredictable because the interplay of regional recombination rate and demographic history is poorly understood. We have compared the distribution of LD across two genomic regions differing in crossing-over activity – Xq13 (0.166 cM/Mb) and Xp22 (1.3 cM/Mb) – in 15 Eurasian populations. Demographic events predicted to increase the LD level – genetic drift, bottleneck and admixture – had a very strong impact on extent and patterns of regional LD across Xq13 compared to Xp22. The haplotype distribution of the DXS1225-DXS8082 microsatellites from Xq13 exhibiting strong association in all populations was remarkably influenced by population history. European populations shared one common haplotype with a frequency of 25-40%. The Volga-Ural populations studied, living at the geographic borderline of Europe, showed elevated LD as well as harboring a significant fraction of haplotypes originating from East Asia, thus reflecting their past migrations and admixture. In the young Kuusamo isolate from Finland, a bottleneck has led to allelic associations between loci and shifted the haplotype distribution, but has much less affected single microsatellite allele frequencies compared to the main Finnish population. The data show that the footprint of a demographic event is longer preserved in haplotype distribution within a region of low crossing-over rate, than in the information content of a single marker, or between actively recombining markers. As the knowledge of LD patterns is often chosen to assist association mapping of common disease, our conclusions emphasise the importance of understanding the history, structure and variation of a study population. PMID:15657606

Association of KIR genotypes and haplotypes with susceptibility to chronic hepatitis B virus infection in Chinese Han population.

PubMed

Lu, Zhiming; Zhang, Bingchang; Chen, Shijun; Gai, Zhongtao; Feng, Zhaolei; Liu, Xiangdong; Liu, Yiqing; Wen, Xin; Li, Li; Jiao, Yulian; Ma, Chunyan; Shao, Song; Cui, Xiangfa; Chen, Guojian; Li, Jianfeng; Zhao, Yueran

2008-12-01

Killer immunoglobulin-like receptor (KIR) genes can regulate the activation of NK and T cells upon interaction with HLA class I molecules. Hepatitis B virus (HBV) infection has been regarded as a multi-factorial disorder disease. Previous studies revealed that KIRs were involved in HCV and HIV infection or clearance. The aim of this study was to explore the possibility of the inheritance of KIR genotypes and haplotypes as a candidate for susceptibility to persistent HBV infection or HBV clearance. The sequence specific primer polymerase chain reaction (SSP-PCR) was employed to identify the KIR genes and pseudogenes in 150 chronic hepatitis B (CHB) patients, 251 spontaneously recovered (SR) controls, and 412 healthy controls. The frequencies of genotype G, M, FZ1 increased in CHB patients compared with healthy control subjects. The frequency of genotype AH was higher in SR controls than that in both CHB patients and healthy controls. The carriage frequencies of genotype G and AH were higher; while, the frequencies of AF and AJ were lower in SR controls than those in healthy control subjects. The frequency of A haplotype was lower, whereas, the frequency of B haplotype was higher in CHB patients and SR controls than those in healthy controls. In healthy controls, haplotype 4 was found lower compared with that in CHB patients and SR controls and the frequency of haplotype 5 was higher in SR controls than that in other two groups. Based on these findings, it seems that the genotypes M and FZ1 are HBV susceptive genotypes; AH, on the other hand, may be protective genotypes that facilitate the clearance of HBV. It appears that the haplotype 4 is HBV susceptive haplotype, whereas, haplotype 5 may be the protective haplotype that facilitates the clearance of HBV.

Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

PubMed

Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

2014-03-01

The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P < 0.05), six significantly downregulated MGMT promoter activity (29-97% decrease; P < 0.05) and one haplotype had no effect. Mechanistic studies conducted support the conclusion that MGMT P/E haplotypes, rather than individual SNPs, differentially regulate MGMT transcription and could thus play a significant role in human sensitivity to environmental and therapeutic alkylating agents.

Genetic differences in the two main groups of the Japanese population based on autosomal SNPs and haplotypes.

PubMed

Yamaguchi-Kabata, Yumi; Tsunoda, Tatsuhiko; Kumasaka, Natsuhiko; Takahashi, Atsushi; Hosono, Naoya; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki

2012-05-01

Although the Japanese population has a rather low genetic diversity, we recently confirmed the presence of two main clusters (the Hondo and Ryukyu clusters) through principal component analysis of genome-wide single-nucleotide polymorphism (SNP) genotypes. Understanding the genetic differences between the two main clusters requires further genome-wide analyses based on a dense SNP set and comparison of haplotype frequencies. In the present study, we determined haplotypes for the Hondo cluster of the Japanese population by detecting SNP homozygotes with 388,591 autosomal SNPs from 18,379 individuals and estimated the haplotype frequencies. Haplotypes for the Ryukyu cluster were inferred by a statistical approach using the genotype data from 504 individuals. We then compared the haplotype frequencies between the Hondo and Ryukyu clusters. In most genomic regions, the haplotype frequencies in the Hondo and Ryukyu clusters were very similar. However, in addition to the human leukocyte antigen region on chromosome 6, other genomic regions (chromosomes 3, 4, 5, 7, 10 and 12) showed dissimilarities in haplotype frequency. These regions were enriched for genes involved in the immune system, cell-cell adhesion and the intracellular signaling cascade. These differentiated genomic regions between the Hondo and Ryukyu clusters are of interest because they (1) should be examined carefully in association studies and (2) likely contain genes responsible for morphological or physiological differences between the two groups.

[Frequency distribution of HLA antigens and haplotypes in newly arrived inhabitants of Magadan].

PubMed

Solovenchuk, L L; Pereverzeva, V V; Nevretdinova, Z G

1994-09-01

Peculiarities of the frequency distribution of antigens and haplotypes of A, B, and Cw subloci of the HLA system in 924 Slavic inhabitants of Magadan are described. Significant differences in gene and haplotype frequencies between inhabitants of Magadan and those of Moscow, Odessa, Poles'e, Latvia, and England were revealed, which could not be attributed solely to the specificity of migration processes. On the basis of an analysis of gamete associations of the A and B subloci, an attempt was made to explain the specificity of the frequency distribution of HLA system alleles and haplotypes in the investigated sample from an ecological point of view.

Sequence polymorphism at the human apolipoprotein AII gene ( APOA2): unexpected deficit of variation in an African-American sample.

PubMed

Fullerton, Stephanie M; Clark, Andrew G; Weiss, Kenneth M; Taylor, Scott L; Stengård, Jari H; Salomaa, Veikko; Boerwinkle, Eric; Nickerson, Deborah A

2002-07-01

A 3.3-kb region, encompassing the APOA2 gene and 2 kb of 5' and 3' flanking DNA, was re-sequenced in a "core" sample of 24 individuals, sampled without regard to the health from each of three populations: African-Americans from Jackson (Miss., USA), Europeans from North Karelia (Finland), and non-Hispanic European-Americans from Rochester, (Minn., USA). Fifteen variable sites were identified (14 SNPs and one multi-allelic microsatellite, all silent), and these sites segregated as 18 sequence haplotypes (or nine, if SNPs only are considered). The haplotype distribution in the core African-American sample was unusual, with a deficit of particular haplotypes compared with those found in the other two samples, and a significantly (P<0.05) low level of nucleotide diversity relative to patterns of polymorphism and divergence at other human loci. Six of the 14 SNPs, whose variation captured the haplotype structure of the core data, were then genotyped by oligonucleotide ligation assay in an additional 2183 individuals from the same three populations (n=843, n=452, and n=888, respectively). All six sites varied in each of the larger "epidemiological" samples, and together, they defined 19 SNP haplotypes, seven with relative frequencies greater than 1% in the total sample; all of these common haplotypes had been identified earlier in the core re-sequencing survey. Here also, the African-American sample showed significantly lower SNP heterozygosity and haplotype diversity than the other two samples. The deficit of polymorphism is consistent with a population-specific non-neutral increase in the relative frequency of several haplotypes in Jackson.

Genetic differentiation among North Atlantic killer whale populations.

PubMed

Foote, Andrew D; Vilstrup, Julia T; De Stephanis, Renaud; Verborgh, Philippe; Abel Nielsen, Sandra C; Deaville, Robert; Kleivane, Lars; Martín, Vidal; Miller, Patrick J O; Oien, Nils; Pérez-Gil, Monica; Rasmussen, Morten; Reid, Robert J; Robertson, Kelly M; Rogan, Emer; Similä, Tiu; Tejedor, Maria L; Vester, Heike; Víkingsson, Gísli A; Willerslev, Eske; Gilbert, M Thomas P; Piertney, Stuart B

2011-02-01

Population genetic structure of North Atlantic killer whale samples was resolved from differences in allele frequencies of 17 microsatellite loci, mtDNA control region haplotype frequencies and for a subset of samples, using complete mitogenome sequences. Three significantly differentiated populations were identified. Differentiation based on microsatellite allele frequencies was greater between the two allopatric populations than between the two pairs of partially sympatric populations. Spatial clustering of individuals within each of these populations overlaps with the distribution of particular prey resources: herring, mackerel and tuna, which each population has been seen predating. Phylogenetic analyses using complete mitogenomes suggested two populations could have resulted from single founding events and subsequent matrilineal expansion. The third population, which was sampled at lower latitudes and lower density, consisted of maternal lineages from three highly divergent clades. Pairwise population differentiation was greater for estimates based on mtDNA control region haplotype frequencies than for estimates based on microsatellite allele frequencies, and there were no mitogenome haplotypes shared among populations. This suggests low or no female migration and that gene flow was primarily male mediated when populations spatially and temporally overlap. These results demonstrate that genetic differentiation can arise through resource specialization in the absence of physical barriers to gene flow. © 2010 Blackwell Publishing Ltd.

Association Between Chloroplast DNA and Mitochondrial DNA Haplotypes in Prunus spinosa L. (Rosaceae) Populations across Europe

PubMed Central

MOHANTY, APARAJITA; MARTÍN, JUAN PEDRO; GONZÁLEZ, LUIS MIGUEL; AGUINAGALDE, ITZIAR

2003-01-01

Chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA) were studied in 24 populations of Prunus spinosa sampled across Europe. The cpDNA and mtDNA fragments were amplified using universal primers and subsequently digested with restriction enzymes to obtain the polymorphisms. Combinations of all the polymorphisms resulted in 33 cpDNA haplotypes and two mtDNA haplotypes. Strict association between the cpDNA haplotypes and the mtDNA haplotypes was detected in most cases, indicating conjoint inheritance of the two genomes. The most frequent and abundant cpDNA haplotype (C20; frequency, 51 %) is always associated with the more frequent and abundant mtDNA haplotype (M1; frequency, 84 %). All but two of the cpDNA haplotypes associated with the less frequent mtDNA haplotype (M2) are private haplotypes. These private haplotypes are phylogenetically related but geographically unrelated. They form a separate cluster on the minimum‐length spanning tree. PMID:14534199

Kullback-Leibler divergence for detection of rare haplotype common disease association.

PubMed

Lin, Shili

2015-11-01

Rare haplotypes may tag rare causal variants of common diseases; hence, detection of such rare haplotypes may also contribute to our understanding of complex disease etiology. Because rare haplotypes frequently result from common single-nucleotide polymorphisms (SNPs), focusing on rare haplotypes is much more economical compared with using rare single-nucleotide variants (SNVs) from sequencing, as SNPs are available and 'free' from already amassed genome-wide studies. Further, associated haplotypes may shed light on the underlying disease causal mechanism, a feat unmatched by SNV-based collapsing methods. In recent years, data mining approaches have been adapted to detect rare haplotype association. However, as they rely on an assumed underlying disease model and require the specification of a null haplotype, results can be erroneous if such assumptions are violated. In this paper, we present a haplotype association method based on Kullback-Leibler divergence (hapKL) for case-control samples. The idea is to compare haplotype frequencies for the cases versus the controls by computing symmetrical divergence measures. An important property of such measures is that both the frequencies and logarithms of the frequencies contribute in parallel, thus balancing the contributions from rare and common, and accommodating both deleterious and protective, haplotypes. A simulation study under various scenarios shows that hapKL has well-controlled type I error rates and good power compared with existing data mining methods. Application of hapKL to age-related macular degeneration (AMD) shows a strong association of the complement factor H (CFH) gene with AMD, identifying several individual rare haplotypes with strong signals.

Probability distribution of haplotype frequencies under the two-locus Wright-Fisher model by diffusion approximation.

PubMed

Boitard, Simon; Loisel, Patrice

2007-05-01

The probability distribution of haplotype frequencies in a population, and the way it is influenced by genetical forces such as recombination, selection, random drift ...is a question of fundamental interest in population genetics. For large populations, the distribution of haplotype frequencies for two linked loci under the classical Wright-Fisher model is almost impossible to compute because of numerical reasons. However the Wright-Fisher process can in such cases be approximated by a diffusion process and the transition density can then be deduced from the Kolmogorov equations. As no exact solution has been found for these equations, we developed a numerical method based on finite differences to solve them. It applies to transient states and models including selection or mutations. We show by several tests that this method is accurate for computing the conditional joint density of haplotype frequencies given that no haplotype has been lost. We also prove that it is far less time consuming than other methods such as Monte Carlo simulations.

HLA-G, -A haplotypes in Amerindians (Ecuador): HLA-G*01:05N World distribution.

PubMed

Arnaiz-Villena, Antonio; Palacio-Gruber, Jose; Enriquez de Salamanca, Mercedes; Juárez, Ignacio; Campos, Cristina; Nieto, Jorge; Muñiz, Ester; Martin-Villa, Jose Manuel

2018-02-01

HLA-G and HLA-A frequencies have been analysed in Amerindians from Ecuador. HLA-G allele frequencies are found to be closer to those of other Amerindians (Mayas from Guatemala and Uros from Peru) and closer to European ones than to Far East Asians groups, particularly, regarding to HLA-G*01:04 allele. HLA-G/-A haplotypes have been calculated for the first time in Amerindians. It is remarkable that HLA-G*01:05N "null" allele is found in a very low frequency (like in Amerindian Mayas and Uros) and is also found in haplotypes belonging to the HLA-A19 group of alleles (HLA-A*30, -A*31, -A*33). It was previously postulated that HLA-G*01:05N appeared in HLA-A*30/-B*13 haplotypes in Middle East Mediterraneans. It may be hypothesized that in Evolution, HLA-G*01:05N existed primarily in one of the HLA extant or extinct -A19 haplotype, whether this haplotype was placed in Middle East or other World areas, including America. However, the highest present day HLA-G*01:05N frequencies are found in Middle East Mediterraneans. Copyright © 2017. Published by Elsevier Inc.

Dimensional Anxiety Mediates Linkage of GABRA2 Haplotypes With Alcoholism

PubMed Central

Enoch, Mary-Anne; Schwartz, Lori; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

2015-01-01

The GABAAα2 receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-configuration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P α0.007, OR α2.1, Plains Indians: P α0.040, OR α1.9). Non-alcoholics had intermediate frequencies. Our results suggest that within the distal GABRA2 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety. PMID:16874763

Genomic adaptation of admixed dairy cattle in East Africa

PubMed Central

Kim, Eui-Soo; Rothschild, Max F.

2014-01-01

Dairy cattle in East Africa imported from the U.S. and Europe have been adapted to new environments. In small local farms, cattle have generally been maintained by crossbreeding that could increase survivability under a severe environment. Eventually, genomic ancestry of a specific breed will be nearly fixed in genomic regions of local breeds or crossbreds when it is advantageous for survival or production in harsh environments. To examine this situation, 25 Friesians and 162 local cattle produced by crossbreeding of dairy breeds in Kenya were sampled and genotyped using 50K SNPs. Using principal component analysis (PCA), the admixed local cattle were found to consist of several imported breeds, including Guernsey, Norwegian Red, and Holstein. To infer the influence of parental breeds on genomic regions, local ancestry mapping was performed based on the similarity of haplotypes. As a consequence, it appears that no genomic region has been under the complete influence of a specific parental breed. Nonetheless, the ancestry of Holstein-Friesians was substantial in most genomic regions (>80%). Furthermore, we examined the frequency of the most common haplotypes from parental breeds that have changed substantially in Kenyan crossbreds during admixture. The frequency of these haplotypes from parental breeds, which were likely to be selected in temperate regions, has deviated considerably from expected frequency in 11 genomic regions. Additionally, extended haplotype homozygosity (EHH) based methods were applied to identify the regions responding to recent selection in crossbreds, called candidate regions, resulting in seven regions that appeared to be affected by Holstein-Friesians. However, some signatures of selection were less dependent on Holsteins-Friesians, suggesting evidence of adaptation in East Africa. The analysis of local ancestry is a useful approach to understand the detailed genomic structure and may reveal regions of the genome required for specialized adaptation when combined with methods for searching for the recent changes of haplotype frequency in an admixed population. PMID:25566325

Spatial and temporal distribution of the neutral polymorphisms in the last ZFX intron: analysis of the haplotype structure and genealogy.

PubMed Central

Jaruzelska, J; Zietkiewicz, E; Batzer, M; Cole, D E; Moisan, J P; Scozzari, R; Tavaré, S; Labuda, D

1999-01-01

With 10 segregating sites (simple nucleotide polymorphisms) in the last intron (1089 bp) of the ZFX gene we have observed 11 haplotypes in 336 chromosomes representing a worldwide array of 15 human populations. Two haplotypes representing 77% of all chromosomes were distributed almost evenly among four continents. Five of the remaining haplotypes were detected in Africa and 4 others were restricted to Eurasia and the Americas. Using the information about the ancestral state of the segregating positions (inferred from human-great ape comparisons), we applied coalescent analysis to estimate the age of the polymorphisms and the resulting haplotypes. The oldest haplotype, with the ancestral alleles at all the sites, was observed at low frequency only in two groups of African origin. Its estimated age of 740 to 1100 kyr corresponded to the time to the most recent common ancestor. The two most frequent worldwide distributed haplotypes were estimated at 550 to 840 and 260 to 400 kyr, respectively, while the age of the continentally restricted polymorphisms was 120 to 180 kyr and smaller. Comparison of spatial and temporal distribution of the ZFX haplotypes suggests that modern humans diverged from the common ancestral stock in the Middle Paleolithic era. Subsequent range expansion prevented substantial gene flow among continents, separating African groups from populations that colonized Eurasia and the New World. PMID:10388827

Spatial and temporal distribution of the neutral polymorphisms in the last ZFX intron: analysis of the haplotype structure and genealogy.

PubMed

Jaruzelska, J; Zietkiewicz, E; Batzer, M; Cole, D E; Moisan, J P; Scozzari, R; Tavaré, S; Labuda, D

1999-07-01

With 10 segregating sites (simple nucleotide polymorphisms) in the last intron (1089 bp) of the ZFX gene we have observed 11 haplotypes in 336 chromosomes representing a worldwide array of 15 human populations. Two haplotypes representing 77% of all chromosomes were distributed almost evenly among four continents. Five of the remaining haplotypes were detected in Africa and 4 others were restricted to Eurasia and the Americas. Using the information about the ancestral state of the segregating positions (inferred from human-great ape comparisons), we applied coalescent analysis to estimate the age of the polymorphisms and the resulting haplotypes. The oldest haplotype, with the ancestral alleles at all the sites, was observed at low frequency only in two groups of African origin. Its estimated age of 740 to 1100 kyr corresponded to the time to the most recent common ancestor. The two most frequent worldwide distributed haplotypes were estimated at 550 to 840 and 260 to 400 kyr, respectively, while the age of the continentally restricted polymorphisms was 120 to 180 kyr and smaller. Comparison of spatial and temporal distribution of the ZFX haplotypes suggests that modern humans diverged from the common ancestral stock in the Middle Paleolithic era. Subsequent range expansion prevented substantial gene flow among continents, separating African groups from populations that colonized Eurasia and the New World.

Y-SNPs haplotype diversity in four Chinese cattle breeds.

PubMed

Zhang, Runfeng; Cheng, Ming; Li, Xiaofeng; Chen, Fuying; Zheng, Jing; Wang, Xiaofei; Meng, Quanke

2013-01-01

To investigate the genetic diversity of Chinese cattle, 96 male samples of 4 Chinese native cattle breeds were investigated using 5 single nucleotide polymorphisms specific to the bovine Y chromosome. Two previously described haplotypes (taurine Y2 and indicine Y3) were detected in 74 and 22 animals, respectively. The haplotype frequencies varied amongst the four native breeds. The taurine Y2 haplotype dominated in the Qinchuan, Dabieshan, and Yunba breeds. However, the indicine Y3 haplotype occurred in high frequency in the Enshi breed. Among the four native breeds, Yunba had the highest haplotype diversity (0.4330 ± 0.0750), followed by Qinchuan (0.2899 ± 0.1028) and Enshi (0.2222 ± 0.1662), Dabieshan was the least differentiated (0.1079 ± 0.0680). Compared with some foreign cattle breeds, the low level of haplotype diversity was detected in our breeds (0.2633 ± 0.1030).

Molecular analysis and association with clinical and laboratory manifestations in children with sickle cell anemia

PubMed Central

Camilo-Araújo, Roberta Faria; Amancio, Olga Maria Silverio; Figueiredo, Maria Stella; Cabanãs-Pedro, Ana Carolina; Braga, Josefina Aparecida Pellegrini

2014-01-01

Objectives To analyze the frequency of βS-globin haplotypes and alpha-thalassemia, and their influence on clinical manifestations and the hematological profile of children with sickle cell anemia. Method The frequency of βS-globin haplotypes and alpha-thalassemia and any association with clinical and laboratorial manifestations were determined in 117 sickle cell anemia children aged 3–71 months. The confirmation of hemoglobin SS and determination of the haplotypes were achieved by polymerase chain reaction-restriction fragment length polymorphism, and alpha-thalassemia genotyping was by multiplex polymerase chain reaction (single-tube multiplex-polymerase chain reaction). Results The genotype distribution of haplotypes was 43 (36.7%) Central African Republic/Benin, 41 (35.0%) Central African Republic/Central African Republic, 20 (17.0%) Rare/atypical, and 13 (11.1%) Benin/Benin. The frequency of the α3.7 deletion was 1.71% as homozygous (−α3.7/−α3.7) and 11.9% as heterozygous (−α3.7/αα). The only significant association in respect to haplotypes was related to the mean corpuscular volume. The presence of alpha-thalassemia was significantly associated to decreases in mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte count and to an increase in the red blood cell count. There were no significant associations of βS-globin haplotypes and alpha-thalassemia with clinical manifestations. Conclusions In the study population, the frequency of alpha-thalassemia was similar to published data in Brazil with the Central African Republic haplotype being the most common, followed by the Benin haplotype. βS-globin haplotypes and interaction between alpha-thalassemia and sickle cell anemia did not influence fetal hemoglobin concentrations or the number of clinical manifestations. PMID:25305165

TUMOR HAPLOTYPE ASSEMBLY ALGORITHMS FOR CANCER GENOMICS

PubMed Central

AGUIAR, DEREK; WONG, WENDY S.W.; ISTRAIL, SORIN

2014-01-01

The growing availability of inexpensive high-throughput sequence data is enabling researchers to sequence tumor populations within a single individual at high coverage. But, cancer genome sequence evolution and mutational phenomena like driver mutations and gene fusions are difficult to investigate without first reconstructing tumor haplotype sequences. Haplotype assembly of single individual tumor populations is an exceedingly difficult task complicated by tumor haplotype heterogeneity, tumor or normal cell sequence contamination, polyploidy, and complex patterns of variation. While computational and experimental haplotype phasing of diploid genomes has seen much progress in recent years, haplotype assembly in cancer genomes remains uncharted territory. In this work, we describe HapCompass-Tumor a computational modeling and algorithmic framework for haplotype assembly of copy number variable cancer genomes containing haplotypes at different frequencies and complex variation. We extend our polyploid haplotype assembly model and present novel algorithms for (1) complex variations, including copy number changes, as varying numbers of disjoint paths in an associated graph, (2) variable haplotype frequencies and contamination, and (3) computation of tumor haplotypes using simple cycles of the compass graph which constrain the space of haplotype assembly solutions. The model and algorithm are implemented in the software package HapCompass-Tumor which is available for download from http://www.brown.edu/Research/Istrail_Lab/. PMID:24297529

MHC Class II haplotypes of Colombian Amerindian tribes

PubMed Central

Yunis, Juan J.; Yunis, Edmond J.; Yunis, Emilio

2013-01-01

We analyzed 1041 individuals belonging to 17 Amerindian tribes of Colombia, Chimila, Bari and Tunebo (Chibcha linguistic family), Embera, Waunana (Choco linguistic family), Puinave and Nukak (Maku-Puinave linguistic families), Cubeo, Guanano, Tucano, Desano and Piratapuyo (Tukano linguistic family), Guahibo and Guayabero (Guayabero Linguistic Family), Curripaco and Piapoco (Arawak linguistic family) and Yucpa (Karib linguistic family). for MHC class II haplotypes (HLA-DRB1, DQA1, DQB1). Approximately 90% of the MHC class II haplotypes found among these tribes are haplotypes frequently encountered in other Amerindian tribes. Nonetheless, striking differences were observed among Chibcha and non-Chibcha speaking tribes. The DRB1*04:04, DRB1*04:11, DRB1*09:01 carrying haplotypes were frequently found among non-Chibcha speaking tribes, while the DRB1*04:07 haplotype showed significant frequencies among Chibcha speaking tribes, and only marginal frequencies among non-Chibcha speaking tribes. Our results suggest that the differences in MHC class II haplotype frequency found among Chibcha and non-Chibcha speaking tribes could be due to genetic differentiation in Mesoamerica of the ancestral Amerindian population into Chibcha and non-Chibcha speaking populations before they entered into South America. PMID:23885196

[Gene and haplotype frequencies for the loci HLA-A, B and DRB1 in 11755 north Chinese Han bone marrow registry donors].

PubMed

Wu, Qiang-Ju; Liu, Meng-Li; Qi, Jun; Liu, Sheng; Zhang, Yan; Wei, Xiao-Qian

2007-04-01

The study was aimed to investigate the human leukocyte antigen (HLA)-A, B, DRB1 alleles and haplotype frequencies and the characteristics of linkage disequilibrium in north Chinese Han bone marrow donors. HLA phenotype data of 11 755 north Chinese Han bone marrow donors were identified by PCR-SSP and PCR-SSO. HLA-A, B, DRB1 allele and haplotype frequencies were calculated by computer software named Arleguin which was based on Expectation-Maximization (EM) algorithms. The results showed that the population of 11755 unrelated-donors was tested by Hardy-Weinberg equilibrium, and 18,42 and 15 specificities of HLA alleles were identified on the HLA-A, B, DRB1 locus respectively, including HLA-A25, B42, B53, B73 and DR3 which were rarely reported in Han population. HLA-A36, A43, A80, B78, B82 and DR18 were not detected in this study. The most frequent alleles with a frequency of over 0.05 were HLA-A*02, A*11, A*24, A*33, A*30, A*01, A*03, A*13, B62, B*51, B*46, B60, B61, B*35, B*44, DRB1*15, DRB1*09, DRB1*04, DRB1*07, DRB1*12, DRB1*11, DRB1*14, DRB1*08, DRB1*13. There were a total of 2 026 kinds of HLA-A-B-DR haplotypes (with a frequency of over 10(-6)) to be obtained. The each frequency of 26 kinds of three-locus haplotypes including HLA-A30-B13-DR7, A2-B46-DR9, A33-B58-DR17 etc was higher than 0.005. A30-B13-DR7 was the most frequent haplotype in north Chinese Han population. There were a total of 538 kinds of haplotypes for HLA-A-B, 227 kinds for A-DR and 522 kinds for B-DR to be obtained, and there were 409, 195, 423 kinds of haplotypes respectively with a frequency higher than 10 - 6. There were 28 kinds of HLA-A-B haplotypes including A30-B13, A2-B46, A33-B58 etc, 26 kinds of HLA-A-DR haplotypes including A2-DR9, A2-DR15, A30-DR7 etc, and 24 kinds of HLA-B-DR haplotypes including B13-DR7, B46-DR9, B13-DR12 etc with a frequency higher than 0.01. 296 (72%) kinds of HLA-A-B, 130 (67%) kinds of A-DR and 308 (73%) kinds of B-DR haplotypes were statistical linkage disequilibrium. HLA-A30-B13, A33-B58, A1-B37, A30-DR7, A33-DR13, A1-DR10, B37-DR10, B8-DR17, B13-DR7, B58-DR17 were significant positive linkage disequilibrium. It is concluded that this HLA-A, B, DRB1 gene and haplotype frequencies and linkage disequilibrium data with the largest sample size up to now is unique in north Chinese Han population. The study will be helpful to find matched donors for patients and establish the important foundation for further studying of transplantation immunity, HLA-related diseases and population genetics of this area.

Estimating haplotype frequencies by combining data from large DNA pools with database information.

PubMed

Gasbarra, Dario; Kulathinal, Sangita; Pirinen, Matti; Sillanpää, Mikko J

2011-01-01

We assume that allele frequency data have been extracted from several large DNA pools, each containing genetic material of up to hundreds of sampled individuals. Our goal is to estimate the haplotype frequencies among the sampled individuals by combining the pooled allele frequency data with prior knowledge about the set of possible haplotypes. Such prior information can be obtained, for example, from a database such as HapMap. We present a Bayesian haplotyping method for pooled DNA based on a continuous approximation of the multinomial distribution. The proposed method is applicable when the sizes of the DNA pools and/or the number of considered loci exceed the limits of several earlier methods. In the example analyses, the proposed model clearly outperforms a deterministic greedy algorithm on real data from the HapMap database. With a small number of loci, the performance of the proposed method is similar to that of an EM-algorithm, which uses a multinormal approximation for the pooled allele frequencies, but which does not utilize prior information about the haplotypes. The method has been implemented using Matlab and the code is available upon request from the authors.

Human leukocyte antigen alleles, genotypes and haplotypes frequencies in renal transplant donors and recipients from West Central India.

PubMed

Patel, Jaina S; Patel, Manisha M; Koringa, Prakash G; Shah, Tejas M; Patel, Amrutlal K; Tripathi, Ajai K; Mathew, Anila; Rajapurkar, Mohan M; Joshi, Chaitanya G

2013-04-01

Human leukocyte antigen (HLA) is comprised of a highly polymorphic set of genes which determines the histocompatibility of organ transplantation. The present study was undertaken to identify HLA class I and class II allele, genotype and haplotype frequencies in renal transplant recipients and donors from West Central India. HLA typing was carried out using Polymerase Chain Reaction-Sequence Specific Primer in 552 live related and unrelated renal transplant recipients and donors. The most frequent HLA class I and class II alleles and their frequencies in recipients were HLA-AFNx0101 (0.1685) and AFNx0102 (0.1649), HLA-BFNx0135 (0.1322), and HLA-DR beta 1 (DRB 1)FNx0115 (0.2192), whereas in donors, these were HLA-AFNx0102 (0.1848) and AFNx0101 (0.1667), HLA-BFNx0135 (0.1359), and HLA-DRB1FNx0115 (0.2409). The two-locus haplotype statistical analysis revealed HLA-AFNx0102-B61 as the most common haplotype with the frequency of 0.0487 and 0.0510 in recipients and donors, respectively. Further, among the three locus haplotypes HLA-AFNx0133-BFNx0144-DRB1FNx0107 and HLA-AFNx0102-BFNx0161-DRB1FNx0115 were the most common haplotypes with frequencies 0.0362 and 0.0326, respectively in recipients and 0.0236 and 0.0323, respectively in donors. Genotype frequency revealed a high prevalence of genotype HLA-AFNx0102/AFNx0124 in recipients (0.058) compared to donors (0.0109) whereas low prevalence of HLA-AFNx0101/AFNx0102 in recipients (0.0435) than in donors (0.0797). The phylogenetic and principal component analysis of HLA allele and haplotype frequency distribution revealed genetic similarities of various ethnic groups. Further, case control analysis provides preliminary evidence of association of HLA-A genotype (P < 0.05) with renal failure. This study will be helpful in suitable donor search besides providing valuable information for population genetics and HLA disease association analysis.

Analysis of betaS and betaA genes in a Mexican population with African roots.

PubMed

Magaña, María Teresa; Ongay, Zoyla; Tagle, Juan; Bentura, Gilberto; Cobián, José G; Perea, F Javier; Casas-Castañeda, Maricela; Sánchez-López, Yoaly J; Ibarra, Bertha

2002-01-01

To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

ABO, Rhesus, and Kell Antigens, Alleles, and Haplotypes in West Bengal, India

PubMed Central

Basu, Debapriya; Datta, Suvro Sankha; Montemayor, Celina; Bhattacharya, Prasun; Mukherjee, Krishnendu; Flegel, Willy A.

2018-01-01

Background Few studies have documented the blood group antigens in the population of eastern India. Frequencies of some common alleles and haplotypes were unknown. We describe phenotype, allele, and haplotype frequencies in the state of West Bengal, India. Methods We tested 1,528 blood donors at the Medical College Hospital, Kolkata. The common antigens of the ABO, Rhesus, and Kell blood group systems were determined by standard serologic methods in tubes. Allele and haplotype frequencies were calculated with an iterative method that yielded maximum-likelihood estimates under the assumption of a Hardy-Weinberg equilibrium. Results The prevalence of ABO antigens were B (34%), O (32%), A (25%), and AB (9%) with ABO allele frequencies for O = 0.567, A = 0.189, and B = 0.244. The D antigen (RH1) was observed in 96.6% of the blood donors with RH haplotype frequencies, such as for CDe = 0.688809, cde = 0.16983 and CdE = 0.000654. The K antigen (K1) was observed in 12 donors (0.79%) with KEL allele frequencies for K = 0.004 and k = 0.996. Conclusions: For the Bengali population living in the south of West Bengal, we established the frequencies of the major clinically relevant antigens in the ABO, Rhesus, and Kell blood group systems and derived estimates for the underlying ABO and KEL alleles and RH haplotypes. Such blood donor screening will improve the availability of compatible red cell units for transfusion. Our approach using widely available routine methods can readily be applied in other regions, where the sufficient supply of blood typed for the Rh and K antigens is lacking. PMID:29593462

Identification of specific angiotensin-converting enzyme variants and haplotypes that confer risk and protection against type 2 diabetic nephropathy.

PubMed

Ezzidi, Intissar; Mtiraoui, Nabil; Kacem, Maha; Chaieb, Molka; Mahjoub, Touhami; Almawi, Wassim Y

2009-11-01

Cross-sectional and family studies identified angiotensin-converting enzyme (ACE) gene as a risk factor for diabetic nephropathy (DN). The contribution of ACE gene variants to DN development and progression is controversial and varies among different ethnic/racial groups. We investigated the association of three ACE gene variants with DN, rs1799752 insertion/deletion (I/D), rs1800764T/C and rs12449782A/G in 917 Tunisian type 2 diabetic (T2DM) patients: 515 with (DN) and 402 without (DWN) nephropathy. ACE genotyping was done by PCR-based assays; haplotype estimation was performed using H-Plus software (chi(2)-test based). Genotype frequency distributions of the three studied variants were in Hardy-Weinberg equilibrium. Minor allele frequency of rs1800764 was higher in DN patients than DWN patients or healthy controls, and minor allele frequency of rs1799752 was higher in DN than DWN patients. Higher frequency of rs1799752 and rs1800764 homozygous mutant genotypes was seen in DN compared to DWN patients. Of the three variants, only rs1799752 deletion/deletion (D/D) genotype was associated with a significant increase in albumin to creatinine ratios levels, and D/D carriers had elevated low-density lipoprotein, total cholesterol and urea. Three locus haplotype [rs1799752(I/D)/rs1800764(T/C)/rs12449782(A/G)] analysis revealed that the frequency of DCG haplotype was higher, while that of ITG and ICA haplotypes were lower among unselected type 2 diabetic patients. Taking ITA haplotype as reference, multivariate regression analysis confirmed the negative (ITG), and positive (DCG, DTG, DCA and DTA) association of specific ACE haplotypes with DN, after adjusting for potential nephropathy-linked covariates. Our results support the involvement of specific ACE variants in DN pathogenesis and demonstrate the presence of DN-specific haplotypes at the ACE locus.

Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore.

PubMed

Lee, Yi Chuan; Chan, Soh Ha; Ren, Ee Chee

2008-11-01

Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.

Global variation in CYP2C8–CYP2C9 functional haplotypes

PubMed Central

Speed, William C; Kang, Soonmo Peter; Tuck, David P; Harris, Lyndsay N; Kidd, Kenneth K

2009-01-01

We have studied the global frequency distributions of 10 single nucleotide polymorphisms (SNPs) across 132 kb of CYP2C8 and CYP2C9 in ∼2500 individuals representing 45 populations. Five of the SNPs were in noncoding sequences; the other five involved the more common missense variants (four in CYP2C8, one in CYP2C9) that change amino acids in the gene products. One haplotype containing two CYP2C8 coding variants and one CYP2C9 coding variant reaches an average frequency of 10% in Europe; a set of haplotypes with a different CYP2C8 coding variant reaches 17% in Africa. In both cases these haplotypes are found in other regions of the world at <1%. This considerable geographic variation in haplotype frequencies impacts the interpretation of CYP2C8/CYP2C9 association studies, and has pharmacogenomic implications for drug interactions. PMID:19381162

HLA-A, -B, -DRB1 allele and haplotype frequencies of 920 cord blood units from Central Chile.

PubMed

Schäfer, Christian; Sauter, Jürgen; Riethmüller, Tobias; Kashi, Zahra Mehdizadeh; Schmidt, Alexander H; Barriga, Francisco J

2016-08-01

We present human leukocyte antigen (HLA) haplotype and allele/antigenic group frequencies derived from a data set of 920 umbilical cord blood units collected in Central Chile. HLA-A and -B genotypes were typed using sequence specific oligonucleotide probe methods while HLA-DRB1 genotypes were obtained from sequencing-based typing. The most frequent haplotype is A*29~B*44~DRB1*07:01 with an estimated frequency of 2.1%. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Haplotype analysis of the HFE gene among populations of Northern Eurasia, in patients with metabolic disorders or stomach cancer, and in long-lived people.

PubMed

Mikhailova, S V; Babenko, V N; Ivanoshchuk, D E; Gubina, M A; Maksimov, V N; Solovjova, I G; Voevoda, M I

2016-06-17

Previously, it was shown that the HFE gene (associated with human hereditary hemochromatosis) has several haplotypes of intronic polymorphisms. Some haplotype frequencies are race specific and hence can be used in phylogenetic analysis. We assumed that analysis of Caucasoid patients-living now in Western Siberia and having diseases associated with dietary habits and metabolic rate-will allow us to understand the processes of possible selection during settling of the northern part of Asia. Haplotype analysis of Northern Eurasian native and recently settled ethnic groups was performed on polymorphisms rs1799945, rs1800730, rs1800562, rs2071303, rs1800708, rs1572982, rs2794719, rs807209, and rs2032451 of this gene. The CCA haplotype of the rs2071303, rs1800708, and rs1572982 was found to be associated with HLA-A2 (39 %) in Asian populations. Haplotype analysis for the rs1799945, rs1800730, rs1800562, rs2071303, rs1800708, and rs1572982 was performed on Russian patients with some metabolic disorders or stomach cancer and among long-lived people. Decreased frequencies of the TTA haplotype (T in rs2071303, T in rs1800708, and A in rs1572982) were observed in the groups of patients with diseases associated with overweight (fatty liver disease, type 2 diabetes mellitus, or metabolic syndrome + arterial hypertension) as compared with the control sample. We detected significant differences in this haplotype's frequency between the patients with type 2 diabetes mellitus and Russian adolescents, elderly citizens, and long-lived people (χ(2) P value = 0.003, 0.010, and 0.015, respectively). No significant differences in frequencies of the alleles with mutations in coding regions of the HFE gene (C282Y, H63D, and S65C) were detected between the analyzed patients (with stomach cancer, metabolic syndrome, fatty liver disease, or type 2 diabetes mellitus) and the control Caucasoid sample. Monophyletic origin of H63D (rs1799945) was confirmed in Caucasoids and Northern Asians. The reasons for a sharp increase in the frequency of CCA haplotype of HFE in the Asian race remain unclear.

[Analysis of HLA haplotype frequency and linkage disequilibrium in patients with acute lymphoblastic leukemia from Northern Chinese Han].

PubMed

Gao, Su-qing; Cheng, Liang-hong; Lu, Liang; Jing, Shi-zheng; Cheng, Xi; Zhang, Yin-ze; Zou, Hong-yan; Deng, Zhi-hui

2009-02-01

To analyze the difference between the frequencies of HLA-A-B, B-DRB1 and A-B-DRB1 haplotype, as well as their linkage disequilibrium pattern in patients with acute lymphoblastic leukemia(ALL) and healthy controls from Northern Chinese Han. The frequencies of HLA-A-B, B-DRB1, A-B-DR haplotypes and linkage disequilibrium were estimated by Expectation Maximization method based on the genotypes of 643 patients with ALL and 2 0359 unrelated healthy donors, and the statistical significance between the two groups were estimated by chi-square test. Linkage disequilibrium was analyzed with population genetic methods. The most common HLA-A-B, B-DRB1, and A-B-DR haplotypes were A30-B13, A2-B46, A33-B58, B13-DR7, B46-DR9, B52-DR15, B58-DR17, A30-B13-DR7, A33-B58-DR17 and A1-B37-DR10 in both groups. The frequencies of A30-B13, A2-B46, A33-B44, B13-DR7, A30-B13-DR7 and A2-B46-DR9 haplotypes and linkage disequilibrium value were significantly decreased (P<0.05) in the patient group than that in the control group. On the other hand, the frequencies of A2-B52, A31-B61, A24- B8, B60-DR9, B27-DR4, B52-DR14, B44-DR17, B27-DR12 and A11-B27-DR12 haplotypes and linkage disequilibrium value were significantly increased (P<0.05) in the patient group than that in the control group. There are some common and positive linkage disequilibrium haplotypes in both the ALL patients and the healthy donors in Northern Chinese Han. Interestingly, some haplotypes and their linkage disequilibrium patterns had significantly different distributions between the two groups. The study provided basic data for the relationship of ALL and HLA haplotype and for finding the HLA-A, B, DR matching donors.

Genetic structure among continental and island populations of gyrfalcons.

PubMed

Johnson, Jeff A; Burnham, Kurt K; Burnham, William A; Mindell, David P

2007-08-01

Little is known about the possible influence that past glacial events have had on the phylogeography and population structure of avian predators in the Arctic and sub-Arctic. In this study, we use microsatellite and mitochondrial control region DNA variation to investigate the population genetic structure of gyrfalcons (Falco rusticolus) throughout a large portion of their circumpolar distribution. In most locations sampled, the mtDNA data revealed little geographic structure; however, five out of eight mtDNA haplotypes were unique to a particular geographic area (Greenland, Iceland, or Alaska) and the Iceland population differed from others based on haplotype frequency differences (F(ST)). With the microsatellite results, significant population structure (F(ST), principal components analysis, and cluster analysis) was observed identifying Greenland and Iceland as separate populations, while Norway, Alaska and Canada were identified as a single population consistent with contemporary gene flow across Russia. Within Greenland, differing levels of gene flow between western and eastern sampling locations was indicated with apparent asymmetric dispersal in western Greenland from north to south. This dispersal bias is in agreement with the distribution of plumage colour variants with white gyrfalcons in much higher proportion in northern Greenland. Lastly, because the mtDNA control region sequence differed by only one to four nucleotides from a common haplotype among all gyrfalcons, we infer that the observed microsatellite population genetic structure has developed since the last glacial maximum. This conclusion is further supported by our finding that a closely related species, the saker falcon (Falco cherrug), has greater genetic heterogeneity, including mtDNA haplotypes differing by 1-16 nucleotide substitutions from a common gyrfalcon haplotype. This is consistent with gyrfalcons having expanded rapidly from a single glacial-age refugium to their current circumpolar distribution. Additional sampling of gyrfalcons from Fennoscandia and Russia throughout Siberia is necessary to test putative gene flow between Norway and Alaska and Canada as suggested by this study.

Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification.

PubMed

Retsas, Theodoros; Huse, Klaus; Lazaridis, Lazaros-Dimitrios; Karampela, Niki; Bauer, Michael; Platzer, Matthias; Kolonia, Virginia; Papageorgiou, Eirini; Giamarellos-Bourboulis, Evangelos J; Dimopoulos, George

2018-02-01

Several articles have provided conflicting results regarding the role of single nucleotide polymorphisms (SNPs) in the promoter region of the TNF gene in susceptibility to sepsis. Former articles have been based on previous definitions of sepsis. This study investigated the influence of TNF haplotypes on the development of sepsis using the new Sepsis-3 definitions. DNA was isolated from patients suffering from infection and systemic inflammatory response syndrome. Haplotyping was performed for six SNPs of TNF. The serum levels of tumour necrosis factor alpha (TNF-α) of these patients were measured using an enzyme immunosorbent assay. Patients were classified into infection and sepsis categories using the Sepsis-3 definitions. Associations between the TNF haplotypes and the clinical characteristics and serum TNF-α levels of the patients were examined. The most common TNF haplotype h1 was composed of major alleles of the studied SNPs. Carriage of haplotypes composed of minor frequency alleles was associated with a lower risk of developing sepsis (odds ratio 0.41, 95% confidence interval 0.19-0.88, p=0.022), but this did not affect the 28-day outcome. Serum TNF-α levels were significantly higher among patients homozygous for h1 haplotypes who developed sepsis compared to infection (p=0.032); a similar result was not observed for patients carrying other haplotypes. Haplotypes containing minor frequency SNP alleles of TNF protect against the development of sepsis without affecting the outcome. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Measuring Ambiguity in HLA Typing Methods

PubMed Central

Madbouly, Abeer; Freeman, John; Maiers, Martin

2012-01-01

In hematopoietic stem cell transplantation, donor selection is based primarily on matching donor and patient HLA genes. These genes are highly polymorphic and their typing can result in exact allele assignment at each gene (the resolution at which patients and donors are matched), but it can also result in a set of ambiguous assignments, depending on the typing methodology used. To facilitate rapid identification of matched donors, registries employ statistical algorithms to infer HLA alleles from ambiguous genotypes. Linkage disequilibrium information encapsulated in haplotype frequencies is used to facilitate prediction of the most likely haplotype assignment. An HLA typing with less ambiguity produces fewer high-probability haplotypes and a more reliable prediction. We estimated ambiguity for several HLA typing methods across four continental populations using an information theory-based measure, Shannon's entropy. We used allele and haplotype frequencies to calculate entropy for different sets of 1,000 subjects with simulated HLA typing. Using allele frequencies we calculated an average entropy in Caucasians of 1.65 for serology, 1.06 for allele family level, 0.49 for a 2002-era SSO kit, and 0.076 for single-pass SBT. When using haplotype frequencies in entropy calculations, we found average entropies of 0.72 for serology, 0.73 for allele family level, 0.05 for SSO, and 0.002 for single-pass SBT. Application of haplotype frequencies further reduces HLA typing ambiguity. We also estimated expected confirmatory typing mismatch rates for simulated subjects. In a hypothetical registry with all donors typed using the same method, the entropy values based on haplotype frequencies correspond to confirmatory typing mismatch rates of 1.31% for SSO versus only 0.08% for SBT. Intermediate-resolution single-pass SBT contains the least ambiguity of the methods we evaluated and therefore the most certainty in allele prediction. The presented measure objectively evaluates HLA typing methods and can help define acceptable HLA typing for donor recruitment. PMID:22952712

The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model

PubMed Central

Fields, Peter D.; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

2017-01-01

Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis. PMID:28222092

The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model.

PubMed

Bento, Gilberto; Routtu, Jarkko; Fields, Peter D; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

2017-02-01

Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.

HLA-A*02 allele frequencies and haplotypic associations in Koreans.

PubMed

Park, M H; Whang, D H; Kang, S J; Han, K S

2000-03-01

We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans.

Ontogeny-Driven rDNA Rearrangement, Methylation, and Transcription, and Paternal Influence

PubMed Central

Shiao, Yih-Horng; Leighty, Robert M.; Wang, Cuiju; Ge, Xin; Crawford, Erik B.; Spurrier, Joshua M.; McCann, Sean D.; Fields, Janet R.; Fornwald, Laura; Riffle, Lisa; Driver, Craig; Quiñones, Octavio A.; Wilson, Ralph E.; Kasprzak, Kazimierz S.; Travlos, Gregory S.; Alvord, W. Gregory; Anderson, Lucy M.

2011-01-01

Gene rearrangement occurs during development in some cell types and this genome dynamics is modulated by intrinsic and extrinsic factors, including growth stimulants and nutrients. This raises a possibility that such structural change in the genome and its subsequent epigenetic modifications may also take place during mammalian ontogeny, a process undergoing finely orchestrated cell division and differentiation. We tested this hypothesis by comparing single nucleotide polymorphism-defined haplotype frequencies and DNA methylation of the rDNA multicopy gene between two mouse ontogenic stages and among three adult tissues of individual mice. Possible influences to the genetic and epigenetic dynamics by paternal exposures were also examined for Cr(III) and acid saline extrinsic factors. Variables derived from litters, individuals, and duplicate assays in large mouse populations were examined using linear mixed-effects model. We report here that active rDNA rearrangement, represented by changes of haplotype frequencies, arises during ontogenic progression from day 8 embryos to 6-week adult mice as well as in different tissue lineages and is modifiable by paternal exposures. The rDNA methylation levels were also altered in concordance with this ontogenic progression and were associated with rDNA haplotypes. Sperm showed highest level of methylation, followed by lungs and livers, and preferentially selected haplotypes that are positively associated with methylation. Livers, maintaining lower levels of rDNA methylation compared with lungs, expressed more rRNA transcript. In vitro transcription demonstrated haplotype-dependent rRNA expression. Thus, the genome is also dynamic during mammalian ontogeny and its rearrangement may trigger epigenetic changes and subsequent transcriptional controls, that are further influenced by paternal exposures. PMID:21765958

Detection of Ancestry Informative HLA Alleles Confirms the Admixed Origins of Japanese Population

PubMed Central

Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

2013-01-01

The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

PubMed

Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

2013-01-01

The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago.

Diversity and population structure of Plasmodium falciparum in Thailand based on the spatial and temporal haplotype patterns of the C-terminal 19-kDa domain of merozoite surface protein-1.

PubMed

Simpalipan, Phumin; Pattaradilokrat, Sittiporn; Siripoon, Napaporn; Seugorn, Aree; Kaewthamasorn, Morakot; Butcher, Robert D J; Harnyuttanakorn, Pongchai

2014-02-12

The 19-kDa C-terminal region of the merozoite surface protein-1 of the human malaria parasite Plasmodium falciparum (PfMSP-119) constitutes the major component on the surface of merozoites and is considered as one of the leading candidates for asexual blood stage vaccines. Because the protein exhibits a level of sequence variation that may compromise the effectiveness of a vaccine, the global sequence diversity of PfMSP-119 has been subjected to extensive research, especially in malaria endemic areas. In Thailand, PfMSP-119 sequences have been derived from a single parasite population in Tak province, located along the Thailand-Myanmar border, since 1995. However, the extent of sequence variation and the spatiotemporal patterns of the MSP-119 haplotypes along the Thai borders with Laos and Cambodia are unknown. Sixty-three isolates of P. falciparum from five geographically isolated populations along the Thai borders with Myanmar, Laos and Cambodia in three transmission seasons between 2002 and 2008 were collected and culture-adapted. The msp-1 gene block 17 was sequenced and analysed for the allelic diversity, frequency and distribution patterns of PfMSP-119 haplotypes in individual populations. The PfMSP-119 haplotype patterns were then compared between parasite populations to infer the population structure and genetic differentiation of the malaria parasite. Five conserved polymorphic positions, which accounted for five distinct haplotypes, of PfMSP-119 were identified. Differences in the prevalence of PfMSP-119 haplotypes were detected in different geographical regions, with the highest levels of genetic diversity being found in the Kanchanaburi and Ranong provinces along the Thailand-Myanmar border and Trat province located at the Thailand-Cambodia border. Despite this variability, the distribution patterns of individual PfMSP-119 haplotypes seemed to be very similar across the country and over the three malarial transmission seasons, suggesting that gene flow may operate between parasite populations circulating in Thailand and the three neighboring countries. The major MSP-119 haplotypes of P. falciparum populations in all endemic populations during three transmission seasons in Thailand were identified, providing basic information on the common haplotypes of MSP-119 that is of use for malaria vaccine development and inferring the population structure of P. falciparum populations in Thailand.

High-resolution HLA-A, HLA-B, and HLA-DRB1 haplotype frequencies from the French Bone Marrow Donor Registry.

PubMed

Gourraud, Pierre-Antoine; Pappas, Derek James; Baouz, Amar; Balère, Marie-Lorraine; Garnier, Federico; Marry, Evelyne

2015-05-01

We have estimated human leukocyte antigen (HLA) haplotype frequencies using the maximum likelihood mode, which accommodates typing ambiguities. The results of the frequency distribution of the 7015 haplotypes obtained are presented here. These include a total of 114 HLA-A, 185 HLA-B, and 76 HLA-DRB1 unique alleles at each locus. Across all populations, although the most common individual HLA alleles were HLA-A(∗)02:01 (29.0%), HLA-B(∗)07:02 (11.4%), and HLA-DRB1(∗)07:01 (15.9%), the most frequent haplotype was found to be HLA-A(∗)01:01∼B(∗)08:01∼DRB1(∗)03:01. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya.

PubMed

Kariuki, Simon K; Njunge, James; Muia, Ann; Muluvi, Geofrey; Gatei, Wangeci; Ter Kuile, Feiko; Terlouw, Dianne J; Hawley, William A; Phillips-Howard, Penelope A; Nahlen, Bernard L; Lindblade, Kim A; Hamel, Mary J; Slutsker, Laurence; Shi, Ya Ping

2013-08-27

Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-1(19kDa)) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children <5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001). A total of 12 MSP-1(19kDa) haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P. falciparum were the most prevalent (range 32-37%), with an overall haplotype diversity of > 0.7. No MSP-1(19kDa) 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points. High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide information that could be useful in the design of future malaria vaccines for deployment in endemic areas with high ITN coverage and in interpretation of efficacy data for malaria vaccines based on 3D7 parasite strains.

TNF-alpha SNP haplotype frequencies in equidae.

PubMed

Brown, J J; Ollier, W E R; Thomson, W; Matthews, J B; Carter, S D; Binns, M; Pinchbeck, G; Clegg, P D

2006-05-01

Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine that plays a crucial role in the regulation of inflammatory and immune responses. In all vertebrate species the genes encoding TNF-alpha are located within the major histocompatability complex. In the horse TNF-alpha has been ascribed a role in a variety of important disease processes. Previously two single nucleotide polymorphisms (SNPs) have been reported within the 5' un-translated region of the equine TNF-alpha gene. We have examined the equine TNF-alpha promoter region further for additional SNPs by analysing DNA from 131 horses (Equus caballus), 19 donkeys (E. asinus), 2 Grant's zebras (E. burchellii boehmi) and one onager (E. hemionus). Two further SNPs were identified at nucleotide positions 24 (T/G) and 452 (T/C) relative to the first nucleotide of the 522 bp polymerase chain reaction product. A sequence variant at position 51 was observed between equidae. SNaPSHOT genotyping assays for these and the two previously reported SNPs were performed on 457 horses comprising seven different breeds and 23 donkeys to determine the gene frequencies. SNP frequencies varied considerably between different horse breeds and also between the equine species. In total, nine different TNF-alpha promoter SNP haplotypes and their frequencies were established amongst the various equidae examined, with some haplotypes being found only in horses and others only in donkeys or zebras. The haplotype frequencies observed varied greatly between different horse breeds. Such haplotypes may relate to levels of TNF-alpha production and disease susceptibility and further investigation is required to identify associations between particular haplotypes and altered risk of disease.

Practical interpretation of CYP2D6 haplotypes: Comparison and integration of automated and expert calling.

PubMed

Ruaño, Gualberto; Kocherla, Mohan; Graydon, James S; Holford, Theodore R; Makowski, Gregory S; Goethe, John W

2016-05-01

We describe a population genetic approach to compare samples interpreted with expert calling (EC) versus automated calling (AC) for CYP2D6 haplotyping. The analysis represents 4812 haplotype calls based on signal data generated by the Luminex xMap analyzers from 2406 patients referred to a high-complexity molecular diagnostics laboratory for CYP450 testing. DNA was extracted from buccal swabs. We compared the results of expert calls (EC) and automated calls (AC) with regard to haplotype number and frequency. The ratio of EC to AC was 1:3. Haplotype frequencies from EC and AC samples were convergent across haplotypes, and their distribution was not statistically different between the groups. Most duplications required EC, as only expansions with homozygous or hemizygous haplotypes could be automatedly called. High-complexity laboratories can offer equivalent interpretation to automated calling for non-expanded CYP2D6 loci, and superior interpretation for duplications. We have validated scientific expert calling specified by scoring rules as standard operating procedure integrated with an automated calling algorithm. The integration of EC with AC is a practical strategy for CYP2D6 clinical haplotyping. Copyright © 2016 Elsevier B.V. All rights reserved.

HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies of 10 918 Koreans from bone marrow donor registry in Korea.

PubMed

Park, H; Lee, Y-J; Song, E Y; Park, M H

2016-10-01

The human leucocyte antigen (HLA) system is the most polymorphic genetic system in humans, and HLA matching is crucial in organ transplantation, especially in hematopoietic stem cell transplantation. We investigated HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from bone marrow donor registry in Korea. Intermediate resolution HLA typing was performed using Luminex technology (Wakunaga, Japan), and additional allelic level typing was performed using PCR-single-strand conformation polymorphism method and/or sequence-based typing (Abbott Molecular, USA). Allele and haplotype frequencies were calculated by direct counting and maximum likelihood methods, respectively. A total of 39 HLA-A, 66 HLA-B and 47 HLA-DRB1 alleles were identified. High-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA-B (B*15:01, *35:01, *44:03, *51:01, 54:01 and *58:01) and 8 HLA-DRB1 (DRB1*01:01, *04:05, *04:06, *07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12 and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA-A-B-DRB1 haplotypes were estimated with frequencies of ≥0.05%, ≥0.1% and ≥0.5%, respectively. The five most common haplotypes with frequencies of ≥2.0% were A*33:03-B*44:03-DRB1*13:02 (4.97%), A*33:03-B*58:01-DRB1*13:02, A*33:03-B*44:03-DRB1*07:01, A*24:02-B*07:02-DRB1*01:01 and A*24:02-B*52:01-DRB1*15:02. Among 34 serologic HLA-A-B-DR haplotypes with frequencies of ≥0.5%, 17 haplotypes revealed allele-level diversity and majority of the allelic variation was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype diversity obtained in this study is the most comprehensive data thus far reported in Koreans, and the information will be useful for unrelated stem cell transplantation as well as for disease association studies. © 2016 John Wiley & Sons Ltd.

The distribution of HLA haplotypes in the ethnic groups that make up the Brazilian Bone Marrow Volunteer Donor Registry (REDOME).

PubMed

Halagan, Michael; Oliveira, Danielli Cristina; Maiers, Martin; Fabreti-Oliveira, Raquel A; Moraes, Maria Elisa Hue; Visentainer, Jeane Eliete Laguila; Pereira, Noemi Farah; Romero, Matilde; Cardoso, Juliana Fernandes; Porto, Luís Cristóvão

2018-04-26

The Registries of Bone Marrow Donors around the world include more than 30 million volunteer donors from 57 different countries, and were responsible for over 17,000 hematopoietic stem cell transplants in 2016. The Brazilian Bone Marrow Volunteer Donor Registry (REDOME) was established in 1993 and is the third largest registry in the world with more than 4.3 million donors. We characterized HLA allele and haplotypes frequencies from REDOME comparing them with the donor self-reported race group classification. Five-locus haplotype frequencies (A~C~B~DRB1~DQB1) were estimated for each of the six race groups, resolving phase and allelic ambiguity using the expectation-maximization (EM) algorithm. The top 100 haplotypes in the race groups were separated into eight clusters of haplotypes, based on haplotype similarity, using CLUTO. We present HLA allele and haplotype frequency data from six race groups from 2,938,259 individuals from REDOME. The most frequent haplotype was the same for all groups: A*01:01g~C*07:01g~B*08:01g~DRB1*03:01g~DQB1*02:01g. Some frequent haplotypes such as A*02:01g~C*16:01g~B*44:03~DRB1*07:01g~DQB1*02:01g was not found in people with Preta (Sub-Saharan African descent). A cluster including Branca (European) and Parda or non-informed (admixed) could be distinguished from both Preta (SubSaharan) and Indígena (Amerindian) groups, and from the Amarela (Asian) ones, which clustered with their original population. These results have implications on cross-population matching and can help in donor searches and population-based recruitment strategies.

Haplotype Frequency Distribution in Northeastern European Saduria entomon (Crustacea: Isopoda) Populations. A Phylogeographic Approach

NASA Astrophysics Data System (ADS)

Sell, Jerzy

2003-11-01

The distribution pattern of mtDNA haplotypes in distinct populations of the glacial relict crustacean Saduria entomon was examined to assess phylogeographic relationships among them. Populations from the Baltic, the White Sea and the Barents Sea were screened for mtDNA variation using PCR-based RFLP analysis of a 1150 bp fragment containing part of the CO I and CO II genes. Five mtDNA haplotypes were recorded. An analysis of geographical heterogeneity in haplotype frequency distributions revealed significant differences among populations. The isolated populations of S. entomon have diverged since the retreat of the last glaciation. The geographical pattern of variation is most likely the result of stochastic (founder effect, genetic drift) mechanisms and suggests that the haplotype differentiation observed is probably older than the isolation of the Baltic and Arctic seas.

VNTR internal structure mapping at the {alpha}-globin 3{prime}HVR locus reveals a hierachy of related lineages in oceania

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinson, J.J.; Clegg, J.B.; Boyce, A.J.

1994-09-01

Analysis of the {alpha}-globin gene complex in Oceania has revealed many different rearrangements which remove one of the adult globin genes. Frequencies of these deletion chromosomes are elevated by malarial resistance conferred by the resulting {alpha}-thalassaemia. One particular deletion chromosome, designated -{alpha}{sup 3.7}III, is found at high levels in Melanesia and Polynesia: RFLP haplotype analysis shows that this deletion is always found on chromosomes bearing the IIIa haplotype and is likely to be the product of one single rearrangement event. A subset of the -{alpha}{sup 3.7}III chromosomes carries a more recent mutation which generates the haemoglobin variant HbJ{sup Tongariki}. Wemore » have characterized the allelic variation at the 3{prime}HVR VNTR locus located 6 kb from the globin genes in each of these groups of chromosomes. We have determined the internal structure of these alleles by RFLP mapping of PCR-amplified DNA: within each group, the allelic diversity results from the insertion and/or deletion of small {open_quotes}motifs{close_quotes} of up to 6 adjacent repeats. Mapping of 3{prime}HVR alleles associated with other haplotypes reveals that these are composed of repeat arrays that are substantially different to those derived from IIIa chromosomes, indicating that interchromosomal recombination between heterologous haplotypes does not account for any of the diversity seen to date. We have recently shown that allelic size variation at the two VNTR loci flanking the {alpha}-globin complex is very closely linked to the haplotypes known to be present at this locus. Here we show that, within a haplotype, VNTR alleles are very closely related to each other on the basis of internal structure and demonstrate that intrachromosomal mutation processes involving small numbers of tandem repeats are the main cause of variation at this locus.« less

Genetic Diversity of Bactrocera dorsalis (Diptera: Tephritidae) on the Hawaiian Islands: Implications for an Introduction Pathway Into California.

PubMed

Barr, Norman B; Ledezma, Lisa A; Leblanc, Luc; San Jose, Michael; Rubinoff, Daniel; Geib, Scott M; Fujita, Brian; Bartels, David W; Garza, Daniel; Kerr, Peter; Hauser, Martin; Gaimari, Stephen

2014-10-01

Population genetic diversity of the oriental fruit fly, Bactrocera dorsalis (Hendel), on the Hawaiian islands of Oahu, Maui, Kauai, and Hawaii (the Big Island) was estimated using DNA sequences of the mitochondrial cytochrome c oxidase subunit I gene. In total, 932 flies representing 36 sampled sites across the four islands were sequenced for a 1,500-bp fragment of the gene named the C1500 marker. Genetic variation was low on the Hawaiian Islands with >96% of flies having just two haplotypes: C1500-Haplotype 1 (63.2%) or C1500-Haplotype 2 (33.3%). The other 33 flies (3.5%) had haplotypes similar to the two dominant haplotypes. No population structure was detected among the islands or within islands. The two haplotypes were present at similar frequencies at each sample site, suggesting that flies on the various islands can be considered one population. Comparison of the Hawaiian data set to DNA sequences of 165 flies from outbreaks in California between 2006 and 2012 indicates that a single-source introduction pathway of Hawaiian origin cannot explain many of the flies in California. Hawaii, however, could not be excluded as a maternal source for 69 flies. There was no clear geographic association for Hawaiian or non-Hawaiian haplotypes in the Bay Area or Los Angeles Basin over time. This suggests that California experienced multiple, independent introductions from different sources. © 2014 Entomological Society of America.

Reducing animal sequencing redundancy by preferentially selecting animals with low-frequency haplotypes

USDA-ARS?s Scientific Manuscript database

Many studies leverage targeted whole genome sequencing (WGS) experiments in order to identify rare and causal variants within populations. As a natural consequence of experimental design, many of these surveys tend to sequence redundant haplotype segments due to high frequency in the base population...

Young Alu insertions within the MHC class I region in native American populations: insights into the origin of the MHC-Alu repeats.

PubMed

Gómez-Pérez, Luis; Alfonso-Sánchez, Miguel A; Dipierri, José E; Sánchez, Dora; Espinosa, Ibone; De Pancorbo, Marian M; Peña, José A

2013-01-01

Genetic heterogeneity of two Amerindian populations (Jujuy province, Argentina, and Waorani tribe, Ecuador) was characterized by analyzing data on polymorphic Alu insertions within the human major histocompatibility complex (MHC) class I region (6p21.31), which are completely nonexistent in Native Americans. We further evaluated the haplotype distribution and genetic diversity among continental ancestry groups and their potential implications for the dating of the origin of MHC-Alus. Five MHC-Alu elements (AluMicB, AluTF, AluHJ, AluHG, and AluHF) were typed in samples from Jujuy (N = 108) and Waorani (N = 36). Allele and haplotype frequency data on worldwide populations were compiled to explore spatial structuring of the MHC-Alu diversity through AMOVA tests. We utilized the median-joining network approach to illustrate the continental distribution of the MHC-Alu haplotypes and their phylogenetic relationships. Allele and haplotype distributions differed significantly between Jujuy and Waorani. The Waorani featured a low average heterozygosity attributable to strong population isolation. Overall, Alu markers showed great genetic heterogeneity both within and among populations. The haplotype distribution was distinctive of each continental ancestry group. Contrary to expectations, Africans showed the lowest MHC-Alu diversity. Genetic drift mainly associated to population bottlenecks seems to be reflected in the low MHC-Alu diversity of the Amerindians, mainly in Waorani. Geographical structuring of the haplotype distribution supports the efficiency of the MHC-Alu loci as lineage (ancestry) markers. The markedly low Alu diversity of African populations relative to other continental clusters suggests that these MHC-Alus might have arisen after the anatomically modern humans expanded out of Africa. Copyright © 2013 Wiley Periodicals, Inc.

µ-Calpain, calpastatin, and growth hormone receptor genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in Angus cattle selected to increase minor haplotype ... frequencies

USDA-ARS?s Scientific Manuscript database

Genetic marker effects and interactions are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to increase divergent haplotype and minor marker allele frequencies to 1) estimate effect size an...

HLA-DR2-associated DRB1 and DRB5 alleles and haplotypes in Koreans.

PubMed

Song, E Y; Kang, S J; Lee, Y J; Park, M H

2000-09-01

There are considerable racial differences in the distribution of HLA-DR2-associated DRB1 and DRB5 alleles and the characteristics of linkage disequilibrium between these alleles. In this study, the frequencies of DR2-associated DRB1 and DRB5 alleles and related haplotypes were analyzed in 186 DR2-positive individuals out of 800 normal Koreans registered for unrelated bone marrow donors. HLA class I antigen typing was performed by the serological method and DRB1 and DRB5 genotyping by the PCR-single strand conformational polymorphism method. Only 3 alleles were detected for DR2-associated DRB1 and DRB5 genes, respectively: DRB1(*)1501 (gene frequency 8.0%), (*)1502 (3.2%), (*)1602 (0.9%); DRB5(*)0101 (8.0%), (*)0102 (3.2%), and (*)0202 (0.9%). DRB1-DRB5 haplotype analysis showed an exclusive association between these alleles: DRB1*1501-DRB5*0101 (haplotype frequency 8.0%), DRB1(*)1502-DRB5(*)0102 (3.2%), and DRB1(*)1602-DRB5(*)0202 (0.9%). The 5 most common DR2-associated A-B-DRB1 haplotypes occurring at frequencies of > or = 0.5% were A24-B52-DRB1(*)1502 (1.8%), A2-B62-DRB1(*)1501, A2-B54-DRB1(*)1501, A26-B61-DRB1(*)1501, and A24-B51-DRB1(*)1501. The remarkable homogeneity in the haplotypic associations between DR2-associated DRB1 and DRB5 alleles in Koreans would be advantageous for organ transplantation compared with other ethnic groups showing considerable heterogeneity in the distribution of DRB1-DRB5 haplotypes.

High-resolution HLA allele and haplotype frequencies in majority and minority populations of Costa Rica and Nicaragua: Differential admixture proportions in neighboring countries.

PubMed

Arrieta-Bolaños, E; Madrigal-Sánchez, J J; Stein, J E; Órlich-Pérez, P; Moreira-Espinoza, M J; Paredes-Carias, E; Vanegas-Padilla, Y; Salazar-Sánchez, L; Madrigal, J A; Marsh, S G E; Shaw, B E

2018-06-01

The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high-resolution HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub-Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub-Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro-descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high-resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Highly Conserved Keratin-Associated Protein 7-1 Gene in Yak, Taurine and Zebu Cattle.

PubMed

Arlud, S; He, N; Sari, E M; Ma, Z-J; Zhang, H; An, T-W; Han, J-L

2017-01-01

Keratin-associated proteins (KRTAPs) play a critical role in cross-linking the keratin intermediate filaments to build a hair shaft. The genetic polymorphisms of the bovine KRTAP7-1 gene were investigated for the first time in this study. The complete coding sequence of the KRTAP7-1 gene in 108 domestic yak, taurine and zebu cattle from China and Indonesia were successfully amplified using polymerase chain reaction and then directly sequenced. Only two single-nucleotide polymorphisms (one nonsynonymous at c.7C/G and another synonymous at c.21C/T) and three haplotypes (BOVIN-KRTAP7-1*A, B and C) were identified in the complete coding sequence of the bovine KRTAP7-1 gene among all animals. There was no polymorphism across three Chinese indigenous yak breeds and one Indonesian zebu cattle population, all sharing the BOVINKRTAP71*A haplotype. The four taurine cattle populations also had BOVIN-KRTAP7-1*A as the most common haplotype with a frequency of 0.80. The frequency of novel haplotype BOVIN-KRTAP7-1*B was only 0.07 present in one heterozygous animal in each of the four taurine cattle populations, while BOVINKRTAP7- 1*C was only found in a Simmental and a local Chinese Yellow cattle population with frequencies of 0.17 and 0.36, respectively. The monomorphic yak KRTAP7-1 gene in particular, and highly conserved bovine, sheep and goat KRTAP7-1 genes in general, demonstrated its unique intrinsic structural property (e.g., > 21% high glycine content) and primary functional importance in supporting the mechanical strength and shape of hair.

Divergence at the casein haplotypes in dairy and meat goat breeds.

PubMed

Küpper, Julia; Chessa, Stefania; Rignanese, Daniela; Caroli, Anna; Erhardt, Georg

2010-02-01

Casein genes have been proved to have an influence on milk properties, and are in addition appropriate for phylogeny studies. A large number of casein polymorphisms exist in goats, making their analysis quite complex. The four casein loci were analyzed by molecular techniques for genetic polymorphism detection in the two dairy goat breeds Bunte Deutsche Edelziege (BDE; n=96), Weisse Deutsche Edelziege (WDE; n=91), and the meat goat breed Buren (n=75). Of the 35 analyzed alleles, 18 were found in BDE, and 17 in Buren goats and WDE. In addition, a new allele was identified at the CSN1S1 locus in the BDE, showing a frequency of 0.05. This variant, named CSN1S1*A', is characterized by a t-->c transversion in intron 9. Linkage disequilibrium was found at the casein haplotype in all three breeds. A total of 30 haplotypes showed frequencies higher than 0.01. In the Buren breed only one haplotype showed a frequency higher than 0.1. The ancestral haplotype B-A-A-B (in the order: CSN1S1-CSN2-CSN1S2-CSN3) occurred in all three breeds, showing a very high frequency (>0.8) in the Buren.

Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11

PubMed Central

Olivier, Michael; Wang, Xujing; Cole, Regina; Gau, Brian; Kim, Jessica; Rubin, Edward M.; Pennacchio, Len A.

2009-01-01

Members of the apolipoprotein gene cluster (APOA1/C3/A4/A5) on human chromosome 11q23 play an important role in lipid metabolism. Polymorphisms in both APOA5 and APOC3 are strongly associated with plasma triglyceride concentrations. The close genomic locations of these two genes as well as their functional similarity have hindered efforts to define whether each gene independently influences human triglyceride concentrations. In this study, we examined the linkage disequilibrium and haplotype structure of 49 SNPs in a 150-kb region spanning the gene cluster. We identified a total of five common APOA5 haplotypes with a frequency of greater than 8% in samples of northern European origin. The APOA5 haplotype block did not extend past the 7 SNPs in the gene and was separated from the other apolipoprotein gene in the cluster by a region of significantly increased recombination. Furthermore, one previously identified triglyceride risk haplotype of APOA5 (APOA5*3) showed no association with three APOC3 SNPs previously associated with triglyceride concentrations, in contrast to the other risk haplotype (APOA5*2), which was associated with all three minor APOC3 SNP alleles. These results highlight the complex genetic relationship between APOA5 and APOC3 and support the notion that APOA5 represents an independent risk gene affecting plasma triglyceride concentrations in humans. PMID:15081120

Recombinant structures expand and contract inter and intragenic diversification at the KIR locus

PubMed Central

2013-01-01

Background The human KIR genes are arranged in at least six major gene-content haplotypes, all of which are combinations of four centromeric and two telomeric motifs. Several less frequent or minor haplotypes also exist, including insertions, deletions, and hybridization of KIR genes derived from the major haplotypes. These haplotype structures and their concomitant linkage disequilibrium among KIR genes suggest that more meaningful correlative data from studies of KIR genetics and complex disease may be achieved by measuring haplotypes of the KIR region in total. Results Towards that end, we developed a KIR haplotyping method that reports unambiguous combinations of KIR gene-content haplotypes, including both phase and copy number for each KIR. A total of 37 different gene content haplotypes were detected from 4,512 individuals and new sequence data was derived from haplotypes where the detailed structure was not previously available. Conclusions These new structures suggest a number of specific recombinant events during the course of KIR evolution, and add to an expanding diversity of potential new KIR haplotypes derived from gene duplication, deletion, and hybridization. PMID:23394822

Molecular Variation at the HLA-A, B, C, DRB1, DQA1, and DQB1 Loci in Full Heritage American Indians in Arizona: Private Haplotypes and Their Evolution

PubMed Central

Williams, Robert; Chen, Yao-Fong; Endres, Robert; Middleton, Derek; Trucco, Massimo; Knowler, William

2009-01-01

A sample of 492 full heritage, unrelated residents of the Gila River Indian Community (GRIC) of Arizona were characterized for their high resolution DNA alleles at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci. Only 5 allelic categories are found at HLA-A, 10 at HLA-B, 8 at HLA-C and HLA-DR, and 4 at DQA1 and DQB1. There is little evidence for population structure at the 6 loci. Two “private” alleles, B*5102 and B*4005, that are found nearly exclusively in American Indian populations in the desert southwest and northern Mexico, are likely new mutations after the first inhabitation of the area, the evolution of which are reflected in the contemporary distribution of their respective haplotypes. DRB1*1402 has the highest reported frequency of any specificity at the DRB1 locus, 0.7461, and serves as a sensitive probe for locating related east Asian populations. The haplotypes in this population also exhibit a highly restricted distribution and strong genetic disequilibria, which has important implications for matching solid organ and bone marrow allografts. It is shown that, when one considers HLA-A-B-DRB1 homozygotes as allograft donors for all full heritage members of the GRIC, 50% of the community would find a non-mismatched organ within the homozygotes for the 6 most common haplotypes. This raises questions about transplantation policy and whether, in the presence of high frequency private alleles and a restricted number of haplotypes, the full heritage American Indian community of the desert southwest should act as its own pool of donors for its affected members. PMID:19845915

Molecular variation at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci in full heritage American Indians in Arizona: private haplotypes and their evolution.

PubMed

Williams, R; Chen, Y-F; Endres, R; Middleton, D; Trucco, M; Williams, J Dunn; Knowler, W

2009-12-01

A sample of 492 full heritage, unrelated residents of the Gila River Indian Community (GRIC) of Arizona were characterized for their high-resolution DNA alleles at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci. Only five allelic categories are found at HLA-A, 10 at HLA-B, 8 at HLA-C and HLA-DR, and 4 at DQA1 and DQB1. There is little evidence for population structure at the 6 loci. Two 'private' alleles, B*5102 and B*4005, which are found nearly exclusively in American Indian populations in the desert southwest and northern Mexico, are likely new mutations after the first inhabitation of the area, the evolution of which are reflected in the contemporary distribution of their respective haplotypes. DRB1*1402 has the highest reported frequency of any specificity at the DRB1 locus, 0.7461, and serves as a sensitive probe for locating related east Asian populations. The haplotypes in this population also exhibit a highly restricted distribution and strong genetic disequilibria, which has important implications for matching solid organ and bone marrow allografts. It is shown that, when one considers HLA-A-B-DRB1 homozygotes as allograft donors for all full heritage members of the GRIC, 50% of the community would find a non-mismatched organ within the homozygotes for the six most common haplotypes. This raises questions about transplantation policy and whether, in the presence of high-frequency private alleles and a restricted number of haplotypes, the full heritage American Indian community of the desert southwest should act as its own pool of donors for its affected members.

HERC1 polymorphisms: population-specific variations in haplotype composition.

PubMed

Yuasa, Isao; Umetsu, Kazuo; Nishimukai, Hiroaki; Fukumori, Yasuo; Harihara, Shinji; Saitou, Naruya; Jin, Feng; Chattopadhyay, Prasanta K; Henke, Lotte; Henke, Jürgen

2009-08-01

Human HERC1 is one of six HERC proteins and may play an important role in intracellular membrane trafficking. The human HERC1 gene is suggested to have been affected by local positive selection. To assess the global frequency distributions of coding and non-coding single nucleotide polymorphisms (SNPs) in the HERC1 gene, we developed a new simultaneous genotyping method for four SNPs, and applied this method to investigate 1213 individuals from 12 global populations. The results confirmed remarked differences in the allele and haplotype frequencies between East Asian and non-East Asian populations. One of the three common haplotypes observed was found to be characteristic of East Asians, who showed a relatively uniform distribution of haplotypes. Information on haplotypes would be useful for testing the function of polymorphisms in the HERC1 gene. This is the first study to investigate the distribution of HERC1 polymorphisms in various populations. (c) 2009 John Wiley & Sons, Ltd.

Temporal genetic changes in Plasmodium vivax apical membrane antigen 1 over 19 years of transmission in southern Mexico.

PubMed

Flores-Alanis, Alejandro; González-Cerón, Lilia; Santillán, Frida; Ximenez, Cecilia; Sandoval, Marco A; Cerritos, René

2017-05-02

Mexico advanced to the pre-elimination phase in 2009 due to a significant reduction in malaria cases, and since 2000, Plasmodium vivax is the only species transmitted. During the last two decades, malaria transmission has been mostly local and isolated to a few regions. It is important to gain further insights into the impact of control measures on the parasite population structure. Hence, the aim of the current study was to determine detailed changes in P. vivax genetic diversity and population structure based on analysing the gene that encodes the apical membrane antigen 1 (pvama1). This analysis covered from control to pre-elimination (1993-2011) in a hypo-endemic region in southern Mexico. The 213 pvama1 I-II sequences presently analysed were grouped into six periods of three years each. They showed low genetic diversity, with 15 haplotypes resolved. Among the DNA sequences, there was a gradual decrease in genetic diversity, the number of mixed genotype infections and the intensity of positive selection, in agreement with the parallel decline in malaria cases. At the same time, linkage disequilibrium (R 2 ) increased. The three-dimensional haplotype network revealed that pvama1 I-II haplotypes were separated by 1-11 mutational steps, and between one another by 0-3 unsampled haplotypes. In the temporal network, seven haplotypes were detected in at least two of the six-time layers, and only four distinct haplotypes were evidenced in the pre-elimination phase. Structure analysis indicated that three subpopulations fluctuated over time. Only 8.5% of the samples had mixed ancestry. In the pre-elimination phase, subpopulation P1 was drastically reduced, and the admixture was absent. The results suggest that P. vivax in southern Mexico evolved based on local adaptation into three "pseudoclonal" subpopulations that diversified at the regional level and persisted over time, although with varying frequency. Control measures and climate events influenced the number of malaria cases and the genetic structure. The sharp decrease in parasite diversity and other related genetic parameters during the pre-elimination phase suggests that malaria elimination is possible in the near future. These results are useful for epidemiological surveillance.

Frequency and origin of haplotypes associated with the beta-globin gene cluster in individuals with trait and sickle cell anemia in the Atlantic and Pacific coastal regions of Colombia

PubMed Central

Fong, Cristian; Lizarralde-Iragorri, María Alejandra; Rojas-Gallardo, Diana; Barreto, Guillermo

2013-01-01

Sickle cell anemia is a genetic disease with high prevalence in people of African descent. There are five typical haplotypes associated with this disease and the haplotypes associated with the beta-globin gene cluster have been used to establish the origin of African-descendant people in America. In this work, we determined the frequency and the origin of haplotypes associated with hemoglobin S in a sample of individuals with sickle cell anemia (HbSS) and sickle cell hemoglobin trait (HbAS) in coastal regions of Colombia. Blood samples from 71 HbAS and 79 HbSS individuals were obtained. Haplotypes were determined based on the presence of variable restriction sites within the β-globin gene cluster. On the Pacific coast of Colombia the most frequent haplotype was Benin, while on the Atlantic coast Bantu was marginally higher than Benin. Eight atypical haplotypes were observed on both coasts, being more diverse in the Atlantic than in the Pacific region. These results suggest a differential settlement of the coasts, dependent on where slaves were brought from, either from the Gulf of Guinea or from Angola, where the haplotype distributions are similar. Atypical haplotypes probably originated from point mutations that lost or gained a restriction site and/or by recombination events. PMID:24385850

β-globin gene cluster haplotypes in ethnic minority populations of southwest China

PubMed Central

Sun, Hao; Liu, Hongxian; Huang, Kai; Lin, Keqin; Huang, Xiaoqin; Chu, Jiayou; Ma, Shaohui; Yang, Zhaoqing

2017-01-01

The genetic diversity and relationships among ethnic minority populations of southwest China were investigated using seven polymorphic restriction enzyme sites in the β-globin gene cluster. The haplotypes of 1392 chromosomes from ten ethnic populations living in southwest China were determined. Linkage equilibrium and recombination hotspot were found between the 5′ sites and 3′ sites of the β-globin gene cluster. 5′ haplotypes 2 (+−−−), 6 (−++−+), 9 (−++++) and 3′ haplotype FW3 (−+) were the predominant haplotypes. Notably, haplotype 9 frequency was significantly high in the southwest populations, indicating their difference with other Chinese. The interpopulation differentiation of southwest Chinese minority populations is less than those in populations of northern China and other continents. Phylogenetic analysis shows that populations sharing same ethnic origin or language clustered to each other, indicating current β-globin cluster diversity in the Chinese populations reflects their ethnic origin and linguistic affiliations to a great extent. This study characterizes β-globin gene cluster haplotypes in southwest Chinese minorities for the first time, and reveals the genetic variability and affinity of these populations using β-globin cluster haplotype frequencies. The results suggest that ethnic origin plays an important role in shaping variations of the β-globin gene cluster in the southwestern ethnic populations of China. PMID:28205625

PCR/oligonucleotide probe typing of HLA class II alleles in a Filipino population reveals an unusual distribution of HLA haplotypes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bugawan, T.L.; Chang, J.D.; Erlich, H.A.

1994-02-01

The authors have analyzed the distribution of HLA class II alleles and haplotypes in a Filipino population by PCR amplification of the DRB1, DQB1, and DPB1 second-exon sequences from buccal swabs obtained from 124 family members and 53 unrelated individuals. The amplified DNA was typed by using nonradioactive sequence-specific oligonucleotide probes. Twenty-two different DRB1 alleles, including the novel Filipino *1105, and 46 different DRB1/DQB1 haplotypes, including the unusual DRB1*0405-DQB1*0503, were identified. An unusually high frequency (f = .383) of DPB1*0101, a rare allele in other Asian populations, was also observed. In addition, an unusual distribution of DRB1 alleles and haplotypesmore » was seen in this population, with DR2 (f = .415) and DRB1*1502-DQB1*0502 (f = .233) present at high frequencies. This distribution of DRB1 alleles differs from the typical HLA population distribution, in which the allele frequencies are more evenly balanced. The distribution of HLA class II alleles and haplotypes in this Filipino population is different from that of other Asian and Pacific groups: of those populations studied to date, the Indonesian population is the most similar. DRB1*1502-DQB1*0502 was in strong linkage disequilibrium (D[prime] = .41) with DPB 1*0101 (f = .126, for the extended haplotype), which is consistent with selection for this DR, DQ, DP haplotype being responsible for the high frequency of these three class II alleles in this populations. 30 refs., 2 figs., 6 tabs.« less

Population structure of the giant garter snake, Thamnophis gigas

USGS Publications Warehouse

Paquin, M.M.; Wylie, G.D.; Routman, E.J.

2006-01-01

The giant garter snake, Thamnophis gigas, is a threatened species endemic to California's Central Valley. We tested the hypothesis that current watershed boundaries have caused genetic differentiation among populations of T. gigas. We sampled 14 populations throughout the current geographic range of T. gigas and amplified 859 bp from the mitochondrial gene ND4 and one nuclear microsatellite locus. DNA sequence variation from the mitochondrial gene indicates there is some genetic structuring of the populations, with high F ST values and unique haplotypes occurring at high frequency in several populations. We found that clustering populations by watershed boundary results in significant between-region genetic variance for mtDNA. However, analysis of allele frequencies at the microsatellite locus NSU3 reveals very low F ST values and little between-region variation in allele frequencies. The discordance found between mitochondrial and microsatellite data may be explained by aspects of molecular evolution and/or T. gigas life history characteristics. Differences in effective population size between mitochondrial and nuclear DNA, or male-biased gene flow, result in a lower migration rate of mitochondrial haplotypes relative to nuclear alleles. However, we cannot exclude homoplasy as one explanation for homogeneity found for the single microsatellite locus. The mitochondrial nucleotide sequence data supports conservation practices that identify separate management units for T. gigas. ?? Springer 2006.

Insights into HLA-G Genetics Provided by Worldwide Haplotype Diversity

PubMed Central

Castelli, Erick C.; Ramalho, Jaqueline; Porto, Iane O. P.; Lima, Thálitta H. A.; Felício, Leandro P.; Sabbagh, Audrey; Donadi, Eduardo A.; Mendes-Junior, Celso T.

2014-01-01

Human leukocyte antigen G (HLA-G) belongs to the family of non-classical HLA class I genes, located within the major histocompatibility complex (MHC). HLA-G has been the target of most recent research regarding the function of class I non-classical genes. The main features that distinguish HLA-G from classical class I genes are (a) limited protein variability, (b) alternative splicing generating several membrane bound and soluble isoforms, (c) short cytoplasmic tail, (d) modulation of immune response (immune tolerance), and (e) restricted expression to certain tissues. In the present work, we describe the HLA-G gene structure and address the HLA-G variability and haplotype diversity among several populations around the world, considering each of its major segments [promoter, coding, and 3′ untranslated region (UTR)]. For this purpose, we developed a pipeline to reevaluate the 1000Genomes data and recover miscalled or missing genotypes and haplotypes. It became clear that the overall structure of the HLA-G molecule has been maintained during the evolutionary process and that most of the variation sites found in the HLA-G coding region are either coding synonymous or intronic mutations. In addition, only a few frequent and divergent extended haplotypes are found when the promoter, coding, and 3′UTRs are evaluated together. The divergence is particularly evident for the regulatory regions. The population comparisons confirmed that most of the HLA-G variability has originated before human dispersion from Africa and that the allele and haplotype frequencies have probably been shaped by strong selective pressures. PMID:25339953

Homozygosity of single nucleotide polymorphisms in the 3' region of the canine estrogen receptor 1 gene is greater in Toy Poodles than in Miniature Dachshunds and Chihuahuas.

PubMed

Pathirana, Indunil N; Tanaka, Kakeru; Kawate, Noritoshi; Tsuji, Makoto; Hatoya, Shingo; Inaba, Toshio; Tamada, Hiromichi

2011-06-01

Differences in the distribution of single nucleotide polymorphisms (SNPs) and haplotypes in the estrogen receptor α gene (ESR1) were examined in Miniature Dachshunds (n = 48), Chihuahuas (n = 20) and Toy Poodles (n = 18). Five DNA fragments located in the 40-kb region at the 3' end of ESR1 were amplified by polymerase chain reaction and were directly sequenced. We compared allele, genotype and estimated haplotype frequencies at each SNP in the 3' end of ESR1 for these three breeds of small dog. The frequency of the major allele and the genotype frequency of the major allele homozygotes, were significantly higher in Toy Poodles for five SNPs (SNP #5, #14-17) than in Miniature Dachshunds, and significantly higher in Toy Poodles than Chihuahuas for three SNPs (SNP #15-17). A common haplotype block was identified in an approximately 20-kb region encompassing four SNPs (SNPs # 14-17). The frequencies of the most abundant estimated haplotype (GTTG) and GTTG homozygotes were significantly higher in Toy Poodles than in the other two breeds. These results imply that homozygosity for the allele, genotype and haplotype distribution within the block at the 3' end of ESR1 is greater in Toy Poodles than in Miniature Dachshunds and Chihuahuas. © 2011 The Authors; Animal Science Journal © 2011 Japanese Society of Animal Science.

Genetic diversity and natural selection of Plasmodium vivax multi-drug resistant gene (pvmdr1) in Mesoamerica.

PubMed

González-Cerón, Lilia; Montoya, Alberto; Corzo-Gómez, Josselin C; Cerritos, Rene; Santillán, Frida; Sandoval, Marco A

2017-07-01

The Plasmodium vivax multidrug resistant 1 gene (pvmdr1) codes for a transmembrane protein of the parasite's digestive vacuole. It is likely that the pvmdr1 gene mutations occur at different sites by convergent evolution. In here, the genetic variation of pvmdr1 at three sites of the Mesoamerican region was studied. Since 1950s, malarious patients of those areas have been treated only with chloroquine and primaquine. Blood samples from patients infected with P. vivax were obtained in southern Mexico (SMX), in the Northwest (NIC-NW) and in the northeast (NIC-NE) of Nicaragua. Genomic DNA was obtained and fragments of pvmdr1 were amplified and sequenced. The nucleotide and amino acid changes as well as the haplotype frequency in pvmdr1 were determined per strain and per geographic site. The sequences of pvmdr1 obtained from the studied regions were compared with homologous sequences from the GenBank database to explore the P. vivax genetic structure. In 141 parasites, eight nucleotide changes (two changes were synonymous and other six were nonsynonymous) were detected in 1536 bp. The PvMDR1 amino acid changes Y976F, F1076FL were predominant in endemic parasites from NIC-NE and outbreak parasites in NIC-NW but absent in SMX. Thirteen haplotypes were resolved, and found to be closely related, but their frequency at each geographic site was different (P = 0.0001). The pvmdr1 codons 925-1083 gene fragment showed higher genetic and haplotype diversity in parasites from NIC-NE than the other areas outside Latin America. The haplotype networks suggested local diversification of pvmdr1 and no significant departure from neutrality. The F ST values were low to moderate regionally, but high between NIC-NE or NIC-NW and other regions inside and outside Latin America. The pvmdr1 gene might have diversified recently at regional level. In the absence of significant natural, genetic drift might have caused differential pvmdr1 haplotype frequencies at different geographic sites in Mesoamerica. A very recent expansion of divergent pvmdr1 haplotypes in NIC-NE/NIC-NW produced high differentiation between these and parasites from other sites including SMX. These data are useful to set a baseline for epidemiological surveillance.

Hereditary tyrosinemia type I: strong association with haplotype 6 in French Canadians permits simple carrier detection and prenatal diagnosis.

PubMed Central

Demers, S. I.; Phaneuf, D.; Tanguay, R. M.

1994-01-01

Hereditary tyrosinemia type 1 (HT1), a severe inborn error of tyrosine catabolism, is caused by deficiency of the terminal enzyme, fumarylacetoacetate hydrolase (FAH). The highest reported frequency of HT1 is in the French Canadian population, especially in the Saguenay-Lac-St-Jean region. Using human FAH cDNA probes, we have identified 10 haplotypes with TaqI, KpnI, RsaI, BglII, and MspI RFLPs in 118 normal chromosomes from the French Canadian population. Interestingly, in 29 HT1 children, a prevalent haplotype, haplotype 6, was found to be strongly associated with the disease, at a frequency of 90% of alleles, as compared with approximately 18% in 35 control individuals. This increased to 96% in the 24 patients originating from Saguenay-Lac-St-Jean. These results suggest that one or only a few prevailing mutations are responsible for most of the HT1 cases in Saguenay-Lac-St-Jean. Since most patients were found to be homozygous for a specific haplotype in this population, FAH RFLPs have permitted simple carrier detection in nine different informative HT1 families, with a confidence level of 99.9%. Heterozygosity rate values obtained from 52 carriers indicated that approximately 88% of families at risk from Saguenay-Lac-St-Jean are fully or partially informative. Prenatal diagnosis was also achieved in an American family. Analysis of 24 HT1 patients from nine countries gave a frequency of approximately 52% for haplotype 6, suggesting a relatively high association, worldwide, of HT1 with this haplotype. Images Figure 1 PMID:7913582

Detecting structure of haplotypes and local ancestry

USDA-ARS?s Scientific Manuscript database

We present a two-layer hidden Markov model to detect the structure of haplotypes for unrelated individuals. This allows us to model two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local an...

Maximum likelihood estimation of linkage disequilibrium in half-sib families.

PubMed

Gomez-Raya, L

2012-05-01

Maximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of δ=0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of δ were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated δ was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium.

Maximum Likelihood Estimation of Linkage Disequilibrium in Half-Sib Families

PubMed Central

Gomez-Raya, L.

2012-01-01

Maximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of δ = 0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of δ were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated δ was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium. PMID:22377635

Beta-globin gene cluster haplotypes of Amerindian populations from the Brazilian Amazon region.

PubMed

Guerreiro, J F; Figueiredo, M S; Zago, M A

1994-01-01

We have determined the beta-globin cluster haplotypes for 80 Indians from four Brazilian Amazon tribes: Kayapó, Wayampí, Wayana-Apalaí, and Arára. The results are analyzed together with 20 Yanomámi previously studied. From 2 to 4 different haplotypes were identified for each tribe, and 7 of the possible 32 haplotypes were found in a sample of 172 chromosomes for which the beta haplotypes were directly determined or derived from family studies. The haplotype distribution does not differ significantly among the five populations. The two most common haplotypes in all tribes were haplotypes 2 and 6, with average frequencies of 0.843 and 0.122, respectively. The genetic affinities between Brazilian Indians and other human populations were evaluated by estimates of genetic distance based on haplotype data. The lowest values were observed in relation to Asians, especially Chinese, Polynesians, and Micronesians.

Factor IX gene haplotypes in Amerindians.

PubMed

Franco, R F; Araújo, A G; Zago, M A; Guerreiro, J F; Figueiredo, M S

1997-02-01

We have determined the haplotypes of the factor IX gene for 95 Indians from 5 Brazilian Amazon tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5', nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron 3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The results of the haplotype distribution and the allele frequencies for each of the factor IX gene polymorphisms in Amerindians were similar to the results reported for Asian populations but differed from results for other ethnic groups. Only five haplotypes were identified within the entire Amerindian study population, and the haplotype distribution was significantly different among the five tribes, with one (Arára) to four (Wayampí) haplotypes being found per tribe. These findings indicate a significant heterogeneity among the Indian tribes and contrast with the homogeneous distribution of the beta-globin gene cluster haplotypes but agree with our recent findings on the distribution of alpha-globin gene cluster haplotypes and the allele frequencies for six VNTRs in the same Amerindian tribes. Our data represent the first study of factor IX-associated polymorphisms in Amerindian populations and emphasizes the applicability of these genetic markers for population and human evolution studies.

A TNF region haplotype offers protection from typhoid fever in Vietnamese patients

PubMed Central

2009-01-01

The genomic region surrounding the TNF locus on human chromosome 6 has previously been associated with typhoid fever in Vietnam. We used a haplotypic approach to understand this association further. Eighty single nucleotide polymorphisms (SNPs) spanning a 150 kb region were genotyped in 95 Vietnamese individuals (typhoid case/mother/father trios). A subset of data from 33 SNPs with a minor allele frequency of >4.3% was used to construct haplotypes. Fifteen SNPs, which tagged the 42 constructed haplotypes were selected. The haplotype tagging SNPs (T1-T15) were genotyped in 380 confirmed typhoid cases and 380 Vietnamese ethnically matched controls. Allelic frequencies of seven SNPs (T1, T2, T3, T5, T6, T7, T8) were significantly different between typhoid cases and controls. Logistic regression results support the hypothesis that there is just one signal associated with disease at this locus. Haplotype-based analysis of the tag SNPs provided positive evidence of association with typhoid (posterior probability 0.821). The analysis highlighted a low-risk cluster of haplotypes that each carry the minor allele of T1 or T7, but not both, and otherwise carry the combination of alleles *12122*1111 at T1-T11, further supporting the one associated signal hypothesis. Finally, individuals that carry the typhoid fever protective haplotype *12122*1111 also produce a relatively low TNF-α response to LPS. PMID:17503085

HLA-A, -B, -C, -DQB1, and -DRB1,3,4,5 allele and haplotype frequencies in the Costa Rica Central Valley Population and its relationship to worldwide populations.

PubMed

Arrieta-Bolaños, Esteban; Maldonado-Torres, Hazael; Dimitriu, Oana; Hoddinott, Michael A; Fowles, Finnuala; Shah, Anila; Orlich-Pérez, Priscilla; McWhinnie, Alasdair J; Alfaro-Bourrouet, Wilbert; Buján-Boza, Willem; Little, Ann-Margaret; Salazar-Sánchez, Lizbeth; Madrigal, J Alejandro

2011-01-01

The human leukocyte antigen (HLA) system is the most polymorphic in humans. Its allele, genotype, and haplotype frequencies vary significantly among different populations. Molecular typing data on HLA are necessary for the development of stem cell donor registries, cord blood banks, HLA-disease association studies, and anthropology studies. The Costa Rica Central Valley Population (CCVP) is the major population in this country. No previous study has characterized HLA frequencies in this population. Allele group and haplotype frequencies of HLA genes in the CCVP were determined by means of molecular typing in a sample of 130 unrelated blood donors from one of the country's major hospitals. A comparison between these frequencies and those of 126 populations worldwide was also carried out. A minimum variance dendrogram based on squared Euclidean distances was constructed to assess the relationship between the CCVP sample and populations from all over the world. Allele group and haplotype frequencies observed in this study are consistent with a profile of a dynamic and diverse population, with a hybrid ethnic origin, predominantly Caucasian-Amerindian. Results showed that populations genetically closest to the CCVP are a Mestizo urban population from Venezuela, and another one from Guadalajara, Mexico. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. All rights reserved.

Association of polymorphisms and haplotypes in the cytochrome P450 1B1 gene with uterine leiomyoma: A case control study

PubMed Central

SALIMI, SAEEDEH; KHODAMIAN, MARYAM; NAROOIE-NEJAD, MEHRNAZ; HAJIZADEH, AZAM; FAZELI, KIMIA; NAMAZI, LIDA; YAGHMAEI, MINOO

2015-01-01

Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus and estrogen metabolizing enzymes affect its promotion and progression. The aim of the present study was to evaluate the association between four single-nucleotide polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) gene and UL risk. Four SNPs of the CYP1B1 gene in 105 UL patients and 112 unrelated healthy controls were genotyped using a direct sequencing method. Haplotype analyses were performed with UNPHASED software and linkage disequilibrium (LD) was assessed by Haploview software. There were no associations between Leu432Val (rs1056836), Asp449Asp (rs1056837) and Asn453Ser (rs1800440) polymorphisms of the CYP1B1 gene and UL. Although the genotypic frequencies of the Arg368His (rs79204362) polymorphism did not differ between the two groups, the frequency of A (His) allele was significantly higher in UL females (P=0.02). In addition, the frequency of GTAA haplotype was significantly higher in the controls and played a protective role in UL susceptibility. A strong LD between the three common SNPs (rs1056836, rs1056837 and rs1800440) in the CYP1B1 gene was observed in the population. In conclusion, a higher frequency of the CYP1B1 368His (A) allele was observed in UL females. The frequency of the GTAA haplotype was significantly higher in healthy females and this haplotype played a protective role in UL susceptibility. PMID:26075073

Hb S [β6(A3)Glu→Val, GAG>GTG] in Mexican Mestizos: frequency and analysis of the 5' β-globin haplotype.

PubMed

Guzmán, Luis F; Perea, Francisco J; Magaña, María T; Morales-González, Karina R; Chávez-Velazco, M Luz; Ibarra, Bertha

2010-01-01

Between 1978 and 2009, we studied 1,863 Mexican Mestizo patients with clinical data compatible with a hemoglobinopathy. Of these patients, 382 had some hemoglobin (Hb) abnormality (20.5%), 128 had a sickle cell hemoglobinopathy, representing a general frequency of 6.9%, which is similar to the percentage observed in previous studies on Mexican Mestizos. We analyzed the 5' β-globin haplotype (5'Hp) in 79 unrelated β(S) chromosomes (26 β(S)/β(S), 14 β(S)/β(Thal), nine β(S)/β(A) and four β(S)/β(D)), and four haplotypes were observed: 72.2% CAR 24.1% Benin, 2.5% Senegal and 1.2% Cameroon; the last two are reported for first time in Mexico. In some Latin American populations such as Brazil, the Bantu haplotype predominates, while in others such as Jamaica, the Benin haplotype is the most frequent, showing heterogeneity of African genes as a consequence of different regions involved in the slave trade.

Tribal ethnicity and CYP2B6 genetics in Ugandan and Zimbabwean populations in the UK: implications for efavirenz dosing in HIV infection.

PubMed

Jamshidi, Y; Moreton, M; McKeown, D A; Andrews, S; Nithiyananthan, T; Tinworth, L; Holt, D W; Sadiq, S T

2010-12-01

To determine differences in CYP2B6 loss of function (LoF) single nucleotide polymorphisms (SNPs) and haplotypes between Zimbabweans and Ugandans, and within Ugandan populations (Bantu and Nilotic). Genetic epidemiological study enrolling adult black African Ugandan and Zimbabwean patients attending a UK HIV-1 clinic, irrespective of antiretroviral therapy status. Genomic DNA was extracted from whole blood and the presence of CYP2B6 alleles was determined by direct sequencing of all nine exons of the CYP2B6 gene. Blood was also collected, where appropriate, for determination of efavirenz concentrations. Frequency of SNPs in all patients and LoF haplotype frequencies were calculated. The relationship between the number of LoF haplotype alleles possessed and efavirenz trough concentration (ETC) was determined. Thirty-six Zimbabweans and 74 Ugandans (58 Bantu and 16 Nilotic) were recruited. The definite haplotypes determined were *6, *18, *20 and *27 as LoF and *4 as gain of function. Among those with definite genotypes, the frequency of LoF alleles was 65% [95% confidence interval (95% CI): 51-80] of Zimbabweans versus 22% (95% CI: 12-31) of Ugandan Bantus (P = 10(-6)) and versus 39% (95% CI: 14-64) of Ugandan Nilotics (P = 0.09). Among the 19 patients with definite genotype and with available ETCs, log ETCs were associated with a greater number of LoF haplotype alleles [848 ng/mL (n = 12), 1069 ng/mL (n = 4) and 1813 ng/mL (n = 3) for 0, 1 or 2 LoF haplotypes, respectively (P = 0.016)]. Among Zimbabweans, LoF haplotypes constitute the majority of CYP2B6 alleles and are significantly higher in prevalence compared with Ugandans. Frequencies of LoF haplotypes and SNPs in Ugandan Nilotics appear to lie between those of Zimbabweans and Ugandan Bantus. These findings may have relevance to pharmacokinetics and dosing of efavirenz in African populations.

HLA-A, HLA-B, HLA-DRB1 allele and haplotype frequencies in 6384 umbilical cord blood units and transplantation matching and engraftment statistics in the Zhejiang cord blood bank of China.

PubMed

Wang, F; He, J; Chen, S; Qin, F; Dai, B; Zhang, W; Zhu, F M; Lv, H J

2014-02-01

Umbilical cord blood (UCB) is a widely accepted source of progenitor cells, and now, many cord blood banks were established. Here, we analysed the HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies, HLA matching possibilities for searching potential donors and outcome of UCB transplantations in Zhejiang cord blood bank of China. A total of 6384 UCB units were characterized for 17 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles at the first field resolution level. Additionally, B*14, B*15 and B*40 were typed to the second field level. A total of 1372 distinct A-B-DRB1 haplotypes were identified. The frequencies of 7 haplotypes were more than 1%, and 439 haplotypes were <0.01%. A*02-B*46-DRB1*09, A*33-B*58-DRB1*03 and A*30-B*13-DRB1*07 were the most common haplotypes, with frequencies of 4.4%, 3.3%, and 2.9%, respectively. Linkage disequilibrium(LD) analysis showed that there were 83 A-B, 106 B-DRB1, 54 A-DRB1 haplotypes with positive LD, in which 51 A-B, 60 B-DRB1, 32 A-DRB1 haplotypes exhibited a significant LD (P < 0.05). In 682 search requests, 12.9%, 40.0% and 42.7% of patients were found to have 6 of 6, 5 of 6 and 4 of 6 HLA-A, HLA-B and HLA-DRB1 matching donors, respectively. A total of 30 UCB units were transplanted to 24 patients (3 patients not evaluated due to early death); 14 of 21 patients (66.7%) engrafted. This study reveals the HLA distribution and its transplantation application in the cord blood bank of Zhejiang province. These data can help to select potential UCB donors for transplantation and used to assess the scale of new cord blood banking endeavours. © 2013 John Wiley & Sons Ltd.

[Determination of HLA-A, -B and -DRB1 polymorphism in brain dead organ donors representative of the Colombian general population, 2007-2014].

PubMed

Arias, Yazmin Rocío; Osorio-Arango, Karime; Bayona, Brayan; Ercilla, Guadalupe; Beltrán-Durán, Mauricio

2017-06-01

Genes encoding for human leukocyte antigens (HLA) are highly polymorphic and of great importance in organ transplantation procedures, as determining allelic frequencies in defined populations is taken into account among the scientific criteria for organ allocation. The objective of this study was to establish the antigen HLA-A, -B, and -DRB1 haplotype frequencies in organ donors representative of the Colombian population after brain death. We conducted a descriptive retrospective study involving 2,506 cadaveric organ donors including an allelic and haplotype analysis of HLA-A, -B and -DRB1; we also determined the Hardy-Weinberg equilibrium. We identified 21, 43 and 15 allelic loci for groups A*, B* and DRB1*, respectively. We detected 1,268 HLA-A, -B and -DR, 409 HLA-A-B, 383 HLA-DR-B, and 218 HLA-A-DR haplotypes. The three loci were found to be in Hardy-Weinberg equilibrium between the number of heterozygotes observed and the expected number, with p values of ;0.05. This study provides information on the allelic distribution of HLA class I and II in organ donors from the six regions in which Colombia is structurally divided to provide transplant services.

HLA in North Colombia Chimila Amerindians.

PubMed

Arnaiz-Villena, Antonio; Palacio-Grüber, Jose; Juarez, Ignacio; Hernández, Ennio; Muñiz, Ester; Bayona, Brayan; Campos, Cristina; Nieto, Jorge; Martin-Villa, Manuel; Silvera, Carlos

2018-04-01

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci. Copyright © 2018. Published by Elsevier Inc.

Population Structure of Sclerotinia subarctica and Sclerotinia sclerotiorum in England, Scotland and Norway

PubMed Central

Clarkson, John P.; Warmington, Rachel J.; Walley, Peter G.; Denton-Giles, Matthew; Barbetti, Martin J.; Brodal, Guro; Nordskog, Berit

2017-01-01

Sclerotinia species are important fungal pathogens of a wide range of crops and wild host plants. While the biology and population structure of Sclerotinia sclerotiorum has been well-studied, little information is available for the related species S. subarctica. In this study, Sclerotinia isolates were collected from different crop plants and the wild host Ranuculus ficaria (meadow buttercup) in England, Scotland, and Norway to determine the incidence of Sclerotinia subarctica and examine the population structure of this pathogen for the first time. Incidence was very low in England, comprising only 4.3% of isolates while moderate and high incidence of S. subarctica was identified in Scotland and Norway, comprising 18.3 and 48.0% of isolates respectively. Characterization with eight microsatellite markers identified 75 haplotypes within a total of 157 isolates over the three countries with a few haplotypes in Scotland and Norway sampled at a higher frequency than the rest across multiple locations and host plants. In total, eight microsatellite haplotypes were shared between Scotland and Norway while none were shared with England. Bayesian and principal component analyses revealed common ancestry and clustering of Scottish and Norwegian S. subarctica isolates while English isolates were assigned to a separate population cluster and exhibited low diversity indicative of isolation. Population structure was also examined for S. sclerotiorum isolates from England, Scotland, Norway, and Australia using microsatellite data, including some from a previous study in England. In total, 484 haplotypes were identified within 800 S. sclerotiorum isolates with just 15 shared between England and Scotland and none shared between any other countries. Bayesian and principal component analyses revealed a common ancestry and clustering of the English and Scottish isolates while Norwegian and Australian isolates were assigned to separate clusters. Furthermore, sequencing part of the intergenic spacer (IGS) region of the rRNA gene resulted in 26 IGS haplotypes within 870 S. sclerotiorum isolates, nine of which had not been previously identified and two of which were also widely distributed across different countries. S. subarctica therefore has a multiclonal population structure similar to S. sclerotiorum, but has a different ancestry and distribution across England, Scotland, and Norway. PMID:28421039

Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR.

PubMed

Tyson, Jess; Armour, John A L

2012-12-11

Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in) regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.

Origin and dispersal of atypical aldehyde dehydrogenase ALDH2487Lys.

PubMed

Luo, Huai-Rong; Wu, Gui-Sheng; Pakstis, Andrew J; Tong, Li; Oota, Hiroki; Kidd, Kenneth K; Zhang, Ya-Ping

2009-04-15

The East Asian respond with a marked facial flushing and mild to moderate symptoms of intoxication after drinking the amounts of alcohol that has no detectable effect on European. The alcohol sensitivity in Orientals is due to a delayed oxidation of acetaldehyde by an atypical aldehyde dehydrogenase ALDH2487Lys, which is resulted from a structural mutation in gene ALDH2. The atypical ALDH2487Lys allele has been associated with various phenotypic statuses, such as protective against alcohol dependence and the risk of alcohol-related digestive tract cancers. Here, we have examined this SNP, adjacent four non-coding SNPs, and one downstream STRP on ALDH2 gene, in total of 1072 unrelated healthy individuals from 14 Chinese populations and 130 Indian individuals. Five major haplotypes based on five SNPs across the ALDH2 gene 40 kb were found in all East Asian populations. The frequencies of the ancestral haplotype GCCTG and the East Asian special haplotype GCCTA containing the atypical ALDH2487Lys allele were 44.8% and 14.9%, respectively. The frequency of the atypical ALDH2487Lys allele or the East Asian specific haplotype GCCTA is high in Yunnan, South coastal, east coastal of China, and decreased gradually toward inland China, West, Northwest and North China. Combined with demographic history in East Asian, our results showed that the presence of ALDH2487Lys allele in peripheral regions of China might be the results of historical migration events from China to these regions. The origin of ALDH2487Lys could be possibly traced back to ancient Pai-Yuei tribe in South China.

Evidence from mitochondrial DNA that head lice and body lice of humans (Phthiraptera: Pediculidae) are conspecific.

PubMed

Leo, N P; Campbell, N J H; Yang, X; Mumcuoglu, K; Barker, S C

2002-07-01

The specific status of the head and body lice of humans has been debated for more than 200 yr. To clarify the specific status of head and body lice, we sequenced 524 base pairs (bp) of the cytochrome oxidase I (COI) gene of 28 head and 28 body lice from nine countries. Ten haplotypes that differed by 1-5 bp at 11 nucleotide positions were identified. A phylogeny of these sequences indicates that these head and body lice are not from reciprocally monophyletic lineages. Indeed, head and body lice share three of the 10 haplotypes we found. F(ST) values and exact tests of haplotype frequencies showed significant differences between head and body lice. However, the same tests also showed significant differences among lice from different countries. Indeed, more of the variation in haplotype frequencies was explained by differences among lice from different countries than by differences between head and body lice. Our results indicate the following: (1) head and body lice do not represent reciprocally monophyletic lineages and are conspecific; (2) gene flow among populations of lice from different countries is limited; and (3) frequencies of COI haplotypes can be used to study maternal gene flow among populations of head and body lice and thus transmission of lice among their human hosts.

High-resolution HLA haplotype frequencies of stem cell donors in Germany with foreign parentage: how can they be used to improve unrelated donor searches?

PubMed

Pingel, Julia; Solloch, Ute V; Hofmann, Jan A; Lange, Vinzenz; Ehninger, Gerhard; Schmidt, Alexander H

2013-03-01

In hematopoietic stem cell transplantation, human leukocyte antigens (HLA), usually HLA loci A, B, C, DRB1 and DQB1, are required to check histocompatibility between a potential donor and the recipient suffering from a malignant or non-malignant blood disease. As databases of potential unrelated donors are very heterogeneous with respect to typing resolution and number of typed loci, donor registries make use of haplotype frequency-based algorithms to provide matching probabilities for each potentially matching recipient/donor pair. However, it is well known that HLA allele and haplotype frequencies differ significantly between populations. We estimated high-resolution HLA-A, -B, -C, -DRB1 haplotype and allele frequencies of donors within DKMS German Bone Marrow Donor Center with parentage from 17 different countries: Turkey, Poland, Italy, Russian Federation, Croatia, Greece, Austria, Kazakhstan, France, The Netherlands, Republic of China, Romania, Portugal, USA, Spain, United Kingdom and Bosnia and Herzegovina. 5-locus haplotypes including HLA-DQB1 are presented for Turkey, Poland, Italy and Russian Federation. We calculated linkage disequilibria for each sample. Genetic distances between included countries could be shown to reflect geography. We further demonstrate how genetic differences between populations are reflected in matching probabilities of recipient/donor pairs and how they influence the search for unrelated donors as well as strategic donor center typings. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Frequency distribution of interleukin-10 haplotypes (-1082 A>G, -819 C>T, and -592 C>A) in a Mexican population.

PubMed

Vázquez-Villamar, M; Palafox-Sánchez, C A; Hernández-Bello, J; Muñoz-Valle, J F; Valle, Y; Cruz, A; Alatorre-Meza, A I; Oregon-Romero, E

2016-11-03

Interleukin 10 (IL-10) is an immunoregulatory cytokine with multiple roles in the immune system. Three single nucleotide polymorphisms at positions -1082 (A>G), -819 (C>T), and -592 (C>A) in the promoter region of the IL10 gene are believed to be associated with different inflammatory, infectious, and autoimmune diseases. These polymorphisms exhibit a strong linkage disequilibrium (LD) and form three principal haplotypes (GCC, ACC, and ATA). The GCC and ATA haplotypes have been associated with high and low levels of IL-10 production, respectively. The aim of this study was to establish the allele and haplotype frequencies of the IL10 polymorphisms in Mestizos from western Mexico. SNPs were analyzed in 340 healthy unrelated Mestizos from western Mexico by polymerase chain reaction-restriction fragment length polymorphism. The studied population presented significant differences, in the distribution of IL10 polymorphisms, from the Asian, African, and European populations. We also observed a strong LD within -1082 A>G, -819 C>T, and -592 C>A (100% pc = 7.735 x 10 -18 ). The haplotypes ACC (45.4%), ATA (22.0%), GTA (14.9%), and GCC (13.9%) were most frequently observed in this population. The haplotype frequencies, however, differed from those reported previously in Mestizos from central Mexico, Asians, Africans, and European Caucasians, suggesting a differential gene flow in the Mexican Mestizo population. This could account for the genetic variability between Mexicans and populations of other ethnicities. The study of these polymorphisms and their haplotypes could help in expanding our knowledge to design future disease-risk studies on the western Mexican population.

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots

PubMed Central

Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7–8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry. PMID:28622394

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots.

PubMed

Heraclides, Alexandros; Bashiardes, Evy; Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis; Cariolou, Marios A

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7-8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry.

Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR

PubMed Central

2012-01-01

Background Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in) regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. Results In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. Conclusion This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example. PMID:23231411

Population genetic structure of Santa Ynez rainbow trout – 2001 based on microsatellite and mtDNA analyses

USGS Publications Warehouse

Nielsen, Jennifer L.; Zimmerman, Christian E.; Olsen, Jeffrey B.; Wiacek, Talia; Kretschmer, E.J.; Greenwald, Glenn M.; Wenburg, John K.

2003-01-01

Microsatellite allelic and mitochondrial DNA (mtDNA) haplotype diversity are analyzed in eight rainbow trout (Oncorhynchus mykiss) collections: two from tributaries flowing into the upper Santa Ynez River watershed at Gibraltar Reservoir (Camuesa and Gidney creeks); three from tributaries between Gibraltar and Jameson reservoirs (Fox, Blue Canyon, and Alder creeks); one from a tributary above Jameson Reservoir (Juncal Creek); Jameson Reservoir; and one from the mainstem Santa Ynez River above the Jameson Reservoir. Both analyses reveal a high degree of population structure. Thirteen microsatellite loci are amplified from 376 fish. Population pairwise comparisons show significant differences in allelic frequency among all populations with the exception of Juncal Creek and Jameson Reservoir (p = 0.4). Pairwise Fst values range from 0.001 (Juncal Creek and Jameson Reservoir) to 0.17 (Camuesa and Juncal creeks) with an overall value of 0.021. Regression analyses (Slatkin 1993) supports an isolation-bydistance model in the five populations below Jameson Reservoir (intercept = 1.187, slope = -0.41, r2 = 0.67). A neighbor-joining bootstrap value of 100% (based on 2000 replicate trees) separates the populations sampled above and below Juncal Dam. Composite haplotypes from 321 fish generated using mtDNA sequence data (Dloop) reveal four previously described haplotypes (MYS1, MYS3, MYS5 and MYS8; Nielsen et al. 1994a), and one (MYS5) was found in all populations. Mean haplotype diversity is 0.48. Pairwise Fst values from mtDNA range from -0.019 to 0.530 (0.177 over all populations) and are larger than those for microsatellites in 26 of 28 pairwise comparisons. In addition, the mtDNA and microsatellites provide contrasting evidence of the relationship of Fox and Alder creeks to the other six populations. Discrepancies between the two markers are likely due to the unique properties of the two marker types and their value in revealing historic (mtDNA) versus contemporary (microsatellites) genetic relationships. The contrasting results may indicate how relationships among the upper Santa Ynez River populations have changed since the installation of Juncal Dam. Comparisons of mtDNA haplotype frequencies from fish collected for this study with samples analyzed previously in JLN’s laboratory (1993) reveal significant differences in mtDNA haplotypes for Fox and Alder creeks. In the 2001 samples from this study, there is a loss of three haplotypes despite larger sample sizes. AMOVA analysis of what we term “upper” (Alder, Fox, Blue Canyon, Camuesa, Gidney creeks and the upper Santa Ynez mainstem) and “lower” (Hilton, Salsipuedes and the lower mainstem Santa Ynez River) Santa Ynez River populations (1993-2001) reveal that 11% of the variance in haplotypes is found between the upper and lower drainage. A comparison of the mtDNA data from this study with those available for southern California coastal and California hatchery O. mykiss populations yields Fst values of 0.15 and 0.47, respectively. Differentiation of mtDNA haplotypes for population pairs of Santa Ynez River and hatchery fish show no significant differentiation between wild and at least one hatchery strain in Cachuma Reservoir, Hilton Creek, and the Lower Santa Ynez River.

Y-STR haplotypes of Native American populations from the Brazilian Amazon region.

PubMed

Palha, Teresinha Jesus Brabo Ferreira; Rodrigues, Elzemar Martins Ribeiro; dos Santos, Sidney Emanuel Batista

2010-10-01

The allele and haplotype frequencies of nine Y-STRs (DYS19, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393, DYS385 I/II) were determined in a sample of six native tribes from the Brazilian Amazon (Tiriyó, Awa-Guajá, Waiãpi, Urubu-Kaapor, Zoé and Parakanã). Forty-eight different haplotypes were identified, 28 of which unique. Five haplotypes are very frequent and were shared by over 10 individuals. The estimated haplotype diversity (0.9114) was very low compared to other geographic groups, including Africans, Europeans and Asians. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program

PubMed Central

Zhou, Xiao-Yang; Zhu, Fa-Ming; Li, Jian-Ping; Mao, Wei; Zhang, De-Mei; Liu, Meng-Li; Hei, Ai-Lian; Dai, Da-Peng; Jiang, Ping; Shan, Xiao-Yan; Zhang, Bo-Wei; Zhu, Chuan-Fu; Shen, Jie; Deng, Zhi-Hui; Wang, Zheng-Lei; Yu, Wei-Jian; Chen, Qiang; Qiao, Yan-Hui; Zhu, Xiang-Ming; Lv, Rong; Li, Guo-Ying; Li, Guo-Liang; Li, Heng-Cong; Zhang, Xu; Pei, Bin; Jiao, Li-Xin; Shen, Gang; Liu, Ying; Feng, Zhi-Hui; Su, Yu-Ping; Xu, Zhao-Xia; Di, Wen-Ying; Jiang, Yao-Qin; Fu, Hong-Lei; Liu, Xiang-Jun; Liu, Xiang; Zhou, Mei-Zhen; Du, Dan; Liu, Qi; Han, Ying; Zhang, Zhi-Xin; Cai, Jian-Ping

2015-01-01

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies. PMID:26421847

Round and large: morphological and genetic consequences of artificial selection on the gourd tree Crescentia cujete by the Maya of the Yucatan Peninsula, Mexico

PubMed Central

Aguirre-Dugua, Xitlali; Eguiarte, Luis E.; González-Rodríguez, Antonio; Casas, Alejandro

2012-01-01

Background and Aims Artificial selection, the main driving force of domestication, depends on human perception of intraspecific variation and operates through management practices that drive morphological and genetic divergences with respect to wild populations. This study analysed the recognition of varieties of Crescentia cujete by Maya people in relation to preferred plant characters and documents ongoing processes of artificial selection influencing differential chloroplast DNA haplotype distribution in sympatric wild and home-garden populations. Methods Fifty-three home gardens in seven villages (93 trees) and two putative wild populations (43 trees) were sampled. Through semi-structured interviews we documented the nomenclature of varieties, their distinctive characters, provenance, frequency and management. Phenotypic divergence of fruits was assessed with morphometric analyses. Genetic analyses were performed through five cpDNA microsatellites. Key Results The Maya recognize two generic (wild/domesticated) and two specific domesticated (white/green) varieties of Crescentia cujete. In home gardens, most trees (68 %) were from domesticated varieties while some wild individuals (32 %) were tolerated. Cultivation involves mainly vegetative propagation (76 %). Domesticated fruits were significantly rounder, larger and with thicker pericarp than wild fruits. Haplotype A was dominant in home gardens (76 %) but absent in wild populations. Haplotypes B–F were found common in the wild but at low frequency (24 %) in home gardens. Conclusions The gourd tree is managed through clonal and sexual propagules, fruit form and size being the main targets of artificial selection. Domesticated varieties belong to a lineage preserved by vegetative propagation but propagation by seeds and tolerance of spontaneous trees favour gene flow from wild populations. Five mutational steps between haplotypes A and D suggest that domesticated germplasm has been introduced to the region. The close relationship between Maya nomenclature and artificial selection has maintained the morphological and haplotypic identity (probably for centuries) of domesticated Crescentia despite gene flow from wild populations. PMID:22499854

Round and large: morphological and genetic consequences of artificial selection on the gourd tree Crescentia cujete by the Maya of the Yucatan Peninsula, Mexico.

PubMed

Aguirre-Dugua, Xitlali; Eguiarte, Luis E; González-Rodríguez, Antonio; Casas, Alejandro

2012-06-01

Artificial selection, the main driving force of domestication, depends on human perception of intraspecific variation and operates through management practices that drive morphological and genetic divergences with respect to wild populations. This study analysed the recognition of varieties of Crescentia cujete by Maya people in relation to preferred plant characters and documents ongoing processes of artificial selection influencing differential chloroplast DNA haplotype distribution in sympatric wild and home-garden populations. Fifty-three home gardens in seven villages (93 trees) and two putative wild populations (43 trees) were sampled. Through semi-structured interviews we documented the nomenclature of varieties, their distinctive characters, provenance, frequency and management. Phenotypic divergence of fruits was assessed with morphometric analyses. Genetic analyses were performed through five cpDNA microsatellites. The Maya recognize two generic (wild/domesticated) and two specific domesticated (white/green) varieties of Crescentia cujete. In home gardens, most trees (68 %) were from domesticated varieties while some wild individuals (32 %) were tolerated. Cultivation involves mainly vegetative propagation (76 %). Domesticated fruits were significantly rounder, larger and with thicker pericarp than wild fruits. Haplotype A was dominant in home gardens (76 %) but absent in wild populations. Haplotypes B-F were found common in the wild but at low frequency (24 %) in home gardens. The gourd tree is managed through clonal and sexual propagules, fruit form and size being the main targets of artificial selection. Domesticated varieties belong to a lineage preserved by vegetative propagation but propagation by seeds and tolerance of spontaneous trees favour gene flow from wild populations. Five mutational steps between haplotypes A and D suggest that domesticated germplasm has been introduced to the region. The close relationship between Maya nomenclature and artificial selection has maintained the morphological and haplotypic identity (probably for centuries) of domesticated Crescentia despite gene flow from wild populations.

Mapping a New Spontaneous Preterm Birth Susceptibility Gene, IGF1R, Using Linkage, Haplotype Sharing, and Association Analysis

PubMed Central

Luukkonen, Aino; Teramo, Kari; Puttonen, Hilkka; Ojaniemi, Marja; Varilo, Teppo; Chaudhari, Bimal P.; Plunkett, Jevon; Murray, Jeffrey C.; McCarroll, Steven A.; Muglia, Louis J.; Palotie, Aarno; Hallman, Mikko

2011-01-01

Preterm birth is the major cause of neonatal death and serious morbidity. Most preterm births are due to spontaneous onset of labor without a known cause or effective prevention. Both maternal and fetal genomes influence the predisposition to spontaneous preterm birth (SPTB), but the susceptibility loci remain to be defined. We utilized a combination of unique population structures, family-based linkage analysis, and subsequent case-control association to identify a susceptibility haplotype for SPTB. Clinically well-characterized SPTB families from northern Finland, a subisolate founded by a relatively small founder population that has subsequently experienced a number of bottlenecks, were selected for the initial discovery sample. Genome-wide linkage analysis using a high-density single-nucleotide polymorphism (SNP) array in seven large northern Finnish non-consanginous families identified a locus on 15q26.3 (HLOD 4.68). This region contains the IGF1R gene, which encodes the type 1 insulin-like growth factor receptor IGF-1R. Haplotype segregation analysis revealed that a 55 kb 12-SNP core segment within the IGF1R gene was shared identical-by-state (IBS) in five families. A follow-up case-control study in an independent sample representing the more general Finnish population showed an association of a 6-SNP IGF1R haplotype with SPTB in the fetuses, providing further evidence for IGF1R as a SPTB predisposition gene (frequency in cases versus controls 0.11 versus 0.05, P = 0.001, odds ratio 2.3). This study demonstrates the identification of a predisposing, low-frequency haplotype in a multifactorial trait using a well-characterized population and a combination of family and case-control designs. Our findings support the identification of the novel susceptibility gene IGF1R for predisposition by the fetal genome to being born preterm. PMID:21304894

Cultural traditions across a migratory network shape the genetic structure of southern right whales around Australia and New Zealand.

PubMed

Carroll, E L; Baker, C S; Watson, M; Alderman, R; Bannister, J; Gaggiotti, O E; Gröcke, D R; Patenaude, N; Harcourt, R

2015-11-09

Fidelity to migratory destinations is an important driver of connectivity in marine and avian species. Here we assess the role of maternally directed learning of migratory habitats, or migratory culture, on the population structure of the endangered Australian and New Zealand southern right whale. Using DNA profiles, comprising mitochondrial DNA (mtDNA) haplotypes (500 bp), microsatellite genotypes (17 loci) and sex from 128 individually-identified whales, we find significant differentiation among winter calving grounds based on both mtDNA haplotype (FST = 0.048, ΦST = 0.109, p < 0.01) and microsatellite allele frequencies (FST = 0.008, p < 0.01), consistent with long-term fidelity to calving areas. However, most genetic comparisons of calving grounds and migratory corridors were not significant, supporting the idea that whales from different calving grounds mix in migratory corridors. Furthermore, we find a significant relationship between δ(13)C stable isotope profiles of 66 Australian southern right whales, a proxy for feeding ground location, and both mtDNA haplotypes and kinship inferred from microsatellite-based estimators of relatedness. This indicates migratory culture may influence genetic structure on feeding grounds. This fidelity to migratory destinations is likely to influence population recovery, as long-term estimates of historical abundance derived from estimates of genetic diversity indicate the South Pacific calving grounds remain at <10% of pre-whaling abundance.

HLA-A, -B and -DRB1 polymorphism in Koreans defined by sequence-based typing of 4128 cord blood units.

PubMed

Huh, J Y; Yi, D Y; Eo, S-H; Cho, H; Park, M H; Kang, M S

2013-12-01

Human leucocyte antigen (HLA) alleles and haplotypes differ significantly among different ethnic groups, and high-resolution typing methods allow for the detection of a wider spectrum of HLA variations. In this study, HLA-A, -B and -DRB1 genotypes were analysed in 4128 cord blood units obtained from Korean women using the sequence-based typing method. A total of 44 HLA-A, 67 HLA-B and 48 HLA-DRB1 most probable alleles were identified. Of these, high-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, A*02:06, A*11:01, A*24:02, A*31:01, A*33:03), 5 HLA-B (B*15:01, B*44:03, B*51:01, B*54:01, B*58:01) and 7 HLA-DRB1 (DRB1*01:01, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01) alleles. At each locus, A*02, B*15 and DRB1*04 generic groups were most diverse at allelic level, consisting of 8, 11 and 10 different alleles, respectively. Two- and three-locus haplotypes estimated by the maximum likelihood method revealed 73 A-B, 74 B-DRB1 and 42 A-B-DRB1 haplotypes with frequencies of ≥0.3%. A total of 193 A-B-DRB1 haplotypes found at a frequency of ≥0.1% were presented, and the six most common haplotypes were A*33:03-B*44:03-DRB1*13:02 (4.6%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.7%), A*33:03-B*44:03-DRB1*07:01 (2.5%), A*30:01-B*13:02-DRB1*07:01 (2.2%) and A*24:02-B*52:01-DRB1*15:02 (2.1%). Compared with previous smaller scale studies, this study further delineated the allelic and haplotypic diversity in Koreans including low-frequency alleles and haplotypes. Information obtained in this study will be useful for the search for unrelated bone marrow donors and for anthropologic and disease association studies. © 2013 John Wiley & Sons Ltd.

The analysis of APOL1 genetic variation and haplotype diversity provided by 1000 Genomes project.

PubMed

Peng, Ting; Wang, Li; Li, Guisen

2017-08-11

The APOL1 gene variants has been shown to be associated with an increased risk of multiple kinds of diseases, particularly in African Americans, but not in Caucasians and Asians. In this study, we explored the single nucleotide polymorphism (SNP) and haplotype diversity of APOL1 gene in different races provided by 1000 Genomes project. Variants of APOL1 gene in 1000 Genome Project were obtained and SNPs located in the regulatory region or coding region were selected for genetic variation analysis. Total 2504 individuals from 26 populations were classified as four groups that included Africa, Europe, Asia and Admixed populations. Tag SNPs were selected to evaluate the haplotype diversities in the four populations by HaploStats software. APOL1 gene was surrounded by some of the most polymorphic genes in the human genome, variation of APOL1 gene was common, with up to 613 SNP (1000 Genome Project reported) and 99 of them (16.2%) with MAF ≥ 1%. There were 79 SNPs in the URR and 92 SNPs in 3'UTR. Total 12 SNPs in URR and 24 SNPs in 3'UTR were considered as common variants with MAF ≥ 1%. It is worth noting that URR-1 was presents lower frequencies in European populations, while other three haplotypes taken an opposite pattern; 3'UTR presents several high-frequency variation sites in a short segment, and the differences of its haplotypes among different population were significant (P < 0.01), UTR-1 and UTR-5 presented much higher frequency in African population, while UTR-2, UTR-3 and UTR-4 were much lower. APOL1 coding region showed that two SNP of G1 with higher frequency are actually pull down the haplotype H-1 frequency when considering all populations pooled together, and the diversity among the four populations be widen by the G1 two mutation (P 1  = 3.33E-4 vs P 2  = 3.61E-30). The distributions of APOL1 gene variants and haplotypes were significantly different among the different populations, in either regulatory or coding regions. It could provide clues for the future genetic study of APOL1 related diseases.

APC Yin-Yang haplotype associated with colorectal cancer risk

PubMed Central

GARRE, P.; DE LA HOYA, M.; INIESTA, P.; ROMERA, A.; LLOVET, P.; GONZALEZ, S.; PEREZ-SEGURA, P.; CAPELLA, G.; DIAZ-RUBIO, E.; CALDES, T.

2010-01-01

The Yin-Yang haplotype is defined as two mismatched haplotypes (Yin and Yang) representing the majority of the existing haplotypes in a particular genomic region. The human adenomatous polyposis coli (APC) gene shows a Yin-Yang haplotype pattern accounting for 84% of all of the haplotypes existing in the Spanish population. Several association studies have been published regarding APC gene variants (SNPs and haplotypes) and colorectal cancer (CRC) risk. However, no studies concerning diplotype structure and CRC risk have been conducted. The aim of the present study was to investigate whether the APC Yin-Yang homozygote diplotype is over-represented in patients with sporadic CRC when compared to its distribution in controls, and its association with CRC risk. TaqMan® assays were used to genotype three tagSNPs selected across the APC Yin-Yang region. Frequencies of the APC Yin-Yang tagSNP alleles, haplotype and diplotype of 378 CRC cases and 642 controls were compared. Two Spanish CRC group samples were included [Hospital Clínico San Carlos in Madrid (HCSC) and Instituto Catalán de Oncología in Barcelona (ICO)]. Analysis of 157 consecutive CRC patients and 405 control subjects from HCSC showed a significative effect for the risk of CRC (OR=1.93; 95% CI 1.32–2.81; P=0.001). However, this effect was not confirmed in 221 CRC patients and 237 control subjects from ICO (OR=0.89; 95% CI 0.61–1.28; P=0.521). We found a significant association between the APC homozygote Yin-Yang diplotype and the risk of colorectal cancer in the HCSC samples. However, we did not observe this association in the ICO samples. These observations suggest that a study with a larger Spanish cohort is necessary to confirm the effects of the APC Yin-Yang diplotype on the risk of CRC. PMID:22993613

APC Yin-Yang haplotype associated with colorectal cancer risk.

PubMed

Garre, P; DE LA Hoya, M; Iniesta, P; Romera, A; Llovet, P; Gonzalez, S; Perez-Segura, P; Capella, G; Diaz-Rubio, E; Caldes, T

2010-09-01

The Yin-Yang haplotype is defined as two mismatched haplotypes (Yin and Yang) representing the majority of the existing haplotypes in a particular genomic region. The human adenomatous polyposis coli (APC) gene shows a Yin-Yang haplotype pattern accounting for 84% of all of the haplotypes existing in the Spanish population. Several association studies have been published regarding APC gene variants (SNPs and haplotypes) and colorectal cancer (CRC) risk. However, no studies concerning diplotype structure and CRC risk have been conducted. The aim of the present study was to investigate whether the APC Yin-Yang homozygote diplotype is over-represented in patients with sporadic CRC when compared to its distribution in controls, and its association with CRC risk. TaqMan(®) assays were used to genotype three tagSNPs selected across the APC Yin-Yang region. Frequencies of the APC Yin-Yang tagSNP alleles, haplotype and diplotype of 378 CRC cases and 642 controls were compared. Two Spanish CRC group samples were included [Hospital Clínico San Carlos in Madrid (HCSC) and Instituto Catalán de Oncología in Barcelona (ICO)]. Analysis of 157 consecutive CRC patients and 405 control subjects from HCSC showed a significative effect for the risk of CRC (OR=1.93; 95% CI 1.32-2.81; P=0.001). However, this effect was not confirmed in 221 CRC patients and 237 control subjects from ICO (OR=0.89; 95% CI 0.61-1.28; P=0.521). We found a significant association between the APC homozygote Yin-Yang diplotype and the risk of colorectal cancer in the HCSC samples. However, we did not observe this association in the ICO samples. These observations suggest that a study with a larger Spanish cohort is necessary to confirm the effects of the APC Yin-Yang diplotype on the risk of CRC.

Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry

PubMed Central

Ingram, Charlotte; Schlaphoff, Terry; Borrill, Veronica; Christoffels, Alan

2018-01-01

Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies. PMID:29850621

Regional HLA Differences in Poland and Their Effect on Stem Cell Donor Registry Planning

PubMed Central

Schmidt, Alexander H.; Solloch, Ute V.; Pingel, Julia; Sauter, Jürgen; Böhme, Irina; Cereb, Nezih; Dubicka, Kinga; Schumacher, Stephan; Wachowiak, Jacek; Ehninger, Gerhard

2013-01-01

Regional HLA frequency differences are of potential relevance for the optimization of stem cell donor recruitment. We analyzed a very large sample (n = 123,749) of registered Polish stem cell donors. Donor figures by 1-digit postal code regions ranged from n = 5,243 (region 9) to n = 19,661 (region 8). Simulations based on region-specific haplotype frequencies showed that donor recruitment in regions 0, 2, 3 and 4 (mainly located in the south-eastern part of Poland) resulted in an above-average increase of matching probabilities for Polish patients. Regions 1, 7, 8, 9 (mainly located in the northern part of Poland) showed an opposite behavior. However, HLA frequency differences between regions were generally small. A strong indication for regionally focused donor recruitment efforts can, therefore, not be derived from our analyses. Results of haplotype frequency estimations showed sample size effects even for sizes between n≈5,000 and n≈20,000. This observation deserves further attention as most published haplotype frequency estimations are based on much smaller samples. PMID:24069237

Single nucleotide polymorphisms and haplotype frequencies of CYP3A5 in a Japanese population.

PubMed

Saeki, Mayumi; Saito, Yoshiro; Nakamura, Takahiro; Murayama, Norie; Kim, Su-Ryang; Ozawa, Shogo; Komamura, Kazuo; Ueno, Kazuyuki; Kamakura, Shiro; Nakajima, Toshiharu; Saito, Hirohisa; Kitamura, Yutaka; Kamatani, Naoyuki; Sawada, Jun-ichi

2003-06-01

In order to identify single nucleotide polymorphisms (SNPs) and haplotype frequencies of CYP3A5 in a Japanese population, we sequenced the proximal promoter region, all exons, and the surrounding intronic regions using genomic DNA from 187 Japanese subjects. Thirteen SNPs, including seven novel ones: 13108T>C, 16025A>G, 16903A>G, 16993C>G, 27448C>A, 29782A>G, and 31551T>C (A of the translational start codon of GenBank Accession # NG_000004.2 is numbered 1 according to the CYP Allele Nomenclature), were identified. The most common SNP was 6986A>G (key SNP for CYP3A5*3), with a 0.759 frequency. Two novel SNPs, 29782A>G (I456V) and 31551T>C (I488T), as well as 12952T>C (*5 marker) were found, but these alterations were always associated with the *3A marker SNPs, 6986A>G and 31611C>T. Using these 13 SNPs, haplotype analysis was performed and five novel *1 haplotypes (subtypes) (*1e to *1i) and six novel *3 haplotypes (subtypes) (*3d to *3i) were identified. Our findings suggest that CYP3A5*3 is the major defective allele and that other functional exonic SNPs are rare in the Japanese. Copyright 2003 Wiley-Liss, Inc.

How Have Self-Incompatibility Haplotypes Diversified? Generation of New Haplotypes during the Evolution of Self-Incompatibility from Self-Compatibility.

PubMed

Sakai, Satoki

2016-08-01

I developed a gametophytic self-incompatibility (SI) model to study the conditions leading to diversification in SI haplotypes. In the model, the SI system is assumed to be incomplete, and the pollen expressing a given specificity is not fully rejected by the pistils expressing the same specificity. I also assumed that mutations can occur that enhance the rejection of pollen by pistils with the same haplotype variant and reduce rejection by pistils with other variants in the same haplotype. I found that if such mutations occur, the new haplotypes (mutant variants) can stably coexist with the ancestral haplotype in which the mutant arose. This is because pollen bearing the new haplotype is most strongly rejected by pistils bearing the same new haplotype among the pistils in the population; hence, negative frequency-dependent selection prevents their fixation. I also performed simulations and found that the nearly complete SI system evolves from completely self-compatible populations and that SI haplotypes can increase to about 40-50 within a few thousand generations. On the basis of my findings, I propose that diversification of SI haplotypes occurred during the evolution of SI from self-compatibility.

HLA class I antigen and HLA-A, -B, and -C haplotype frequencies in Uruguayans.

PubMed

Alvarez, Ines; Bengochea, Milka; Toledo, Roberto; Carretto, Elena; Hidalgo, Pedro C

2006-08-01

HLA class I antigens were determined for 959 unrelated Uruguayans. The predominant HLA alleles were A2, Cw4, and B35, and the most frequently observed two-loci haplotypes were A2-B44 and B35-Cw4. The most frequent three-loci HLA haplotype was A2-Cw5-B44. We compared the Uruguayan sample with similar data from other populations.

Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.

PubMed

Patil, N; Berno, A J; Hinds, D A; Barrett, W A; Doshi, J M; Hacker, C R; Kautzer, C R; Lee, D H; Marjoribanks, C; McDonough, D P; Nguyen, B T; Norris, M C; Sheehan, J B; Shen, N; Stern, D; Stokowski, R P; Thomas, D J; Trulson, M O; Vyas, K R; Frazer, K A; Fodor, S P; Cox, D R

2001-11-23

Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.

Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes

PubMed Central

Rood, M; Keijsers, V; van der Linden, M W; Tong, T; Borggreve, S; Verweij, C; Breedveld, F; Huizinga, T

1999-01-01

OBJECTIVE—To investigate the association of interleukin 10 (IL10) promoter polymorphisms and neuropsychiatric manifestations of systemic lupus erythematosus (SLE).
METHODS—IL10 haplotypes of 11 healthy volunteers were cloned to confirm that in the Dutch population, only the three common haplotypes (-1082/-819/-592) GCC, ACC and ATA exist. The IL10 promoter polymorphisms of 92 SLE patients and 162 healthy controls were determined. The medical records of the SLE patients were screened for the presence of neuropsychiatric involvement.
RESULTS—All cloned haplotypes were either GCC, ACC or ATA. Forty two SLE patients had suffered from neuropsychiatric manifestations (NP-SLE). In NP-SLE patients, the frequency of the ATA haplotype is 30% versus 18% in the controls and 17% in the non-NP-SLE group (odds ratios 1.9, p=0.02, and 2.1, p=0.04, respectively), whereas the GCC haplotype frequency is lower in the NP-SLE group compared with controls and non-NP-SLE patients (40% versus 55% and 61%, odds ratios 0.6, p=0.02 and 0.4 p=0.006). The odds ratio for the presence of NP-SLE is inversely proportional to the number of GCC haplotypes per genotype when the NP-SLE group is compared with non-NP-SLE patients.
CONCLUSIONS—The IL10 locus is associated with neuropsychiatric manifestations in SLE. This suggests that IL10 is implicated in the immunopathogenesis of neuropsychiatric manifestations in SLE.

 Keywords: systemic lupus erythematosus; neuropsychiatric manifestations; genetics; interleukin 10 promoter haplotypes PMID:10343522

African gene flow to north Brazil as revealed by HBB*S gene haplotype analysis.

PubMed

Lemos Cardoso, Greice; Farias Guerreiro, João

2006-01-01

Haplotypes linked to the HBB*S gene were analyzed in a sample of 260 chromosomes of Brazilian sickle cell anemia patients from the population of Belém, state of Pará, to evaluate if the present-day haplotype frequencies correlate as well as expected with historical information on the geographic origin of African slaves sent directly to Northern Brazil. The HBB*S gene haplotype distribution (66% Bantu, 21.8% Benin, 10.9% Senegal, and 1.3% Cameroon) is in agreement with those observed for other Brazilian populations regarding the highest proportion of the Bantu type, followed by the Benin type, but it differs significantly concerning the Senegal type as this haplotype is rare or absent in samples from other Brazilian regions already studied. In addition, our results are in accordance with historical records that establish that about 90% of the slaves sent to Northern Brazil were from Angola, Congo, and Mozambique, where the Bantu haplotype predominates, in contrast to 10% of slaves from Senegambia, Guine-Bissau, and Cape Verde, where the Senegal haplotype is the most common. On the other hand, the observed frequency of the Benin haplotype in Belém was much higher than that expected by historical data. This fact corroborates the suggestion that the high prevalence of the Benin type in Belém is due to domestic slave trade and later internal migrations, mainly from the Northeast, since there are no historical records of direct slave trade from Central West Africa to North Brazil. Am. J. Hum. Biol. 18:93-98, 2006. (c) 2005 Wiley-Liss, Inc.

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

PubMed

Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

2015-10-01

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Genotypic and symbiotic diversity of Rhizobium populations associated with cultivated lentil and pea in sub-humid and semi-arid regions of Eastern Algeria.

PubMed

Riah, Nassira; Béna, Gilles; Djekoun, Abdelhamid; Heulin, Karine; de Lajudie, Philippe; Laguerre, Gisèle

2014-07-01

The genetic structure of rhizobia nodulating pea and lentil in Algeria, Northern Africa was determined. A total of 237 isolates were obtained from root nodules collected on lentil (Lens culinaris), proteaginous and forage pea (Pisum sativum) growing in two eco-climatic zones, sub-humid and semi-arid, in Eastern Algeria. They were characterised by PCR-restriction fragment length polymorphism (RFLP) of the 16S-23S rRNA intergenic region (IGS), and the nodD-F symbiotic region. The combination of these haplotypes allowed the isolates to be clustered into 26 distinct genotypes, and all isolates were classified as Rhizobium leguminosarum. Symbiotic marker variation (nodD-F) was low but with the predominance of one nod haplotype (g), which had been recovered previously at a high frequency in Europe. Sequence analysis of the IGS further confirmed its high variability in the studied strains. An AMOVA analysis showed highly significant differentiation in the IGS haplotype distribution between populations from both eco-climatic zones. This differentiation was reflected by differences in dominant genotype frequencies. Conversely, no host plant effect was detected. The nodD gene sequence-based phylogeny suggested that symbiotic gene diversity in pea and lentil nodulating rhizobial populations in Algeria was low compared to that reported elsewhere in the world. Copyright © 2014 Elsevier GmbH. All rights reserved.

A comprehensive literature review of haplotyping software and methods for use with unrelated individuals.

PubMed

Salem, Rany M; Wessel, Jennifer; Schork, Nicholas J

2005-03-01

Interest in the assignment and frequency analysis of haplotypes in samples of unrelated individuals has increased immeasurably as a result of the emphasis placed on haplotype analyses by, for example, the International HapMap Project and related initiatives. Although there are many available computer programs for haplotype analysis applicable to samples of unrelated individuals, many of these programs have limitations and/or very specific uses. In this paper, the key features of available haplotype analysis software for use with unrelated individuals, as well as pooled DNA samples from unrelated individuals, are summarised. Programs for haplotype analysis were identified through keyword searches on PUBMED and various internet search engines, a review of citations from retrieved papers and personal communications, up to June 2004. Priority was given to functioning computer programs, rather than theoretical models and methods. The available software was considered in light of a number of factors: the algorithm(s) used, algorithm accuracy, assumptions, the accommodation of genotyping error, implementation of hypothesis testing, handling of missing data, software characteristics and web-based implementations. Review papers comparing specific methods and programs are also summarised. Forty-six haplotyping programs were identified and reviewed. The programs were divided into two groups: those designed for individual genotype data (a total of 43 programs) and those designed for use with pooled DNA samples (a total of three programs). The accuracy of programs using various criteria are assessed and the programs are categorised and discussed in light of: algorithm and method, accuracy, assumptions, genotyping error, hypothesis testing, missing data, software characteristics and web implementation. Many available programs have limitations (eg some cannot accommodate missing data) and/or are designed with specific tasks in mind (eg estimating haplotype frequencies rather than assigning most likely haplotypes to individuals). It is concluded that the selection of an appropriate haplotyping program for analysis purposes should be guided by what is known about the accuracy of estimation, as well as by the limitations and assumptions built into a program.

Contribution of HLA-A/B/C/DRB1/DQB1 common haplotypes to donor search outcome in unrelated hematopoietic stem cell transplantation.

PubMed

Pédron, Béatrice; Guérin-El Khourouj, Valérie; Dalle, Jean-Hugues; Ouachée-Chardin, Marie; Yakouben, Karima; Corroyez, France; Auvrignon, Anne; Petit, Arnaud; Landman-Parker, Judith; Leverger, Guy; Baruchel, André; Sterkers, Ghislaine

2011-11-01

In unrelated hematopoietic stem cell transplantation (HSCT), the prediction of donor search outcome at the time of search initiation is of great value for the physicians to delineate the strategy of patient care. The probability of finding an unrelated donor is high for patients who carry at least 1 of the 10 most common HLA haplotypes in Caucasians. As only 10% to 20% patients respond to this criterion, here we aimed at finding additional common haplotypes to improve the prediction of a successful search. HLA broad HLA-A/B/DRB1 haplotypes that were observed with frequencies ≥0.19% in patient families of European origin and that split into ≤2 predominant 4-digit HLA-A/B/C/DRB1/DQB1 haplotypes were considered as common. Carriage of at least 1 of those in 168 patients of various geographic areas with no family donor was confronted to the chance of finding ≥9/10 HLA-matched unrelated donors. Fifty common 4-digit haplotypes were identified. A higher (P < 5 × 10(-6)) chance of finding a suitable donor was found for 55 of 170 (32%) recipients that carried at least 1 of these common haplotypes. Up to now, estimates classified patients into ≥3 groups of probability with ≥1 intermediate group of poor utility for the clinicians. Considering carriage of these common haplotypes together with the frequencies of alleles and of B/C and DRB1/DQB1 associations, which are carried by patient HLA haplotypes, we could classify the patients into 2 groups of probability with a 98% and 26% chance of finding a donor, respectively. Prediction of search outcome could be improved by including the 50 most common HLA haplotypes in the current approaches. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Shared and Unique Components of Human Population Structure and Genome-Wide Signals of Positive Selection in South Asia

PubMed Central

Metspalu, Mait; Romero, Irene Gallego; Yunusbayev, Bayazit; Chaubey, Gyaneshwer; Mallick, Chandana Basu; Hudjashov, Georgi; Nelis, Mari; Mägi, Reedik; Metspalu, Ene; Remm, Maido; Pitchappan, Ramasamy; Singh, Lalji; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

2011-01-01

South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes. PMID:22152676

Westwards and northwards dispersal of Triosteum himalayanum (Caprifoliaceae) from the Hengduan Mountains region based on chloroplast DNA phylogeography.

PubMed

Liu, Hai-Rui; Gao, Qing-Bo; Zhang, Fa-Qi; Khan, Gulzar; Chen, Shi-Long

2018-01-01

The varying topography and environment that resulted from paleoorogeny and climate fluctuations of the Himalaya-Hengduan Mountains (HHM) areas had a considerable impact on the evolution of biota during the Quaternary. To understand the phylogeographic pattern and historical dynamics of Triosteum himalayanum (Caprifoliaceae), we sequenced three chloroplast DNA fragments ( rbcL-accD , rps15-ycf1 , and trnH-psbA ) from 238 individuals representing 20 populations. Nineteen haplotypes (H1-H19) were identified based on 23 single-site mutations and eight indels. Most haplotypes were restricted to a single population or neighboring populations. Analysis of molecular variance revealed that variations among populations were much higher than that within populations for the overall gene pool, as well as for the East Himalayan group (EH group) and the North Hengduan group (NHM group), but not for the Hengduan Mountains group (HM group). Ecoregions representing relatively high genetic diversity or high frequencies of private haplotypes were discovered, suggesting that this alpine herbaceous plant underwent enhanced allopatric divergence in isolated and fragmented locations during the Quaternary glaciations. The current phylogeographic structure of T. himalayanum might be due to heterogeneous habitats and Quaternary climatic oscillations. Based on the phylogeographic structure of T. himalayanum populations, the phylogenetic relationship of identified haplotypes and palaeodistributional reconstruction, we postulated both westwards and northwards expansion from the HM group for this species. The westwards dispersal corridor could be long, narrow mountain areas and/or the Yarlung Zangbo Valley, while the northwards movement path could be south-north oriented mountains and low-elevation valleys.

Haplotype combination of the bovine CFL2 gene sequence variants and association with growth traits in Qinchuan cattle.

PubMed

Sun, Yujia; Lan, Xianyong; Lei, Chuzhao; Zhang, Chunlei; Chen, Hong

2015-06-01

The aim of this study was to examine the association of cofilin2 (CFL2) gene polymorphisms with growth traits in Chinese Qinchuan cattle. Three single nucleotide polymorphisms (SNPs) were identified in the bovine CFL2 gene using DNA sequencing and (forced) PCR-RFLP methods. These polymorphisms included a missense mutation (NC_007319.5: g. C 2213 G) in exon 4, one synonymous mutation (NC_007319.5: g. T 1694 A) in exon 4, and a mutation (NC_007319.5: g. G 1500 A) in intron 2, respectively. In addition, we evaluated the haplotype frequency and linkage disequilibrium coefficient of three sequence variants in 488 individuals in QC cattle. All the three SNPs in QC cattle belonged to an intermediate level of genetic diversity (0.250.33). Association analysis indicated that SNP G 1500 A, T 1694 A and C 2213 G were significantly associated with growth traits in the QC population. The results of our study suggest that the CFL2 gene may be a strong candidate gene that affects growth traits in the QC cattle breeding program. Copyright © 2015 Elsevier B.V. All rights reserved.

HLA Haplotype Frequency Estimation from Real-Life Data with the Hapl-o-Mat Software.

PubMed

Sauter, Jürgen; Schäfer, Christian; Schmidt, Alexander H

2018-01-01

HLA haplotype frequencies are of use in a variety of settings. Such data is typically derived either from family pedigree data by targeted typing or statistical analysis of large population-specific genotype samples. As established tools for the latter approach lacked ability to treat the amount, ambiguity, and inhomogeneity found in genotype data in hematopoietic stem cell donor registries, we developed Hapl-o-Mat to alleviate these specific shortcomings.

HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFE C282Y homozygosity in central Alabama.

PubMed

Barton, James C; Acton, Ronald T

2002-10-07

We wanted to quantify HLA-A and -B allele and haplotype frequencies in Alabama hemochromatosis probands with HFE C282Y homozygosity and controls, and to compare results to those in other populations. Alleles were detected using DNA-based typing (probands) and microlymphocytotoxicity (controls). Alleles were determined in 139 probands (1,321 controls) and haplotypes in 118 probands (605 controls). In probands, A*03 positivity was 0.7482 (0.2739 controls; p = or < 0.0001; odds ratio (OR) 7.9); positivity for B*07, B*14, and B*56 was also increased. In probands, haplotypes A*03-B*07 and A*03-B*14 were more frequent (p < 0.0001, respectively; OR = 12.3 and 11.1, respectively). The haplotypes A*01-B*60, A*02-B*39, A*02-B*62, A*03-B*13, A*03-B*15, A*03-B*27, A*03-B*35, A*03-B*44, A*03-B*47, and A*03-B*57 were also significantly more frequent in probands. 37.3% of probands were HLA-haploidentical with other proband(s). A*03 and A*03-B*07 frequencies are increased in Alabama probands, as in other hemochromatosis cohorts. Increased absolute frequencies of A*03-B*35 have been reported only in the present Alabama probands and in hemochromatosis patients in Italy. Increased absolute frequencies of A*01-B*60, A*02-B*39, A*02-B*62, A*03-B*13, A*03-B*15, A*03-B*27, A*03-B*44, A*03-B*47, and A*03-B*57 in hemochromatosis cohorts have not been reported previously.

Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2.

PubMed

Fritz, Sébastien; Capitan, Aurelien; Djari, Anis; Rodriguez, Sabrina C; Barbat, Anne; Baur, Aurélia; Grohs, Cécile; Weiss, Bernard; Boussaha, Mekki; Esquerré, Diane; Klopp, Christophe; Rocha, Dominique; Boichard, Didier

2013-01-01

The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10(-4)) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle.

Lack of spatial genetic structure among nesting and wintering King Eiders

USGS Publications Warehouse

Pearce, J.M.; Talbot, S.L.; Pierson, Barbara J.; Petersen, M.R.; Scribner, K.T.; Dickson, D.L.; Mosbech, A.

2004-01-01

The King Eider (Somateria spectabilis) has been delineated into two broadly distributed breeding populations in North America (the western and eastern Arctic) on the basis of banding data and their use of widely separated Pacific and Atlantic wintering areas. Little is known about the level of gene flow between these two populations. Also unknown is whether behavioral patterns common among migratory waterfowl, such as site fidelity to wintering areas and pair formation at these sites, have existed for sufficient time to create a population structure defined by philopatry to wintering rather than to nesting locations. We used six nuclear microsatellite DNA loci and cytochrome b mitochondrial DNA sequence data to estimate the extent of spatial genetic differentiation among nesting and wintering areas of King Eiders across North America and adjacent regions. Estimates of interpopulation variance in microsatellite allele and mtDNA haplotype frequency were both low and nonsignificant based on samples from three wintering and four nesting areas. Results from nested clade analysis, mismatch distributions, and coalescent-based analyses suggest historical population growth and gene flow that collectively may have homogenized gene frequencies. The presence of several unique mtDNA haplotypes among birds wintering near Greenland suggests that gene flow may now be more limited between the western and eastern Arctic, which is consistent with banding data.

Population demographics and genetic diversity in remnant and translocated populations of sea otters

USGS Publications Warehouse

Bodkin, James L.; Ballachey, Brenda E.; Cronin, M.A.; Scribner, K.T.

1999-01-01

The effects of small population size on genetic diversity and subsequent population recovery are theoretically predicted, but few empirical data are available to describe those relations. We use data from four remnant and three translocated sea otter (Enhydra lutris) populations to examine relations among magnitude and duration of minimum population size, population growth rates, and genetic variation. Metochondrial (mt)DNA haplotype diversity was correlated with the number of years at minimum population size (r = -0.741, p = 0.038) and minimum population size (r = 0.709, p = 0.054). We found no relation between population growth and haplotype diversity, altough growth was significantly greater in translocated than in remnant populations. Haplotype diversity in populations established from two sources was higher than in a population established from a single source and was higher than in the respective source populations. Haplotype frequencies in translocated populations of founding sizes of 4 and 28 differed from expected, indicating genetic drift and differential reproduction between source populations, whereas haplotype frequencies in a translocated population with a founding size of 150 did not. Relations between population demographics and genetic characteristics suggest that genetic sampling of source and translocated populations can provide valuable inferences about translocations.

HLA DPA1, DPB1 alleles and haplotypes contribute to the risk associated with type 1 diabetes: analysis of the type 1 diabetes genetics consortium families.

PubMed

Varney, Michael D; Valdes, Ana Maria; Carlson, Joyce A; Noble, Janelle A; Tait, Brian D; Bonella, Persia; Lavant, Eva; Fear, Anna Lisa; Louey, Anthony; Moonsamy, Priscilla; Mychaleckyj, Josyf C; Erlich, Henry

2010-08-01

To determine the relative risk associated with DPA1 and DPB1 alleles and haplotypes in type 1 diabetes. The frequency of DPA1 and DPB1 alleles and haplotypes in type 1 diabetic patients was compared to the family based control frequency in 1,771 families directly and conditional on HLA (B)-DRB1-DQA1-DQB1 linkage disequilibrium. A relative predispositional analysis (RPA) was performed in the presence or absence of the primary HLA DR-DQ associations and the contribution of DP haplotype to individual DR-DQ haplotype risks examined. Eight DPA1 and thirty-eight DPB1 alleles forming seventy-four DPA1-DPB1 haplotypes were observed; nineteen DPB1 alleles were associated with multiple DPA1 alleles. Following both analyses, type 1 diabetes susceptibility was significantly associated with DPB1*0301 (DPA1*0103-DPB1*0301) and protection with DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 but not DPA1*0201-DPB1*0101. In addition, DPB1*0202 (DPA1*0103-DPB1*0202) and DPB1*0201 (DPA1*0103-DPB1*0201) were significantly associated with susceptibility in the presence of the high risk and protective DR-DQ haplotypes. Three associations (DPB1*0301, *0402, and *0202) remained statistically significant when only the extended HLA-A1-B8-DR3 haplotype was considered, suggesting that DPB1 alone may delineate the risk associated with this otherwise conserved haplotype. HLA DP allelic and haplotypic diversity contributes significantly to the risk for type 1 diabetes; DPB1*0301 (DPA1*0103-DPB1*0301) is associated with susceptibility and DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 with protection. Additional evidence is presented for the susceptibility association of DPB1*0202 (DPA1*0103-DPB1*0202) and for a contributory role of individual amino acids and DPA1 or a gene in linkage disequilibrium in DR3-DPB1*0101 positive haplotypes.

[Polymorphisms of the multiple drug resistance gene (MDR1) in Mapuche, Mestizo and Maori populations in Chile].

PubMed

Wielandt, Ana María; Vollrath, Valeska; Chianale, José

2004-09-01

There are significant differences in drug responses among different ethnic groups. The multidrug transporter P-gp, encoded by the MDR1 gene, plays a key role in determining drug bioavailability, and an association between a polymorphism in exon 26 (C3435T) and lower P-gp expression has been found. The co-segregation of this polymorphism with the polymorphism in exon 12 (C1236T) and in exon 21 (G2677T/A) determines several MDR1 haplotypes in humans. To characterize the polymorphisms of exons 26, 21 and 12 of the MDR1 gene in different Chilean populations. Using a polymerase chain reaction and restriction fragment length polymorphism technique, we studied the allelic frequencies and the distribution of MDR1 haplotypes in 3 Chilean populations: Mestizo (n=104), Mapuche (n=96, living in the National Reservation of the Huapi Island, Ranico Lake) and Maori (n=52, living in Eastern Island). The frequency of the normal MDR1*1 haplotype, without mutations, was lower in Mapuches than in Mestizos or Maoris (p<0.005) but similar to that reported in Asian population (p=0.739), probably due to the Asian origin of the Amerindian populations. In addition, the MDR1*l haplotype fequency hin Mestizos was similar to the frequency reported in Caucasians (p=0.49), in agreement with the origin of our population, with a strong influence of Caucasian genes from the Spanish conquerors. The MDR1*2 haplotype distribution, with the three polymoyphisms and probably lower multidrug transporter expression, was similar in the three Chilean populations studied (p>0.0.5), but lower than the frequencies reported in Caucasians or Asians (p<0.05). We found significant differences in the frequencies of genetic polymorphisms of the MDR1 gene in Chilean populations, related to the ethnic origins of our ancestors.

Extensive paternal mtDNA leakage in natural populations of Drosophila melanogaster.

PubMed

Nunes, Maria D S; Dolezal, Marlies; Schlötterer, Christian

2013-04-01

Strict maternal inheritance is considered a hallmark of animal mtDNA. Although recent reports suggest that paternal leakage occurs in a broad range of species, it is still considered an exceptionally rare event. To evaluate the impact of paternal leakage on the evolution of mtDNA, it is essential to reliably estimate the frequency of paternal leakage in natural populations. Using allele-specific real-time quantitative PCR (RT-qPCR), we show that heteroplasmy is common in natural populations with at least 14% of the individuals carrying multiple mitochondrial haplotypes. However, the average frequency of the minor mtDNA haplotype is low (0.8%), which suggests that this pervasive heteroplasmy has not been noticed before due to a lack of power in sequencing surveys. Based on the distribution of mtDNA haplotypes in the offspring of heteroplasmic mothers, we found no evidence for strong selection against one of the haplotypes. We estimated that the rate of paternal leakage is 6% and that at least 100 generations are required for complete sorting of mtDNA haplotypes. Despite the high proportion of heteroplasmic individuals in natural populations, we found no evidence for recombination between mtDNA molecules, suggesting that either recombination is rare or recombinant haplotypes are counter-selected. Our results indicate that evolutionary studies using mtDNA as a marker might be biased by paternal leakage in this species. © 2013 Blackwell Publishing Ltd.

Association of genetic variants in the 3'UTR of HLA-G with Recurrent Pregnancy Loss.

PubMed

Amodio, Giada; Canti, Valentina; Maggio, Luana; Rosa, Susanna; Castiglioni, Maria Teresa; Rovere-Querini, Patrizia; Gregori, Silvia

2016-10-01

Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of the 3' Un-Translated Region (UTR) of HLA-G, previously associated with HLA-G mRNA post-transcriptional regulation, in women with unexplained Recurrent Pregnancy Loss (RPL), with 2 pregnancy losses (RPL-2, n=28), or 3 or more pregnancy losses (RPL-3, n=24), and in 30 women with a history of successful pregnancy. Results showed in RPL-2, but not in RPL-3, women compared to controls: i) higher frequency of the 14bp Ins allele, in single and in double copy; ii) significantly lower frequency of DelG/X genotype, iii) reduced frequency of the UTR-2, and UTR-3 haplotypes; iv) higher frequencies of the UTR-5, UTR-7, and UTR-8 haplotypes. This pilot study supports the relevance of performing 3'UTR HLA-G genetic screening, not limited to a specific polymorphism, but considering the extended haplotypes, as a possible predictor of pregnancy outcome. Copyright © 2016. Published by Elsevier Inc.

Genetic Differentiation in a Sample from Northern Mexico City Detected by HLA System Analysis: Impact in the Study of Population Immunogenetics.

PubMed

Cortés, Eva D Juárez; Sieck, Miguel A Contreras; Perea, Agustín J Arriaga; Medrano, Rosa M Macías; Jaime, Anaí Balbuena; Martínez, Paola Everardo; Zúñiga, Joaquín; Alonzo, Víctor Acuña; Granados, Julio; Barquera, Rodrigo

2017-07-01

The major histocompatibility complex is directly involved in the immune response, and thus the genes coding for its proteins are useful markers for the study of genetic diversity, susceptibility to disease (autoimmunity and infections), transplant medicine, and pharmacogenetics, among others. The polymorphism of the system also allows researchers to use it as a proxy for population genetics analysis, such as genetic admixture and genetic structure. In order to determine the immunogenetic characteristics of a sample from the northern part of Mexico City and to use them to analyze the genetic differentiation from other admixed populations, including those from previous studies of Mexico City population, we analyzed molecular typing results of donors and patients from the Histocompatibility Laboratory of the Central Blood Bank of the Centro Médico Nacional La Raza selected according to their geographic origin. HLA-A, -B, -DRB1, and -DQB1 alleles were typed by polymerase chain reaction with sequence-specific primers. Allelic and haplotype frequencies, as well as population genetics parameters, were obtained by maximum likelihood methods. The most frequent haplotypes found were HLA-A * 02/-B * 39/-DRB1 * 04/-DQB1 * 03:02P, HLA-A * 02/-B * 35/-DRB1 * 04/-DQB1 * 03:02P, HLA-A * 68/-B * 39/-DRB1 * 04/-DQB1 * 03:02P, and HLA-A * 02/-B * 35/-DRB1 * 08/-DQB1 * 04. Importantly, the second most frequent haplotype found in our sample (HLA-A * 02/-B * 35/-DRB1 * 04/-DQB1 * 03:02P) has not been previously reported in any mixedancestry populations from Mexico but is commonly encountered in Native American human groups, which can reflect the impact of migration dynamics in the genetic conformation of the northern part of Mexico City, and the limitations of previous studies with regard to the genetic diversity of the analyzed groups. Differences found in haplotype frequencies demonstrated that large urban conglomerates cannot be analyzed as one homogeneous entity but, rather, should be understood as a set of structures in which social, political, and economical factors influence their genesis and dynamics.

Cultural traditions across a migratory network shape the genetic structure of southern right whales around Australia and New Zealand

PubMed Central

Carroll, E. L.; Baker, C. S.; Watson, M.; Alderman, R.; Bannister, J.; Gaggiotti, O. E.; Gröcke, D. R.; Patenaude, N.; Harcourt, R.

2015-01-01

Fidelity to migratory destinations is an important driver of connectivity in marine and avian species. Here we assess the role of maternally directed learning of migratory habitats, or migratory culture, on the population structure of the endangered Australian and New Zealand southern right whale. Using DNA profiles, comprising mitochondrial DNA (mtDNA) haplotypes (500 bp), microsatellite genotypes (17 loci) and sex from 128 individually-identified whales, we find significant differentiation among winter calving grounds based on both mtDNA haplotype (FST = 0.048, ΦST = 0.109, p < 0.01) and microsatellite allele frequencies (FST = 0.008, p < 0.01), consistent with long-term fidelity to calving areas. However, most genetic comparisons of calving grounds and migratory corridors were not significant, supporting the idea that whales from different calving grounds mix in migratory corridors. Furthermore, we find a significant relationship between δ13C stable isotope profiles of 66 Australian southern right whales, a proxy for feeding ground location, and both mtDNA haplotypes and kinship inferred from microsatellite-based estimators of relatedness. This indicates migratory culture may influence genetic structure on feeding grounds. This fidelity to migratory destinations is likely to influence population recovery, as long-term estimates of historical abundance derived from estimates of genetic diversity indicate the South Pacific calving grounds remain at <10% of pre-whaling abundance. PMID:26548756

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel.

PubMed

Delaneau, Olivier; Marchini, Jonathan

2014-06-13

A major use of the 1000 Genomes Project (1000 GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000 GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants.

Haplotype Analysis of the Melanopsin Gene in Seasonal Affective Disorder and Controls

DTIC Science & Technology

2007-06-19

Cole, P. A. (2002). Serotonin n-acetyltransferase: Mechanism and inhibition. Current Medicinal Chemistry , 9(12), 1187-1199. 152 APPENDIX A STRUCTURED ...such that low light levels fall below this threshold during winter in individuals with SAD. The present study investigated the haplotype structure of...Association Studies 51 Advantages of Population-Based Case-Control Samples 52 Haplotype Structure 53 Linkage Disequilibrium: A Measure of Correlation Between

Identification of parental line specific effects of MLF2 on resistance to coccidiosis in chickens

PubMed Central

2011-01-01

Background MLF2 was the candidate gene associated with coccidiosis resistance in chickens. Although single marker analysis supported the association between MLF2 and coccidiosis resistance, causative mutation relevant to coccidiosis was not identified yet. Thus, this study suggested segregation analysis of MLF2 haplotype and the association test of the other candidate genes using improved data transformation. Results A haplotype probably originated from one parental line was found out of 4 major haplotypes of MLF2. Frequency of this haplotype was 0.2 in parental chickens and its offspring in 12 families. Allele substitution effect of the MLF2 haplotype originated from a specific line was associated with increased body weight and fecal egg count explaining coccidiosis resistance. Nevertheless Box-Cox transformation was able to improve normality; association test did not produce obvious different results compared with analysis with log transformed phenotype. Conclusion Allele substitution effect analysis and classification of MLF2 haplotype identified the segregation of haplotype associated with coccidiosis resistance. The haplotype originated from a specific parental line was associated with improving disease resistance. Estimating effect of MLF2 haplotype on coccidiosis resistance will provide useful information for selecting animals or lines for future study. PMID:21645301

The discrete Laplace exponential family and estimation of Y-STR haplotype frequencies.

PubMed

Andersen, Mikkel Meyer; Eriksen, Poul Svante; Morling, Niels

2013-07-21

Estimating haplotype frequencies is important in e.g. forensic genetics, where the frequencies are needed to calculate the likelihood ratio for the evidential weight of a DNA profile found at a crime scene. Estimation is naturally based on a population model, motivating the investigation of the Fisher-Wright model of evolution for haploid lineage DNA markers. An exponential family (a class of probability distributions that is well understood in probability theory such that inference is easily made by using existing software) called the 'discrete Laplace distribution' is described. We illustrate how well the discrete Laplace distribution approximates a more complicated distribution that arises by investigating the well-known population genetic Fisher-Wright model of evolution by a single-step mutation process. It was shown how the discrete Laplace distribution can be used to estimate haplotype frequencies for haploid lineage DNA markers (such as Y-chromosomal short tandem repeats), which in turn can be used to assess the evidential weight of a DNA profile found at a crime scene. This was done by making inference in a mixture of multivariate, marginally independent, discrete Laplace distributions using the EM algorithm to estimate the probabilities of membership of a set of unobserved subpopulations. The discrete Laplace distribution can be used to estimate haplotype frequencies with lower prediction error than other existing estimators. Furthermore, the calculations could be performed on a normal computer. This method was implemented in the freely available open source software R that is supported on Linux, MacOS and MS Windows. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of the ancestral haplotype for apolipoprotein B suggests an African origin of Homo sapiens sapiens and traces their subsequent migration to Europe and the Pacific.

PubMed Central

Rapacz, J; Chen, L; Butler-Brunner, E; Wu, M J; Hasler-Rapacz, J O; Butler, R; Schumaker, V N

1991-01-01

The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB haplotype is likely to be applicable to many other genes. PMID:1996341

Population data for 15 Y-chromosome STRs in a population sample from Quito (Ecuador).

PubMed

Baeza, Carlos; Guzmán, Rodrigo; Tirado, Miriam; López-Parra, Ana María; Rodríguez, Tatiana; Mesa, María Soledad; Fernández, Eva; Arroyo-Pardo, Eduardo

2007-12-20

Population frequencies for the 9 Y-STR loci included in the "minimal haplotype" from Y-STR Haplotype Reference Database (YHRD), plus other 6 Y-STRs (DYS437, DYS438, DYS439, GATA A7.2, GATA H4 and GATA A10) were obtained for a sample of 120 males from Quito (Ecuador). One hundred and sixteen unique haplotypes were identified within the sample. Haplotype diversity (0.9994) was among the highest in comparison to other populations from Iberia and South-America. Genetic distances were calculated and our sample presented significative differences with all other samples, the lowest values being with a Guinean sample.

Identification of the ancestral haplotype for apolipoprotein B suggests an African origin of Homo sapiens sapiens and traces their subsequent migration to Europe and the Pacific

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rapacz, J.; Hasler-Rapacz, J.O.; Chen, L.

1991-02-15

The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB haplotype is likely to be applicable to many other genes.

Distribution of HLA class I alleles and haplotypes in Korean.

PubMed Central

Kim, T. G.; Han, H.; Lim, B. U.; Kim, W.; Kim, S. M.

1993-01-01

The antigen (phenotype), gene (allele) and haplotype frequencies of HLA class I were analysed in 4,622 Koreans. With allele frequencies of over 0.05, the most frequent HLA-A,-B and -C antigens were A2, A24, A33, A11, A26, A31; B62, B51, B44, B54, B61, B35, B58, B60; Cw3, Cw1, Cw4, Cw7. Of these A2, A24, Cw1 and Cw3 were present in very high frequencies, respectively (0.3211, 0.2200, 0.2204, and 0.3737). The most common haplotypes with frequencies larger than 0.02 were A2-Blank, A33-B44, A33-B58, A11-B62, A24-B51, A24-B54, A2-B27, B54-Cw1, B58-Cw3, B51-Blank, B61-Cw3, B62-Cw4, B35-Cw3, B44-Blank, B60-Cw3, B27-Cw1, A2-Cw3, A2-Cw1, A24-Cw1, A33-Cw3, A26-Cw3, and A11-Cw4. A significant negative linkage disequilibrium was found for the haplotypes of A2-B7, A2-B44, A2-B58, A24-B13, A24-B27, A33-B54 and A33-B62, of which frequencies were larger than 0.003. The B-C and A-C haplotypes which showed the significant negative linkage disequilibrium were B44-Cw1, B51-Cw1, B44-Cw3,B62-Blank, A2-Cw4, A2-Blank, A11-Cw3, A11-Blank and A33-Cw1 and had frequencies higher than 0.01. The findings presented here could be used per se to estimate the populational relationships or as the control data for HLA-disease investigation. Furthermore they could provide the scope for the definition of new antigens. PMID:8240747

Population structure and genetic variability within isolates of Grapevine fanleaf virus from a naturally infected vineyard in France: evidence for mixed infection and recombination.

PubMed

Vigne, Emmanuelle; Bergdoll, Marc; Guyader, Sébastien; Fuchs, Marc

2004-08-01

The nematode-borne Grapevine fanleaf virus, from the genus Nepovirus in the family Comoviridae, causes severe degeneration of grapevines in most vineyards worldwide. We characterized 347 isolates from transgenic and conventional grapevines from two vineyard sites in the Champagne region of France for their molecular variant composition. The population structure and genetic diversity were examined in the coat protein gene by IC-RT-PCR-RFLP analysis with EcoRI and StyI, and nucleotide sequencing, respectively. RFLP data suggested that 55 % (191 of 347) of the isolates had a population structure consisting of one predominant variant. Sequencing data of 51 isolates representing the different restrictotypes confirmed the existence of mixed infection with a frequency of 33 % (17 of 51) and showed two major predominant haplotypes representing 71 % (60 of 85) of the sequence variants. Comparative nucleotide diversity among population subsets implied a lack of genetic differentiation according to host (transgenic vs conventional) or field site for most restrictotypes (17 of 18 and 13 of 18) and for haplotypes in most phylogenetic groups (seven of eight and six of eight), respectively. Interestingly, five of the 85 haplotypes sequenced had an intermediate divergence (0.036-0.066) between the lower (0.005-0.028) and upper range (0.083-0.138) of nucleotide variability, suggesting the occurrence of homologous RNA recombination. Sequence alignments clearly indicated a mosaic structure for four of these five variants, for which recombination sites were identified and parental lineages proposed. This is the first in-depth characterization of the population structure and genetic diversity in a nepovirus.

A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy.

PubMed

Toyota, Kentaro; Hashimoto, Taeko; Ogino, Daisuke; Matsunaga, Akira; Ito, Minoru; Masakane, Ikuto; Degawa, Noriyuki; Sato, Hiroshi; Shirai, Sayuri; Umetsu, Kazuo; Tamiya, Gen; Saito, Takao; Hayasaka, Kiyoshi

2013-05-01

Lipoprotein glomerulopathy (LPG) is a hereditary disease characterized by lipoprotein thrombi in the glomerulus, hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (APOE). More than 12 APOE mutations have been identified as causes of LPG, and APOE-Sendai (Arg145Pro) mutation was frequently detected in patients from the eastern part of Japan including Yamagata prefecture. Recently, effective therapy with intensive lipid-lowering agents was established, and epidemiologic data are required for early diagnosis. We determined the haplotype structure of APOE-Sendai in 13 patients from 9 unrelated families with LPG, and found that the haplotype of all APOE-Sendai mutations was identical, suggesting that APOE-Sendai mutation is common in Japanese patients probably through a founder effect. We also studied the gene frequency of APOE-Sendai in 2023 control subjects and 418 patients receiving hemodialysis in Yamagata prefecture using the TaqMan method, but did not identify any subjects carrying the mutation, indicating that it is very rare in the general population even in the eastern part of Japan. In addition to APOE mutation, other genetic and/or epigenetic factors are considered to be involved in the pathogenesis of LPG because of its low penetrance. The patients did not have a common haplotype of the counterpart APOE allele, and some patients had the same haplotype of the counterpart APOE allele as the asymptomatic carriers. These results suggest that the counterpart APOE allele is not likely associated with the onset of LPG. Further study is required to clarify the pathogenesis of LPG.

Development of an Italian RM Y-STR haplotype database: Results of the 2013 GEFI collaborative exercise.

PubMed

Robino, C; Ralf, A; Pasino, S; De Marchi, M R; Ballantyne, K N; Barbaro, A; Bini, C; Carnevali, E; Casarino, L; Di Gaetano, C; Fabbri, M; Ferri, G; Giardina, E; Gonzalez, A; Matullo, G; Nutini, A L; Onofri, V; Piccinini, A; Piglionica, M; Ponzano, E; Previderè, C; Resta, N; Scarnicci, F; Seidita, G; Sorçaburu-Cigliero, S; Turrina, S; Verzeletti, A; Kayser, M

2015-03-01

Recently introduced rapidly mutating Y-chromosomal short tandem repeat (RM Y-STR) loci, displaying a multiple-fold higher mutation rate relative to any other Y-STRs, including those conventionally used in forensic casework, have been demonstrated to improve the resolution of male lineage differentiation and to allow male relative separation usually impossible with standard Y-STRs. However, large and geographically-detailed frequency haplotype databases are required to estimate the statistical weight of RM Y-STR haplotype matches if observed in forensic casework. With this in mind, the Italian Working Group (GEFI) of the International Society for Forensic Genetics launched a collaborative exercise aimed at generating an Italian quality controlled forensic RM Y-STR haplotype database. Overall 1509 male individuals from 13 regional populations covering northern, central and southern areas of the Italian peninsula plus Sicily were collected, including both "rural" and "urban" samples classified according to population density in the sampling area. A subset of individuals was additionally genotyped for Y-STR loci included in the Yfiler and PowerPlex Y23 (PPY23) systems (75% and 62%, respectively), allowing the comparison of RM and conventional Y-STRs. Considering the whole set of 13 RM Y-STRs, 1501 unique haplotypes were observed among the 1509 sampled Italian men with a haplotype diversity of 0.999996, largely superior to Yfiler and PPY23 with 0.999914 and 0.999950, respectively. AMOVA indicated that 99.996% of the haplotype variation was within populations, confirming that genetic-geographic structure is almost undetected by RM Y-STRs. Haplotype sharing among regional Italian populations was not observed at all with the complete set of 13 RM Y-STRs. Haplotype sharing within Italian populations was very rare (0.27% non-unique haplotypes), and lower in urban (0.22%) than rural (0.29%) areas. Additionally, 422 father-son pairs were investigated, and 20.1% of them could be discriminated by the whole set of 13 RM Y-STRs, which was very close to the theoretically expected estimate of 19.5% given the mutation rates of the markers used. Results obtained from a high-coverage Italian haplotype dataset confirm on the regional scale the exceptional ability of RM Y-STRs to resolve male lineages previously observed globally, and attest the unsurpassed value of RM Y-STRs for male-relative differentiation purposes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

No shortcut solution to the problem of Y-STR match probability calculation.

PubMed

Caliebe, Amke; Jochens, Arne; Willuweit, Sascha; Roewer, Lutz; Krawczak, Michael

2015-03-01

Match probability calculation is deemed much more intricate for lineage genetic markers, including Y-chromosomal short tandem repeats (Y-STRs), than for autosomal markers. This is because, owing to the lack of recombination, strong interdependence between markers is likely, which implies that haplotype frequency estimates cannot simply be obtained through the multiplication of allele frequency estimates. As yet, however, the practical relevance of this problem has not been studied in much detail using real data. In fact, such scrutiny appears well warranted because the high mutation rates of Y-STRs and the possibility of backward mutation should have worked against the statistical association of Y-STRs. We examined haplotype data of 21 markers included in the PowerPlex(®)Y23 set (PPY23, Promega Corporation, Madison, WI) originating from six different populations (four European and two Asian). Assessing the conditional entropies of the markers, given different subsets of markers from the same panel, we demonstrate that the PowerPlex(®)Y23 set cannot be decomposed into smaller marker subsets that would be (conditionally) independent. Nevertheless, in all six populations, >94% of the joint entropy of the 21 markers is explained by the seven most rapidly mutating markers. Although this result might render a reduction in marker number a sensible option for practical casework, the partial haplotypes would still be almost as diverse as the full haplotypes. Therefore, match probability calculation remains difficult and calls for the improvement of currently available methods of haplotype frequency estimation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia.

PubMed

Metspalu, Mait; Romero, Irene Gallego; Yunusbayev, Bayazit; Chaubey, Gyaneshwer; Mallick, Chandana Basu; Hudjashov, Georgi; Nelis, Mari; Mägi, Reedik; Metspalu, Ene; Remm, Maido; Pitchappan, Ramasamy; Singh, Lalji; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

2011-12-09

South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study.

PubMed

Hallman, D Michael; Srinivasan, Sathanur R; Chen, Wei; Boerwinkle, Eric; Berenson, Gerald S

2006-12-01

Polymorphisms in the APOC3 and APOA5 genes, from the APOA1/APOC3/APOA4/APOA5 gene cluster on chromosome 11q23, have been associated with interindividual variation in plasma triglycerides. APOA5 polymorphisms implicated include 2 in the promoter region (-1131 T/C and -3 A/G) and 1 in exon 2 (+56 C/G). APOC3 polymorphisms implicated include 1 (SstI) in the 3' untranslated region and 1 (-2854 G/T) in the APOC3-APOA4 intergenic region. We analyzed the associations of haplotypes and multilocus genotypes of these polymorphisms on longitudinal serum triglyceride profiles in 360 African American and 823 white subjects from the Bogalusa Heart Study. Subjects were examined from 2 to 8 times (mean +/- SD, 5.4 +/- 1.3) between 1973 and 1996, at ages ranging from 4 to 38 years, with 1978 observations in African Americans and 4465 in whites. Serum triglycerides were significantly higher among whites across all ages. Allele frequencies differed significantly between African Americans and whites at all but the APOA5 +56 C/G locus. Linkage disequilibrium among the loci was higher in whites and haplotype diversity lower: 6 haplotypes had estimated frequencies of more than 1% in African Americans, 5 in whites. Individually, all polymorphisms except APOC3 -2854 G/T showed significant associations with triglyceride levels in the full sample. However, genotype models including all 5 loci showed significant triglyceride associations for only 3 (APOC3 SstI, APOA5 -1131 T/C, and APOA5 +56 C/G); significant interactions among them indicated their effects were not independent. Neither APOC3 -2854 G/T nor APOA5 -3 A/G had significant effects when the other 3 loci were in the models. The EM algorithm was used to estimate haplotype frequencies and assign haplotype probabilities to individuals, which is conditional on their genotypes; individuals' haplotype probability vectors were then used as predictors in multilevel mixed models of longitudinal triglyceride profiles. Of haplotypes comprising, in order, APOC3 SstI and -2854 G/T and APOA5 -1131 T/C, -3 A/G, and +56 C/G, 3 were significantly associated with higher triglycerides, even after adjusting for multiple tests: GGTAG (P = .002), GTTAG (P < .0001), and CGCGC (P = .0002). Each GGTAG haplotype carried would be expected to raise triglyceride levels (relative to those of GTTAC homozygotes) by approximately 19 mg/dL, each GTTAG haplotype by approximately 15 mg/dL, and each CGCGC haplotype by approximately 7 mg/dL. Haplotypes comprising the 3 loci implicated by genotype analyses (SstI, -1131 T/C, and +56 C/G) were also tested: haplotypes C_C_C and G_T_G significantly raised triglycerides, even after adjustment for multiple comparisons (P < .002 for both), with each copy of C_C_C expected to raise triglycerides by approximately 7 mg/dL and each copy of G_T_G by approximately 15 mg/dL. Overall, our findings support those of others in associating specific polymorphisms and haplotypes in the APOA1/C3/A4/A5 gene cluster with higher serum triglyceride levels. However, the degree to which polymorphisms in the APOC3 and APOA5 genes may be independently associated with triglyceride levels remains to be determined.

The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes

PubMed Central

Lindenau, Juliana D.; Wagner, Sandrine C.; de Castro, Simone M.; Hutz, Mara H.

2016-01-01

Abstract Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta (β) globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the β-globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The distribution of βS haplotypes among Brazilian populations showed a predominance of the CAR haplotype. American populations were clustered in two groups defined by CAR or BEN haplotype frequencies. This scenario is compatible with historical records about the slave trade in the Americas. When all world populations where the sickle cell gene occurs were analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype predominance. These patterns may change in the next decades due to recent migrations waves. Since these haplotypes show different clinical characteristics, these recent migrations events raise the necessity to develop optimized public health programs for sickle cell disease screening and management. PMID:27706371

Association between the KRAS Gene Polymorphisms and Papillary Thyroid Carcinoma in a Chinese Han Population.

PubMed

Ning, Lifeng; Rao, Wenwang; Yu, Yaqin; Liu, Xiaoli; Pan, Yuchen; Ma, Yuan; Liu, Rui; Zhang, Shangchao; Sun, Hui; Yu, Qiong

2016-01-01

Several studies have reported the association between MAPK signaling pathway gene polymorphisms and papillary thyroid carcinoma (PTC). KRAS gene, an oncogene from the mammalian RAS gene family plays an important role in the MAPK pathway. This study aimed to identify the potential association of KRAS gene polymorphisms with susceptibility to PTC in a Han Chinese population. A total of 861 patients with PTC, 562 disease controls with nodular goiter and 897 healthy controls were recruited. Four tagSNP polymorphisms (rs12427141, rs712, rs7315339 and rs7960917) of KRAS gene were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) . Statistical analyses and haplotype estimations were conducted using Haploview and Unphased softwares. Only significant differences were observed in genotypic frequencies of the rs7315339 polymorphism (χ 2 =7.234, df=2, p=0.027) between PTC and disease controls. Statistically significant differences in both allelic and genotypic genotypes frequencies for rs712 (Genotype, χ 2 =8.258, p=0.016) and rs12427141 (Allele, χ 2 =3.992, p=0.046; Genotype, χ 2 =8.140, p=0.017) were observed between PTC patients and controls. Haplotype analyses revealed higher frequencies of GA and TA haplotypes (p=0.039 and p=0.003, respectively) from rs712- rs12427141 (two-SNP) or TGA and TTG haplotype containing the alleles from rs7960917, rs712 and rs12427141, as well as the GAT haplotype containing the alleles from rs712, rs12427141 and rs7315339 in PTC patients than in healthy controls (p=0.042, p=0.037, p=0.027, respectively). Inversely, the haplotype TTA from rs7960917, rs712 and rs12427141 or the haplotype TAC from rs712, rs12427141 and rs7315339 was significantly less frequent in the PTC patients than in normal control (p=0.003, p=0.003, respectively). These findings suggest the role of these KRAS gene variants in susceptibility to PTC. Moreover, significant differences of the KRAS gene polymorphisms may occur between nodular goiter and PTC.

Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population.

PubMed

Fukushima-Uesaka, Hiromi; Saito, Yoshiro; Watanabe, Hidemi; Shiseki, Kisho; Saeki, Mayumi; Nakamura, Takahiro; Kurose, Kouichi; Sai, Kimie; Komamura, Kazuo; Ueno, Kazuyuki; Kamakura, Shiro; Kitakaze, Masafumi; Hanai, Sotaro; Nakajima, Toshiharu; Matsumoto, Kenji; Saito, Hirohisa; Goto, Yu-ichi; Kimura, Hideo; Katoh, Masaaki; Sugai, Kenji; Minami, Narihiro; Shirao, Kuniaki; Tamura, Tomohide; Yamamoto, Noboru; Minami, Hironobu; Ohtsu, Atsushi; Yoshida, Teruhiko; Saijo, Nagahiro; Kitamura, Yutaka; Kamatani, Naoyuki; Ozawa, Shogo; Sawada, Jun-ichi

2004-01-01

In order to identify single nucleotide polymorphisms (SNPs) and haplotype frequencies of CYP3A4 in a Japanese population, the distal enhancer and proximal promoter regions, all exons, and the surrounding introns were sequenced from genomic DNA of 416 Japanese subjects. We found 24 SNPs, including 17 novel ones: two in the distal enhancer, four in the proximal promoter, one in the 5'-untranslated region (UTR), seven in the introns, and three in the 3'-UTR. The most common SNP was c.1026+12G>A (IVS10+12G>A), with a 0.249 frequency. Four non-synonymous SNPs, c.554C>G (p.T185S, CYP3A4(*)16), c.830_831insA (p.E277fsX8, (*)6), c.878T>C (p.L293P, (*)18), and c.1088 C>T (p.T363M, (*)11) were found with frequencies of 0.014, 0.001, 0.028, and 0.002, respectively. No SNP was found in the known nuclear transcriptional factor-binding sites in the enhancer and promoter regions. Using these 24 SNPs, 16 haplotypes were unambiguously identified, and nine haplotypes were inferred by aid of an expectation-maximization-based program. In addition, using data from 186 subjects enabled a close linkage to be found between CYP3A4 and CYP3A5 SNPs, especially among the SNPs at c.1026+12 in CYP3A4 and c.219-237 (IVS3-237, a key SNP site for CYP3A5(*)3), c.865+77 (IVS9+77) and c.1523 in CYP3A5. This result suggested that CYP3A4 and CYP3A5 are within the same gene block. Haplotype analysis between CYP3A4 and CYP3A5 revealed several major haplotype combinations in the CYP3A4-CYP3A5 block. Our findings provide fundamental and useful information for genotyping CYP3A4 (and CYP3A5) in the Japanese, and probably Asian populations. Copyright 2003 Wiley-Liss, Inc.

Discovery, evaluation and distribution of haplotypes of the wheat Ppd-D1 gene.

PubMed

Guo, Zhiai; Song, Yanxia; Zhou, Ronghua; Ren, Zhenglong; Jia, Jizeng

2010-02-01

Ppd-D1 is one of the most potent genes affecting the photoperiod response of wheat (Triticum aestivum). Only two alleles, insensitive Ppd-D1a and sensitive Ppd-D1b, were known previously, and these did not adequately explain the broad adaptation of wheat to photoperiod variation. In this study, five diagnostic molecular markers were employed to identify Ppd-D1 haplotypes in 492 wheat varieties from diverse geographic locations and 55 accessions of Aegilops tauschii, the D genome donor species of wheat. Six Ppd-D1 haplotypes, designated I-VI, were identified. Types II, V and VI were considered to be more ancient and types I, III and IV were considered to be derived from type II. The transcript abundances of the Ppd-D1 haplotypes showed continuous variation, being highest for haplotype I, lowest for haplotype III, and correlating negatively with varietal differences in heading time. These haplotypes also significantly affected other agronomic traits. The distribution frequency of Ppd-D1 haplotypes showed partial correlations with both latitudes and altitudes of wheat cultivation regions. The evolution, expression and distribution of Ppd-D1 haplotypes were consistent evidentially with each other. What was regarded as a pair of alleles in the past can now be considered a series of alleles leading to continuous variation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pirastu, M.; Galanello, R.; Doherty, M.A.

The predominant ..beta..-thalassemia in Sardinia is the ..beta../sup 0/ type in which no ..beta..-globin chains are synthesized in the homozygous state. The authors determined the ..beta..-thalassemia mutations in this population by the oligonucleotide-probe method and defined the chromosome haplotypes on which the mutation resides. The same ..beta../sup 39(CAG..-->..TAG)/ nonsense mutation was found on nine different chromosome haplotypes. Although this mutation may have arisen more than once, the multiple haplotypes could also be generated by crossing over and gene conversion events. These findings underscore the frequency of mutational events in the ..beta..-globin gene region.

Selection Signature Analysis Implicates the PC1/PCSK1 Region for Chicken Abdominal Fat Content

PubMed Central

Wang, Zhipeng; Zhang, Yuandan; Wang, Shouzhi; Wang, Ning; Ma, Li; Leng, Li; Wang, Shengwen; Wang, Qigui; Wang, Yuxiang; Tang, Zhiquan; Li, Ning; Da, Yang; Li, Hui

2012-01-01

We conducted a selection signature analysis using the chicken 60k SNP chip in two chicken lines that had been divergently selected for abdominal fat content (AFC) for 11 generations. The selection signature analysis used multiple signals of selection, including long-range allele frequency differences between the lean and fat lines, long-range heterozygosity changes, linkage disequilibrium, haplotype frequencies, and extended haplotype homozygosity. Multiple signals of selection identified ten signatures on chromosomes 1, 2, 4, 5, 11, 15, 20, 26 and Z. The 0.73 Mb PC1/PCSK1 region of the Z chromosome at 55.43-56.16 Mb was the most heavily selected region. This region had 26 SNP markers and seven genes, Mar-03, SLC12A2, FBN2, ERAP1, CAST, PC1/PCSK1 and ELL2, where PC1/PCSK1 are the chicken/human names for the same gene. The lean and fat lines had two main haplotypes with completely opposite SNP alleles for the 26 SNP markers and were virtually line-specific, and had a recombinant haplotype with nearly equal frequency (0.193 and 0.196) in both lines. Other haplotypes in this region had negligible frequencies. Nine other regions with selection signatures were PAH-IGF1, TRPC4, GJD4-CCNY, NDST4, NOVA1, GALNT9, the ESRP2-GALR1 region with five genes, the SYCP2-CADH4 with six genes, and the TULP1-KIF21B with 14 genes. Genome-wide association analysis showed that nearly all regions with evidence of selection signature had SNP effects with genome-wide significance (P<10–6) on abdominal fat weight and percentage. The results of this study provide specific gene targets for the control of chicken AFC and a potential model of AFC in human obesity. PMID:22792402

Selection signature analysis implicates the PC1/PCSK1 region for chicken abdominal fat content.

PubMed

Zhang, Hui; Hu, Xiaoxiang; Wang, Zhipeng; Zhang, Yuandan; Wang, Shouzhi; Wang, Ning; Ma, Li; Leng, Li; Wang, Shengwen; Wang, Qigui; Wang, Yuxiang; Tang, Zhiquan; Li, Ning; Da, Yang; Li, Hui

2012-01-01

We conducted a selection signature analysis using the chicken 60k SNP chip in two chicken lines that had been divergently selected for abdominal fat content (AFC) for 11 generations. The selection signature analysis used multiple signals of selection, including long-range allele frequency differences between the lean and fat lines, long-range heterozygosity changes, linkage disequilibrium, haplotype frequencies, and extended haplotype homozygosity. Multiple signals of selection identified ten signatures on chromosomes 1, 2, 4, 5, 11, 15, 20, 26 and Z. The 0.73 Mb PC1/PCSK1 region of the Z chromosome at 55.43-56.16 Mb was the most heavily selected region. This region had 26 SNP markers and seven genes, Mar-03, SLC12A2, FBN2, ERAP1, CAST, PC1/PCSK1 and ELL2, where PC1/PCSK1 are the chicken/human names for the same gene. The lean and fat lines had two main haplotypes with completely opposite SNP alleles for the 26 SNP markers and were virtually line-specific, and had a recombinant haplotype with nearly equal frequency (0.193 and 0.196) in both lines. Other haplotypes in this region had negligible frequencies. Nine other regions with selection signatures were PAH-IGF1, TRPC4, GJD4-CCNY, NDST4, NOVA1, GALNT9, the ESRP2-GALR1 region with five genes, the SYCP2-CADH4 with six genes, and the TULP1-KIF21B with 14 genes. Genome-wide association analysis showed that nearly all regions with evidence of selection signature had SNP effects with genome-wide significance (P<10(-6)) on abdominal fat weight and percentage. The results of this study provide specific gene targets for the control of chicken AFC and a potential model of AFC in human obesity.

Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity

PubMed Central

Wang, Danxin; Poi, Ming J.; Sun, Xiaochun; Gaedigk, Andrea; Leeder, J. Steven; Sadee, Wolfgang

2014-01-01

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of 25% of clinically used drugs. Genetic polymorphisms cause substantial variation in CYP2D6 activity and serve as biomarkers guiding drug therapy. However, genotype–phenotype relationships remain ambiguous except for poor metabolizers carrying null alleles, suggesting the presence of yet unknown genetic variants. Searching for regulatory CYP2D6 polymorphisms, we find that a SNP defining the CYP2D6*2 allele, rs16947 [R296C, 17–60% minor allele frequency (MAF)], previously thought to convey normal activity, alters exon 6 splicing, thereby reducing CYP2D6 expression at least 2-fold. In addition, two completely linked SNPs (rs5758550/rs133333, MAF 13–42%) increase CYP2D6 transcription more than 2-fold, located in a distant downstream enhancer region (>100 kb) that interacts with the CYP2D6 promoter. In high linkage disequilibrium (LD) with each other, rs16947 and the enhancer SNPs form haplotypes that affect CYP2D6 enzyme activity in vivo. In a pediatric cohort of 164 individuals, rs16947 alone (minor haplotype frequency 28%) was associated with reduced CYP2D6 metabolic activity (measured as dextromethorphan/metabolite ratios), whereas rs5758550/rs133333 alone (frequency 3%) resulted in increased CYP2D6 activity, while haplotypes containing both rs16947 and rs5758550/rs133333 were similar to the wild-type. Other alleles used in biomarker panels carrying these variants such as CYP2D6*41 require re-evaluation of independent effects on CYP2D6 activity. The occurrence of two regulatory variants of high frequency and in high LD, residing on a long haplotype, highlights the importance of gene architecture, likely shaped by evolutionary selection pressures, in determining activity of encoded proteins. PMID:23985325

Y chromosomal haplotype characteristics of domestic sheep (Ovis aries) in China.

PubMed

Wang, Yutao; Xu, Lei; Yan, Wei; Li, Shaobin; Wang, Jiqing; Liu, Xiu; Hu, Jiang; Luo, Yuzhu

2015-07-10

Investigations on the variation present at the male-specific Y chromosome region provide strong information to understand the origin and evolution of domestic sheep. One SNP OY1 (g.88A>G) in the upstream region of SRY gene, and the microsatellite SRYM18 locus within ovine Y chromosome were analyzed in one hundred and forty five samples collected from eleven breeds in China. SNP OY1 was analyzed using PCR-SSCP method and sequencing. Two different PCR-SSCP patterns represented two specific sequences with sequence analysis revealing SNP-OY1 (g.88A>G) were observed, while SNP A-OY1 showed the most common frequency (82.8%). Sequencing of the SRYM18 region revealed one novel size fragment (A2) with different repetitive units. Seven haplotypes (H4, H5, H6, H7, H8, H9 and H12) and two novel haplotypes (Ha and Hb) were established using combined genotype analysis. H6 showed the highest frequency (43.4%) across all breeds, and H8 showed the second frequency (24.1%). Ha was only found in one breed (Tan), while Hb was present in three breeds (Gansu alpine, White Suffolk and Duolang). Our findings reveal one novel allele in SRYM18 region and two novel male haplotypes of domestic sheep in China. Copyright © 2015 Elsevier B.V. All rights reserved.

HLA-A, HLA-B, and HLA-DRB1 Allele and Haplotype Frequencies in Renal Transplant Candidates in a Population in Southern Brazil.

PubMed

Saito, Patrícia Keiko; Yamakawa, Roger Haruki; Noguti, Erika Noda; Bedendo, Gustavo Borelli; Júnior, Waldir Veríssimo da Silva; Yamada, Sérgio Seiji; Borelli, Sueli Donizete

2016-05-01

Very few studies have examined the diversity of human leukocyte antigens (HLA) in the Brazilian renal transplant candidates. The frequencies of the HLA-A, HLA-B, and HLA-DRB1 alleles, haplotypes and phenotypes were studied in 522 patients with chronic renal failure, renal transplant candidates, registered at the Transplant Centers in north/northwestern Paraná State, southern Brazil. Patients were classified according to the ethnic group (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans, Africans, and Amerindians; browns or "pardos"] and 69 blacks). The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO), combined with Luminex technology. In the analysis of the total samples, 20 HLA-A, 32 HLA-B, and 13 HLA-DRB1 allele groups were identified. The most frequent allele groups for each HLA locus were HLA-A*02 (25.4%), HLA-B*44 (10.9%), and HLA-DRB1*13 (13.9%). The most frequent haplotypes were HLA-A*01-B*08-DRB1*03 (2.3%), A*02-B*44-DRB1*07 (1.2%), and A*03-B*07-DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA-A*68, B*08, and B*58 allele frequencies among ethnic groups. This study provides the first data on the HLA-A, HLA-B, and HLA-DRB1 allele, phenotype and haplotype frequencies of renal transplant candidates in a population in southern Brazil. © 2015 Wiley Periodicals, Inc.

The α‐synuclein gene in multiple system atrophy

PubMed Central

Ozawa, T; Healy, D G; Abou‐Sleiman, P M; Ahmadi, K R; Quinn, N; Lees, A J; Shaw, K; Wullner, U; Berciano, J; Moller, J C; Kamm, C; Burk, K; Josephs, K A; Barone, P; Tolosa, E; Goldstein, D B; Wenning, G; Geser, F; Holton, J L; Gasser, T; Revesz, T; Wood, N W

2006-01-01

Background The formation of α‐synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested. Method The linkage disequilibrium (LD) structure of the α‐synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated. Results and conclusion In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag‐defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases. PMID:16543523

Sequence variations of the human MPDZ gene and association with alcoholism in subjects with European ancestry.

PubMed

Karpyak, Victor M; Kim, Jeong-Hyun; Biernacka, Joanna M; Wieben, Eric D; Mrazek, David A; Black, John L; Choi, Doo-Sup

2009-04-01

Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice. To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon-intron boundaries, and 2 kilobases in the 5' region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To explore potential associations of the human MPDZ gene with alcoholism and AWS, single SNP and haplotype analyses were performed using 13 common variants. Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019). Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS. Further functional genomic analysis of MPDZ variants and investigation of their association with a broader array of alcoholism-related phenotypes could reveal additional genetic markers of alcoholism.

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel.

PubMed

Huang, Jie; Howie, Bryan; McCarthy, Shane; Memari, Yasin; Walter, Klaudia; Min, Josine L; Danecek, Petr; Malerba, Giovanni; Trabetti, Elisabetta; Zheng, Hou-Feng; Gambaro, Giovanni; Richards, J Brent; Durbin, Richard; Timpson, Nicholas J; Marchini, Jonathan; Soranzo, Nicole

2015-09-14

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.

Dual Origins of Dairy Cattle Farming – Evidence from a Comprehensive Survey of European Y-Chromosomal Variation

PubMed Central

Edwards, Ceiridwen J.; Ginja, Catarina; Kantanen, Juha; Pérez-Pardal, Lucía; Tresset, Anne; Stock, Frauke; Gama, Luis T.; Penedo, M. Cecilia T.; Bradley, Daniel G.; Lenstra, Johannes A.; Nijman, Isaäc J.

2011-01-01

Background Diversity patterns of livestock species are informative to the history of agriculture and indicate uniqueness of breeds as relevant for conservation. So far, most studies on cattle have focused on mitochondrial and autosomal DNA variation. Previous studies of Y-chromosomal variation, with limited breed panels, identified two Bos taurus (taurine) haplogroups (Y1 and Y2; both composed of several haplotypes) and one Bos indicus (indicine/zebu) haplogroup (Y3), as well as a strong phylogeographic structuring of paternal lineages. Methodology and Principal Findings Haplogroup data were collected for 2087 animals from 138 breeds. For 111 breeds, these were resolved further by genotyping microsatellites INRA189 (10 alleles) and BM861 (2 alleles). European cattle carry exclusively taurine haplotypes, with the zebu Y-chromosomes having appreciable frequencies in Southwest Asian populations. Y1 is predominant in northern and north-western Europe, but is also observed in several Iberian breeds, as well as in Southwest Asia. A single Y1 haplotype is predominant in north-central Europe and a single Y2 haplotype in central Europe. In contrast, we found both Y1 and Y2 haplotypes in Britain, the Nordic region and Russia, with the highest Y-chromosomal diversity seen in the Iberian Peninsula. Conclusions We propose that the homogeneous Y1 and Y2 regions reflect founder effects associated with the development and expansion of two groups of dairy cattle, the pied or red breeds from the North Sea and Baltic coasts and the spotted, yellow or brown breeds from Switzerland, respectively. The present Y1-Y2 contrast in central Europe coincides with historic, linguistic, religious and cultural boundaries. PMID:21253012

Investigation of extended Y chromosome STR haplotypes in Sardinia.

PubMed

Lacerenza, D; Aneli, S; Di Gaetano, C; Critelli, R; Piazza, A; Matullo, G; Culigioni, C; Robledo, R; Robino, C; Calò, C

2017-03-01

Y-chromosomal variation of selected single nucleotide polymorphisms (SNPs) and 32 short tandem repeat (STR) loci was evaluated in Sardinia in three open population groups (Northern Sardinia, n=40; Central Sardinia, n=56; Southern Sardinia, n=91) and three isolates (Desulo, n=34; Benetutti, n=45, Carloforte, n=42). The tested Y-STRs consisted of Yfiler ® Plus markers and the seven rapidly mutating (RM) loci not included in the YFiler ® Plus kit (DYF399S1, DYF403S1ab, DYF404S1, DYS526ab, DYS547, DYS612, and DYS626). As expected, inclusion of additional Y-STR loci increased haplotype diversity (h), though complete differentiation of male lineages was impossible even by means of RM Y-STRs (h=0.99997). Analysis of molecular variance indicated that the three open populations were fairly homogeneous, whereas signs of genetic heterogeneity could be detected when the three isolates were also included in the analysis. Multidimensional scaling analysis showed that, even for extended haplotypes including RM Y-STR markers, Sardinians were clearly differentiated from populations of the Italian peninsula and Sicily. The only exception was represented by the Carloforte sample that, in accordance with its peculiar population history, clustered with Northern/Central Italian populations. The introduction of extended forensic Y-STR panels, including highly variable RM Y-STR markers, is expected to reduce the impact of population structure on haplotype frequency estimations. However, our results show that the availability of geographically detailed reference databases is still important for the assessment of the evidential value of a Y-haplotype match. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART, SHBG and SLC37A2

PubMed Central

Fritz, Sébastien; Capitan, Aurelien; Djari, Anis; Rodriguez, Sabrina C.; Barbat, Anne; Baur, Aurélia; Grohs, Cécile; Weiss, Bernard; Boussaha, Mekki; Esquerré, Diane; Klopp, Christophe; Rocha, Dominique; Boichard, Didier

2013-01-01

The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10−4) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle. PMID:23762392

A search for the primary abnormality in adult-onset type II citrullinemia.

PubMed

Kobayashi, K; Shaheen, N; Kumashiro, R; Tanikawa, K; O'Brien, W E; Beaudet, A L; Saheki, T

1993-11-01

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, we show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. We also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus.

Short communication: milk protein genetic variation and casein haplotype structure in the Original Pinzgauer cattle.

PubMed

Caroli, A; Rizzi, R; Lühken, G; Erhardt, G

2010-03-01

Milk protein genetic polymorphisms are often used for characterizing domesticated mammalian species and breeds, and for studying associations with economic traits. The aim of this work was to analyze milk protein genetic variation in the Original Pinzgauer, a dual-purpose (dairy and beef) cattle breed of European origin that was influenced in the past by human movements from different regions as well as by crossbreeding with Red Holstein. A total of 485 milk samples from Original Pinzgauer from Austria (n=275) and Germany (n=210) were typed at milk proteins alpha(S1)-casein, beta-casein, kappa-casein, alpha-lactalbumin, and beta-lactoglobulin by isoelectrofocusing to analyze the genetic variation affecting the protein amino acid charge. The Original Pinzgauer breed is characterized by a rather high genetic variation affecting the amino acid charge of milk proteins, with a total of 15 alleles, 12 of which were found at a frequency >0.05. The most polymorphic protein was beta-casein with 4 alleles detected. The prevalent alleles were CSN1S1*B, CSN2*A(2), CSN1S2*A, CSN3*A, LGB*A, and LAA*B. A relatively high frequency of CSN1S2*B (0.202 in the whole data set) was found, mainly occurring within the C-A(2)-B-A haplotype (in the order CSN1S1-CSN2-CSN1S2-CSN3), which seems to be peculiar to the Original Pinzgauer, possibly because the survival of an ancestral haplotype or the introgression of Bos indicus.

Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion.

PubMed

Demetriou, Charalambos; Abu-Amero, Sayeda; White, Shawnelle; Peskett, Emma; Markoff, Arseni; Stanier, Philip; Moore, Gudrun E; Regan, Lesley

2015-11-01

Annexin A5 is a placental anti-coagulant protein that contains four nucleotide substitutions (M2 haplotype) in its promoter. This haplotype is a risk factor for recurrent spontaneous abortion (RSA). The influence of the M2 haplotype in the gestational timing of spontaneous abortions, paternal risk and relationships with known risk factors were investigated. European couples (n = 500) who had experienced three or more consecutive spontaneous abortions, and two fertile control groups, were selected for this study. The allele frequency of M2 was significantly higher among patients who had experienced early RSA than among controls (P = 0.002). No difference was found between controls and patients who had undergone late spontaneous abortions. No difference was found between patients who had experienced RSA who had a live birth or no live births, or between patients who were positive or negative for known risk factors. Male and female partners in each group had similar allele frequencies of M2. The M2 haplotype is a risk factor for early spontaneous abortions, before the 12th week of gestation, and confers about the same relative risk to carriers of both sexes. Having one or more M2 allele(s) in combination with other risk factors further increases the RSA risk. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A Unified Approach to Genotype Imputation and Haplotype-Phase Inference for Large Data Sets of Trios and Unrelated Individuals

PubMed Central

Browning, Brian L.; Browning, Sharon R.

2009-01-01

We present methods for imputing data for ungenotyped markers and for inferring haplotype phase in large data sets of unrelated individuals and parent-offspring trios. Our methods make use of known haplotype phase when it is available, and our methods are computationally efficient so that the full information in large reference panels with thousands of individuals is utilized. We demonstrate that substantial gains in imputation accuracy accrue with increasingly large reference panel sizes, particularly when imputing low-frequency variants, and that unphased reference panels can provide highly accurate genotype imputation. We place our methodology in a unified framework that enables the simultaneous use of unphased and phased data from trios and unrelated individuals in a single analysis. For unrelated individuals, our imputation methods produce well-calibrated posterior genotype probabilities and highly accurate allele-frequency estimates. For trios, our haplotype-inference method is four orders of magnitude faster than the gold-standard PHASE program and has excellent accuracy. Our methods enable genotype imputation to be performed with unphased trio or unrelated reference panels, thus accounting for haplotype-phase uncertainty in the reference panel. We present a useful measure of imputation accuracy, allelic R2, and show that this measure can be estimated accurately from posterior genotype probabilities. Our methods are implemented in version 3.0 of the BEAGLE software package. PMID:19200528

World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection.

PubMed

Liebert, Anke; López, Saioa; Jones, Bryony Leigh; Montalva, Nicolas; Gerbault, Pascale; Lau, Winston; Thomas, Mark G; Bradman, Neil; Maniatis, Nikolas; Swallow, Dallas M

2017-11-01

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.

Study of Colombia North Wiwa El Encanto Amerindians HLA- genes: Pacific Islanders relatedness.

PubMed

Arnaiz-Villena, Antonio; Palacio-Grüber, Jose; Juarez, Ignacio; Muñiz, Ester; Hernández, Ennio; Bayona, Brayan; Campos, Cristina; Nuñez, Jorge; Lopez-Nares, Adrian; Martin-Villa, Manuel; Silvera, Carlos

2018-07-01

We have studied Wiwa/Sanja Amerindians HLA-A, -B, -C, -DRB1 and DQB1 allele frequencies and extended haplotypes in 52 unrelated individuals from "El Encanto" town at Guanachaca riverside. High frequency alleles were in general present in other Amerindian populations. Also, three extended haplotypes and eight ones were respectively both "new found" and already described in Amerindians from North, Central and South America, including Lakota-Sioux, Mayas, Teeneks, Quechua and Aymaras. Analyses of HLA-A*24:02 and -C*01:02 Wiwa high frequency alleles suggested a specific relatedness with another Amerindian and Pacific Islander ethnic groups (these two particular alleles bearing in high frequencies); they include New Zealand Maoris, Taiwanese, Japanese, Papua New Guinea, and Samoans among others. This may indicate that selective forces are maintaining these two alleles high frequency within this wide American/Pacific area. Copyright © 2018. Published by Elsevier Inc.

Relationship of the bovine growth hormone gene to carcass traits in Japanese black cattle.

PubMed

Tatsuda, K; Oka, A; Iwamoto, E; Kuroda, Y; Takeshita, H; Kataoka, H; Kouno, S

2008-02-01

The bovine growth hormone gene (bGH) possesses three haplotypes, A, B and C, that differ by amino acid mutations at positions 127 and 172 in the fifth exon: (leucine 127, threonine 172), (valine 127, threonine 172) and (valine 127, methionine 172) respectively. The correlation between meat quality or carcass weight and these haplotypes was investigated in Japanese black cattle. Altogether, 940 bGH haplotypes were compared with respect to six carcass traits: carcass weight, longissimus muscle area, rib thickness, subcutaneous fat thickness, beef marbling score and beef colour. The frequency of the B haplotype was higher (0.421) than that of A (0.269) and C (0.311). High carcass weight and low beef marbling were associated with haplotype A (p < 0.05 and p < 0.01 respectively), whereas beef marbling was increased by haplotype C (p < 0.05). Estimated regression coefficient of the A haplotype substitution effect for carcass weight and beef marbling score were 5.55 (13.1% of the phenotypic SD) and -0.31 (17.0%) respectively. That of the C haplotype for beef marbling score was 0.20 (11.0%). The other traits showed no relationship to the haplotypes examined. The results of this investigation suggest that information pertaining to bGH polymorphisms in Japanese black cattle could be used to improve the selection of meat traits.

Ancient mitochondrial haplotypes and evidence for intragenic recombination in a gynodioecious plant.

PubMed

Städler, Thomas; Delph, Lynda F

2002-09-03

Because of their extremely low nucleotide mutation rates, plant mitochondrial genes are generally not expected to show variation within species. Remarkably, we found nine distinct cytochrome b sequence haplotypes in the gynodioecious alpine plant Silene acaulis, with two or more haplotypes coexisting locally in each of three sampled regions. Moreover, there is evidence for intragenic recombination in the history of the haplotype sample, implying at least transient heteroplasmy of mitochondrial DNA (mtDNA). Heteroplasmy might be achieved by one of two potential mechanisms, either continuous coexistence of subgenomic fragments in low stoichiometry, or occasional paternal leakage of mtDNA. On the basis of levels of synonymous nucleotide substitutions, the average divergence time between haplotypes is estimated to be at least 15 million years. Ancient coalescence of extant haplotypes is further indicated by the paucity of fixed differences in haplotypes obtained from related species, a pattern expected under trans-specific evolution. Our data are consistent with models of frequency-dependent selection on linked cytoplasmic male-sterility factors, the putative molecular basis of females in gynodioecious populations. However, associations between marker loci and the inferred male-sterility genes can be maintained only with very low rates of recombination. Heteroplasmy and recombination between divergent haplotypes imply unexplored consequences for the evolutionary dynamics of gynodioecy, a widespread plant breeding system.

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

PubMed

Anelli, Luisa; Zagaria, Antonella; Specchia, Giorgina; Albano, Francesco

2018-04-11

The germline JAK2 haplotype known as "GGCC or 46/1 haplotype" (haplotype GGCC_46/1 ) consists of a combination of single nucleotide polymorphisms (SNPs) mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 ( INLS4 ) gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) generating a "GGCC" combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN) positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotype GGCC_46/1 and mutations in other genes, such as thrombopoietin receptor ( MPL ) and calreticulin ( CALR ), or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotype GGCC_46/1 in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotype GGCC_46/1 and blood cell count, survival, or disease progression.

Genetic diversity and haplotype structure of 21 Y-STRs, including nine noncore loci, in South Tunisian Population: Forensic relevance.

PubMed

Makki-Rmida, Faten; Kammoun, Arwa; Mahfoudh, Nadia; Ayadi, Adnene; Gibriel, Abdullah Ahmed; Mallek, Bakhta; Maalej, Leila; Hammami, Zouheir; Maatoug, Samir; Makni, Hafedh; Masmoudi, Saber

2015-12-01

Y chromosome STRs (Y-STRs) are being used frequently in forensic laboratories. Previous studies of Y-STR polymorphisms in different groups of the Tunisian population identified low levels of diversity and discrimination capacity (DC) using various commercial marker sets. This definitely limits the use of such systems for Y-STRs genotyping in Tunisia. In our investigation on South Tunisia, 200 unrelated males were typed for the 12 conventional Y-STRs included in the PowerPlex® Y System. Additional set of nine noncore Y-STRs including DYS446, DYS456, DYS458, DYS388, DYS444, DYS445, DYS449, DYS710, and DYS464 markers were genotyped and evaluated for their potential in improving DC. Allele frequency, gene diversity, haplotype diversity (HD), and DC calculation revealed that DYS464 was the most diverse marker followed by DYS710 and DYS449 markers. The standard panel of 12 Y-STRs (DC = 80.5%) and the nine markers were combined to obtain DC of 99%. Among the 198 different haplotypes observed, 196 haplotypes were unique (HD = 99.999). Out of the nine noncore set, six Y-STRs (DYS458, DYS456, DYS449, DYS710, DYS444, and DYS464) had the greatest impact on enhancing DC. Our data provided putative Y-STRs combination to be used for genetic and forensic applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Population genetics studies of the walrus (Odobenus rosmarus): A summary and interpretation of results and research needs

USGS Publications Warehouse

Scribner, Kim T.; Hills, Susan; Fain, Steven R.; Cronin, Matthew A.; Dizon, Andrew E.; Chivers, Susan J.; Perrin, William F.

1997-01-01

A summary of population genetics data is presented for the walrus (Odobenus rosmarus). Current information on the ecology and behavior of the species is highlighted to aid in the interpretation of genetics results and to suggest future areas of research. Walruses are discontinuously distributed across the Arctic and are currently subdivided into six regional populations on the basis of historical distribution and morphology. Few population genetics studies have been conducted on the walrus. Only three of the six trigonal populations have been surveyed with biochemical or molecular techniques. Analysis of mitochondrial DNA (mtDNA) variation among walruses from the northern Pacific (Chukchi Sea) and western Atlantic (Greenland) regions revealed 13 haplotypes; 6 were found only in Pacific walruses while 7 were unique to the Atlantic subspecies. Estimates of sequence divergence between Atlantic and Pacific haplotypes were 1.0%-1.6%. No evidence of microgeographic structuring within the northern Pacific or western Atlantic regional populations was found on the basis of mtDNA haplotype frequency distributions or multilocus minisatellite band sharing. Minisatellite analysis of adult-juvenile and adult-adult pairs suggests that assemblages of walruses on individual ice floes are made up at least in part by groups of related individuals from more than one generation. Furthermore, high mtDNA haplotype diversities and low minisatellite band-sharing values suggest that both the northern Pacific and western Atlantic walruses have retained a high degree of genetic variability.

Mitochondrial genetic variations in natural house fly (Musca domestica L.) populations from the western and southern parts of Turkey.

PubMed

Doğaç, Ersin

2016-09-01

The house fly Musca domestica Linnaeus (Diptera) is one of the most studied species that is globally distributed and well known to everyone. In order to ensure baseline knowledge for the genetic resources of the species, genetic variation in M. domestica populations from western and southern parts of Turkey was investigated using nucleotide sequence analysis of 348 base pairs (bp) in the mitochondrial cytochrome oxidase subunit I gene (COI). Samples of 192 individuals were collected from 16 localities of Turkey. There were 10 variable sites defining two haplotypes of COI in this species. There was no difference in geographical distribution frequency between the two regions of Turkey. Overall, haplotype diversity (h) was low, ranging from 0 to 0.5606 with the average overall value of 0.178 ± 0.04 and nucleotide diversity (π), ranged from 0 to 0.0056 with the overall mean of 0.0016. Analysis of molecular variance (AMOVA) indicated that genetic differentiation within individuals and populations was low and significant (p < 0.05). Except Afyon population, conventional population statistic FST showed no significant genetic structure along the range of M. domestica populations. Sixteen populations clustered under six haplotypes and two of them are unique to Turkey. Haplotype networks suggested that house fly populations in Turkey are grouped with the Palearctic region, which is the most probable place for the origin of this species.

Generalizing Terwilliger's likelihood approach: a new score statistic to test for genetic association.

PubMed

el Galta, Rachid; Uitte de Willige, Shirley; de Visser, Marieke C H; Helmer, Quinta; Hsu, Li; Houwing-Duistermaat, Jeanine J

2007-09-24

In this paper, we propose a one degree of freedom test for association between a candidate gene and a binary trait. This method is a generalization of Terwilliger's likelihood ratio statistic and is especially powerful for the situation of one associated haplotype. As an alternative to the likelihood ratio statistic, we derive a score statistic, which has a tractable expression. For haplotype analysis, we assume that phase is known. By means of a simulation study, we compare the performance of the score statistic to Pearson's chi-square statistic and the likelihood ratio statistic proposed by Terwilliger. We illustrate the method on three candidate genes studied in the Leiden Thrombophilia Study. We conclude that the statistic follows a chi square distribution under the null hypothesis and that the score statistic is more powerful than Terwilliger's likelihood ratio statistic when the associated haplotype has frequency between 0.1 and 0.4 and has a small impact on the studied disorder. With regard to Pearson's chi-square statistic, the score statistic has more power when the associated haplotype has frequency above 0.2 and the number of variants is above five.

The distribution and most recent common ancestor of the 17q21 inversion in humans.

PubMed

Donnelly, Michael P; Paschou, Peristera; Grigorenko, Elena; Gurwitz, David; Mehdi, Syed Qasim; Kajuna, Sylvester L B; Barta, Csaba; Kungulilo, Selemani; Karoma, N J; Lu, Ru-Band; Zhukova, Olga V; Kim, Jong-Jin; Comas, David; Siniscalco, Marcello; New, Maria; Li, Peining; Li, Hui; Manolopoulos, Vangelis G; Speed, William C; Rajeevan, Haseena; Pakstis, Andrew J; Kidd, Judith R; Kidd, Kenneth K

2010-02-12

The polymorphic inversion on 17q21, sometimes called the microtubular associated protein tau (MAPT) inversion, is an approximately 900 kb inversion found primarily in Europeans and Southwest Asians. We have identified 21 SNPs that act as markers of the inverted, i.e., H2, haplotype. The inversion is found at the highest frequencies in Southwest Asia and Southern Europe (frequencies of approximately 30%); elsewhere in Europe, frequencies vary from < 5%, in Finns, to 28%, in Orcadians. The H2 inversion haplotype also occurs at low frequencies in Africa, Central Asia, East Asia, and the Americas, though the East Asian and Amerindian alleles may be due to recent gene flow from Europe. Molecular evolution analyses indicate that the H2 haplotype originally arose in Africa or Southwest Asia. Though the H2 inversion has many fixed differences across the approximately 900 kb, short tandem repeat polymorphism data indicate a very recent date for the most recent common ancestor, with dates ranging from 13,600 to 108,400 years, depending on assumptions and estimation methods. This estimate range is much more recent than the 3 million year age estimated by Stefansson et al. in 2005. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The molecular epidemiology of Huntington disease is related to intermediate allele frequency and haplotype in the general population.

PubMed

Kay, Chris; Collins, Jennifer A; Wright, Galen E B; Baine, Fiona; Miedzybrodzka, Zosia; Aminkeng, Folefac; Semaka, Alicia J; McDonald, Cassandra; Davidson, Mark; Madore, Steven J; Gordon, Erynn S; Gerry, Norman P; Cornejo-Olivas, Mario; Squitieri, Ferdinando; Tishkoff, Sarah; Greenberg, Jacquie L; Krause, Amanda; Hayden, Michael R

2018-04-01

Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD-associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries. © 2018 Wiley Periodicals, Inc.

Coevolution of the Ile1,016 and Cys1,534 Mutations in the Voltage Gated Sodium Channel Gene of Aedes aegypti in Mexico.

PubMed

Vera-Maloof, Farah Z; Saavedra-Rodriguez, Karla; Elizondo-Quiroga, Armando E; Lozano-Fuentes, Saul; Black Iv, William C

2015-12-01

Worldwide the mosquito Aedes aegypti (L.) is the principal urban vector of dengue viruses. Currently 2.5 billion people are at risk for infection and reduction of Ae. aegypti populations is the most effective means to reduce the risk of transmission. Pyrethroids are used extensively for adult mosquito control, especially during dengue outbreaks. Pyrethroids promote activation and prolong the activation of the voltage gated sodium channel protein (VGSC) by interacting with two distinct pyrethroid receptor sites [1], formed by the interfaces of the transmembrane helix subunit 6 (S6) of domains II and III. Mutations of S6 in domains II and III synergize so that double mutants have higher pyrethroid resistance than mutants in either domain alone. Computer models predict an allosteric interaction between mutations in the two domains. In Ae. aegypti, a Ile1,016 mutation in the S6 of domain II was discovered in 2006 and found to be associated with pyrethroid resistance in field populations in Mexico. In 2010 a second mutation, Cys1,534 in the S6 of domain III was discovered and also found to be associated with pyrethroid resistance and correlated with the frequency of Ile1,016. A linkage disequilibrium analysis was performed on Ile1,016 and Cys1,534 in Ae. aegypti collected in Mexico from 2000-2012 to test for statistical associations between S6 in domains II and III in natural populations. We estimated the frequency of the four dilocus haplotypes in 1,016 and 1,534: Val1,016/Phe1,534 (susceptible), Val1,016/Cys1,534, Ile1,016/Phe1,534, and Ile1,016/Cys1,534 (resistant). The susceptible Val1,016/Phe1,534 haplotype went from near fixation to extinction and the resistant Ile1,016/Cys1,534 haplotype increased in all collections from a frequency close to zero to frequencies ranging from 0.5-0.9. The Val1,016/Cys1,534 haplotype increased in all collections until 2008 after which it began to decline as Ile1,016/Cys1,534 increased. However, the Ile1,016/Phe1,534 haplotype was rarely detected; it reached a frequency of only 0.09 in one collection and subsequently declined. Pyrethroid resistance in the vgsc gene requires the sequential evolution of two mutations. The Ile1,016/Phe1,534 haplotype appears to have low fitness suggesting that Ile1,016 was unlikely to have evolved independently. Instead the Cys1,534 mutation evolved first but conferred only a low level of resistance. Ile1,016 in S6 of domain II then arose from the Val1,016/Cys1,534 haplotype and was rapidly selected because double mutants confer higher pyrethroid resistance. This pattern suggests that knowledge of the frequencies of mutations in both S6 in domains II and III are important to predict the potential of a population to evolve kdr. Susceptible populations with high Val1,016/Cys1,534 frequencies are at high risk for kdr evolution, whereas susceptible populations without either mutation are less likely to evolve high levels of kdr, at least over a 10 year period.

Correlation between angiotensinogen gene and primary hypertension with cerebral infarction in the Li nationality of China.

PubMed

Wang, Tan; Chen, Zhi-Bin; Jin, Shui-Jing; Su, Qing-Jie

2007-09-01

To investigate the relationship of four single nucleotide polymorphism (SNP) haplotypes in the angiotensinogen (AGT) gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China. Total 300 subjects were allocated into three different groups: Group 1, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four polymorphisms at position -152 (G-A), -20 (A-C), -18 (C-T), and -6 (A-G) in the promoter region of AGT. The frequencies of CT genotype of AGT-18 and T allele in Group 1 (P = 0.003, P = 0.004) and Group 2 (P = 0.002, P = 0.002) were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group (P = 0.016), while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 (P = 0.003) compared with the control group, while H5 haplotype frequency which included -20C and -18T was significantly increased in Group 1 (P = 0.006) versus the control. The -20 (A-C) and -18 (C-T) of the AGT may play an important role in pathogenesis of primary hypertension; and -20 (A-C), -18 (C-T), and -6 (A-G) may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Hainan, China.

Absence of the tag polymorphism for the risk haplotype HLA-DR2 for multiple sclerosis in Wixárika subjects from Mexico.

PubMed

González-Enríquez, G V; Torres-Mendoza, B M; Márquez-Pedroza, J; Macías-Islas, M A; Ortiz, G G; Cruz-Ramos, J A

2018-02-03

The HLA-DRB1*15:01 allele has a demonstrated risk for the development of multiple sclerosis (MS) in most populations around the world. The single nucleotide polymorphism (SNP) rs3129934 is found in linkage disequilibrium with the risk haplotype formed by the HLA-DRB1*15:01 and HLA-DQB1*06:02 alleles, and it is considered a reliable marker of the presence of this haplotype. Native Americans have a null or low prevalence of MS. In this study, we sought to identify the frequency of rs3129934 in the Wixárika ethnic group as well as in Mestizo (mixed race) patients with MS and in controls from western Mexico. Through real-time polymerase chain reaction (PCR) using TaqMan probes, we analyzed the allele and genotype frequencies of rs3129934 in Mestizo individuals with and without MS and in 73 Wixárika subjects from the state of Jalisco, Mexico. The Wixárika subjects were homozygote for the C allele of rs3129934. The allele and genotype frequency in Mestizos with MS was similar to that of other MS populations with Caucasian ancestry. The absence of the T risk allele rs3129934 (associated with the haplotype HLA-DRB1*15:01, HLA-DQ1*06:02) in this sample of Wixárika subjects is consistent with the unreported MS in this Amerindian group, related to absence of such paramount genetic risk factor.

The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura.

PubMed

Sinkovits, György; Szilágyi, Ágnes; Farkas, Péter; Inotai, Dóra; Szilvási, Anikó; Tordai, Attila; Rázsó, Katalin; Réti, Marienn; Prohászka, Zoltán

2017-02-01

The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying ADAMTS13-deficiency is caused by inhibitory autoantibodies against the protease. Human leukocyte antigens (HLA), responsible for antigen presentation, play an important role in the development of antibodies. The loci coding HLA DR and DQ molecules are inherited in linkage as haplotypes. The c.1858C>T polymorphism of the PTPN22 gene, which codes a protein tyrosine phosphatase important in lymphocyte activation, predisposes to a number of autoimmune diseases. We determined the HLA-DRB1-DQB1 haplotypes and the PTPN22 c.1858C>T genotypes in 75 patients with acquired idiopathic TTP and in healthy controls, in order to assess the role of these genetic factors and their interactions in the susceptibility to TTP. We found that the carrier frequencies of the DRB1 ∗ 11-DQB1 ∗ 03 and DRB1 ∗ 15-DQB1 ∗ 06 haplotypes were higher, while those of the DRB1 ∗ 07-DQB1 ∗ 02 and DRB1 ∗ 13-DQB1 ∗ 06 haplotypes were lower in TTP patients. There was no difference in the overall frequency of the PTPN22 c.1858T allele between TTP patients and controls. In conclusion, we identified four HLA-DRB1-DQB1 haplotypes associated with an increased (DRB1 ∗ 11-DQB1 ∗ 03 and DRB1 ∗ 15-DQB1 ∗ 06) or a decreased (DRB1 ∗ 07-DQB1 ∗ 02 and DRB1 ∗ 13-DQB1 ∗ 06) susceptibility to acquired idiopathic TTP. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Enhancing the mathematical properties of new haplotype homozygosity statistics for the detection of selective sweeps.

PubMed

Garud, Nandita R; Rosenberg, Noah A

2015-06-01

Soft selective sweeps represent an important form of adaptation in which multiple haplotypes bearing adaptive alleles rise to high frequency. Most statistical methods for detecting selective sweeps from genetic polymorphism data, however, have focused on identifying hard selective sweeps in which a favored allele appears on a single haplotypic background; these methods might be underpowered to detect soft sweeps. Among exceptions is the set of haplotype homozygosity statistics introduced for the detection of soft sweeps by Garud et al. (2015). These statistics, examining frequencies of multiple haplotypes in relation to each other, include H12, a statistic designed to identify both hard and soft selective sweeps, and H2/H1, a statistic that conditional on high H12 values seeks to distinguish between hard and soft sweeps. A challenge in the use of H2/H1 is that its range depends on the associated value of H12, so that equal H2/H1 values might provide different levels of support for a soft sweep model at different values of H12. Here, we enhance the H12 and H2/H1 haplotype homozygosity statistics for selective sweep detection by deriving the upper bound on H2/H1 as a function of H12, thereby generating a statistic that normalizes H2/H1 to lie between 0 and 1. Through a reanalysis of resequencing data from inbred lines of Drosophila, we show that the enhanced statistic both strengthens interpretations obtained with the unnormalized statistic and leads to empirical insights that are less readily apparent without the normalization. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined genotype and haplotype distributions of MTHFR C677T and A1298C polymorphisms

PubMed Central

Fan, Shujun; Yang, Boyi; Zhi, Xueyuan; Wang, Yanxun; Zheng, Quanmei; Sun, Guifan

2016-01-01

Abstract Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are, independently and/or in combination, associated with many disorders. However, data on the combined genotype and haplotype distributions of the 2 polymorphisms in Chinese population were limited. We recruited 13,473 adult women from 9 Chinese provinces, collected buccal cell samples, and determined genotypes, to estimate the combined genotype and haplotype distributions of the MTHFR C677T and A1298C polymorphisms. In the total sample, the 6 common combined genotypes were CT/AA (29.5%), TT/AA (21.9%), CC/AA (15.4%), CC/AC (14.9%), CT/AC (13.7%), and CC/CC (3.4%); the 3 frequent haplotypes were 677T-1298A (43.6%), 677C-1298A (37.9%), and 677C-1298C (17.6%). Importantly, we observed that there were 51 (0.4%) individuals with the CT/CC genotype, 92 (0.7%) with the TT/AC genotype, 17 (0.1%) with the TT/CC genotype, and that the frequency of the 677T-1298C haplotype was 0.9%. In addition, the prevalence of some combined genotypes and haplotypes varied among populations residing in different areas and even showed apparent geographical gradients. Further linkage disequilibrium analysis showed that the D’ and r2 values were 0.883 and 0.143, respectively. In summary, the findings of our study provide further strong evidence that the MTHFR C677T and A1298C polymorphisms are usually in trans and occasionally in cis configurations. The frequencies of mutant genotype combinations were relatively higher in Chinese population than other populations, and showed geographical variations. These baseline data would be useful for future related studies and for developing health management programs. PMID:27902594

Strong association between a splice mutation (IVS12+5G{r_arrow}A) and haplotype 6 in hereditary tyrosinemia type I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanguay, R.M.; St-Louis, M.; Gibson, K.

1994-09-01

Hereditary tyrosinemia type I (HT I; McKusick 276700) is a severe inborn error of tyrosine catabolism pathway caused by a deficiency of fumarylacetoacetate hydrolase (FAH). The highest frequency reported is the one in Saguenay-Lac St-Jean (Quebec, Canada) where 1:1,846 births are affected. The FAH gene has been cloned and several mutations have been described. Allele specific oligonucleotide (ASO) hybridization was used to examine the frequency of a splice (IVS12-5G{r_arrow}A) mutation recently reported and RFLP analysis was done to identify haplotypes related to HT I. The splice mutation was found on 45/50 alleles (90%) in patients from SLSJ and 12/66 (18%)more » alleles from patients world-wide. All 25 patients from the SLSJ region were positive with 20 being homozygous, indicating that this mutation is the major cause of HT I in French Canada. Of these 25 patients, 96% were positive for one haplotype called no 6 which is these 25 patients, 96% were positive for one haplotype called no 6 which is identified by TaqI, RsaI, BglII, MspI and KpnI digestions. These data show a really strong association between the mutation (IVS12+5G{r_arrow}A) and haplotype 6. Among our patients from around the world, {approximately}52% were positive for haplotype 6 indicating its strong relation with HT I. These results provide the rationale for DNA-based carrier testing for HT I in the F-C population at risk as well as in HT I patients in general.« less

Echinococcus ortleppi (G5) and Echinococcus granulosus sensu stricto (G1) loads in cattle from Southern Brazil.

PubMed

Balbinotti, Helier; Santos, Guilherme B; Badaraco, Jeferson; Arend, Ana C; Graichen, Daniel Ângelo S; Haag, Karen L; Zaha, Arnaldo

2012-09-10

Echinococcus granulosus sensu stricto (G1) and Echinococcus ortleppi (G5) are haplotypes of the parasite formerly known as Echinococcus granulosus sensu lato, which in its larval stage causes cystic hydatid disease, endemic in Southern Brazil. Epidemiological and molecular knowledge about the haplotypes occurring in a region is essential to control the spread of the disease. The aim of this work was to analyze the haplotype frequency and fertility of hydatid cysts in cattle from the state of Rio Grande do Sul. Cysts were collected and classified according to their fertility status. DNA was extracted from protoscoleces and germinal layers and then used as template for the amplification of the cytochrome c oxidase subunit 1 gene by PCR. Amplicons were purified and sequenced, and the sequences were analyzed for haplotype identification. A total of 638 fertile cysts collected in the last ten years were genotyped. On average, G1 (56.6%) was more frequent than G5 (43.4%). In lungs, the G5 haplotype exhibited a higher parasite load (52.8%), whereas in the liver, G1 was more frequent (90.4%). The analysis revealed an increase in the frequency of G5 haplotype cysts during the period of sampling, and an increase in the abundance of fertile cysts has also been observed in the last several years. Most infertile cysts were genotyped as G1. The possible factors involved in the increase in the proportion of E. ortleppi (G5) and the consequences of this increase are discussed. This study suggests that the proportion of E. ortleppi (G5) loads in cattle may be increasing overtime. Copyright © 2012 Elsevier B.V. All rights reserved.

Haplotype-Based Association Analysis via Variance-Components Score Test

PubMed Central

Tzeng, Jung-Ying ; Zhang, Daowen 

2007-01-01

Haplotypes provide a more informative format of polymorphisms for genetic association analysis than do individual single-nucleotide polymorphisms. However, the practical efficacy of haplotype-based association analysis is challenged by a trade-off between the benefits of modeling abundant variation and the cost of the extra degrees of freedom. To reduce the degrees of freedom, several strategies have been considered in the literature. They include (1) clustering evolutionarily close haplotypes, (2) modeling the level of haplotype sharing, and (3) smoothing haplotype effects by introducing a correlation structure for haplotype effects and studying the variance components (VC) for association. Although the first two strategies enjoy a fair extent of power gain, empirical evidence showed that VC methods may exhibit only similar or less power than the standard haplotype regression method, even in cases of many haplotypes. In this study, we report possible reasons that cause the underpowered phenomenon and show how the power of the VC strategy can be improved. We construct a score test based on the restricted maximum likelihood or the marginal likelihood function of the VC and identify its nontypical limiting distribution. Through simulation, we demonstrate the validity of the test and investigate the power performance of the VC approach and that of the standard haplotype regression approach. With suitable choices for the correlation structure, the proposed method can be directly applied to unphased genotypic data. Our method is applicable to a wide-ranging class of models and is computationally efficient and easy to implement. The broad coverage and the fast and easy implementation of this method make the VC strategy an effective tool for haplotype analysis, even in modern genomewide association studies. PMID:17924336

Influences of APOA5 Variants on Plasma Triglyceride Levels in Uyghur Population

PubMed Central

Wang, Yi; Wu, Di; Jin, Li; Wang, Xiaofeng

2014-01-01

Objective Single nucleotide polymorphisms (SNPs) in apolipoprotein A5 (APOA5) gene are associated with triglyceride (TG) levels. However, the minor allele frequencies and linkage disequilibriums (LDs) of the SNPs in addition to their effects on TG levels vary greatly between Caucasians and East Asians. The distributions of the SNPs/haplotypes and their associations with TG levels in Uyghur population, an admixture population of Caucasians and East Asians, have not been reported to date. Here, we performed a cross-sectional study to address these. Methods Genotyping of four SNPs in APOA5 (rs662799, rs3135506, rs2075291, and rs2266788) was performed in 1174 unrelated Uyghur subjects. SNP/haplotype and TG association analyses were conducted. Results The frequencies of the SNPs in Uyghurs were in between those in Caucasians and East Asians. The LD between rs662799 and rs2266788 in Uyghurs was stronger than that in East Asians but weaker than that in Caucasians, and the four SNPs resulted in four haplotypes (TGGT, CGGC, TCGT, and CGTT arranged in the order of rs662799, rs3135506, rs2075291, and rs2266788) representing 99.2% of the population. All the four SNPs were significantly associated with TG levels. Compared with non-carriers, carriers of rs662799-C, rs3135506-C, rs2075291-T, and rs2266788-C alleles had 16.0%, 15.1%, 17.1%, and 12.4% higher TG levels, respectively. When haplotype TGGT was defined as the reference, the haplotypes CGGC, TCGT, and CGTT resulted in 16.1%, 19.0%, and 19.8% higher TG levels, respectively. The proportions of variance in TG explained by APOA5 locus were 2.5%, 0.3%, 0.4%, and 1.9% for single SNP rs662799, rs3135506, rs2075291, and rs2266788, respectively, and 3.0% for the haplotypes constructed by them. Conclusions The association profiles between the SNPs and haplotypes at APOA5 locus and TG levels in this admixture population differed from those in Caucasians and East Asians. The functions of these SNPs and haplotypes need to be elucidated comprehensively. PMID:25313938

Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations

PubMed Central

Liu, Xuanyao; Ong, Rick Twee-Hee; Pillai, Esakimuthu Nisha; Elzein, Abier M.; Small, Kerrin S.; Clark, Taane G.; Kwiatkowski, Dominic P.; Teo, Yik-Ying

2013-01-01

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. PMID:23731540

HTR1A Gene Polymorphisms and 5-HT1A Receptor Partial Agonist Antipsychotics Efficacy in Schizophrenia.

PubMed

Takekita, Yoshiteru; Fabbri, Chiara; Kato, Masaki; Nonen, Shinpei; Sakai, Shiho; Sunada, Naotaka; Koshikawa, Yosuke; Wakeno, Masataka; Okugawa, Gaku; Kinoshita, Toshihiko; Serretti, Alessandro

2015-06-01

Individual differences in serotonin 1A (5-HT1A) receptor may result in variable response to antipsychotics with 5-HT1A receptor partial agonism. We investigated the relationship between 5-HT1A receptor gene (HTR1A) single nucleotide polymorphisms (SNPs) and efficacy of antipsychotics with 5-HT1A receptor partial agonism in Japanese patients with schizophrenia. Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. Candidate SNPs were rs6295 (which affects HTR1A expression and function), rs1364043, rs878567, and rs10042486. Efficacy at week 12 of treatment was evaluated using the Positive and Negative Syndrome Scale (PANSS) 5-factor subscales (excitement/hostility, depression/anxiety, cognition, positive, and negative). Rs1364043 T allele was correlated with the percent change in the PANSS 5-factor negative score (P < 0.01). Haplotype analysis showed that the rs10042486-rs6295-rs1364043 T-C-G haplotype was correlated with worse negative score improvement (haplotype frequency, 0.675; P = 0.014), and the relatively rare T-G-T haplotype correlated with better efficacy (haplotype frequency, 0.05; P = 0.031). This is the first study to show that rs10042486-rs6295-rs1364043 HTR1A variants may be correlated with the improvement of the PANSS 5-factor negative score during treatment with 5-HT1A partial agonist antipsychotics. Studies with larger sample sizes and in different ethnic groups are warranted.

Mitochondrial-DNA variation among subspecies and populations of sea otters (Enhydra lutris)

USGS Publications Warehouse

Cronin, Matthew A.; Bodkin, James L.; Ballachey, Brenda E.; Estes, James A.; Patton, John C.

1996-01-01

We used restriction-enzyme analysis of polymerase-chain reaction-amplified, mitochondrial DNA (mtDNA) to assess genetic differentiation of subspecies and populations of sea otters, Enhydra lutris, throughout the range of the species. There were several haplotypes of mtDNA in each subspecies and geographically separate populations. MtDNA sequence divergence of haplotypes of sea otters was 0.0004–0.0041 base substitutions per nucleotide. E. L nereis appears to have monophyletic mitochondrial DNA, while E. I. lutris and E. I. kenyoni do not. Different frequencies of haplotypes of mtDNA among populations reflect current restriction of gene flow and the unique histories of different populations. There are two or three haplotypes of mtDNA and diversity of haplotypes is 0.1376–0.5854 in each population of otters. This is consistent with theoretical work, which suggests that population bottlenecks of sea otters probably did not result in major losses of genetic variation for individual populations, or the species as a whole.

Addiction Genetics and Pleiotropic Effects of Common Haplotypes that Make Polygenic Contributions to Vulnerability to Substance Dependence

PubMed Central

Uhl, George R.; Drgon, Tomas; Johnson, Catherine; Liu, Qing-Rong

2016-01-01

Abundant evidence from family, adoption, and twin studies point to large genetic contributions to individual differences in vulnerability to develop dependence on one or more addictive substances. Twin data suggest that most of this genetic vulnerability is shared by individuals who are dependent on a variety of addictive substances. Molecular genetic studies, especially genomewide and candidate gene association studies, have elucidated common haplotypes in dozens of genes that appear to make polygenic contributions to vulnerability to developing dependence. Most genes that harbor currently identified addiction-associated haplotypes are expressed in the brain. Haplotypes in many of the same genes are identified in genomewide association studies that compare allele frequencies in substance dependent vs. control individuals from European, African, and Asian racial/ethnic backgrounds. Many of these addiction-associated haplotypes display pleiotropic influences on a variety of related brain-based phenotypes that display 1) substantial heritability and 2) clinical cooccurence with substance dependence. PMID:19152208

Linkage disequilibrium in HLA cannot be explained by selective recombination.

PubMed

Termijtelen, A; D'Amaro, J; van Rood, J J; Schreuder, G M

1995-11-01

Some combinations of HLA-A, -B and -DR antigens occur more frequently than would be expected from their gene frequencies in the population. This phenomenon, referred to as Linkage Disequilibrium (LD) has been the origin of many speculations. One hypothesis to explain LD is that some haplotypes are protected from recombination. A second hypothesis is that these HLA antigens preferentially recombine after cross-over to create an LD haplotype. We tested these 2 hypotheses: from a pool of over 10,000 families typed in our department, we analyzed 126 families in which HLA-A:B or B:DR recombinant offspring was documented. To overcome a possible bias in our material, we used the non-recombined haplotypes from the same 126 families as a control group. Our results show that the number of cross-overs through LD haplotypes is not significantly lower then would be expected if recombination occurred randomly. Also the number of LD haplotypes created upon recombination was not significantly increased.

Genetic structure of Plasmodium vivax using the merozoite surface protein 1 icb5-6 fragment reveals new hybrid haplotypes in southern Mexico

PubMed Central

2014-01-01

Background Plasmodium vivax is a protozoan parasite with an extensive worldwide distribution, being highly prevalent in Asia as well as in Mesoamerica and South America. In southern Mexico, P. vivax transmission has been endemic and recent studies suggest that these parasites have unique biological and genetic features. The msp1 gene has shown high rate of nucleotide substitutions, deletions, insertions, and its mosaic structure reveals frequent events of recombination, maybe between highly divergent parasite isolates. Methods The nucleotide sequence variation in the polymorphic icb5-6 fragment of the msp1 gene of Mexican and worldwide isolates was analysed. To understand how genotype diversity arises, disperses and persists in Mexico, the genetic structure and genealogical relationships of local isolates were examined. To identify new sequence hybrids and their evolutionary relationships with other P. vivax isolates circulating worldwide two haplotype networks were constructed questioning that two portions of the icb5-6 have different evolutionary history. Results Twelve new msp1 icb5-6 haplotypes of P. vivax from Mexico were identified. These nucleotide sequences show mosaic structure comprising three partially conserved and two variable subfragments and resulted into five different sequence types. The variable subfragment sV1 has undergone recombination events and resulted in hybrid sequences and the haplotype network allocated the Mexican haplotypes to three lineages, corresponding to the Sal I and Belem types, and other more divergent group. In contrast, the network from icb5-6 fragment but not sV1 revealed that the Mexican haplotypes belong to two separate lineages, none of which are closely related to Sal I or Belem sequences. Conclusions These results suggest that the new hybrid haplotypes from southern Mexico were the result of at least three different recombination events. These rearrangements likely resulted from the recombination between haplotypes of highly divergent lineages that are frequently distributed in South America and Asia and diversified rapidly. PMID:24472213

[Construction of haplotype and haplotype block based on tag single nucleotide polymorphisms and their applications in association studies].

PubMed

Gu, Ming-liang; Chu, Jia-you

2007-12-01

Human genome has structures of haplotype and haplotype block which provide valuable information on human evolutionary history and may lead to the development of more efficient strategies to identify genetic variants that increase susceptibility to complex diseases. Haplotype block can be divided into discrete blocks of limited haplotype diversity. In each block, a small fraction of ptag SNPsq can be used to distinguish a large fraction of the haplotypes. These tag SNPs can be potentially useful for construction of haplotype and haplotype block, and association studies in complex diseases. There are two general classes of methods to construct haplotype and haplotype blocks based on genotypes on large pedigrees and statistical algorithms respectively. The author evaluate several construction methods to assess the power of different association tests with a variety of disease models and block-partitioning criteria. The advantages, limitations and applications of each method and the application in the association studies are discussed equitably. With the completion of the HapMap and development of statistical algorithms for addressing haplotype reconstruction, ideas of construction of haplotype based on combination of mathematics, physics, and computer science etc will have profound impacts on population genetics, location and cloning for susceptible genes in complex diseases, and related domain with life science etc.

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

PubMed Central

Anelli, Luisa; Zagaria, Antonella; Specchia, Giorgina

2018-01-01

The germline JAK2 haplotype known as “GGCC or 46/1 haplotype” (haplotypeGGCC_46/1) consists of a combination of single nucleotide polymorphisms (SNPs) mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 (INLS4) gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) generating a “GGCC” combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN) positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotypeGGCC_46/1 and mutations in other genes, such as thrombopoietin receptor (MPL) and calreticulin (CALR), or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotypeGGCC_46/1 in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotypeGGCC_46/1 and blood cell count, survival, or disease progression. PMID:29641446

Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients.

PubMed

Chowbay, Balram; Cumaraswamy, Sivathasan; Cheung, Yin Bun; Zhou, Qingyu; Lee, Edmund J D

2003-02-01

Intestinal cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) both play a vital role in the metabolism of oral cyclosporine (CsA). We investigated the genetic polymorphisms in CYP3A4(promoter region and exons 5, 7 and 9) and MDR1 (exons 12, 21 and 26) genes and the impact of these polymorphisms on the pharmacokinetics of oral CsA in stable heart transplant patients (n = 14). CYP3A4 polymorphisms were rare in the Asian population and transplant patients. Haplotype analysis revealed 12 haplotypes in the Chinese, eight in the Malays and 10 in the Indians. T-T-T was the most common haplotype in all ethnic groups. The frequency of the homozygous mutant genotype at all three loci (TT-TT-TT) was highest in the Indians (31%) compared to 19% and 15% in the Chinese and Malays, respectively. In heart transplant patients, CsA exposure (AUC(0-4 h), AUC(0-12 h) and C(max)) was high in patients with the T-T-T haplotypes compared to those with C-G-C haplotypes. These findings suggest that haplotypes rather than genotypes influence CsA disposition in transplant patients.

Population structure and phylogeography of Toda buffalo in Nilgiris throw light on possible origin of aboriginal Toda tribe of South India.

PubMed

Kathiravan, P; Kataria, R S; Mishra, B P; Dubey, P K; Sadana, D K; Joshi, B K

2011-08-01

We report the genetic structure and evolutionary relationship of the endangered Toda buffalo of Nilgiris in South India with Kanarese and two other riverine buffalo breeds. The upgma phylogeny drawn using Nei's distance grouped South Kanara and Toda buffaloes at a single node while Marathwada and Murrah together formed a separate node. Principal component analysis was performed with pairwise interindividual chord distances which revealed clustering of Murrah and Marathwada buffaloes distinctly, while individuals of Toda and South Kanara breeds completely intermingled with each other. Furthermore, there were highly significant group variances (p < 0.01) when the breeds were grouped based on phylogeny, thus revealing the existence of cryptic genetic structure within these buffalo breeds. To know the evolutionary relationship among these breeds, 537-bp D-loop region of mitochondrial DNA was analysed. The phylogenetic analysis of mtDNA haplotypes following NJ algorithm with Chinese swamp buffalo as outgroup revealed a major cluster that included haplotypes from all the four investigated breeds and two minor clusters formed by South Kanara and Toda haplotypes. Reduced median network analysis revealed haplotypes of South Kanara and Toda to be quite distinct from the commonly found haplotypes indicating that these might have been ancestral to all the present-day haplotypes. Few mutations in two of the haplotypes of South Kanara buffalo were found to have contributed to ancestral haplotypes of Toda buffalo suggesting the possible migration of buffaloes from Kanarese region towards Nilgiris along the Western Ghats. Considering the close social, economic and cultural association of Todas with their buffaloes, the present study supports the theory of migration of Toda tribe from Kanarese/Mysore region along with their buffaloes. © 2011 Blackwell Verlag GmbH.

H1 tau haplotype-related genomic variation at 17q21.3 as an Asian heritage of the European Gypsy population.

PubMed

Almos, P Z; Horváth, S; Czibula, A; Raskó, I; Sipos, B; Bihari, P; Béres, J; Juhász, A; Janka, Z; Kálmán, J

2008-11-01

In this study, we examine the frequency of a 900 kb inversion at 17q21.3 in the Gypsy and Caucasian populations of Hungary, which may reflect the Asian origin of Gypsy populations. Of the two haplotypes (H1 and H2), H2 is thought to be exclusively of Caucasian origin, and its occurrence in other racial groups is likely to reflect admixture. In our sample, the H1 haplotype was significantly more frequent in the Gypsy population (89.8 vs 75.5%, P<0.001) and was in Hardy-Weinberg disequilibrium (P=0.017). The 17q21.3 region includes the gene of microtubule-associated protein tau, and this result might imply higher sensitivity to H1 haplotype-related multifactorial tauopathies among Gypsies.

Comparison of allele frequencies of Plasmodium falciparum merozoite antigens in malaria infections sampled in different years in a Kenyan population.

PubMed

Ochola-Oyier, Lynette Isabella; Okombo, John; Wagatua, Njoroge; Ochieng, Jacob; Tetteh, Kevin K; Fegan, Greg; Bejon, Philip; Marsh, Kevin

2016-05-06

Plasmodium falciparum merozoite antigens elicit antibody responses in malaria-endemic populations, some of which are clinically protective, which is one of the reasons why merozoite antigens are the focus of malaria vaccine development efforts. Polymorphisms in several merozoite antigen-encoding genes are thought to arise as a result of selection by the human immune system. The allele frequency distribution of 15 merozoite antigens over a two-year period, 2007 and 2008, was examined in parasites obtained from children with uncomplicated malaria. In the same population, allele frequency changes pre- and post-anti-malarial treatment were also examined. Any gene which showed a significant shift in allele frequencies was also assessed longitudinally in asymptomatic and complicated malaria infections. Fluctuating allele frequencies were identified in codons 147 and 148 of reticulocyte-binding homologue (Rh) 5, with a shift from HD to YH haplotypes over the two-year period in uncomplicated malaria infections. However, in both the asymptomatic and complicated malaria infections YH was the dominant and stable haplotype over the two-year and ten-year periods, respectively. A logistic regression analysis of all three malaria infection populations between 2007 and 2009 revealed, that the chance of being infected with the HD haplotype decreased with time from 2007 to 2009 and increased in the uncomplicated and asymptomatic infections. Rh5 codons 147 and 148 showed heterogeneity at both an individual and population level and may be under some degree of immune selection.

Molecular Population Genetics of the Alcohol Dehydrogenase Gene Region of DROSOPHILA MELANOGASTER

PubMed Central

Aquadro, Charles F.; Desse, Susan F.; Bland, Molly M.; Langley, Charles H.; Laurie-Ahlberg, Cathy C.

1986-01-01

Variation in the DNA restriction map of a 13-kb region of chromosome II including the alcohol dehydrogenase structural gene (Adh) was examined in Drosophila melanogaster from natural populations. Detailed analysis of 48 D. melanogaster lines representing four eastern United States populations revealed extensive DNA sequence variation due to base substitutions, insertions and deletions. Cloning of this region from several lines allowed characterization of length variation as due to unique sequence insertions or deletions [nine sizes; 21–200 base pairs (bp)] or transposable element insertions (several sizes, 340 bp to 10.2 kb, representing four different elements). Despite this extensive variation in sequences flanking the Adh gene, only one length polymorphism is clearly associated with altered Adh expression (a copia element approximately 250 bp 5' to the distal transcript start site). Nonetheless, the frequency spectra of transposable elements within and between Drosophila species suggests they are slightly deleterious. Strong nonrandom associations are observed among Adh region sequence variants, ADH allozyme (Fast vs. Slow), ADH enzyme activity and the chromosome inversion ln(2L) t. Phylogenetic analysis of restriction map haplotypes suggest that the major twofold component of ADH activity variation (high vs. low, typical of Fast and Slow allozymes, respectively) is due to sequence variation tightly linked to and possibly distinct from that underlying the allozyme difference. The patterns of nucleotide and haplotype variation for Fast and Slow allozyme lines are consistent with the recent increase in frequency and spread of the Fast haplotype associated with high ADH activity. These data emphasize the important role of evolutionary history and strong nonrandom associations among tightly linked sequence variation as determinants of the patterns of variation observed in natural populations. PMID:3026893

Phylogeography of Japanese horse chestnut (Aesculus turbinata) in the Japanese Archipelago based on chloroplast DNA haplotypes.

PubMed

Sugahara, Kanako; Kaneko, Yuko; Ito, Satoshi; Yamanaka, Keisuke; Sakio, Hitoshi; Hoshizaki, Kazuhiko; Suzuki, Wajiro; Yamanaka, Norikazu; Setoguchi, Hiroaki

2011-01-01

Japanese horse chestnut (Aesculus turbinata: Hippocastanaceae) is one of the typical woody plants that grow in temperate riparian forests in the Japanese Archipelago. To analyze the phylogeography of this plant in the Japanese Archipelago, we determined cpDNA haplotypes for 337 samples from 55 populations covering the entire distribution range. Based on 1,313 bp of two spacers, we determined ten haplotypes that are distinguished from adjacent haplotypes by one or two steps. Most of the populations had a single haplotype, suggesting low diversity. Spatial analysis of molecular variance suggested three obvious phylogeographic structures in western Japan, where Japanese horse chestnut is scattered and isolated in mountainous areas. Conversely, no clear phylogeographic structure was observed from the northern to the southern limit of this species, including eastern Japan, where this plant is more common. Rare and private haplotypes were also found in southwestern Japan, where Japanese horse chestnuts are distributed sparsely. These findings imply that western Japan might have maintained a relatively large habitat for A. turbinata during the Quaternary climatic oscillations, while northerly regions could not.

Gene Flow Patterns of the Mayfly Fallceon quilleri in San Diego County, California.

NASA Astrophysics Data System (ADS)

Zickovich, J.; Bohonak, A. J.

2005-05-01

Management decisions and conservation strategies for freshwater invertebrates critically depend on an understanding of gene flow and genetic structure. We collected the mayfly Fallceon quilleri (Ephemeroptera: Baetidae) from 15 streams across three geographically distinct watersheds in San Diego County, California (San Dieguito, Santa Margarita, and Tijuana) and one site in Anza-Borrego desert. We sequenced a 667 base pair region of the mitochondrial DNA (COI) to assess genetic structure and gene flow. We found eight haplotypes across all populations. San Dieguito and Santa Margarita each contained six haplotypes. Tijuana and Anza Borrego each contained four haplotypes. The expected heterozygosity for San Dieguito, Santa Margarita, Tijuana, and Anza Borrego was 0.81, 0.83, 0.75, and 1.0, respectively. A hierarchical AMOVA analysis indicated restricted gene flow and a pairwise comparison indicated that Tijuana watershed differs significantly from San Dieguito and Anza Borrego. A haplotype cladogram revealed two internal ancestral haplotypes and six derived tip haplotypes that are unique to particular watersheds. These results suggest that Tijuana (the southernmost and the most impacted watershed) is more genetically distinct and isolated than the other watersheds sampled.

Geographic Patterns of Genetic Variation in a Broadly Distributed Marine Vertebrate: New Insights into Loggerhead Turtle Stock Structure from Expanded Mitochondrial DNA Sequences

PubMed Central

Shamblin, Brian M.; Bolten, Alan B.; Abreu-Grobois, F. Alberto; Bjorndal, Karen A.; Cardona, Luis; Carreras, Carlos; Clusa, Marcel; Monzón-Argüello, Catalina; Nairn, Campbell J.; Nielsen, Janne T.; Nel, Ronel; Soares, Luciano S.; Stewart, Kelly R.; Vilaça, Sibelle T.; Türkozan, Oguz; Yilmaz, Can; Dutton, Peter H.

2014-01-01

Previous genetic studies have demonstrated that natal homing shapes the stock structure of marine turtle nesting populations. However, widespread sharing of common haplotypes based on short segments of the mitochondrial control region often limits resolution of the demographic connectivity of populations. Recent studies employing longer control region sequences to resolve haplotype sharing have focused on regional assessments of genetic structure and phylogeography. Here we synthesize available control region sequences for loggerhead turtles from the Mediterranean Sea, Atlantic, and western Indian Ocean basins. These data represent six of the nine globally significant regional management units (RMUs) for the species and include novel sequence data from Brazil, Cape Verde, South Africa and Oman. Genetic tests of differentiation among 42 rookeries represented by short sequences (380 bp haplotypes from 3,486 samples) and 40 rookeries represented by long sequences (∼800 bp haplotypes from 3,434 samples) supported the distinction of the six RMUs analyzed as well as recognition of at least 18 demographically independent management units (MUs) with respect to female natal homing. A total of 59 haplotypes were resolved. These haplotypes belonged to two highly divergent global lineages, with haplogroup I represented primarily by CC-A1, CC-A4, and CC-A11 variants and haplogroup II represented by CC-A2 and derived variants. Geographic distribution patterns of haplogroup II haplotypes and the nested position of CC-A11.6 from Oman among the Atlantic haplotypes invoke recent colonization of the Indian Ocean from the Atlantic for both global lineages. The haplotypes we confirmed for western Indian Ocean RMUs allow reinterpretation of previous mixed stock analysis and further suggest that contemporary migratory connectivity between the Indian and Atlantic Oceans occurs on a broader scale than previously hypothesized. This study represents a valuable model for conducting comprehensive international cooperative data management and research in marine ecology. PMID:24465810

Philopatry of male marine turtles inferred from mitochondrial DNA markers

PubMed Central

FitzSimmons, Nancy N.; Limpus, Colin J.; Norman, Janette A.; Goldizen, Alan R.; Miller, Jeffrey D.; Moritz, Craig

1997-01-01

Recent studies of mitochondrial DNA (mtDNA) variation among marine turtle populations are consistent with the hypothesis that females return to beaches in their natal region to nest as adults. In contrast, less is known about breeding migrations of male marine turtles and whether they too are philopatric to natal regions. Studies of geographic structuring of restriction fragment and microsatellite polymorphisms at anonymous nuclear loci in green turtle (Chelonia mydas) populations indicate that nuclear gene flow is higher than estimates from mtDNA analyses. Regional populations from the northern and southern Great Barrier Reef were distinct for mtDNA but indistinguishable at nuclear loci, whereas the Gulf of Carpentaria (northern Australia) population was distinct for both types of marker. To assess whether this result was due to reduced philopatry of males across the Great Barrier Reef, we determined the mtDNA haplotypes of breeding males at courtship areas for comparison with breeding females from the same three locations. We used a PCR-restriction fragment length polymorphism approach to determine control region haplotypes and designed mismatch primers for the identification of specific haplotypes. The mtDNA haplotype frequencies were not significantly different between males and females at any of the three areas and estimates of Fst among the regions were similar for males and females (Fst = 0.78 and 0.73, respectively). We conclude that breeding males, like females, are philopatric to courtship areas within their natal region. Nuclear gene flow between populations is most likely occurring through matings during migrations of both males and females through nonnatal courtship areas. PMID:9238077

Estimating Time to the Common Ancestor for a Beneficial Allele

PubMed Central

Smith, Joel; Coop, Graham; Stephens, Matthew; Novembre, John

2018-01-01

Abstract The haplotypes of a beneficial allele carry information about its history that can shed light on its age and the putative cause for its increase in frequency. Specifically, the signature of an allele’s age is contained in the pattern of variation that mutation and recombination impose on its haplotypic background. We provide a method to exploit this pattern and infer the time to the common ancestor of a positively selected allele following a rapid increase in frequency. We do so using a hidden Markov model which leverages the length distribution of the shared ancestral haplotype, the accumulation of derived mutations on the ancestral background, and the surrounding background haplotype diversity. Using simulations, we demonstrate how the inclusion of information from both mutation and recombination events increases accuracy relative to approaches that only consider a single type of event. We also show the behavior of the estimator in cases where data do not conform to model assumptions, and provide some diagnostics for assessing and improving inference. Using the method, we analyze population-specific patterns in the 1000 Genomes Project data to estimate the timing of adaptation for several variants which show evidence of recent selection and functional relevance to diet, skin pigmentation, and morphology in humans. PMID:29361025

High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis.

PubMed

Amouri, Ahlem; Talmoudi, Faten; Messaoud, Olfa; d'Enghien, Catherine D; Rekaya, Mariem B; Allegui, Ines; Azaiez, Héla; Kefi, Rym; Abdelhak, Ahlem; Meseddi, Sondes H; Torjemane, Lamia; Ouederni, Monia; Mellouli, Fethi; Abid, Héla B; Aissaoui, Lamia; Bejaoui, Mohamed; Othmen, Tarek B; Lyonnet, Dominique S; Soulier, Jean; Hachicha, Mongia; Dellagi, Koussay; Abdelhak, Sonia; Fanconi, Tunisian

2014-03-01

Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East.

Diversity of the TLR4 Immunity Receptor in Czech Native Cattle Breeds Revealed Using the Pacific Biosciences Sequencing Platform.

PubMed

Novák, Karel; Pikousová, Jitka; Czerneková, Vladimíra; Mátlová, Věra

2017-07-03

The allelic variants of immunity genes in historical breeds likely reflect local infection pressure and therefore represent a reservoir for breeding. Screening to determine the diversity of the Toll-like receptor gene TLR4 was conducted in two conserved cattle breeds: Czech Red and Czech Red Pied. High-throughput sequencing of pooled PCR amplicons using the PacBio platform revealed polymorphisms, which were subsequently confirmed via genotyping techniques. Eight SNPs found in coding and adjacent regions were grouped into 18 haplotypes, representing a significant portion of the known diversity in the global breed panel and presumably exceeding diversity in production populations. Notably, the ancient Czech Red breed appeared to possess greater haplotype diversity than the Czech Red Pied breed, a Simmental variant, although the haplotype frequencies might have been distorted by significant crossbreeding and bottlenecks in the history of Czech Red cattle. The differences in haplotype frequencies validated the phenotypic distinctness of the local breeds. Due to the availability of Czech Red Pied production herds, the effect of intensive breeding on TLR diversity can be evaluated in this model. The advantages of the Pacific Biosciences technology for the resequencing of long PCR fragments with subsequent direct phasing were independently validated.

High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis

PubMed Central

Amouri, Ahlem; Talmoudi, Faten; Messaoud, Olfa; d'Enghien, Catherine D; Rekaya, Mariem B; Allegui, Ines; Azaiez, Héla; Kefi, Rym; Abdelhak, Ahlem; Meseddi, Sondes H; Torjemane, Lamia; Ouederni, Monia; Mellouli, Fethi; Abid, Héla B; Aissaoui, Lamia; Bejaoui, Mohamed; Othmen, Tarek B; Lyonnet, Dominique S; Soulier, Jean; Hachicha, Mongia; Dellagi, Koussay; Abdelhak, Sonia; Fanconi, Tunisian

2014-01-01

Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East. PMID:24689079

A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families.

PubMed

Hettinger, Joe A; Liu, Xudong; Schwartz, Charles E; Michaelis, Ron C; Holden, Jeanette J A

2008-07-05

Individuals with autism spectrum disorders (ASDs) have impairments in executive function and social cognition, with males generally being more severely affected in these areas than females. Because the dopamine D1 receptor (encoded by DRD1) is integral to the neural circuitry mediating these processes, we examined the DRD1 gene for its role in susceptibility to ASDs by performing single marker and haplotype case-control comparisons, family-based association tests, and genotype-phenotype assessments (quantitative transmission disequilibrium tests: QTDT) using three DRD1 polymorphisms, rs265981C/T, rs4532A/G, and rs686T/C. Our previous findings suggested that the dopaminergic system may be more integrally involved in families with affected males only than in other families. We therefore restricted our study to families with two or more affected males (N = 112). There was over-transmission of rs265981-C and rs4532-A in these families (P = 0.040, P = 0.038), with haplotype TDT analysis showing over-transmission of the C-A-T haplotype (P = 0.022) from mothers to affected sons (P = 0.013). In addition, haplotype case-control comparisons revealed an increase of this putative risk haplotype in affected individuals relative to a comparison group (P = 0.004). QTDT analyses showed associations of the rs265981-C, rs4532-A, rs686-T alleles, and the C-A-T haplotype with more severe problems in social interaction, greater difficulties with nonverbal communication and increased stereotypies compared to individuals with other haplotypes. Preferential haplotype transmission of markers at the DRD1 locus and an increased frequency of a specific haplotype support the DRD1 gene as a risk gene for core symptoms of ASD in families having only affected males. Copyright 2008 Wiley-Liss, Inc.

Geographic distribution of haplotype diversity at the bovine casein locus

PubMed Central

Jann, Oliver C; Ibeagha-Awemu, Eveline M; Özbeyaz, Ceyhan; Zaragoza, Pilar; Williams, John L; Ajmone-Marsan, Paolo; Lenstra, Johannes A; Moazami-Goudarzi, Katy; Erhardt, Georg

2004-01-01

The genetic diversity of the casein locus in cattle was studied on the basis of haplotype analysis. Consideration of recently described genetic variants of the casein genes which to date have not been the subject of diversity studies, allowed the identification of new haplotypes. Genotyping of 30 cattle breeds from four continents revealed a geographically associated distribution of haplotypes, mainly defined by frequencies of alleles at CSN1S1 and CSN3. The genetic diversity within taurine breeds in Europe was found to decrease significantly from the south to the north and from the east to the west. Such geographic patterns of cattle genetic variation at the casein locus may be a result of the domestication process of modern cattle as well as geographically differentiated natural or artificial selection. The comparison of African Bos taurus and Bos indicus breeds allowed the identification of several Bos indicus specific haplotypes (CSN1S1*C-CSN2*A2-CSN3*AI/CSN3*H) that are not found in pure taurine breeds. The occurrence of such haplotypes in southern European breeds also suggests that an introgression of indicine genes into taurine breeds could have contributed to the distribution of the genetic variation observed. PMID:15040901

A search for the primary abnormality in adult-onset type II citrullinemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori

1993-11-01

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia.more » The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.« less

Vitamin D receptor gene Alw I, Fok I, Apa I, and Taq I polymorphisms in patients with urinary stone.

PubMed

Seo, Ill Young; Kang, In-Hong; Chae, Soo-Cheon; Park, Seung Chol; Lee, Young-Jin; Yang, Yun Sik; Ryu, Soo Bang; Rim, Joung Sik

2010-04-01

To evaluate vitamin D receptor (VDR) gene polymorphisms in Korean patients so as to identify the candidate genes associated with urinary stones. Urinary stones are a multifactorial disease that includes various genetic factors. A normal control group of 535 healthy subjects and 278 patients with urinary stones was evaluated. Of 125 patients who presented stone samples, 102 had calcium stones on chemical analysis. The VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms were evaluated using the polymerase chain reaction-restriction fragment length polymorphism analysis. Allelic and genotypic frequencies were calculated to identify associations in both groups. The haplotype frequencies of the VDR gene polymorphisms for multiple loci were also determined. For the VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms, there was no statistically significant difference between the patients with urinary stones and the healthy controls. There was also no statistically significant difference between the patients with calcium stones and the healthy controls. A novel haplotype (Ht 4; CTTT) was identified in 13.5% of the patients with urinary stones and in 8.3% of the controls (P = .001). The haplotype frequencies were significantly different between the patients with calcium stones and the controls (P = .004). The VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms does not seem to be candidate genetic markers for urinary stones in Korean patients. However, 1 novel haplotype of the VDR gene polymorphisms for multiple loci might be a candidate genetic marker. Copyright 2010 Elsevier Inc. All rights reserved.

Mitochondrial DNA Polymerase W748S Mutation: A Common Cause of Autosomal Recessive Ataxia with Ancient European Origin

PubMed Central

Hakonen, Anna H.; Heiskanen, Silja; Juvonen, Vesa; Lappalainen, Ilse; Luoma, Petri T.; Rantamäki, Maria; Goethem, Gert Van; Löfgren, Ann; Hackman, Peter; Paetau, Anders; Kaakkola, Seppo; Majamaa, Kari; Varilo, Teppo; Udd, Bjarne; Kääriäinen, Helena; Bindoff, Laurence A.; Suomalainen, Anu

2005-01-01

Mutations in the catalytic subunit of the mitochondrial DNA polymerase γ (POLG) have been found to be an important cause of neurological disease. Recently, we and collaborators reported a new neurodegenerative disorder with autosomal recessive ataxia in four patients homozygous for two amino acid changes in POLG: W748S in cis with E1143G. Here, we studied the frequency of this allele and found it to be among the most common genetic causes of inherited ataxia in Finland. We identified 27 patients with mitochondrial recessive ataxia syndrome (MIRAS) from 15 Finnish families, with a carrier frequency in the general population of 1:125. Since the mutation pair W748S+E1143G has also been described in European patients, we examined the haplotypes of 13 non-Finnish, European patients with the W748S mutation. Haplotype analysis revealed that all the chromosomes carrying these two changes, in patients from Finland, Norway, the United Kingdom, and Belgium, originate from a common ancient founder. In Finland and Norway, long, common, northern haplotypes, outside the core haplotype, could be identified. Despite having identical homozygous mutations, the Finnish patients with this adult- or juvenile-onset disease had surprisingly heterogeneous phenotypes, albeit with a characteristic set of features, including ataxia, peripheral neuropathy, dysarthria, mild cognitive impairment, involuntary movements, psychiatric symptoms, and epileptic seizures. The high carrier frequency in Finland, the high number of patients in Norway, and the ancient European founder chromosome indicate that this newly identified ataxia should be considered in the first-line differential diagnosis of progressive ataxia syndromes. PMID:16080118

Low Genetic Variation of Red-Crowned Cranes on Hokkaido Island, Japan, Over the Hundred Years.

PubMed

Akiyama, Takuya; Momose, Kunikazu; Onuma, Manabu; Matsumoto, Fumio; Masuda, Ryuichi

2017-06-01

The red-crowned crane (Grus japonensis) is recognized internationally as an endangered species. Migratory populations breed in eastern Russia and northeastern China, whereas the resident population inhabits the island of Hokkaido, Japan. Although the population inhabiting Hokkaido had experienced a severe bottleneck by the end of the 19th century, the population size has recovered to about 1500 and continues to increase now thanks to conservation efforts. A previous study reported that no marked genetic differences were seen in the island population, and that the genetic variation of the whole population on Hokkaido was lower than that of the continental population. However, the precise genetic structure of the island population in the past or near present remains unclear. To better understand the spatiotemporal changes in the genetic structure of the island population, we performed mitochondrial DNA (mtDNA) analyses using stuffed specimens (years 1878-2001) and tissue or blood samples (years 1970-2014). We found three haplotypes in the island population, one of which was a novel mtDNA haplotype in 1997 and 2007 samples. In addition, there was no clear difference in the haplotype frequency through the time span. These results suggest that the low genetic variation of the island population persisted for the last hundred years. It is thus nearly impossible for the island population to recover its genetic variation in isolation. Conservation plans for this species should therefore include the promotion of genetic exchanges between the continental and island populations, such as through artificial introduction to Hokkaido.

Mitochondrial DNA haplotype distribution patterns in Pinus ponderosa (Pinaceae): range-wide evolutionary history and implications for conservation.

PubMed

Potter, Kevin M; Hipkins, Valerie D; Mahalovich, Mary F; Means, Robert E

2013-08-01

Ponderosa pine (Pinus ponderosa Douglas ex P. Lawson & C. Lawson) exhibits complicated patterns of morphological and genetic variation across its range in western North America. This study aims to clarify P. ponderosa evolutionary history and phylogeography using a highly polymorphic mitochondrial DNA marker, with results offering insights into how geographical and climatological processes drove the modern evolutionary structure of tree species in the region. We amplified the mtDNA nad1 second intron minisatellite region for 3,100 trees representing 104 populations, and sequenced all length variants. We estimated population-level haplotypic diversity and determined diversity partitioning among varieties, races and populations. After aligning sequences of minisatellite repeat motifs, we evaluated evolutionary relationships among haplotypes. The geographical structuring of the 10 haplotypes corresponded with division between Pacific and Rocky Mountain varieties. Pacific haplotypes clustered with high bootstrap support, and appear to have descended from Rocky Mountain haplotypes. A greater proportion of diversity was partitioned between Rocky Mountain races than between Pacific races. Areas of highest haplotypic diversity were the southern Sierra Nevada mountain range in California, northwestern California, and southern Nevada. Pinus ponderosa haplotype distribution patterns suggest a complex phylogeographic history not revealed by other genetic and morphological data, or by the sparse paleoecological record. The results appear consistent with long-term divergence between the Pacific and Rocky Mountain varieties, along with more recent divergences not well-associated with race. Pleistocene refugia may have existed in areas of high haplotypic diversity, as well as the Great Basin, Southwestern United States/northern Mexico, and the High Plains.

Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.

PubMed

Pompei, Fiorenza; Ciminelli, Bianca Maria; Bombieri, Cristina; Ciccacci, Cinzia; Koudova, Monika; Giorgi, Silvia; Belpinati, Francesca; Begnini, Angela; Cerny, Milos; Des Georges, Marie; Claustres, Mireille; Ferec, Claude; Macek, Milan; Modiano, Guido; Pignatti, Pier Franco

2006-01-01

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.

Extensive population structure in San, Khoe, and mixed ancestry populations from southern Africa revealed by 44 short 5-SNP haplotypes.

PubMed

Schlebusch, Carina M; Soodyall, Himlya

2012-12-01

The San and Khoe people currently represent remnant groups of a much larger and widely distributed population of hunter-gatherers and pastoralists who had exclusive occupation of southern Africa before the arrival of Bantu-speaking groups in the past 1,200 years and sea-borne immigrants within the last 350 years. Genetic studies [mitochondrial deoxyribonucleic acid (DNA) and Y-chromosome] conducted on San and Khoe groups revealed that they harbor some of the most divergent lineages found in living peoples throughout the world. Recently, high-density, autosomal, single-nucleotide polymorphism (SNP)-array studies confirmed the early divergence of Khoe-San population groups from all other human populations. The present study made use of 220 autosomal SNP markers (in the format of both haplotypes and genotypes) to examine the population structure of various San and Khoe groups and their relationship to other neighboring groups. Whereas analyses based on the genotypic SNP data only supported the division of the included populations into three main groups-Khoe-San, Bantu-speakers, and non-African populations-haplotype analyses revealed finer structure within Khoe-San populations. By the use of only 44 short SNP haplotypes (compiled from a total of 220 SNPs), most of the Khoe-San groups could be resolved as separate groups by applying STRUCTURE analyses. Therefore, by carefully selecting a few SNPs and combining them into haplotypes, we were able to achieve the same level of population distinction that was achieved previously in high-density SNP studies on the same population groups. Using haplotypes proved to be a very efficient and cost-effective way to study population structure. Copyright © 2013 Wayne State University Press, Detroit, Michigan 48201-1309.

Alpha-globin gene haplotypes in South American Indians.

PubMed

Zago, M A; Melo Santos, E J; Clegg, J B; Guerreiro, J F; Martinson, J J; Norwich, J; Figueiredo, M S

1995-08-01

The haplotypes of the alpha-globin gene cluster were determined for 99 Indians from the Brazilian Amazon region who belong to 5 tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Three predominant haplotypes were identified: Ia (present in 38.9% of chromosomes), IIIa (25.8%), and IIe (22.1%). The only alpha-globin gene rearrangement detected was alpha alpha alpha 3.7 I gene triplication associated with haplotype IIIa, found in high frequencies (5.6% and 10.6%) in two tribes and absent in the others. alpha-Globin gene deletions that cause alpha-thalassemia were not seen, supporting the argument that malaria was absent in these populations until recently. The heterogeneous distribution of alpha-globin gene haplotypes and rearrangements among the different tribes differs markedly from the homogeneous distribution of beta-globin gene cluster haplotypes and reflects the action of various genetic mechanisms (genetic drift, founder effect, consanguinity) on small isolated population groups with a complicated history of divergence-fusion events. The alpha-globin gene haplotype distribution has some similarities to distributions observed in Southeast Asian and Pacific Island populations, indicating that these populations have considerable genetic affinities. However, the absence of several features of the alpha-globin gene cluster that are consistently present among the Pacific Islanders suggests that the similarity of haplotypes between Brazilian Indians and people from Polynesia, Micronesia, and Melanesia is more likely to result of ancient common ancestry rather than the consequence of recent direct genetic contribution through immigration.

Molecular characterization of a long range haplotype affecting protein yield and mastitis susceptibility in Norwegian Red cattle.

PubMed

Sodeland, Marte; Grove, Harald; Kent, Matthew; Taylor, Simon; Svendsen, Morten; Hayes, Ben J; Lien, Sigbjørn

2011-08-11

Previous fine mapping studies in Norwegian Red cattle (NRC) in the region 86-90.4 Mb on Bos taurus chromosome 6 (BTA6) has revealed a quantitative trait locus (QTL) for protein yield (PY) around 88 Mb and a QTL for clinical mastitis (CM) around 90 Mb. The close proximity of these QTLs may partly explain the unfavorable genetic correlation between these two traits in NRC. A long range haplotype covering this region was introduced into the NRC population through the importation of a Holstein-Friesian bull (1606 Frasse) from Sweden in the 1970s. It has been suggested that this haplotype has a favorable effect on milk protein content but an unfavorable effect on mastitis susceptibility. Selective breeding for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. Association mapping for PY and CM in NRC was performed using genotypes from 556 SNPs throughout the region 86-97 Mb on BTA6 and daughter-yield-deviations (DYDs) from 2601 bulls made available from the Norwegian dairy herd recording system. Highest test scores for PY were found for single-nucleotide polymorphisms (SNPs) within and surrounding the genes CSN2 and CSN1S2, coding for the β-casein and α(S2)-casein proteins. High coverage re-sequencing by high throughput sequencing technology enabled molecular characterization of a long range haplotype from 1606 Frasse encompassing these two genes. Haplotype analysis of a large number of descendants from this bull indicated that the haplotype was not markedly disrupted by recombination in this region. The haplotype was associated with both increased milk protein content and increased susceptibility to mastitis, which might explain parts of the observed genetic correlation between PY and CM in NRC. Plausible causal polymorphisms affecting PY were detected in the promoter region and in the 5'-flanking UTR of CSN1S2. These polymorphisms could affect transcription or translation of CSN1S2 and thereby affect the amount of α(S2)-casein in milk. Highest test scores for CM were found in the region 89-91 Mb on BTA6, very close to a cluster of genes coding for CXC chemokines. Expression levels of some of these CXC chemokines have previously been shown to increase in bovine mammary gland cell lines after exposure to bacterial cell wall components. Molecular characterization of the long range haplotype from the Holstein-Friesian bull 1606 Frasse, imported into NRC in the 1970s, revealed polymorphisms that could affect transcription or translation of the casein gene CSN1S2. Sires with this haplotype had daughters with significantly elevated milk protein content and selection for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. The haplotype was also associated with increased mastitis susceptibility, which might explain parts of the genetic correlation between PY and CM in NRC.

Time-Sampled Population Sequencing Reveals the Interplay of Selection and Genetic Drift in Experimental Evolution of Potato Virus Y

PubMed Central

2017-01-01

ABSTRACT RNA viruses are one of the fastest-evolving biological entities. Within their hosts, they exist as genetically diverse populations (i.e., viral mutant swarms), which are sculpted by different evolutionary mechanisms, such as mutation, natural selection, and genetic drift, and also the interactions between genetic variants within the mutant swarms. To elucidate the mechanisms that modulate the population diversity of an important plant-pathogenic virus, we performed evolution experiments with Potato virus Y (PVY) in potato genotypes that differ in their defense response against the virus. Using deep sequencing of small RNAs, we followed the temporal dynamics of standing and newly generated variations in the evolving viral lineages. A time-sampled approach allowed us to (i) reconstruct theoretical haplotypes in the starting population by using clustering of single nucleotide polymorphisms' trajectories and (ii) use quantitative population genetics approaches to estimate the contribution of selection and genetic drift, and their interplay, to the evolution of the virus. We detected imprints of strong selective sweeps and narrow genetic bottlenecks, followed by the shift in frequency of selected haplotypes. Comparison of patterns of viral evolution in differently susceptible host genotypes indicated possible diversifying evolution of PVY in the less-susceptible host (efficient in the accumulation of salicylic acid). IMPORTANCE High diversity of within-host populations of RNA viruses is an important aspect of their biology, since they represent a reservoir of genetic variants, which can enable quick adaptation of viruses to a changing environment. This study focuses on an important plant virus, Potato virus Y, and describes, at high resolution, temporal changes in the structure of viral populations within different potato genotypes. A novel and easy-to-implement computational approach was established to cluster single nucleotide polymorphisms into viral haplotypes from very short sequencing reads. During the experiment, a shift in the frequency of selected viral haplotypes was observed after a narrow genetic bottleneck, indicating an important role of the genetic drift in the evolution of the virus. On the other hand, a possible case of diversifying selection of the virus was observed in less susceptible host genotypes. PMID:28592544

HLA-E regulatory and coding region variability and haplotypes in a Brazilian population sample.

PubMed

Ramalho, Jaqueline; Veiga-Castelli, Luciana C; Donadi, Eduardo A; Mendes-Junior, Celso T; Castelli, Erick C

2017-11-01

The HLA-E gene is characterized by low but wide expression on different tissues. HLA-E is considered a conserved gene, being one of the least polymorphic class I HLA genes. The HLA-E molecule interacts with Natural Killer cell receptors and T lymphocytes receptors, and might activate or inhibit immune responses depending on the peptide associated with HLA-E and with which receptors HLA-E interacts to. Variable sites within the HLA-E regulatory and coding segments may influence the gene function by modifying its expression pattern or encoded molecule, thus, influencing its interaction with receptors and the peptide. Here we propose an approach to evaluate the gene structure, haplotype pattern and the complete HLA-E variability, including regulatory (promoter and 3'UTR) and coding segments (with introns), by using massively parallel sequencing. We investigated the variability of 420 samples from a very admixed population such as Brazilians by using this approach. Considering a segment of about 7kb, 63 variable sites were detected, arranged into 75 extended haplotypes. We detected 37 different promoter sequences (but few frequent ones), 27 different coding sequences (15 representing new HLA-E alleles) and 12 haplotypes at the 3'UTR segment, two of them presenting a summed frequency of 90%. Despite the number of coding alleles, they encode mainly two different full-length molecules, known as E*01:01 and E*01:03, which corresponds to about 90% of all. In addition, differently from what has been previously observed for other non classical HLA genes, the relationship among the HLA-E promoter, coding and 3'UTR haplotypes is not straightforward because the same promoter and 3'UTR haplotypes were many times associated with different HLA-E coding haplotypes. This data reinforces the presence of only two main full-length HLA-E molecules encoded by the many HLA-E alleles detected in our population sample. In addition, this data does indicate that the distal HLA-E promoter is by far the most variable segment. Further analyses involving the binding of transcription factors and non-coding RNAs, as well as the HLA-E expression in different tissues, are necessary to evaluate whether these variable sites at regulatory segments (or even at the coding sequence) may influence the gene expression profile. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polymorphisms in IL-1 gene cluster and its association with the risk of perinatal HIV transmission, in an Indian cohort.

PubMed

Ahir, Swati; Chaudhari, Deepali; Chavan, Vijay; Samant-Mavani, Padmaja; Nanavati, Ruchi; Mehta, Preeti; Mania-Pramanik, Jayanti

2013-06-01

Host genetic diversity plays a very important role in protecting infants exposed to HIV-1 through their mothers. IL-1 family genes are key mediators of inflammatory responses and no studies are available on its association with perinatal HIV transmission. We aimed to evaluate if single nucleotide polymorphisms in IL-1 family genes are associated with perinatal HIV transmission. Infants of HIV positive women were genotyped for five polymorphic loci in IL1 gene cluster namely; IL1R1 (rs2234650), IL1A (rs1800587), IL1B (rs16944), IL1B (rs1143634), and IL1RN (rs315952) using polymerase chain reaction with sequence specific primers (PCR-SSP) method. Haplotype block structure was determined using Haploview and statistical analysis was done using PyPop. In this cohort based observational study significantly increased frequency of CT genotype in IL1R1 (rs2234650) was observed in positive vs. negative children (76.4% vs. 42.2%, p = 0.023), while CC genotype was significantly (p = 0.022) high in exposed uninfected children compared to infected ones (51.1% vs. 17.6%). These significances, however, did not stand the Bonferroni corrections. Haplotypic analysis demonstrated that the TCCCT haplotype was significantly associated (p = 0.002) with HIV transmission and remained significant even after Bonferroni correction. The children who had the protective CC genotype at IL1R1 (rs2234650) and were still positive had the TTC haplotype for IL1A (rs1800587):IL1B (rs1143634):IL1R1 (rs2234650). In contrast, 16 out of 19 (84.2%) children who had the CT genotype and were still negative had the protective CTC haplotype for IL1A (rs1800587):IL1B (rs16944):IL1B (rs1143634). IL1R1 (rs2234650) polymorphisms CT/CC along the specific haplotypes of the IL-1 gene family can be exploited as possible markers for prediction of perinatal HIV transmission. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese population.

PubMed

Ou, Chih-Ying; Chen, Chiung-Zuei; Hsiue, Tzuen-Ren; Lin, Sheng-Hsiang; Wang, Jiu-Yao

2015-02-01

Although surfactant protein-D (SP-D) has been suggested as a biomarker for chronic obstructive pulmonary disease (COPD), the relationship between genetic variants of SP-D and disease outcome of COPD remains unknown. We hypothesized that genetic polymorphisms of SP-D are associated with COPD-related phenotypes and disease prognosis. A hospital-based, case-controlled study was conducted prospectively. Six single nucleotide polymorphisms of the SFTPD gene were determined for genetic association analysis. Inflammatory cytokines and SP-D serum level were quantified. Frequency of exacerbation and change of lung function were assessed. All-cause 3-year mortality was registered. We studied 320 smokers (192 with COPD and 128 at-risk for COPD) who were prospectively monitored for at least 3 years. The serum levels of SP-D in COPD patients were significantly associated with the degree of airflow obstruction and frequency of exacerbation. Haplotype association analysis revealed that haplotype G-G-C-C-A was associated with lower risk of COPD (P = 0.03) in our study population. COPD patients with haplotype G-G-C-C-A had lower serum SP-D levels (P < 0.001), higher rates of positive response to bronchodilator treatment (P = 0.01), more improvement of forced expiratory volume in 1 s in yearly follow-up (P = 0.03) and better 3-year survival rate than COPD patients with non G-G-C-C-A haplotype (P = 0.03). Genetic haplotype of SP-D may serve as a valuable prognostic indicator in Chinese patients with COPD. © 2014 Asian Pacific Society of Respirology.

Detecting and characterizing genomic signatures of positive selection in global populations.

PubMed

Liu, Xuanyao; Ong, Rick Twee-Hee; Pillai, Esakimuthu Nisha; Elzein, Abier M; Small, Kerrin S; Clark, Taane G; Kwiatkowski, Dominic P; Teo, Yik-Ying

2013-06-06

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease.

PubMed

Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Trégouët, David-Alexandre; Gouni-Berthold, Ioanna

2010-02-01

Ghrelin is involved in several metabolic and cardiovascular processes. Recent evidence suggests its involvement in blood pressure regulation and hypertension. The aim of the study was to determine associations of single-nucleotide polymorphisms (SNPs) and haplotypes of the ghrelin gene (GHRL) with hypertension and atherosclerotic disease. Six GHRL SNPs (rs27647, rs26802, rs34911341, rs696217, rs4684677 and a -473G/A (with no assigned rsID)) were investigated in a sample of 1143 hypertensive subjects and 1489 controls of Caucasian origin. Both single-locus and haplotype association analyses were performed. In single-locus analyses, only the non-synonymous rs34911341 was associated with hypertension (odds ratio (OR)=1.95 (95% confidence interval (CI): 1.26-3.02), P=0.003). Six common haplotypes with frequency >1% were inferred from the studied GHRL SNPs, and their frequency distribution was significantly different between hypertensive subjects and controls (chi(2)=12.96 with 5 d.f. (degree of freedom), P=0.024). The effect of rs26802 was found to be significantly (P=0.017) modulated by other GHRL SNPs, as its C allele conferred either an increased risk (OR=1.30 (1.08-1.57), P=0.005) or a decreased risk (OR=0.50 (0.23-1.06), P=0.07) of hypertension according to the two different haplotypes on which it can be found. No association of GHRL SNPs or haplotypes with atherosclerotic disease was observed. In conclusion, we observed statistical evidence for association between GHRL SNPs and risk of hypertension.

Molecular analysis of aspermic Fasciola flukes from Korea on the basis of the nuclear ITS1 region and mitochondrial DNA markers and comparison with Japanese aspermic Fasciola flukes.

PubMed

Ichikawa, Madoka; Itagaki, Tadashi

2012-07-01

It has been speculated that populations of aspermic Fasciola flukes in Korea and Japan have a close phylogenetic relationship. To evaluate this, we analyzed 33 Korean aspermic Fasciola flukes on the basis of nuclear ribosomal internal transcribed spacer 1 (ITS1) and mitochondrial NADH dehydrogenase subunit 1 (nad1) and cytochrome c oxidase 1 (cox1) sequences. Fh, Fg, and Fh/Fg types were detected in the ITS1 region and displayed the fragment patterns of F. hepatica, F. gigantica, and both species, respectively by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Additionally, three concatenated haplotypes of nad1 and cox1(nad1/cox1) were detected, and 2 of these, Kor1/Kor1 (Fsp1/Fsp1) haplotype and Kor2a/Kor2 (Fsp2/Fsp2) haplotype, were shared by Korean and Japanese aspermic flukes. The Fst value (0.019), calculated using the concatenated sequences, indicated that Korean and Japanese aspermic Fasciola populations were genetically undifferentiated. Interestingly, a combination of the Fh/Fg type and Kor1/Kor1 haplotype was found at the highest frequency in Korean aspermic flukes, whereas the Fg type and Fsp2/Fsp2 haplotype combination was found at a conspicuously high frequency in Japanese aspermic flukes. This indicates that a founder effect caused by the introduction of infected hosts may have played a key role in the introduction of aspermic Fasciola flukes from Korea into Japan.

Population Structure With Localized Haplotype Clusters

PubMed Central

Browning, Sharon R.; Weir, Bruce S.

2010-01-01

We propose a multilocus version of FST and a measure of haplotype diversity using localized haplotype clusters. Specifically, we use haplotype clusters identified with BEAGLE, which is a program implementing a hidden Markov model for localized haplotype clustering and performing several functions including inference of haplotype phase. We apply this methodology to HapMap phase 3 data. With this haplotype-cluster approach, African populations have highest diversity and lowest divergence from the ancestral population, East Asian populations have lowest diversity and highest divergence, and other populations (European, Indian, and Mexican) have intermediate levels of diversity and divergence. These relationships accord with expectation based on other studies and accepted models of human history. In contrast, the population-specific FST estimates obtained directly from single-nucleotide polymorphisms (SNPs) do not reflect such expected relationships. We show that ascertainment bias of SNPs has less impact on the proposed haplotype-cluster-based FST than on the SNP-based version, which provides a potential explanation for these results. Thus, these new measures of FST and haplotype-cluster diversity provide an important new tool for population genetic analysis of high-density SNP data. PMID:20457877

Independent mitochondrial origin and historical genetic differentiation in North Eastern Asian cattle.

PubMed

Mannen, H; Kohno, M; Nagata, Y; Tsuji, S; Bradley, D G; Yeo, J S; Nyamsamba, D; Zagdsuren, Y; Yokohama, M; Nomura, K; Amano, T

2004-08-01

In order to clarify the origin and genetic diversity of cattle in North Eastern Asia, this study examined mitochondrial displacement loop sequence variation and frequencies of Bos taurus and Bos indicus Y chromosome haplotypes in Japanese, Mongolian, and Korean native cattle. In mitochondrial analyses, 20% of Mongolian cattle carried B. indicus mitochondrial haplotypes, but Japanese and Korean cattle carried only B. taurus haplotypes. In contrast, all samples revealed B. taurus Y chromosome haplotypes. This may be due to the import of zebu and other cattle during the Mongol Empire era with subsequent crossing with native taurine cattle. B. taurus mtDNA sequences fall into several geographically distributed haplogroups and one of these, termed here T4, is described in each of the test samples, but has not been observed in Near Eastern, European or African cattle. This may have been locally domesticated from an East Eurasian strain of Bos primigenius.

Linkage Disequilibrium and Haplotype Diversity in the Genes of the Renin–Angiotensin System: Findings From the Family Blood Pressure Program

PubMed Central

Zhu, Xiaofeng; Yan, Denise; Cooper, Richard S.; Luke, Amy; Ikeda, Morna A.; Chang, Yen-Pei C.; Weder, Alan; Chakravarti, Aravinda

2003-01-01

Association studies of candidate genes with complex traits have generally used one or a few single nucleotide polymorphisms (SNPs), although variation in the extent of linkage disequilibrium (LD) within genes markedly influences the sensitivity and precision of association studies. The extent of LD and the underlying haplotype structure for most candidate genes are still unavailable. We sampled 193 blacks (African-Americans) and 160 whites (European-Americans) and estimated the intragenic LD and the haplotype structure in four genes of the renin–angiotensin system. We genotyped 25 SNPs, with all but one of the pairs spaced between 1 and 20 kb, thus providing resolution at small scale. The pattern of LD within a gene was very heterogeneous. Using a robust method to define haplotype blocks, blocks of limited haplotype diversity were identified at each locus; between these blocks, LD was lost owing to the history of recombination events. As anticipated, there was less LD among blacks, the number of haplotypes was substantially larger, and shorter haplotype segments were found, compared with whites. These findings have implications for candidate-gene association studies and indicate that variation between populations of European and African origin in haplotype diversity is characteristic of most genes. [The sequence data described in this paper are available in GenBank under the following accession nos: AGT, MIM 106150; Renin, MIM 179820; ACE, MIM 106180; Angiotensin receptor I, MIM 106165. Supplementary material is available online at http://www.genome.org.] PMID:12566395

Population data on 11 Y-chromosome STRs from Guiné-Bissau.

PubMed

Rosa, Alexandra; Ornelas, Carolina; Brehm, António; Villems, Richard

2006-03-10

The forensic value of Y-STR markers in Guiné-Bissau was accessed by typing of 215 males. Allele and haplotype frequencies, determined for loci DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439 and the duplicated locus DYS385, are within the limits of variation found in other populations south of the Sahara. The level of discrimination achieved is Guineans is higher than for European or other African populations with comparable data. The haplotype diversity of 0.9995 is reduced to 0.9981 when the minimal haplotype is considered thus revealing the importance of increasing the number of typed loci.

Nine-locus Y-STR profiles of Afrikaner Caucasian and mixed ancestry populations from Cape Town, South Africa.

PubMed

Ehrenreich, Liezle; Benjeddou, Mongi; Davison, Sean; D'Amato, Maria; Leat, Neil

2008-07-01

Samples were collected from 108 Afrikaner males and 114 males of mixed ancestry. The term mixed ancestry is being used to denote a complex community which was established with contributions from Asians, Caucasians and Indigenous populations and constitutes a significant proportion of the Cape Town metropolitan population. Allele and haplotype frequencies were determined for nine Y-STR loci (DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393 and the duplicated locus DYS385). Unique haplotypes were obtained for 64 Afrikaner males and 90 males of mixed ancestry. Both population groups shared the same most common haplotype.

Interrelationships between Amerindian tribes of lower Amazonia as manifest by HLA haplotype disequilibria.

PubMed

Black, F L

1984-11-01

HLA B-C haplotypes exhibit common disequilibria in populations drawn from four continents, indicating that they are subject to broadly active selective forces. However, the A-B and A-C associations we have examined show no consistent disequilibrium pattern, leaving open the possibility that these disequilibria are due to descent from common progenitors. By examining HLA haplotype distributions, I have explored the implications that would follow from the hypothesis that biological selection played no role in determining A-C disequilibria in 10 diverse tribes of the lower Amazon Basin. Certain haplotypes are in strong positive disequilibria across a broad geographic area, suggesting that members of diverse tribes descend from common ancestors. On the basis of the extent of diffusion of the components of these haplotypes, one can estimate that the progenitors lived less than 6,000 years ago. One widely encountered lineage entered the area within the last 1,200 years. When haplotype frequencies are used in genetic distance measurements, they give a pattern of relationships very similar to that obtained by conventional chord measurements based on several genetic markers; but more than that, when individual haplotype disequilibria in the several tribes are compared, multiple origins of a single tribe are discernible and relationships are revealed that correlate more closely to geographic and linguistic patterns than do the genetic distance measurements.

Genetic structure of Florida green turtle rookeries as indicated by mitochondrial DNA control region sequences

USGS Publications Warehouse

Shamblin, Brian M.; Bagley, Dean A.; Ehrhart, Llewellyn M.; Desjardin, Nicole A.; Martin, R. Erik; Hart, Kristen M.; Naro-Maciel, Eugenia; Rusenko, Kirt; Stiner, John C.; Sobel, Debra; Johnson, Chris; Wilmers, Thomas; Wright, Laura J.; Nairn, Campbell J.

2014-01-01

Green turtle (Chelonia mydas) nesting has increased dramatically in Florida over the past two decades, ranking the Florida nesting aggregation among the largest in the Greater Caribbean region. Individual beaches that comprise several hundred kilometers of Florida’s east coast and Keys support tens to thousands of nests annually. These beaches encompass natural to highly developed habitats, and the degree of demographic partitioning among rookeries was previously unresolved. We characterized the genetic structure of ten Florida rookeries from Cape Canaveral to the Dry Tortugas through analysis of 817 base pair mitochondrial DNA (mtDNA) control region sequences from 485 nesting turtles. Two common haplotypes, CM-A1.1 and CM-A3.1, accounted for 87 % of samples, and the haplotype frequencies were strongly partitioned by latitude along Florida’s Atlantic coast. Most genetic structure occurred between rookeries on either side of an apparent genetic break in the vicinity of the St. Lucie Inlet that separates Hutchinson Island and Jupiter Island, representing the finest scale at which mtDNA structure has been documented in marine turtle rookeries. Florida and Caribbean scale analyses of population structure support recognition of at least two management units: central eastern Florida and southern Florida. More thorough sampling and deeper sequencing are necessary to better characterize connectivity among Florida green turtle rookeries as well as between the Florida nesting aggregation and others in the Greater Caribbean region.

Chloroplast DNA variation of northern red oak

Treesearch

Jeanne Romero-Severson; Preston Aldrich; Yi Feng; Weilin Sun; Charles Michler

2003-01-01

Chloroplast DNA (cpDNA) variation was examined in 48 northern red oaks at 14 sites representing contrasting glacial histories and age structures within the state of Indiana in the United States. PCR-RFLP of three intergenic regions revealed five haplotypes. Haplotype I was common to seven sites and was the most frequent (17 trees). Haplotype II was common to five sites...

High frequency of C9orf72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis patients from two founder populations sharing the same risk haplotype.

PubMed

Goldstein, Orly; Gana-Weisz, Mali; Nefussy, Beatrice; Vainer, Batel; Nayshool, Omri; Bar-Shira, Anat; Traynor, Bryan J; Drory, Vivian E; Orr-Urtreger, Avi

2018-04-01

We characterized the C9orf72 hexanucleotide repeat expansion (RE) mutation in amyotrophic lateral sclerosis (ALS) patients of 2 distinct origins, Ashkenazi and North Africa Jews (AJ, NAJ), its frequency, and genotype-phenotype correlations. In AJ, 80% of familial ALS (fALS) and 11% of sporadic ALS carried the RE, a total of 12.9% of all AJ-ALS compared to 0.3% in AJ controls (odds ratio [OR] = 44.3, p < 0.0001). In NAJ, 10% of fALS and 9% of sporadic ALS carried the RE, a total of 9.1% of all NAJ-ALS compared to 1% in controls (OR = 9.9, p = 0.0006). We identified a risk haplotype shared among all ALS patients, although an association with age at disease onset, fALS, and dementia were observed only in AJ. Variations were identified downstream the repeats. The risk haplotype and these polymorphisms were at high frequencies in alleles with 8 repeats or more, suggesting sequence instability. The different genotype-phenotype correlations and OR, together with the large range in age at onset, suggest that other modifiers and risk factors may affect penetrance and phenotype in ALS. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic variation and willingness to participate in epidemiologic research: data from three studies.

PubMed

Bhatti, Parveen; Sigurdson, Alice J; Wang, Sophia S; Chen, Jinbo; Rothman, Nathaniel; Hartge, Patricia; Bergen, Andrew W; Landi, Maria Teresa

2005-10-01

The differences in common genetic polymorphism frequencies by willingness to participate in epidemiologic studies are unexplored, but the same threats to internal validity operate as for studies with nongenetic information. We analyzed single nucleotide polymorphism genotypes, haplotypes, and short tandem repeats among control groups from three studies with different recruitment designs that included early, late, and never questionnaire responders, one or more participation incentives, and blood or buccal DNA collection. Among 2,955 individuals, we compared 108 genotypes, 8 haplotypes, and 9 to 15 short tandem repeats by respondent type. Among our main comparisons, single nucleotide polymorphism genotype frequencies differed significantly (P < 0.05) between respondent groups in six instances, with 13 expected by chance alone. When comparing the odds of carrying a variant among the various response groups, 19 odds ratios were /=1.40, levels that might be notably different. Among the various respondent group comparisons, haplotype and short tandem repeat frequencies were not significantly different by willingness to participate. We observed little evidence to suggest that genotype differences underlie response characteristics in molecular epidemiologic studies, but a greater variety of genes should be examined, including those related to behavioral traits potentially associated with willingness to participate. To the extent possible, investigators should evaluate their own genetic data for bias in response categories.

Mitochondrial and nuclear genetic relationships of deer (Odocoileus spp.) in western North America

USGS Publications Warehouse

Cronin, Matthew A.

1991-01-01

Odocoileus hemionus (mule deer and black-tailed deer) and Odocoileus virginanus (white-tailed deer) are sympatric in western North America and are characterized by distinct morphology, behavior, and allozyme allele frequencies. However, there is discordance among nuclear and mitochondrial genetic relationships, as mule deer (O. h. hemionus) and white-tailed deer have similar mitochondrial DNA (mtDNA) which is very different from that of black-tailed deer (O. h. columbianus, O. h. sitkensis). I expanded previous studies to clarify the genetic relationships of these groups by determining mtDNA haplotype and allozyme genotypes for 667 deer from several locations in northwestern North America. Different mtDNA haplotypes in mule deer, black-tailed deer, and white-tailed deer indicate that mitochondrial gene flow is restricted. Allozyme allele frequencies indicate that there is also restriction of nuclear gene flow between O. virginianus and O. hemionus, and to a lesser extent between mule deer and black-tailed deer. There is a low level of introgressive hybridization of mtDNA from mule deer and black-tailed deer into white-tailed deer populations and considerable interbreeding of mule deer and black-tailed deer in a contact zone. The discordance of mitochondrial and nuclear genomes is apparent only if mtDNA sequence divergences, and not haplotype frequencies, are considered.

CYP3A4 and CYP3A5 genotyping by Pyrosequencing

PubMed Central

Garsa, Adam A; McLeod, Howard L; Marsh, Sharon

2005-01-01

Background Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play an important role in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study describes Pyrosequencing assays for key SNPs in CYP3A4 (CYP3A4*1B, CYP3A4*2, and CYP3A4*3) and CYP3A5 (CYP3A5*3C and CYP3A5*6). Methods Genotyping of 95 healthy European and 95 healthy African volunteers was performed using Pyrosequencing. Linkage disequilibrium, haplotype inference, Hardy-Weinberg equilibrium, and tag SNPs were also determined for these samples. Results CYP3A4*1B allele frequencies were 4% in Europeans and 82% in Africans. The CYP3A4*2 allele was found in neither population sample. CYP3A4*3 had an allele frequency of 2% in Europeans and 0% in Africans. The frequency of CYP3A5*3C was 94% in Europeans and 12% in Africans. No CYP3A5*6 variants were found in the European samples, but this allele had a frequency of 16% in the African samples. Allele frequencies and haplotypes show interethnic variation, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of ethnic groups. Conclusion Pyrosequencing is a versatile technique that could improve the efficiency of SNP analysis for pharmacogenomic research with the ultimate goal of pre-screening patients for individual therapy selection. PMID:15882469

The YWHAE gene confers risk to major depressive disorder in the male group of Chinese Han population.

PubMed

Liu, Jie; Zhang, Hong-Xin; Li, Zhi-Qiang; Li, Tao; Li, Jun-Yan; Wang, Ti; Li, You; Feng, Guo-Yin; Shi, Yong-Yong; He, Lin

2017-07-03

Schizophrenia and major depressive disorder are two major psychiatric illnesses that may share specific genetic risk factors to a certain extent. Increasing evidence suggests that the two disorders might be more closely related than previously considered. To investigate whether YWHAE gene plays a significant role in major depressive disorder in Han Chinese population, we recruited 1135 unrelated major depressive disorder patients (485 males, 650 females) and 989 unrelated controls (296 males, 693 females) of Chinese Han origin. Eleven common SNPs were genotyped using TaqMan® technology. In male-group, the allele and genotype frequencies of rs34041110 differed significantly between patients and control (P allele =0.036486, OR[95%CI]: 1.249442(1.013988-1.539571); P genotype =0.045301). Also in this group, allele and genotype frequencies of rs1532976 differed significantly (P allele =0.013242, OR[95%CI]: 1.302007(1.056501-1.604563); genotype: P=0.039152). Haplotype-analyses showed that, in male-group, positive association with major depressive disorder was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ 2 =20.397, P=6.38E-06, OR[95%CI]: 7.442 [2.691-20.583]), its C-A-C-G haplotype (χ 2 =19.122, P=1.24E-05, OR and 95%CI: 0.402 [0.264-0.612]), its C-C-T-G haplotype (χ 2 =9.766, P=0.001785, OR[95%CI]: 5.654 [1.664-19.211]). In female-group, positive association was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ 2 =78.628, P=7.94E-19, OR[95%CI]: 50.043 [11.087-225.876]), its A-C-T-G haplotype (χ 2 =38.806, P=4.83E-10, OR[95%CI]: 0.053 [0.015-0.192]), the C-A-C-G haplotype (χ 2 =18.930, P=1.37E-05, OR[95%CI]: 0.526 [0.392-0.705]), and the C-C-T-G haplotype (χ 2 =38.668, P=5.18E-10, OR[95%CI]: 6.130 [3.207-11.716]). Our findings support YWHAE being a risk gene for Major Depressive Disorder in the Han Chinese population. Copyright © 2017 Elsevier Inc. All rights reserved.

Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population.

PubMed

Lee, K W; Oh, D H; Lee, C; Yang, S Y

2005-05-01

High-resolution human leukocyte antigen (HLA) typing exposes the unique patterns of HLA allele and haplotype frequencies in each population. In this study, HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were analyzed in 485 apparently unrelated healthy Korean individuals. A total of 20 HLA-A, 43 HLA-B, 21 HLA-C, 31 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. Eleven alleles (A*0201, A*1101, A*2402, A*3303, B*1501, Cw*0102, Cw*0302, Cw*0303, DQB1*0301, DQB1*0302, and DQB1*0303) were found in more than 10% of the population. In each serologic group, a maximum of three alleles were found with several exceptions (A2, B62, DR4, DR14, and DQ6). In each serologic group exhibiting multiple alleles, two major alleles were present at 62-96% (i.e. A*0201 and A*0206 comprise 85% of A2-positive alleles). Multiple-locus haplotypes estimated by the maximum likelihood method revealed 51 A-C, 43 C-B, 52 B-DRB1, 34 DRB1-DQB1, 48 A-C-B, 42 C-B-DRB1, 46 B-DRB1-DQB1, and 30 A-C-B-DRB1-DQB1 haplotypes with frequencies of more than 0.5%. In spite of their high polymorphism in B and DRB1, identification of relatively small numbers of two-locus (B-C and DRB1-DQB1) haplotypes suggested strong associations of those two loci, respectively. Five-locus haplotypes defined by high-resolution DNA typing correlated well with previously identified serology-based haplotypes in the population. The five most frequent haplotypes were: A*3303-Cw*1403-B*4403-DRB1*1302-DQB1*0604 (4.2%), A*3303-Cw*0701/6-B*4403-DRB1*0701-DQB1*0201/2 (3.0%), A*3303-Cw*0302-B*5801-DRB1*1302-DQB1*0609 (3.0%), A*2402-Cw*0702-B*0702-DRB1*0101-DQB1*0501 (2.9%), and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0201/2 (2.7%). Several sets of allele level haplotypes that could not be discriminated by routine HLA-A, -B, and -DRB1 low-resolution typing originated from allelic diversity of A2, B61, DR4, and DR8 serologic groups. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology.

Structure of some East African Glossina fuscipes fuscipes populations

PubMed Central

Krafsur, E. S.; Marquez, J. G.; Ouma, J. O.

2008-01-01

Glossina fuscipes fuscipes Newstead 1910 (Diptera: Glossinidae) is the primary vector of human sleeping sickness in Kenya and Uganda. This is the first report on its population structure. A total of 688 nucleotides of mitochondrial ribosomal 16S2 and cytochrome oxidase I genes were sequenced. Twenty-one variants were scored in 79 flies from three geographically diverse natural populations. Four haplotypes were shared among populations, eight were private and nine were singletons. The mean haplotype and nucleotide diversities were 0.84 and 0.009, respectively. All populations were genetically differentiated and were at demographic equilibrium. In addition, a longstanding laboratory culture originating from the Central African Republic (CAR-lab) in 1986 (or before) was examined. Haplotype and nucleotide diversities in this culture were 0.95 and 0.012, respectively. None of its 27 haplotypes were shared with the East African populations. A first approximation of relative effective population sizes was Uganda > CAR-lab > Kenya. It was concluded that the structure of G. f. fuscipes populations in East Africa is localized. PMID:18816270

Non-Ceruloplasmin Copper Distincts Subtypes in Alzheimer's Disease: a Genetic Study of ATP7B Frequency.

PubMed

Squitti, Rosanna; Ventriglia, Mariacarla; Gennarelli, Massimo; Colabufo, Nicola A; El Idrissi, Imane Ghafir; Bucossi, Serena; Mariani, Stefania; Rongioletti, Mauro; Zanetti, Orazio; Congiu, Chiara; Rossini, Paolo M; Bonvicini, Cristian

2017-01-01

Meta-analyses show that serum copper non-bound-to-ceruloplasmin (non-Cp-Cu) is higher in patients with Alzheimer's disease (AD). ATP7B gene variants associate with AD, modulating the size of non-Cp-Cu pool. However, a dedicated genetic study comparing AD patients after stratification for a copper biomarker to demonstrate the existence of a copper subtype of AD has not yet been carried out. An independent patient sample of 287 AD patients was assessed for non-Cp-Cu serum concentrations, rs1801243, rs1061472, and rs732774 ATP7B genetic variants and the APOE4 genotype. Patients were stratified into two groups based on a non-Cp-Cu cutoff (1.9 μM). Single-locus and haplotype-group analyses were performed to define their frequencies in dependence of the non-Cp-Cu group. The two AD subgroups did not differ regarding age, sex, MMSE score, or APOE4 frequency allele, while they did differ regarding non-Cp-Cu concentrations in serum, allele, genotype, and haplotype frequencies of rs1061472 A > G and rs732774 C > T after multiple testing corrections. AD patients with a GG genotype had a 1.76-fold higher risk of having a non-Cp-Cu higher than 1.9 μmol/L (p = 0.029), and those with a TT genotype for rs732774 C > T of 1.8-fold (p = 0.018). After 100,000 permutations for multiple testing corrections, the haplotype containing the AC alleles appeared more frequently in AD patients with normal non-Cp-Cu [43 vs. 33 %; Pm = 0.03], while the haplotype containing the GT risk alleles appeared more frequently in the higher non-Cp-Cu AD (66 vs. 55 %; Pm = 0.01). Genetic heterogeneity sustains a copper AD metabolic subtype; non-Cp-Cu is a marker of this copper AD.

CYP3A variation and the evolution of salt-sensitivity variants.

PubMed

Thompson, E E; Kuttab-Boulos, H; Witonsky, D; Yang, L; Roe, B A; Di Rienzo, A

2004-12-01

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude.

CYP3A Variation and the Evolution of Salt-Sensitivity Variants

PubMed Central

Thompson, E. E.; Kuttab-Boulos, H.; Witonsky, D.; Yang, L.; Roe, B. A.; Di Rienzo, A.

2004-01-01

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude. PMID:15492926

Genome Patterns of Selection and Introgression of Haplotypes in Natural Populations of the House Mouse (Mus musculus)

PubMed Central

Staubach, Fabian; Lorenc, Anna; Messer, Philipp W.; Tang, Kun; Petrov, Dmitri A.; Tautz, Diethard

2012-01-01

General parameters of selection, such as the frequency and strength of positive selection in natural populations or the role of introgression, are still insufficiently understood. The house mouse (Mus musculus) is a particularly well-suited model system to approach such questions, since it has a defined history of splits into subspecies and populations and since extensive genome information is available. We have used high-density single-nucleotide polymorphism (SNP) typing arrays to assess genomic patterns of positive selection and introgression of alleles in two natural populations of each of the subspecies M. m. domesticus and M. m. musculus. Applying different statistical procedures, we find a large number of regions subject to apparent selective sweeps, indicating frequent positive selection on rare alleles or novel mutations. Genes in the regions include well-studied imprinted loci (e.g. Plagl1/Zac1), homologues of human genes involved in adaptations (e.g. alpha-amylase genes) or in genetic diseases (e.g. Huntingtin and Parkin). Haplotype matching between the two subspecies reveals a large number of haplotypes that show patterns of introgression from specific populations of the respective other subspecies, with at least 10% of the genome being affected by partial or full introgression. Using neutral simulations for comparison, we find that the size and the fraction of introgressed haplotypes are not compatible with a pure migration or incomplete lineage sorting model. Hence, it appears that introgressed haplotypes can rise in frequency due to positive selection and thus can contribute to the adaptive genomic landscape of natural populations. Our data support the notion that natural genomes are subject to complex adaptive processes, including the introgression of haplotypes from other differentiated populations or species at a larger scale than previously assumed for animals. This implies that some of the admixture found in inbred strains of mice may also have a natural origin. PMID:22956910

Polymorphic haplotypes and recombination rates at the LDL receptor gene locus in subjects with and without familial hypercholesterolemia who are from different populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miserez, A.R.; Chiodetti, N.; Keller, U.

1993-04-01

RFLPs at the low-density lipoprotein (LDL) receptor locus for TaqI, StuI, HincII, AvaII, ApaLI (5[prime] and 3[prime]), PvuII, and NcoI were studied in Swiss and German families with familial hypercholesterolemia (FH). A total of 1,104 LDL receptor alleles were analyzed using Southern blotting and new PCR-based techniques for detection of the TaqI, StuI, HincII, AvaII, NcoI RFLPs. Two hundred fifty-six independent haplotypes from 368 individuals of 61 unrelated Swiss families, as well as 114 independent haplotypes from 184 subjects of 25 unrelated German families, were constructed. In 76 families, clinical diagnosis of FH was confirmed by cosegregation analysis. Of themore » 43 unique haplotypes consisting of seven RFLPs detected in the Swiss and Germans, only 9 were common in both population samples. Analysis of linkage disequilibrium revealed nonrandom associations between several of the investigated RFLPs. ApaLI (5[prime]), NcoI, PvuII, TaqI, and AvaII or HincII were particularly informative. Relative frequencies, heterozygosity indexes, and PICs of the RFLPs from the Swiss and Germans were compared with values calculated from reported haplotype data for Italians, Icelanders, North American Caucasians, South African Caucasians, and Japanese. Pairwise comparisons of population samples by common RFLPs demonstrated unexpected differences even between geographically adjacent populations (e.g., the Swiss and Germans). Furthermore, genetic distances from the Germans to the other Caucasians were larger than to the Japanese. An unexpected lack of correlation between linkage disequilibria and physical distances was detected for the German and Japanese data, possibly because of nonuniform recombination with excessively high rates between exon 13 and intron 15. Hence, the present study revealed a striking variety of polymorphic haplotypes and heterogeneity of RFLP frequencies and recombination rates among the seven population samples. 60 refs., 2 figs., 8 tabs.« less

An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.

PubMed

Deng, Libin; Zhang, Yuezheng; Kang, Jian; Liu, Tao; Zhao, Hongbin; Gao, Yang; Li, Chaohua; Pan, Hao; Tang, Xiaoli; Wang, Dunmei; Niu, Tianhua; Yang, Huanming; Zeng, Changqing

2008-10-01

Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome-wide scale.

A haplotypic variant at the IRGM locus and rs11747270 are related to the susceptibility for chronic periodontitis.

PubMed

Folwaczny, Matthias; Tsekeri, Eleni; Glas, Jürgen

2018-02-01

Immunity-regulated GTPase M (IRGM) plays a critical role in the defense against intracellular bacteria by regulating autophagy formation. This direct genetic association study aimed to determine whether variants at the IRGM genetic locus are associated with chronic periodontitis. Using PCR and melting curve analysis 390 periodontitis patients and 770 healthy controls have been genotyped regarding six polymorphisms in the IRGM gene (rs13361189, rs10065172, rs4958847, rs1000113, rs11747270, rs931058). Frequency distribution of alleles and genotypes for the six polymorphisms were not significantly different between the periodontitis and the control group. Also following stratification according to gender and smoking no significant linkage was found for any of the IRGM variants with periodontitis. Analysis of a subsample of patients revealed a significant association for rs11747270 with severe periodontitis (p = 0.003). Pairwise linkage analysis revealed one block composed of rs13361189, rs10065172, rs4958847, rs1000113 and 11747270 with strong or even complete linkage disequilibrium (r 2  > 0.9). Four haplotypes showed a frequency of > 1%, among which the haplotype C-T-A-T-G was significantly associated with chronic periodontitis (p = 0.0051; OR 4.66, 95% CI 1.41-15.42). One rare haplotype of the IRGM locus is significantly associated with chronic periodontitis in a German cohort.

No association between polymorphisms/haplotypes of the vascular endothelial growth factor gene and preeclampsia

PubMed Central

2011-01-01

Background Preeclampsia (PE) is the first worldwide cause of death in pregnant women, intra-uterine growth retardation, and fetal prematurity. Some vascular endothelial grown factor gene (VEGF) polymorphisms have been associated to PE and other pregnancy disturbances. We evaluated the associations between VEGF genotypes/haplotypes and PE in Mexican women. Methods 164 pregnant women were enrolled in a case-control study (78 cases and 86 normotensive pregnant controls). The rs699947 (-2578C/A), rs1570360 (-1154G/A), rs2010963 (+405G/C), and rs25648 (-7C/T), VEGF variants were discriminated using Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) methods or Taqman single nucleotide polymorphism (SNP) assays. Results The proportions of the minor allele for rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs were 0.33, 0.2, 0.39, and 0.17 in controls, and 0.39, 0.23, 0.41, and 0.15 in cases, respectively (P values > 0.05). The most frequent haplotypes of rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs, were C-G-C-C and C-G-G-C with frequencies of 0.39, 0.21 in cases and 0.37, 0.25 in controls, respectively (P values > 0.05) Conclusion There was no evidence of an association between VEGF alleles, genotypes, or haplotypes frequencies and PE in our study. PMID:21575227

Disentangling Immediate Adaptive Introgression from Selection on Standing Introgressed Variation in Humans

PubMed Central

Jagoda, Evelyn; Lawson, Daniel J; Wall, Jeffrey D; Lambert, David; Muller, Craig; Westaway, Michael; Leavesley, Matthew; Capellini, Terence D; Mirazón Lahr, Marta; Gerbault, Pascale; Thomas, Mark G; Migliano, Andrea Bamberg; Willerslev, Eske; Metspalu, Mait; Pagani, Luca

2018-01-01

Abstract Recent studies have reported evidence suggesting that portions of contemporary human genomes introgressed from archaic hominin populations went to high frequencies due to positive selection. However, no study to date has specifically addressed the postintrogression population dynamics of these putative cases of adaptive introgression. Here, for the first time, we specifically define cases of immediate adaptive introgression (iAI) in which archaic haplotypes rose to high frequencies in humans as a result of a selective sweep that occurred shortly after the introgression event. We define these cases as distinct from instances of selection on standing introgressed variation (SI), in which an introgressed haplotype initially segregated neutrally and subsequently underwent positive selection. Using a geographically diverse data set, we report novel cases of selection on introgressed variation in living humans and shortlist among these cases those whose selective sweeps are more consistent with having been the product of iAI rather than SI. Many of these novel inferred iAI haplotypes have potential biological relevance, including three that contain immune-related genes in West Siberians, South Asians, and West Eurasians. Overall, our results suggest that iAI may not represent the full picture of positive selection on archaically introgressed haplotypes in humans and that more work needs to be done to analyze the role of SI in the archaic introgression landscape of living humans. PMID:29220488

Analysis of CYP3A4 genetic polymorphisms in Han Chinese.

PubMed

Zhou, Qing; Yu, Xiaomin; Shu, Chang; Cai, Yimei; Gong, Wei; Wang, Xumin; Wang, Duen-mei; Hu, Songnian

2011-06-01

Our study aimed to comprehensively investigate the genetic polymorphisms of CYP3A4 in Han Chinese. We sequenced the gene regions of CYP3A4, including its promoter, exons, surrounding introns and 3' untranslated region (3'UTR), from 100 unrelated-healthy Han Chinese individuals. We detected 11 SNPs, three of which are novel. According to in silico functional prediction of novel variants, 20148 A>G in exon 10, resulting in substitution of Tyr319 with Cys (CYP3A4*21), may induce dramatic alteration of protein conformation, and 26908 G>A in 3'UTR may disrupt post-transcriptional regulation. We identified five alleles in Han Chinese, the allele frequencies of CYP3A4*1, *5, *6, *18 and *21 are 97, 0.5, 1, 1 and 0.5%, respectively. Haplotype inference revealed 14 haplotypes, of which the major haplotype CYP3A4*1A constitutes 59% of the total chromosomes. We also examined the possible role of natural selection in shaping the variation of CYP3A4 and confirmed a trend, consistent with the action of positive selection. We systematically screened the genetic polymorphisms of CYP3A4 in Han Chinese, highlighted possible functional impairment of the novel allele and summarized the distinct allele and haplotype frequency distribution, with an emphasis on detecting the footprint of recent positive selection on the CYP3A4 gene in Han Chinese.

Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.

PubMed

Dissanayake, Vajira H W; Sirisena, Nirmala D; Weerasekera, Lakshini Y; Gammulla, Chumithri G; Seneviratne, Harshalal R; Jayasekara, Rohan W

2012-09-01

Genetic thrombophilias are known to contribute to adverse pregnancy outcomes. Studies in Western populations show that 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and Factor V (F5) 1691G>A (Leiden) polymorphisms are commonly associated with pre-eclampsia and recurrent spontaneous pregnancy loss. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133); 1298A>C (rs1801131) and F5 1691G>A (rs6025); 4070A>G (rs1800595) polymorphisms with pre-eclampsia and recurrent pregnancy loss among Sinhalese women in Sri Lanka. Genotype and allele frequencies at each polymorphic site in the MTHFR and F5 genes and the haplotypes defined by them were determined in 175 Sinhalese women with pre-eclampsia, 171 normotensive controls, 200 Sinhalese women with two or more recurrent pregnancy losses and 200 controls with two or more living children and no pregnancy losses. Genotyping was done by polymerase chain reaction/restriction fragment length polymorphism. Odds ratios and χ(2) -testing were performed to compare genotype/haplotype frequencies at each polymorphic site for both cases and controls. The genotype frequencies at each polymorphic site in the MTHFR 677C>T; 1298A>C; F5 1691G>A and 4070A>G genes and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss. There was no significant association of genetic thrombophilia with either early or late pregnancy losses. The MTHFR and F5 polymorphisms and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss in this group of Sinhalese women. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Distinct genotype distribution and haplotype profiles in MDR1 gene among Chinese Han, Bai, Wa and Tibetan ethnic groups.

PubMed

Lai, Yong; Huang, Min; Li, Hui; Wang, Xue-Ding; Li, Jia-Li

2012-11-01

P-Glycoprotein (P-gp, encoded by MDR1 gene) plays an important role in determining bioavailability and pharmacologic effects of many drugs. There is increasing evidence that P-gp activity may be genetically determined. In this study, we investigated the genotype distribution and the haplotype profiles of MDR1 gene in Chinese Han, Bai, Wa and Tibetan subjects. Much lower frequencies of the 1236T allele and the 2677T allele were found in Wa subjects than those in other three ethnic groups, while the 2677A allele was found about 6-fold more frequently in Han subjects than in subjects of other three ethnic groups. The Han, Bai and Tibetan subjects share the same three predominant haplotypes (T-T-T, T-G-C and C-G-C), and T-T-T is the highest and accounts for more than one third of the number of haplotypes in the subjects from each ethnic group. However, T-T-T was less common than T-G-C, T-G-T and C-G-C and occurring at only 13.8% in Wa subjects, furthermore, higher frequencies of T-G-T, C-T-C, C-G-T and C-T-T were observed in Wa subjects compared to those in other three ethnic groups. Frequencies of C-A-C and T-A-C in Han subjects were higher than those in other three ethnic groups. The findings of this study will be of some relevance in predicting MDR1 phenotype and pharmacokinetics as well as pharmacodynamic effects of many commonly used drugs that are P-gp substrates in these four Chinese ethnic groups.

Cluster analysis of European Y-chromosomal STR haplotypes using the discrete Laplace method.

PubMed

Andersen, Mikkel Meyer; Eriksen, Poul Svante; Morling, Niels

2014-07-01

The European Y-chromosomal short tandem repeat (STR) haplotype distribution has previously been analysed in various ways. Here, we introduce a new way of analysing population substructure using a new method based on clustering within the discrete Laplace exponential family that models the probability distribution of the Y-STR haplotypes. Creating a consistent statistical model of the haplotypes enables us to perform a wide range of analyses. Previously, haplotype frequency estimation using the discrete Laplace method has been validated. In this paper we investigate how the discrete Laplace method can be used for cluster analysis to further validate the discrete Laplace method. A very important practical fact is that the calculations can be performed on a normal computer. We identified two sub-clusters of the Eastern and Western European Y-STR haplotypes similar to results of previous studies. We also compared pairwise distances (between geographically separated samples) with those obtained using the AMOVA method and found good agreement. Further analyses that are impossible with AMOVA were made using the discrete Laplace method: analysis of the homogeneity in two different ways and calculating marginal STR distributions. We found that the Y-STR haplotypes from e.g. Finland were relatively homogeneous as opposed to the relatively heterogeneous Y-STR haplotypes from e.g. Lublin, Eastern Poland and Berlin, Germany. We demonstrated that the observed distributions of alleles at each locus were similar to the expected ones. We also compared pairwise distances between geographically separated samples from Africa with those obtained using the AMOVA method and found good agreement. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia.

PubMed

Klütsch, C F C; Seppälä, E H; Fall, T; Uhlén, M; Hedhammar, A; Lohi, H; Savolainen, P

2011-02-01

The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage. © 2010 The Authors, Animal Genetics © 2010 Stichting International Foundation for Animal Genetics.

Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia

PubMed Central

Klütsch, C F C; Seppälä, E H; Fall, T; Uhlén, M; Hedhammar, Å; Lohi, H; Savolainen, P

2011-01-01

The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60–100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480–3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage. PMID:20497152

[Association of HLA-DPA1 and -DPB1 polymorphisms with Posner-Schlossman syndrome among southern Chinese Han population].

PubMed

Zhao, Jun; Zhu, Tianhui; He, Liumei; Shen, Xiaoli; Wang, Yanjun; Deng, Zhihui

2015-04-01

To assess the association of HLA-DPA1 and -DPB1 polymorphisms with Posner-Schlossman syndrome (PSS) in southern Chinese Han population. A total of 100 randomly selected PSS patients of southern Chinese Han origin were served as the experimental group, while 128 unrelated healthy blood donors of the same origin were served as the control group. All samples were subjected to sequencing-based typing (SBT) for exon 2 of HLA-DPA1 and -DPB1 loci in both directions. HLA genotype was assigned using an Assign 3.5 HLA SBT software. The allele frequencies and haplotype frequencies of HLA-DPA1 and -DPB1 of the two groups were compared. x² test, P value and odds ratio (OR) value were calculated. Six HLA-DPA1 alleles in the experimental group and 4 HLA-DPA1 alleles in the healthy control group were identified. The allelic frequency for HLA-DPA1*02:01 in the experimental group was significantly lower than the control group (4.50% vs. 12.109%; x²=8.124, P=0.004). Sixteen HLA-DPB1 alleles were identified in both the experimental and control groups. The allelic frequencies for HLA-DPB1*14:01 and - DPB1*17:01 in the experimental group were significantly lower than those of the control group ( DPB1*14:01: 1.00% vs. 4.688%, x²=5.130, P=0.024; DPB1*17:01: 0% vs. 2.344%, x²=3.897, P=0.048). The DPA1-DPB1 haplotypes for the experimental and control groups were 23 and 25, respectively. The haplotype frequencies for both DPA1*02:01- DPB1*14:01 and DPA1*02:01- DPB1*17:01 were significantly lower than those of the control group. DPA1*02:01- DPB1*14:01 and DPA1*02:01- DPB1*17:01 haplotypes may provide considerable protection effect against PSS in the southern Chinese Han population.

Exploring and Harnessing Haplotype Diversity to Improve Yield Stability in Crops.

PubMed

Qian, Lunwen; Hickey, Lee T; Stahl, Andreas; Werner, Christian R; Hayes, Ben; Snowdon, Rod J; Voss-Fels, Kai P

2017-01-01

In order to meet future food, feed, fiber, and bioenergy demands, global yields of all major crops need to be increased significantly. At the same time, the increasing frequency of extreme weather events such as heat and drought necessitates improvements in the environmental resilience of modern crop cultivars. Achieving sustainably increase yields implies rapid improvement of quantitative traits with a very complex genetic architecture and strong environmental interaction. Latest advances in genome analysis technologies today provide molecular information at an ultrahigh resolution, revolutionizing crop genomic research, and paving the way for advanced quantitative genetic approaches. These include highly detailed assessment of population structure and genotypic diversity, facilitating the identification of selective sweeps and signatures of directional selection, dissection of genetic variants that underlie important agronomic traits, and genomic selection (GS) strategies that not only consider major-effect genes. Single-nucleotide polymorphism (SNP) markers today represent the genotyping system of choice for crop genetic studies because they occur abundantly in plant genomes and are easy to detect. SNPs are typically biallelic, however, hence their information content compared to multiallelic markers is low, limiting the resolution at which SNP-trait relationships can be delineated. An efficient way to overcome this limitation is to construct haplotypes based on linkage disequilibrium, one of the most important features influencing genetic analyses of crop genomes. Here, we give an overview of the latest advances in genomics-based haplotype analyses in crops, highlighting their importance in the context of polyploidy and genome evolution, linkage drag, and co-selection. We provide examples of how haplotype analyses can complement well-established quantitative genetics frameworks, such as quantitative trait analysis and GS, ultimately providing an effective tool to equip modern crops with environment-tailored characteristics.

Identification of Allelic Imbalance with a Statistical Model for Subtle Genomic Mosaicism

PubMed Central

Xia, Rui; Vattathil, Selina; Scheet, Paul

2014-01-01

Genetic heterogeneity in a mixed sample of tumor and normal DNA can confound characterization of the tumor genome. Numerous computational methods have been proposed to detect aberrations in DNA samples from tumor and normal tissue mixtures. Most of these require tumor purities to be at least 10–15%. Here, we present a statistical model to capture information, contained in the individual's germline haplotypes, about expected patterns in the B allele frequencies from SNP microarrays while fully modeling their magnitude, the first such model for SNP microarray data. Our model consists of a pair of hidden Markov models—one for the germline and one for the tumor genome—which, conditional on the observed array data and patterns of population haplotype variation, have a dependence structure induced by the relative imbalance of an individual's inherited haplotypes. Together, these hidden Markov models offer a powerful approach for dealing with mixtures of DNA where the main component represents the germline, thus suggesting natural applications for the characterization of primary clones when stromal contamination is extremely high, and for identifying lesions in rare subclones of a tumor when tumor purity is sufficient to characterize the primary lesions. Our joint model for germline haplotypes and acquired DNA aberration is flexible, allowing a large number of chromosomal alterations, including balanced and imbalanced losses and gains, copy-neutral loss-of-heterozygosity (LOH) and tetraploidy. We found our model (which we term J-LOH) to be superior for localizing rare aberrations in a simulated 3% mixture sample. More generally, our model provides a framework for full integration of the germline and tumor genomes to deal more effectively with missing or uncertain features, and thus extract maximal information from difficult scenarios where existing methods fail. PMID:25166618

Population genetic structure in Sabatieria (Nematoda) reveals intermediary gene flow and admixture between distant cold seeps from the Mediterranean Sea.

PubMed

De Groote, Annelies; Hauquier, Freija; Vanreusel, Ann; Derycke, Sofie

2017-07-01

There is a general lack of information on the dispersal and genetic structuring for populations of small-sized deep-water taxa, including free-living nematodes which inhabit and dominate the seafloor sediments. This is also true for unique and scattered deep-sea habitats such as cold seeps. Given the limited dispersal capacity of marine nematodes, genetic differentiation between such geographically isolated habitat patches is expected to be high. Against this background, we examined genetic variation in both mitochondrial (COI) and nuclear (18S and 28S ribosomal) DNA markers of 333 individuals of the genus Sabatieria, abundantly present in reduced cold-seep sediments. Samples originated from four Eastern Mediterranean cold seeps, separated by hundreds of kilometers, and one seep in the Southeast Atlantic. Individuals from the Mediterranean and Atlantic were divided into two separate but closely-related species clades. Within the Eastern Mediterranean, all specimens belonged to a single species, but with a strong population genetic structure (Φ ST  = 0.149). The haplotype network of COI contained 19 haplotypes with the most abundant haplotype (52% of the specimens) shared between all four seeps. The number of private haplotypes was high (15), but the number of mutations between haplotypes was low (1-8). These results indicate intermediary gene flow among the Mediterranean Sabatieria populations with no evidence of long-term barriers to gene flow. The presence of shared haplotypes and multiple admixture events indicate that Sabatieria populations from disjunct cold seeps are not completely isolated, with gene flow most likely facilitated through water current transportation of individuals and/or eggs. Genetic structure and molecular diversity indices are comparable to those of epiphytic shallow-water marine nematodes, while no evidence of sympatric cryptic species was found for the cold-seep Sabatieria.

Analysis of single nucleotide polymorphisms in the 3' region of the estrogen receptor 1 gene in normal and cryptorchid Miniature Dachshunds and Chihuahuas.

PubMed

Pathirana, Indunil Nishantha; Tanaka, Kakeru; Kawate, Noritoshi; Tsuji, Makoto; Kida, Kayoko; Hatoya, Shingo; Inaba, Toshio; Tamada, Hiromichi

2010-08-01

This study was performed to examine the distribution of single nucleotide polymorphisms (SNPs) and estimated haplotypes in the canine estrogen receptor (ER) alpha gene (ESR1) and the association of them with different phenotypes of cryptorchidism (CO) in Miniature Dachshunds and Chihuahuas. Forty CO and 68 normal dogs were used, and CO was classified into unilateral (UCO; n=33) and bilateral CO (BCO; n=5) or into abdominal (ACO; n=16) and inguinal CO (ICO; n=22). Thirteen DNA fragments located in the 70-kb region at the 3' end of ESR1 were amplified by PCR and sequenced to examine 13 SNPs (#1-#13) reported in a canine SNP database. Ten SNPs (#1-#4, #7, #8, #10-#13) were not polymorphic, and 5 new SNPs (#14-#18) were discovered. A common haplotype block in normal, CO and CO phenotypes was identified for an approximately 20-kb region encompassing 4 SNPs (#14-#17). Allele, genotype and haplotype frequencies in CO without classification by phenotype and also in UCO, ACO and ICO phenotypes were not statistically different from the normal group. Significant differences in genotype frequencies and homozygosity for the estimated GTTG haplotype within the block were observed in BCO compared with the normal group, although the number of BCO animals was small. Our results demonstrate that the examined SNPs and haplotypes in the 3' end of canine ESR1 are not associated with unilateral, abdominal and inguinal CO phenotypes and CO per se in Miniature Dachshunds and Chihuahuas. Further studies are necessary to suggest a clear association between the ESR1 SNPs and bilateral CO in dogs.

Y chromosome haplotype diversity of domestic sheep (Ovis aries) in northern Eurasia.

PubMed

Zhang, Min; Peng, Wei-Feng; Yang, Guang-Li; Lv, Feng-Hua; Liu, Ming-Jun; Li, Wen-Rong; Liu, Yong-Gang; Li, Jin-Quan; Wang, Feng; Shen, Zhi-Qiang; Zhao, Sheng-Guo; Hehua, Eer; Marzanov, Nurbiy; Murawski, Maziek; Kantanen, Juha; Li, Meng-Hua

2014-12-01

Variation in two SNPs and one microsatellite on the Y chromosome was analyzed in a total of 663 rams representing 59 breeds from a large geographic range in northern Eurasia. SNPA-oY1 showed the highest allele frequency (91.55%) across the breeds, whereas SNPG-oY1 was present in only 56 samples. Combined genotypes established seven haplotypes (H4, H5, H6, H7, H8, H12 and H19). H6 dominated in northern Eurasia, and H8 showed the second-highest frequency. H4, which had been earlier reported to be absent in European breeds, was detected in one European breed (Swiniarka), whereas H7, which had been previously identified to be unique to European breeds, was present in two Chinese breeds (Ninglang Black and Large-tailed Han), one Buryatian (Transbaikal Finewool) and two Russian breeds (North Caucasus Mutton-Wool and Kuibyshev). H12, which had been detected only in Turkish breeds, was also found in Chinese breeds in this work. An overall low level of haplotype diversity (median h = 0.1288) was observed across the breeds with relatively higher median values in breeds from the regions neighboring the Near Eastern domestication center of sheep. H6 is the dominant haplotype in northwestern and eastern China, in which the haplotype distribution could be explained by the historical translocations of the H4 and H8 Y chromosomes to China via the Mongol invasions followed by expansions to northwestern and eastern China. Our findings extend previous results of sheep Y chromosomal genetic variability and indicate probably recent paternal gene flows between sheep breeds from distinct major geographic regions. © 2014 Stichting International Foundation for Animal Genetics.

Association between platelet P2Y12 haplotype and risk of cardiovascular events in chronic coronary disease.

PubMed

Schettert, Isolmar T; Pereira, Alexandre C; Lopes, Neuza H; Hueb, Whady A; Krieger, Jose E

2006-01-01

A positive association was recently described between P2Y12 platelet receptor H1 and H2 haplotypes and peripheral artery disease. We tested the described P2Y12 receptor haplotypes in a group of patients with coronary artery disease. The P2Y12 platelet receptor H1 and H2 haplotypes was tested in a group of 540 patients enrolled in the Medical, Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. After a 3-year follow-up period, the incidence of the composite end point of cardiac death, myocardial infarction, and refractory angina requiring revascularization was determined in the H1/H1, H1/H2 and H2/H2 haplotype groups. We used Student's t-test and the chi-square test to analyze the differences among groups and Kaplan-Meier method to calculate survival curves. Risk was assessed with the use of a Cox proportional-hazards model. The frequency of haplotypes among studied patients were 410 (75.9%) H1/H1, 119 (22.0%) H1/H2 and 11 (2.1%) H2/H2. The baseline clinical characteristics, mean clinical follow-up time and received treatment of each genotype group were similar. We did not disclose any association between haplotype groups regarding the incidence of any of the studied cardiovascular end-points. This is the first report studying the association of P2Y12 platelet receptor H1 and H2 haplotype and cardiovascular events. Our findings do not provide evidence for a strong association between H1/H1 and H1/H2 haplotypes and a increased risk of cardiovascular events in a population with CAD. Future works should address the role of the H2/H2 haplotype as a genetic marker for cardiovascular events.

Impacts of TNF-LTA SNPs/Haplotypes and Lifestyle Factors on Oral Carcinoma in an Indian Population.

PubMed

Bandil, Kapil; Singhal, Pallavi; Sharma, Upma; Hussain, Showket; Basu, Surojit; Parashari, Aditya; Singh, Veena; Sehgal, Ashok; Shivam, Animesh; Ahuja, Puneet; Bharadwaj, Mausumi; Banerjee, Basu Dev; Mehrotra, Ravi

2016-10-01

To investigate a potential association between single-nucleotide polymorphisms (SNPs) and  haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population. In this study, 150 oral precancer/cancer samples (50 precancer and 100 cancer), along with an equal number of control samples, were genotyped. Six SNPs at the TNF-LTA locus (i.e., -238G/A, -308G/A, -857C/T, -863C/A, -1031T/C, and +252A/G) were analyzed by use of a polymerase chain reaction-restriction fragment length polymorphism method, the assay was validated by sequencing 10 % of samples. The allelic frequencies of TNFA and LTA SNPs were found to be significantly associated with the risk of oral cancer and precancerous lesions in comparison with controls (P < 0.0003). Further haplotypic analysis showed that two haplotypes (ATCTGG and ACACGG) served as risk haplotypes for oral cancer. These haplotypes were also found to be significantly and positively associated with lifestyle habits (tobacco chewing P = 0.04, odds ratio [OR] 3.4) and socioeconomic status (P = 0.01, OR 3.4). We noticed an increased percentage of risk haplotypes correlating with the aggressiveness of oral cancer. The percentages of risk haplotypes were found to be threefold higher in precancer and fourfold higher in advanced stages of oral cancer in comparison with controls. Five SNPs at the TNF-LTA locus (i.e., -308G>A, -857C>T, -863C>A, -1031T>C, and +252A>G) were found to be associated with the development of oral cancer. Two haplotypes (ATCTGG and ACACGG) emerged as major risk haplotypes for oral carcinoma progression and were also found to be associated with lifestyle factors and clinical aggressiveness. These findings make the TNF-LTA locus a suitable candidate for a future biomarker, which may be used either for early detection or for helping to improve treatment efficacy and effectiveness.

Construction and forensic genetic characterization of 11 autosomal haplotypes consisting of 22 tri-allelic indels.

PubMed

Zhao, Xiaohong; Chen, Xiaogang; Zhao, Yuancun; Zhang, Shu; Gao, Zehua; Yang, Yiwen; Wang, Yufang; Zhang, Ji

2018-05-01

Insertion/deletion polymorphisms (indels), which combine the advantages of both short tandem repeats and single-nucleotide polymorphisms, are suitable for parentage testing. To overcome the limitations of the low polymorphism of di-allelic indels, we constructed a set of haplotypes with physically linked, multi-allelic indels. Candidate haplotypes were selected from the 1000 Genomes Project database, and were subject to the following criteria for inclusion: (i) each marker must have a minimum allele frequency (MAF) of ≥0.1 in the Han population of China; (ii) markers must exist in a non-coding region; (iii) the physical distance between a pair of candidate indels must be <500 bp; (iv) the allele length variation of each indel from 1 to 20 bp; (v) different haplotypes must be located on different chromosomes or chromosomal arms, or be more than 10 Mb apart if on the same chromosomal arm; and (vi) they must not be located across a recombination hotspot. A multiplex system with 11 haplotype markers, comprising 22 tri-allelic indel loci distributed over 10 chromosomes was developed. To validate the multiplex panel, we investigated the haplotype distribution in sets of two and three-generation pedigrees. The results demonstrated that the haplotypes consisting of multi-allelic indel markers exhibited higher polymorphism than a single indel locus, and thus provide Supplementary information for forensic kinship identification. Copyright © 2018 Elsevier B.V. All rights reserved.

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

PubMed

Long, Ji-Rong; Zhao, Lan-Juan; Liu, Peng-Yuan; Lu, Yan; Dvornyk, Volodymyr; Shen, Hui; Liu, Yong-Jun; Zhang, Yuan-Yuan; Xiong, Dong-Hai; Xiao, Peng; Deng, Hong-Wen

2004-05-24

The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

Unique haplotypes of cacao trees as revealed by trnH-psbA chloroplast DNA

PubMed Central

Gutiérrez-López, Nidia; Ovando-Medina, Isidro; Salvador-Figueroa, Miguel; Molina-Freaner, Francisco; Avendaño-Arrazate, Carlos H.

2016-01-01

Cacao trees have been cultivated in Mesoamerica for at least 4,000 years. In this study, we analyzed sequence variation in the chloroplast DNA trnH-psbA intergenic spacer from 28 cacao trees from different farms in the Soconusco region in southern Mexico. Genetic relationships were established by two analysis approaches based on geographic origin (five populations) and genetic origin (based on a previous study). We identified six polymorphic sites, including five insertion/deletion (indels) types and one transversion. The overall nucleotide diversity was low for both approaches (geographic = 0.0032 and genetic = 0.0038). Conversely, we obtained moderate to high haplotype diversity (0.66 and 0.80) with 10 and 12 haplotypes, respectively. The common haplotype (H1) for both networks included cacao trees from all geographic locations (geographic approach) and four genetic groups (genetic approach). This common haplotype (ancient) derived a set of intermediate haplotypes and singletons interconnected by one or two mutational steps, which suggested directional selection and event purification from the expansion of narrow populations. Cacao trees from Soconusco region were grouped into one cluster without any evidence of subclustering based on AMOVA (FST = 0) and SAMOVA (FST = 0.04393) results. One population (Mazatán) showed a high haplotype frequency; thus, this population could be considered an important reservoir of genetic material. The indels located in the trnH-psbA intergenic spacer of cacao trees could be useful as markers for the development of DNA barcoding. PMID:27076998

Population Structure of Pseudocercospora fijiensis in Costa Rica Reveals Shared Haplotype Diversity with Southeast Asian Populations.

PubMed

Saville, Amanda; Charles, Melodi; Chavan, Suchitra; Muñoz, Miguel; Gómez-Alpizar, Luis; Ristaino, Jean Beagle

2017-12-01

Pseudocercospora fijiensis is the causal pathogen of black Sigatoka, a devastating disease of banana that can cause 20 to 80% yield loss in the absence of fungicides in banana crops. The genetic structure of populations of P. fijiensis in Costa Rica was examined and compared with Honduran and global populations to better understand migration patterns and inform management strategies. In total, 118 isolates of P. fijiensis collected from Costa Rica and Honduras from 2010 to 2014 were analyzed using multilocus genotyping of six loci and compared with a previously published global dataset of populations of P. fijiensis. The Costa Rican and Honduran populations shared haplotype diversity with haplotypes from Southeast Asia, Oceania, and the Americas but not Africa for all but one of the six loci studied. Gene flow and shared haplotype diversity was found in Honduran and Costa Rican populations of the pathogen. The data indicate that the haplotypic diversity observed in Costa Rican populations of P. fijiensis is derived from dispersal from initial outbreak sources in Honduras and admixtures between genetically differentiated sources from Southeast Asia, Oceania, and the Americas.

HLA-DQA1 and HLA-DQB1 allele diversity and its extended haplotypes in Madeira Island (Portugal).

PubMed

Spínola, H; Lemos, A; Couto, A R; Parreira, B; Soares, M; Dutra, I; Bruges-Armas, J; Brehm, A

2017-02-01

This study shows, for the first time, high-resolution allele frequencies of HLA-DQA1 loci in Madeira Island (Portugal) and allows us to better understand and refine present knowledge on DQB1 variation, with the identification of several alleles not previously reported in this population. Estimates on haplotype profile, involving HLA-A, HLA-B, HLA-DRB1, HLA-DQA1 and HLA-DQB1, are also reported. © 2016 John Wiley & Sons Ltd.

Near East mtDNA haplotype variants in Roman cattle from Augusta Raurica, Switzerland, and in the Swiss Evolène breed.

PubMed

Schlumbaum, A; Turgay, M; Schibler, J

2006-08-01

Typical Near East mitochondrial haplotypes of the T2 lineage were found in one cattle metacarpus sample from the Roman period and in two present-day Evolène cattle in Switzerland. Sequences from eight additional Evolène and four Raetian Grey aligned to the European haplotype T3. Analysis of nucleotide diversity within the mitochondrial D-loop of both studied Swiss cattle breeds revealed high haplotype diversity and similar diversity to a European cattle reference group. Mitochondrial T3 haplotypes radiated star-like from two similarly frequent haplotypes, possibly indicating two different expansion routes. The breed structure of Evolène cattle can be explained either by an introduction of diverse female lineages from the domestication centre or by later admixture. The introduction of the Near East lineage to Switzerland must have happened during the Roman time or earlier.

Type 1 diabetes risk for HLA-DR3 haplotypes depends on genotypic context: Association of DPB1 and HLA class I loci among DR3 and DR4 matched Italian patients and controls

PubMed Central

Noble, Janelle A.; Martin, Adelle; Valdes, Ana M.; Lane, Julie A.; Galgani, Andrea; Petrone, Antonio; Lorini, Renata; Pozzilli, Paolo; Buzzetti, Raffaella; Erlich, Henry A.

2008-01-01

Patients with high-risk HLA-DR-DQ genotypes for type 1 diabetes (T1D) were compared to HLA-matched controls to evaluate T1D risk for other HLA loci, including HLA-A, -B, -Cw, and DPB1. Patients (n=133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. Screening of more than 9000 subjects from the Lazio region and northern Italy yielded 162 controls with high- T1D-risk haplotypes. Although the overall distributions were not significantly different, allele frequency differences were discovered between the controls from Lazio and those from Northern Italy for some alleles previously shown to affect T1D risk, such as A*3002, DPB1*0301, and DPB1*0402. Therefore, Lazio patient data were compared both to the Lazio subset of controls (n=53) and to the entire group of controls for association analyses. Significant allele frequency differences between patients and DR-DQ-matched controls were found for specific alleles at all loci. Data for the DR3/DR3 subset of patients and controls showed an increase of Cw*0702 in patients. Reduced patient, compared to control, frequencies were seen for several alleles, including A*0101, B*0801, and Cw*0701, all found on the highly-conserved, extended DR3 haplotype known as 8.1 in DR3/DR3, but not DR3/DR4, subgroup. DPB1*0101, often found on 8.1 haplotypes, was also less frequent in DR3/DR3 patients than controls. Analysis of family-based data from the HBDI repository was consistent with the observed results from the Italian subjects, suggesting the presence of a T1D-protective locus at or near A*0101 and a second T1D-protective locus at or near DPB1*0101. These data suggest that T1D risk conferred by the 8.1 haplotype is genotype dependent. PMID:18486765

Association Between the Lower Extremity Deep Venous Thrombosis, the Warfarin Maintenance Dose, and CYP2C9*3, CYP2D6*10, and CYP3A5*3 Genetic Polymorphisms: A Case-Control Study.

PubMed

Ju, Shang; Gao, Yu; Cao, Xin; Zhang, Xiao-Fu; Yan, Cheng-Cheng; Liu, Feng-Tong

2017-09-01

This study explored the association between the CYP2C9*3/CYP2D6*10/CYP3A5*3 genetic polymorphisms with lower extremity deep venous thrombosis (LEDVT) and the warfarin maintenance dose. Five hundred thirty-six patients who were pathologically diagnosed with LEDVT after surgery were included in the LEDVT group. At the same time, 540 patients without LEDVT who underwent surgery were recruited as the control group. Patients were given warfarin at an initial dose of 2.5-3.0 mg. Blood samples were collected to detect the initial and stable international normalized ratio (INR) values. The warfarin maintenance dose was obtained if the INR remained within a range of 2.0-3.0 for 3 consecutive days. The genotype distribution and haplotype analysis of the CYP2C9*3/CYP2D6*10/CYP3A5*3 alleles were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) testing and SHEsis software, respectively. Logistic regression analysis was used to analyze the risk and protective factors for LEDVT. The A/G genotypes, G/G genotypes, and G allele of CYP3A5*3 in the LEDVT group were observed with increased frequency compared with the control group. The LEDVT group displayed a higher ACG haplotype frequency, and lower ACA and ATA haplotype frequencies than the control group. Age, diabetes, low-density lipoprotein, CYP3A5*3 and the ACG haplotype were independent risk factors for LEDVT. High-density lipoprotein and the ACA haplotype were independent protective factors for LEDVT. The genotype distributions of the CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic polymorphisms were associated with the warfarin maintenance dose. The CYP3A5*3 genetic polymorphism may be an important risk factor for LEDVT. Moreover, CYP2C9*3, CYP2D6*10, and CYP3A5*3 are associated with the warfarin maintenance dose.

The influence of maternal lineages on social affiliations among humpback whales (Megaptera novaeangliae) on their feeding grounds in the southern gulf of Maine.

PubMed

Weinrich, Mason T; Rosenbaum, Howard; Scott Baker, C; Blackmer, Alexis L; Whitehead, Hal

2006-01-01

Humpback whales on their feeding grounds in the Gulf of Maine typically form fluid fission/fusion groups of two to three individuals characterized by noncompetitive and, at times, cooperative behavior. Here we test the hypothesis that, despite the apparent absence of close kinship bonds, the fluid associations between feeding whales are influenced by "maternal lineages" as represented by mtDNA haplotypes. Using skin samples collected with a biopsy dart, variation in the hypervariable segment of the mtDNA control region identified 17 unique haplotypes among 159 individually identified whales from the southern Gulf of Maine. The haplotypes of a further 143 individuals were inferred from known direct maternal (cow-calf) relationships. The frequencies of associations among these 302 individuals were calculated from 21,617 sighting records collected from 1980 to 1995, excluding associations between a cow and her dependent calf. For groups of two where the haplotypes of both individuals were known (n = 3,151), individuals with the same haplotype were together significantly more often (26%) than expected by random association (20%). To account for different group sizes and associations with individuals of unknown haplotype and sex, we used Monte Carlo simulations to test for nonrandom associations in the full data set, as well as known female-only (n = 1,512), male-only (n = 730), and mixed-sex (n = 2,745) groups. Within-haplotype associations were significantly more frequent than expected at random for all groups (P = .002) and female-only groups (P = .011) but not male-only groups, while mixed-sex groups approached significance (P = .062). A Mantel test of individual pairwise association indices and haplotype identity confirmed that within-haplotype associations were more frequent than expected for all sex combinations except male-male associations, with females forming within-haplotype associations 1.7 times more often than expected by random assortment. Partial matrix correlations and permutation analyses indicated that the skew toward within-haplotype associations could not be accounted for by short-term temporal co-occurrence or fine-scale spatial distributions of individuals with shared haplotypes. While the mechanism by which individuals with a common mtDNA haplotype assort remains unknown, our results strongly suggest an influence of maternal lineages on the social organization of humpback whales within a regional feeding ground.

Binary and microsatellite polymorphisms of the Y-chromosome in the Mbenzele pygmies from the Central African Republic.

PubMed

Coia, Valentina; Caglià, Alessandra; Arredi, Barbara; Donati, Francesco; Santos, Fabrício R; Pandya, Arpita; Taglioli, Luca; Paoli, Giorgio; Pascali, Vincenzo; Spedini, Gabriella; Destro-Bisol, Giovanni; Tyler-Smith, Chris

2004-01-01

This study analyzes the variation of six binary polymorphisms and six microsatellites in the Mbenzele Pygmies from the Central African Republic. Five different haplogroups (B2b, E(xE3a), E3a, P and BR(xB2b,DE,P)) were observed, with frequencies ranging from 0.022 (haplogroup P) to 0.609 (haplogroup E3a). A comparison of haplogroup frequencies indicates a close genetic affinity between the Mbenzele and the Biaka Pygmies, a finding consistent with the common origin and the geographical proximity of the two populations. The haplogroups P, BR(xB2b,DE,P) and E(xE3a), which are rare in sub-Saharan Africa but common in western Eurasia, were observed with frequencies ranging from 0.022 (haplogroup P) to 0.087 (haplogroup E(xE3a)). Thirty different microsatellite haplotypes were detected, with frequencies ranging from 0.022 to 0.152. The Mbenzele share the highest percent of microsatellite haplotypes with the Biaka Pygmies. Five out seven haplotypes which are shared by the Mbenzele and Biaka Pygmies belong to haplogroup E3a, which suggests that they are of Bantu origin. The plot based on F(st) genetic distances calculated using microsatellite data provides a picture of population relationships which is in part congruent and in part complementary to that obtained using haplogroup frequencies. Finally, the Mbenzele and Biaka Pygmies were found to be markedly more genetically similar using Y-chromosomal than autosomal microsatellites. We suggest that this could be due to the higher phylogenetic stability of Y-chromosome and to the effect of the male-biased gene flow during the Bantu expansion. Copyright 2003 Wiley-Liss, Inc.

Plasmodium vivax population structure and transmission dynamics in Sabah Malaysia.

PubMed

Abdullah, Noor Rain; Barber, Bridget E; William, Timothy; Norahmad, Nor Azrina; Satsu, Umi Rubiah; Muniandy, Prem Kumar; Ismail, Zakiah; Grigg, Matthew J; Jelip, Jenarun; Piera, Kim; von Seidlein, Lorenz; Yeo, Tsin W; Anstey, Nicholas M; Price, Ric N; Auburn, Sarah

2013-01-01

Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A (S) >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A (S)  = 0.07 [P = 0.0076] in KM, and I A (S) = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for malaria elimination.

Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia

PubMed Central

Abdullah, Noor Rain; Barber, Bridget E.; William, Timothy; Norahmad, Nor Azrina; Satsu, Umi Rubiah; Muniandy, Prem Kumar; Ismail, Zakiah; Grigg, Matthew J.; Jelip, Jenarun; Piera, Kim; von Seidlein, Lorenz; Yeo, Tsin W.; Anstey, Nicholas M.; Price, Ric N.; Auburn, Sarah

2013-01-01

Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A S >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A S  = 0.07 [P = 0.0076] in KM, and I A S = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for malaria elimination. PMID:24358203

Genetic diversity and population structure of Plasmodium vivax in Central China

PubMed Central

2014-01-01

Background In Central China the declining incidence of Plasmodium vivax has been interrupted by epidemic expansions and imported cases. The impact of these changes on the local parasite population, and concurrent risks of future resurgence, was assessed. Methods Plasmodium vivax isolates collected from Anhui and Jiangsu provinces, Central China between 2007 and 2010 were genotyped using capillary electrophoresis at seven polymorphic short tandem repeat markers. Spatial and temporal analyses of within-host and population diversity, population structure, and relatedness were conducted on these isolates. Results Polyclonal infections were infrequent in the 94 isolates from Anhui (4%) and 25 from Jiangsu (12%), with a trend for increasing frequency from 2008 to 2010 (2 to 19%) when combined. Population diversity was high in both provinces and across the years tested (HE = 0.8 – 0.85). Differentiation between Anhui and Jiangsu was modest (F’ ST  = 0.1). Several clusters of isolates with identical multi-locus haplotypes were observed across both Anhui and Jiangsu. Linkage disequilibrium was strong in both populations and in each year tested (IAS = 0.2 – 0.4), but declined two- to four-fold when identical haplotypes were accounted for, indicative of occasional epidemic transmission dynamics. None of five imported isolates shared identical haplotypes to any of the central Chinese isolates. Conclusions The population genetic structure of P. vivax in Central China highlights unstable transmission, with limited barriers to gene flow between the central provinces. Despite low endemicity, population diversity remained high, but the reservoirs sustaining this diversity remain unclear. The challenge of imported cases and risks of resurgence emphasize the need for continued surveillance to detect early warning signals. Although parasite genotyping has potential to inform the management of outbreaks, further studies are required to identify suitable marker panels for resolving local from imported P. vivax isolates. PMID:25008859

Comparative structural analysis of Bru1 region homeologs in Saccharum spontaneum and S. officinarum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jisen; Sharma, Anupma; Yu, Qingyi

Here, sugarcane is a major sugar and biofuel crop, but genomic research and molecular breeding have lagged behind other major crops due to the complexity of auto-allopolyploid genomes. Sugarcane cultivars are frequently aneuploid with chromosome number ranging from 100 to 130, consisting of 70-80 % S. officinarum, 10-20 % S. spontaneum, and 10 % recombinants between these two species. Analysis of a genomic region in the progenitor autoploid genomes of sugarcane hybrid cultivars will reveal the nature and divergence of homologous chromosomes. As a result, to investigate the origin and evolution of haplotypes in the Bru1 genomic regions in sugarcanemore » cultivars, we identified two BAC clones from S. spontaneum and four from S. officinarum and compared to seven haplotype sequences from sugarcane hybrid R570. The results clarified the origin of seven homologous haplotypes in R570, four haplotypes originated from S. officinarum, two from S. spontaneum and one recombinant.. Retrotransposon insertions and sequences variations among the homologous haplotypes sequence divergence ranged from 18.2 % to 60.5 % with an average of 33. 7 %. Gene content and gene structure were relatively well conserved among the homologous haplotypes. Exon splitting occurred in haplotypes of the hybrid genome but not in its progenitor genomes. Tajima's D analysis revealed that S. spontaneum hapotypes in the Bru1 genomic regions were under strong directional selection. Numerous inversions, deletions, insertions and translocations were found between haplotypes within each genome. In conclusion, this is the first comparison among haplotypes of a modern sugarcane hybrid and its two progenitors. Tajima's D results emphasized the crucial role of this fungal disease resistance gene for enhancing the fitness of this species and indicating that the brown rust resistance gene in R570 is from S. spontaneum. Species-specific InDel, sequences similarity and phylogenetic analysis of homologous genes can be used for identifying the origin of S. spontaneum and S. officinarum haplotype in Saccharum hybrids. Comparison of exon splitting among the homologous haplotypes suggested that the genome rearrangements in Saccharum hybrids S. officinarum would be sufficient for proper genome assembly of this autopolyploid genome. Retrotransposon insertions and sequences variations among the homologous haplotypes sequence divergence may allow sequencing and assembling the autopolyploid Saccharum genomes and the auto-allopolyploid hybrid genomes using whole genome shotgun sequencing.« less

Comparative structural analysis of Bru1 region homeologs in Saccharum spontaneum and S. officinarum

DOE PAGES

Zhang, Jisen; Sharma, Anupma; Yu, Qingyi; ...

2016-06-10

Here, sugarcane is a major sugar and biofuel crop, but genomic research and molecular breeding have lagged behind other major crops due to the complexity of auto-allopolyploid genomes. Sugarcane cultivars are frequently aneuploid with chromosome number ranging from 100 to 130, consisting of 70-80 % S. officinarum, 10-20 % S. spontaneum, and 10 % recombinants between these two species. Analysis of a genomic region in the progenitor autoploid genomes of sugarcane hybrid cultivars will reveal the nature and divergence of homologous chromosomes. As a result, to investigate the origin and evolution of haplotypes in the Bru1 genomic regions in sugarcanemore » cultivars, we identified two BAC clones from S. spontaneum and four from S. officinarum and compared to seven haplotype sequences from sugarcane hybrid R570. The results clarified the origin of seven homologous haplotypes in R570, four haplotypes originated from S. officinarum, two from S. spontaneum and one recombinant.. Retrotransposon insertions and sequences variations among the homologous haplotypes sequence divergence ranged from 18.2 % to 60.5 % with an average of 33. 7 %. Gene content and gene structure were relatively well conserved among the homologous haplotypes. Exon splitting occurred in haplotypes of the hybrid genome but not in its progenitor genomes. Tajima's D analysis revealed that S. spontaneum hapotypes in the Bru1 genomic regions were under strong directional selection. Numerous inversions, deletions, insertions and translocations were found between haplotypes within each genome. In conclusion, this is the first comparison among haplotypes of a modern sugarcane hybrid and its two progenitors. Tajima's D results emphasized the crucial role of this fungal disease resistance gene for enhancing the fitness of this species and indicating that the brown rust resistance gene in R570 is from S. spontaneum. Species-specific InDel, sequences similarity and phylogenetic analysis of homologous genes can be used for identifying the origin of S. spontaneum and S. officinarum haplotype in Saccharum hybrids. Comparison of exon splitting among the homologous haplotypes suggested that the genome rearrangements in Saccharum hybrids S. officinarum would be sufficient for proper genome assembly of this autopolyploid genome. Retrotransposon insertions and sequences variations among the homologous haplotypes sequence divergence may allow sequencing and assembling the autopolyploid Saccharum genomes and the auto-allopolyploid hybrid genomes using whole genome shotgun sequencing.« less

Common FABP4 genetic variants and plasma levels of fatty acid binding protein 4 in older adults.

PubMed

Mukamal, Kenneth J; Wilk, Jemma B; Biggs, Mary L; Jensen, Majken K; Ix, Joachim H; Kizer, Jorge R; Tracy, Russell P; Zieman, Susan J; Mozaffarian, Dariush; Psaty, Bruce M; Siscovick, David S; Djoussé, Luc

2013-11-01

We examined common variants in the fatty acid binding protein 4 gene (FABP4) and plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409, rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190 European Americans and 660 African Americans. Among European Americans, the minor alleles of six single nucleotide polymorphisms (SNP) were associated with lower FABP4 levels (all p ≤ 0.01). Among African Americans, the SNP with the lowest minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C-A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in both European Americans (frequency = 16 %; p = 0.001) and African Americans (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron with one in the 3'untranslated region. However, the alleles associated with lower FABP4 levels were associated with higher fasting glucose in meta-analyses from the MAGIC consortium. These results demonstrate associations of common SNP and haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose levels.

African-American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups

PubMed Central

Ely, Bert; Wilson, Jamie Lee; Jackson, Fatimah; Jackson, Bruce A

2006-01-01

Background Mitochondrial DNA (mtDNA) haplotypes have become popular tools for tracing maternal ancestry, and several companies offer this service to the general public. Numerous studies have demonstrated that human mtDNA haplotypes can be used with confidence to identify the continent where the haplotype originated. Ideally, mtDNA haplotypes could also be used to identify a particular country or ethnic group from which the maternal ancestor emanated. However, the geographic distribution of mtDNA haplotypes is greatly influenced by the movement of both individuals and population groups. Consequently, common mtDNA haplotypes are shared among multiple ethnic groups. We have studied the distribution of mtDNA haplotypes among West African ethnic groups to determine how often mtDNA haplotypes can be used to reconnect Americans of African descent to a country or ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA hypervariable segment I (HVS-I) usually provides sufficient information to assign a particular mtDNA to the proper haplogroup, and it contains most of the variation that is available to distinguish a particular mtDNA haplotype from closely related haplotypes. In this study, samples of general African-American and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches recorded for each sample. Results When two independent African-American samples were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly matched common haplotypes that were shared among multiple African ethnic groups. Another 40% did not match any sequence in the database, and fewer than 10% were an exact match to a sequence from a single African ethnic group. Differences in the regional distribution of haplotypes were observed in the African database, and the African-American haplotypes were more likely to match haplotypes found in ethnic groups from West or West Central Africa than those found in eastern or southern Africa. Fewer than 14% of the African-American mtDNA sequences matched sequences from only West Africa or only West Central Africa. Conclusion Our database of sub-Saharan mtDNA sequences includes the most common haplotypes that are shared among ethnic groups from multiple regions of Africa. These common haplotypes have been found in half of all sub-Saharan Africans. More than 60% of the remaining haplotypes differ from the common haplotypes at a single nucleotide position in the HVS-I region, and they are likely to occur at varying frequencies within sub-Saharan Africa. However, the finding that 40% of the African-American mtDNAs analyzed had no match in the database indicates that only a small fraction of the total number of African haplotypes has been identified. In addition, the finding that fewer than 10% of African-American mtDNAs matched mtDNA sequences from a single African region suggests that few African Americans might be able to trace their mtDNA lineages to a particular region of Africa, and even fewer will be able to trace their mtDNA to a single ethnic group. However, no firm conclusions should be made until a much larger database is available. It is clear, however, that when identical mtDNA haplotypes are shared among many ethnic groups from different parts of Africa, it is impossible to determine which single ethnic group was the source of a particular maternal ancestor based on the mtDNA sequence. PMID:17038170

Sparse Tensor Decomposition for Haplotype Assembly of Diploids and Polyploids.

PubMed

Hashemi, Abolfazl; Zhu, Banghua; Vikalo, Haris

2018-03-21

Haplotype assembly is the task of reconstructing haplotypes of an individual from a mixture of sequenced chromosome fragments. Haplotype information enables studies of the effects of genetic variations on an organism's phenotype. Most of the mathematical formulations of haplotype assembly are known to be NP-hard and haplotype assembly becomes even more challenging as the sequencing technology advances and the length of the paired-end reads and inserts increases. Assembly of haplotypes polyploid organisms is considerably more difficult than in the case of diploids. Hence, scalable and accurate schemes with provable performance are desired for haplotype assembly of both diploid and polyploid organisms. We propose a framework that formulates haplotype assembly from sequencing data as a sparse tensor decomposition. We cast the problem as that of decomposing a tensor having special structural constraints and missing a large fraction of its entries into a product of two factors, U and [Formula: see text]; tensor [Formula: see text] reveals haplotype information while U is a sparse matrix encoding the origin of erroneous sequencing reads. An algorithm, AltHap, which reconstructs haplotypes of either diploid or polyploid organisms by iteratively solving this decomposition problem is proposed. The performance and convergence properties of AltHap are theoretically analyzed and, in doing so, guarantees on the achievable minimum error correction scores and correct phasing rate are established. The developed framework is applicable to diploid, biallelic and polyallelic polyploid species. The code for AltHap is freely available from https://github.com/realabolfazl/AltHap . AltHap was tested in a number of different scenarios and was shown to compare favorably to state-of-the-art methods in applications to haplotype assembly of diploids, and significantly outperforms existing techniques when applied to haplotype assembly of polyploids.

Sex differences in TTC12/ANKK1 haplotype associations with daily tobacco smoking in Black and White Americans.

PubMed

David, Sean P; Mezuk, Briana; Zandi, Peter P; Strong, David; Anthony, James C; Niaura, Raymond; Uhl, George R; Eaton, William W

2010-03-01

The 11q23.1 genomic region has been associated with nicotine dependence in Black and White Americans. By conducting linkage disequilibrium analyses of 7 informative single nucleotide polymorphisms (SNPs) within the tetratricopeptide repeat domain 12 (TTC12)/ankyrin repeat and kinase containing 1 (ANKK1)/dopamine (D2) receptor gene cluster, we identified haplotype block structures in 270 Black and 368 White (n = 638) participants, from the Baltimore Epidemiologic Catchment Area cohort study, spanning the TTC12 and ANKK1 genes consisting of three SNPs (rs2303380-rs4938015-rs11604671). Informative haplotypes were examined for sex-specific associations with daily tobacco smoking initiation and cessation using longitudinal data from 1993-1994 and 2004-2005 interviews. There was a Haplotype x Sex interaction such that Black men possessing the GTG haplotype who were smokers in 1993-2004 were more likely to have stopped smoking by 2004-2005 (55.6% GTG vs. 22.0% other haplotypes), while Black women were less likely to have quit smoking if they possessed the GTG (20.8%) versus other haplotypes (24.0%; p = .028). In Whites, the GTG haplotype (vs. other haplotypes) was associated with lifetime history of daily smoking (smoking initiation; odds ratio = 1.6; 95% CI = 1.1-2.4; p = .013). Moreover, there was a Haplotype x Sex interaction such that there was higher prevalence of smoking initiation with GTG (77.6%) versus other haplotypes (57.0%; p = .043). In 2 different ethnic American populations, we observed man-woman variation in the influence of the rs2303380-rs4938015-rs11604671 GTG haplotype on smoking initiation and cessation. These results should be replicated in larger cohorts to establish the relationship among the rs2303380-rs4938015-rs11604671 haplotype block, sex, and smoking behavior.

Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations.

PubMed

Teo, Yik-Ying; Sim, Xueling; Ong, Rick T H; Tan, Adrian K S; Chen, Jieming; Tantoso, Erwin; Small, Kerrin S; Ku, Chee-Seng; Lee, Edmund J D; Seielstad, Mark; Chia, Kee-Seng

2009-11-01

The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human Genome Diversity Project, providing useful insights into the population structure of the three major population groups in Asia. In addition, this resource also surveyed across the genome for variation in regional patterns of LD between the HapMap and SGVP populations, and for signatures of positive natural selection using two well-established metrics: iHS and XP-EHH. The raw and processed genetic data, together with all population genetic summaries, are publicly available for download and browsing through a web browser modeled with the Generic Genome Browser.

Comparative genetic diversity of Lyme disease bacteria in Northern Californian ticks and their vertebrate hosts.

PubMed

Swei, Andrea; Bowie, Verna C; Bowie, Rauri C K

2015-04-01

Vector-borne pathogens are transmitted between vertebrate hosts and arthropod vectors, two immensely different environments for the pathogen. There is further differentiation among vertebrate hosts that often have complex, species-specific immunological responses to the pathogen. All this presents a heterogeneous environmental and immunological landscape with possible consequences on the population genetic structure of the pathogen. We evaluated the differential genetic diversity of the Lyme disease pathogen, Borrelia burgdorferi, in its vector, the western black-legged tick (Ixodes pacificus), and in its mammal host community using the 5S-23S rRNA intergenic spacer region. We found differences in haplotype distribution of B. burgdorferi in tick populations from two counties in California as well as between a sympatric tick and vertebrate host community. In addition, we found that three closely related haplotypes consistently occurred in high frequency in all sample types. Lastly, our study found lower species diversity of the B. burgdorferi species complex, known as B. burgdorferi sensu lato, in small mammal hosts versus the tick populations in a sympatric study area. Copyright © 2015 Elsevier GmbH. All rights reserved.

TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis

PubMed Central

Guerreiro, Rita J.; Schymick, Jennifer C.; Crews, Cynthia; Singleton, Andrew; Hardy, John; Traynor, Bryan J.

2008-01-01

Background TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS. Methodology/Principal Findings To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus. Conclusions Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American. PMID:18545701

Genetic diversity of tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) genes in cattle breeds

PubMed Central

Lourenco-Jaramillo, Diana Lelidett; Sifuentes-Rincón, Ana María; Parra-Bracamonte, Gaspar Manuel; de la Rosa-Reyna, Xochitl Fabiola; Segura-Cabrera, Aldo; Arellano-Vera, Williams

2012-01-01

DNA from four cattle breeds was used to re-sequence all of the exons and 56% of the introns of the bovine tyrosine hydroxylase (TH) gene and 97% and 13% of the bovine dopamine β-hydroxylase (DBH) coding and non-coding sequences, respectively. Two novel single nucleotide polymorphisms (SNPs) and a microsatellite motif were found in the TH sequences. The DBH sequences contained 62 nucleotide changes, including eight non-synonymous SNPs (nsSNPs) that are of particular interest because they may alter protein function and therefore affect the phenotype. These DBH nsSNPs resulted in amino acid substitutions that were predicted to destabilize the protein structure. Six SNPs (one from TH and five from DBH non-synonymous SNPs) were genotyped in 140 animals; all of them were polymorphic and had a minor allele frequency of > 9%. There were significant differences in the intra- and inter-population haplotype distributions. The haplotype differences between Brahman cattle and the three B. t. taurus breeds (Charolais, Holstein and Lidia) were interesting from a behavioural point of view because of the differences in temperament between these breeds. PMID:22888292

Singapore Genome Variation Project: A haplotype map of three Southeast Asian populations

PubMed Central

Teo, Yik-Ying; Sim, Xueling; Ong, Rick T.H.; Tan, Adrian K.S.; Chen, Jieming; Tantoso, Erwin; Small, Kerrin S.; Ku, Chee-Seng; Lee, Edmund J.D.; Seielstad, Mark; Chia, Kee-Seng

2009-01-01

The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human Genome Diversity Project, providing useful insights into the population structure of the three major population groups in Asia. In addition, this resource also surveyed across the genome for variation in regional patterns of LD between the HapMap and SGVP populations, and for signatures of positive natural selection using two well-established metrics: iHS and XP-EHH. The raw and processed genetic data, together with all population genetic summaries, are publicly available for download and browsing through a web browser modeled with the Generic Genome Browser. PMID:19700652

Congruence as a measurement of extended haplotype structure across the genome

PubMed Central

2012-01-01

Background Historically, extended haplotypes have been defined using only a few data points, such as alleles for several HLA genes in the MHC. High-density SNP data, and the increasing affordability of whole genome SNP typing, creates the opportunity to define higher resolution extended haplotypes. This drives the need for new tools that support quantification and visualization of extended haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP data across the major histocompatibility complex (MHC) for 2,300 complete families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC), we developed software for studying extended haplotypes. Methods The software, called ExHap (Extended Haplotype), uses a similarity measurement we term congruence to identify and quantify long-range allele identity. Using ExHap, we analyzed congruence in both the T1DGC data and family-phased data from the International HapMap Project. Results Congruent chromosomes from the T1DGC data have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64 megabases of the MHC (HLA-DRB1 to HLA-A). Thirty-three of 132 DQ-DR-B-A defined haplotype groups have > 50% congruent chromosomes in this region. For example, 92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to HLA-A (99.8% allele identity). We also applied ExHap to all 22 autosomes for both CEU and YRI cohorts from the International HapMap Project, identifying multiple candidate extended haplotypes. Conclusions Long-range congruence is not unique to the MHC region. Patterns of allele identity on phased chromosomes provide a simple, straightforward approach to visually and quantitatively inspect complex long-range structural patterns in the genome. Such patterns aid the biologist in appreciating genetic similarities and differences across cohorts, and can lead to hypothesis generation for subsequent studies. PMID:22369243

No association between polymorphisms and haplotypes of COL1A1 and COL1A2 genes and osteoporotic fracture in postmenopausal Chinese women

PubMed Central

Hu, Wei-wei; He, Jin-wei; Zhang, Hao; Wang, Chun; Gu, Jie-mei; Yue, Hua; Ke, Yao-hua; Hu, Yun-qiu; Fu, Wen-zhen; Li, Miao; Liu, Yu-juan; Zhang, Zhen-lin

2011-01-01

Aim: To study whether genetic polymorphisms of COL1A1 and COL1A2 genes affected the onset of fracture in postmenopausal Chinese women. Methods: SNPs in COL1A1 and COL1A2 genes were identified via direct sequencing in 32 unrelated postmenopausal Chinese women. Ten SNPs were genotyped in 1252 postmenopausal Chinese women. The associations were examined using both single-SNP and haplotype tests using logistic regression. Results: Twenty four (4 novel) and 28 (7 novel) SNPs were identified in COL1A1 and COL1A2 gene, respectively. The distribution frequencies of 2 SNPs in COL1A1 (rs2075554 and rs2586494) and 3 SNPs in COL1A2 (rs42517, rs1801182, and rs42524) were significantly different from those documented for the European Caucasian population. No significant difference was observed between fracture and control groups with respect to allele frequency or genotype distribution in 9 selected SNPs and haplotype. No significant association was found between fragility fracture and each SNP or haplotype. The results remained the same after additional corrections for other risk factors such as weight, height, and bone mineral density. Conclusion: Our results show no association between common genetic variations of COL1A1 and COL1A2 genes and fracture, suggesting the complex genetic background of osteoporotic fractures. PMID:21602843

Review: can diet influence the selective advantage of mitochondrial DNA haplotypes?

PubMed

Ballard, J William O; Youngson, Neil A

2015-11-05

This review explores the potential for changes in dietary macronutrients to differentially influence mitochondrial bioenergetics and thereby the frequency of mtDNA haplotypes in natural populations. Such dietary modification may be seasonal or result from biogeographic or demographic shifts. Mechanistically, mtDNA haplotypes may influence the activity of the electron transport system (ETS), retrograde signalling to the nuclear genome and affect epigenetic modifications. Thus, differential provisioning by macronutrients may lead to selection through changes in the levels of ATP production, modulation of metabolites (including AMP, reactive oxygen species (ROS) and the NAD(+)/NADH ratio) and potentially complex epigenetic effects. The exquisite complexity of dietary influence on haplotype frequency is further illustrated by the fact that macronutrients may differentially influence the selective advantage of specific mutations in different life-history stages. In Drosophila, complex I mutations may affect larval growth because dietary nutrients are fed through this complex in immaturity. In contrast, the majority of electrons are provided to complex III in adult flies. We conclude the review with a case study that considers specific interactions between diet and complex I of the ETS. Complex I is the first enzyme of the mitochondrial ETS and co-ordinates in the oxidation of NADH and transfer of electrons to ubiquinone. Although the supposition that mtDNA variants may be selected upon by dietary macronutrients could be intuitively consistent to some and counter intuitive to others, it must face a multitude of scientific hurdles before it can be recognized. © 2015 Authors.

Prevalence of βS-globin gene haplotypes, α-thalassemia (3.7 kb deletion) and redox status in patients with sickle cell anemia in the state of Paraná, Brazil

PubMed Central

Shimauti, Eliana LitsukoTomimatsu; Silva, Danilo Grunig Humberto; de Souza, Eniuce Menezes; de Almeida, Eduardo Alves; Leal, Francismar Prestes; Bonini-Domingos, Claudia Regina

2015-01-01

The aim of this study was to determine the frequency of beta S-globin gene (βS globin) haplotypes and alpha thalassemia with 3.7 kb deletion (−α3.7kb thalassemia) in the northwest region of Paraná state, and to investigate the oxidative and clinical-hematological profile of βS globin carriers in this population. Of the 77 samples analyzed, 17 were Hb SS, 30 were Hb AS and 30 were Hb AA. The βSglobin haplotypes and −α3.7kb thalassemia were identified using polymerase chain reaction.Trolox equivalent antioxidant capacity (TEAC) and lipid peroxidation (LPO) were assessed spectophotometrically. Serum melatonin levels were determined using high-performance liquid chromatography coupled to coulometric electrochemical detection. The haplotype frequencies in the SS individuals were as follows: Bantu- 21 (62%), Benin - 11 (32%) and Atypical- 2 (6%). Bantu/Benin was the most frequent genotype. Of the 47 SS and AS individuals assessed, 17% (n = 8) had the −α3.7kb mutation. Clinical manifestations, as well as serum melatonin, TEAC and LPO levels did not differ between Bantu/Bantu and Bantu/Benin individuals (p > 0.05). Both genotypes were associated with high LPO and TEAC levels and decreased melatonin concentration. These data suggest that the level of oxidative stress in patients with Bantu/Bantu and Bantu/Benin genotypes may overload the antioxidant capacity. PMID:26500435

Next generation haplotyping to decipher nuclear genomic interspecific admixture in Citrus species: analysis of chromosome 2.

PubMed

Curk, Franck; Ancillo, Gema; Garcia-Lor, Andres; Luro, François; Perrier, Xavier; Jacquemoud-Collet, Jean-Pierre; Navarro, Luis; Ollitrault, Patrick

2014-12-29

The most economically important Citrus species originated by natural interspecific hybridization between four ancestral taxa (Citrus reticulata, Citrus maxima, Citrus medica, and Citrus micrantha) and from limited subsequent interspecific recombination as a result of apomixis and vegetative propagation. Such reticulate evolution coupled with vegetative propagation results in mosaic genomes with large chromosome fragments from the basic taxa in frequent interspecific heterozygosity. Modern breeding of these species is hampered by their complex heterozygous genomic structures that determine species phenotype and are broken by sexual hybridisation. Nevertheless, a large amount of diversity is present in the citrus gene pool, and breeding to allow inclusion of desirable traits is of paramount importance. However, the efficient mobilization of citrus biodiversity in innovative breeding schemes requires previous understanding of Citrus origins and genomic structures. Haplotyping of multiple gene fragments along the whole genome is a powerful approach to reveal the admixture genomic structure of current species and to resolve the evolutionary history of the gene pools. In this study, the efficiency of parallel sequencing with 454 methodology to decipher the hybrid structure of modern citrus species was assessed by analysis of 16 gene fragments on chromosome 2. 454 amplicon libraries were established using the Fluidigm array system for 48 genotypes and 16 gene fragments from chromosome 2. Haplotypes were established from the reads of each accession and phylogenetic analyses were performed using the haplotypic data for each gene fragment. The length of 454 reads and the level of differentiation between the ancestral taxa of modern citrus allowed efficient haplotype phylogenetic assignations for 12 of the 16 gene fragments. The analysis of the mixed genomic structure of modern species and cultivars (i) revealed C. maxima introgressions in modern mandarins, (ii) was consistent with previous hypotheses regarding the origin of secondary species, and (iii) provided a new picture of the evolution of chromosome 2. 454 sequencing was an efficient strategy to establish haplotypes with significant phylogenetic assignations in Citrus, providing a new picture of the mixed structure on chromosome 2 in 48 citrus genotypes.

Population-specific variation in haplotype composition and heterozygosity at the POLB locus.

PubMed

Yamtich, Jennifer; Speed, William C; Straka, Eva; Kidd, Judith R; Sweasy, Joann B; Kidd, Kenneth K

2009-05-01

DNA polymerase beta plays a central role in base excision repair (BER), which removes large numbers of endogenous DNA lesions from each cell on a daily basis. Little is currently known about germline polymorphisms within the POLB locus, making it difficult to study the association of variants at this locus with human diseases such as cancer. Yet, approximately thirty percent of human tumor types show variants of DNA polymerase beta. We have assessed the global frequency distributions of coding and common non-coding SNPs in and flanking the POLB gene for a total of 14 sites typed in approximately 2400 individuals from anthropologically defined human populations worldwide. We have found a marked difference between haplotype frequencies in African populations and in non-African populations.

Nonhomologous Pairing in Mice Heterozygous for a t Haplotype Can Produce Recombinant Chromosomes with Duplications and Deletions

PubMed Central

Sarvetnick, Nora; Fox, Howard S.; Mann, Elizabeth; Mains, Paul E.; Elliott, Rosemary W.; Silver, Lee M.

1986-01-01

We have investigated the structure and properties of a chromosomal product recovered from a rare recombination event between a t haplotype and a wild-type form of mouse chromosome 17. Our embryological and molecular studies indicate that this chromosome (twLub2 ) is characterized by both a deletion and duplication of adjacent genetic material. The deletion appears to be responsible for a dominant lethal maternal effect and a recessive embryonic lethality. The duplication provides an explanation for the twLub2 suppression of the dominant T locus phenotype. A reanalysis of previously described results with another chromosome 17 variant called TtOrl indicates a structure for this chromosome that is reciprocal to that observed for twLub2. We have postulated the existence of an inversion over the proximal portion of all complete t haplotypes in order to explain the generation of the partial t haplotypes t wLub2 and TtOrl. This proximal inversion and the previously described distal inversion are sufficient to account for all of the recombination properties that are characteristic of complete t haplotypes. The structures determined for twLub2 and TtOrl indicate that rare recombination can occur between nonequivalent genomic sequences within the inverted proximal t region when wild-type and t chromosomes are paired in a linear, nonhomologous configuration. PMID:3732789

Cloud computing-based TagSNP selection algorithm for human genome data.

PubMed

Hung, Che-Lun; Chen, Wen-Pei; Hua, Guan-Jie; Zheng, Huiru; Tsai, Suh-Jen Jane; Lin, Yaw-Ling

2015-01-05

Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used.

Cloud Computing-Based TagSNP Selection Algorithm for Human Genome Data

PubMed Central

Hung, Che-Lun; Chen, Wen-Pei; Hua, Guan-Jie; Zheng, Huiru; Tsai, Suh-Jen Jane; Lin, Yaw-Ling

2015-01-01

Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used. PMID:25569088

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrew, S.E.; Goldberg, Y.P.; Squitieri, F.

Huntington disease (HD) is one of 7 disorders now known to be caused by expansion of a trinucleotide repeat. The HD mutation is a polymorphic trinucleotide (CAG) repeat in the 5{prime} region of a novel gene that expands beyond the normal range of 10-35 repeats in persons destined to develop the disease. Haplotype analysis of other dynamic mutation disorders such as myotonic dystrophy and Fragil X have suggested that a rare ancestral expansion event on a normal chromosome is followed by subsequent expansion events, resulting in a pool of chromosomes in the premutation range, which is inherently unstable and pronemore » to further multiple expansion events leading to disease range chromosomes. Haplotype analysis of 67 HD and 84 control chromosomes using 5 polymorphic markers, both intragenic and 5{prime} to the disease mutation, demonstrate that multiple haplotypes underlie HD. However, 94% of the chromosomes can be grouped under two major haplotypes. These two haplotypes are also present in the normal population. A third major haplotype is seen on 38% of normal chromosomes but rarely on HD chromosomes (6%). CAG lengths on the normal chromosomes with the two haplotypes seen in the HD population are higher than those seen on the normal chromosomes with the haplotype rarely seen on HD chromosomes. Furthermore, in populations with a diminished frequency of HD, CAG length on normal chromosomes is significantly less than other populations with higher prevalence rates for HD. These data suggest that CAG length on normal chromosomes may be a significant factor contributing to repeat instability that eventually leads to chromosomes with CAG repeat lengths in the HD range. Haplotypes on the HD chromosomes are identical to those normal chromosomes which have CAG lengths in the high range of normal, suggesting that further expansions of this pool of chromosomes leads to chromosomes with CAG repeat sizes within the disease range, consistent with a multistep model.« less

Molecular and geographic evolutionary support for the essential role of GIGANTEAa in soybean domestication of flowering time.

PubMed

Wang, Yan; Gu, Yongzhe; Gao, Huihui; Qiu, Lijuan; Chang, Ruzhen; Chen, Shouyi; He, Chaoying

2016-04-12

Flowering time is a domestication trait of Glycine max and varies in soybeans, yet, a gene for flowering time variation has not been associated with soybean domestication. GIGANTEA (GI) is a major gene involved in the control of flowering time in Arabidopsis, although three GI homologs complicate this model in the soybean genome. In the present work, we revealed that the geographic evolution of the GIGANTEAa (GIa) haplotypes in G. max (GmGIa) and Glycine soja (GsGIa). Three GIa haplotypes (H1, H2, and H3) were found among cultivated soybeans and their wild relatives, yet an additional 44 diverse haplotypes were observed in wild soybeans. H1 had a premature stop codon in the 10(th) exon, whereas the other haplotypes encoded full-length GIa protein isoforms. In both wild-type and cultivated soybeans, H2 was present in the Southern region of China, and H3 was restricted to areas near the Northeast region of China. H1 was genetically derived from H2, and it was dominant and widely distributed among cultivated soybeans, whereas in wild populations, the ortholog of this domesticated haplotype H1 was only found in Yellow River basin with a low frequency. Moreover, this mutated GIa haplotype significantly correlated with early flowering. We further determined that the differences in gene expression of the three GmGIa haplotypes were not correlated to flowering time variations in cultivated soybeans. However, only the truncated GmGIa H1 could partially rescue gi-2 Arabidopsis from delayed flowering in transgenic plants, whereas both GmGIa H2 and H3 haplotypes could significantly repress flowering in transgenic Arabidopsis with a wild-type background. Thus, GmGIa haplotype diversification may have contributed to flowering time adaptation that facilitated the radiation of domesticated soybeans. In light of the evolution of the GIa gene, soybean domestication history for an early flowering phenotype is discussed.

MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation

PubMed Central

van Asch, Barbara; Pereira, Luísa; Pereira, Filipe; Santa-Rita, Pedro; Lima, Manuela; Amorim, António

2005-01-01

Background The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143) of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data. Results Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds. A review of mtDNA haplotypes in dogs across the world revealed that: (a) breeds tend to display haplotypes belonging to different haplogroups; (b) haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c) haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d) genetic distances between breeds do not correlate with geography. Conclusion MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal) and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog) and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the Azores Cattle Dog descended maternally from Northern European dogs rather than Portuguese mainland dogs. A review of published mtDNA haplotypes identified thirteen non-Portuguese breeds with sufficient data for comparison. Comparisons between these thirteen breeds, and the four Portuguese breeds, demonstrated widespread haplotype sharing, with the greatest diversity among Asian dogs, in accordance with the central role of Asia in canine domestication. PMID:15972107

Crohn’s Disease and Genetic Hitchhiking at IBD5

PubMed Central

Huff, Chad D.; Witherspoon, David J.; Zhang, Yuhua; Gatenbee, Chandler; Denson, Lee A.; Kugathasan, Subra; Hakonarson, Hakon; Whiting, April; Davis, Chadwick T.; Wu, Wilfred; Xing, Jinchuan; Watkins, W. Scott; Bamshad, Michael J.; Bradfield, Jonathan P.; Bulayeva, Kazima; Simonson, Tatum S.; Jorde, Lynn B.; Guthery, Stephen L.

2012-01-01

Inflammatory bowel disease 5 (IBD5) is a 250 kb haplotype on chromosome 5 that is associated with an increased risk of Crohn’s disease in Europeans. The OCTN1 gene is centrally located on IBD5 and encodes a transporter of the antioxidant ergothioneine (ET). The 503F variant of OCTN1 is strongly associated with IBD5 and is a gain-of-function mutation that increases absorption of ET. Although 503F has been implicated as the variant potentially responsible for Crohn’s disease susceptibility at IBD5, there is little evidence beyond statistical association to support its role in disease causation. We hypothesize that 503F is a recent adaptation in Europeans that swept to relatively high frequency and that disease association at IBD5 results not from 503F itself, but from one or more nearby hitchhiking variants, in the genes IRF1 or IL5. To test for evidence of recent positive selection on the 503F allele, we employed the iHS statistic, which was significant in the European CEU HapMap population (P = 0.0007) and European Human Genome Diversity Panel populations (P ≤ 0.01). To evaluate the hypothesis of disease-variant hitchhiking, we performed haplotype association tests on high-density microarray data in a sample of 1,868 Crohn’s disease cases and 5,550 controls. We found that 503F haplotypes with recombination breakpoints between OCTN1 and IRF1 or IL5 were not associated with disease (odds ratio [OR]: 1.05, P = 0.21). In contrast, we observed strong disease association for 503F haplotypes with no recombination between these three genes (OR: 1.24, P = 2.6 × 10−8), as expected if the sweeping haplotype harbored one or more disease-causing mutations in IRF1 or IL5. To further evaluate these disease-gene candidates, we obtained expression data from lower gastrointestinal biopsies of healthy individuals and Crohn’s disease patients. We observed a 72% increase in gene expression of IRF1 among Crohn’s disease patients (P = 0.0006) and no significant difference in expression of OCTN1. Collectively, these data indicate that the 503F variant has increased in frequency due to recent positive selection and that disease-causing variants in linkage disequilibrium with 503F have hitchhiked to relatively high frequency, thus forming the IBD5 risk haplotype. Finally, our association results and expression data support IRF1 as a strong candidate for Crohn’s disease causation. PMID:21816865

Mechanisms of haplotype divergence at the RGA08 nucleotide-binding leucine-rich repeat gene locus in wild banana (Musa balbisiana).

PubMed

Baurens, Franc-Christophe; Bocs, Stéphanie; Rouard, Mathieu; Matsumoto, Takashi; Miller, Robert N G; Rodier-Goud, Marguerite; MBéguié-A-MBéguié, Didier; Yahiaoui, Nabila

2010-07-16

Comparative sequence analysis of complex loci such as resistance gene analog clusters allows estimating the degree of sequence conservation and mechanisms of divergence at the intraspecies level. In banana (Musa sp.), two diploid wild species Musa acuminata (A genome) and Musa balbisiana (B genome) contribute to the polyploid genome of many cultivars. The M. balbisiana species is associated with vigour and tolerance to pests and disease and little is known on the genome structure and haplotype diversity within this species. Here, we compare two genomic sequences of 253 and 223 kb corresponding to two haplotypes of the RGA08 resistance gene analog locus in M. balbisiana "Pisang Klutuk Wulung" (PKW). Sequence comparison revealed two regions of contrasting features. The first is a highly colinear gene-rich region where the two haplotypes diverge only by single nucleotide polymorphisms and two repetitive element insertions. The second corresponds to a large cluster of RGA08 genes, with 13 and 18 predicted RGA genes and pseudogenes spread over 131 and 152 kb respectively on each haplotype. The RGA08 cluster is enriched in repetitive element insertions, in duplicated non-coding intergenic sequences including low complexity regions and shows structural variations between haplotypes. Although some allelic relationships are retained, a large diversity of RGA08 genes occurs in this single M. balbisiana genotype, with several RGA08 paralogs specific to each haplotype. The RGA08 gene family has evolved by mechanisms of unequal recombination, intragenic sequence exchange and diversifying selection. An unequal recombination event taking place between duplicated non-coding intergenic sequences resulted in a different RGA08 gene content between haplotypes pointing out the role of such duplicated regions in the evolution of RGA clusters. Based on the synonymous substitution rate in coding sequences, we estimated a 1 million year divergence time for these M. balbisiana haplotypes. A large RGA08 gene cluster identified in wild banana corresponds to a highly variable genomic region between haplotypes surrounded by conserved flanking regions. High level of sequence identity (70 to 99%) of the genic and intergenic regions suggests a recent and rapid evolution of this cluster in M. balbisiana.

Multi-allelic haplotype model based on genetic partition for genomic prediction and variance component estimation using SNP markers.

PubMed

Da, Yang

2015-12-18

The amount of functional genomic information has been growing rapidly but remains largely unused in genomic selection. Genomic prediction and estimation using haplotypes in genome regions with functional elements such as all genes of the genome can be an approach to integrate functional and structural genomic information for genomic selection. Towards this goal, this article develops a new haplotype approach for genomic prediction and estimation. A multi-allelic haplotype model treating each haplotype as an 'allele' was developed for genomic prediction and estimation based on the partition of a multi-allelic genotypic value into additive and dominance values. Each additive value is expressed as a function of h - 1 additive effects, where h = number of alleles or haplotypes, and each dominance value is expressed as a function of h(h - 1)/2 dominance effects. For a sample of q individuals, the limit number of effects is 2q - 1 for additive effects and is the number of heterozygous genotypes for dominance effects. Additive values are factorized as a product between the additive model matrix and the h - 1 additive effects, and dominance values are factorized as a product between the dominance model matrix and the h(h - 1)/2 dominance effects. Genomic additive relationship matrix is defined as a function of the haplotype model matrix for additive effects, and genomic dominance relationship matrix is defined as a function of the haplotype model matrix for dominance effects. Based on these results, a mixed model implementation for genomic prediction and variance component estimation that jointly use haplotypes and single markers is established, including two computing strategies for genomic prediction and variance component estimation with identical results. The multi-allelic genetic partition fills a theoretical gap in genetic partition by providing general formulations for partitioning multi-allelic genotypic values and provides a haplotype method based on the quantitative genetics model towards the utilization of functional and structural genomic information for genomic prediction and estimation.

Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data.

PubMed

Excoffier, L; Smouse, P E; Quattro, J M

1992-06-01

We present here a framework for the study of molecular variation within a single species. Information on DNA haplotype divergence is incorporated into an analysis of variance format, derived from a matrix of squared-distances among all pairs of haplotypes. This analysis of molecular variance (AMOVA) produces estimates of variance components and F-statistic analogs, designated here as phi-statistics, reflecting the correlation of haplotypic diversity at different levels of hierarchical subdivision. The method is flexible enough to accommodate several alternative input matrices, corresponding to different types of molecular data, as well as different types of evolutionary assumptions, without modifying the basic structure of the analysis. The significance of the variance components and phi-statistics is tested using a permutational approach, eliminating the normality assumption that is conventional for analysis of variance but inappropriate for molecular data. Application of AMOVA to human mitochondrial DNA haplotype data shows that population subdivisions are better resolved when some measure of molecular differences among haplotypes is introduced into the analysis. At the intraspecific level, however, the additional information provided by knowing the exact phylogenetic relations among haplotypes or by a nonlinear translation of restriction-site change into nucleotide diversity does not significantly modify the inferred population genetic structure. Monte Carlo studies show that site sampling does not fundamentally affect the significance of the molecular variance components. The AMOVA treatment is easily extended in several different directions and it constitutes a coherent and flexible framework for the statistical analysis of molecular data.

Common polymorphisms in interleukin genes (IL4, IL6, IL8 and IL12) are not associated with alcoholic liver disease or alcoholism in Spanish men.

PubMed

Marcos, Miguel; Pastor, Isabel; González-Sarmiento, Rogelio; Laso, Francisco-Javier

2009-03-01

Preliminary data suggest that polymorphisms in cytokine genes may be involved in the genetic predisposition to alcoholic liver cirrhosis or alcohol use disorders. We thus analyze the association between these diseases and the following polymorphisms: -33T>C IL4, -174 G>C IL6, -251 T>A IL8 and 1188 A>C IL12B. 258 male alcoholics (161 without liver disease and 97 with liver cirrhosis) and 101 healthy controls were genotyped for the above mentioned polymorphisms. We examined the relationship between genotype and allele frequencies and the presence of disease, as well as the correlation with combinations of putative pro-inflammatory genotypes. Haplotypes were inferred using the expectation-maximization algorithm and haplotype frequencies were compared. We found no statistically significant association between any of these polymorphisms or the combinations of pro-inflammatory polymorphisms and the risk of alcoholic liver cirrhosis or alcohol abuse or dependence. Haplotype analysis of the IL4 and IL12B polymorphisms did not show any statistical relationship either. Our results do not support the hypothesis that the analyzed polymorphisms confer differences in alcoholic liver cirrhosis or alcohol use disorders susceptibility.

Mitochondrial DNA markers reveal high genetic diversity but low genetic differentiation in the black fly Simulium tani Takaoka & Davies along an elevational gradient in Malaysia.

PubMed

Low, Van Lun; Adler, Peter H; Takaoka, Hiroyuki; Ya'cob, Zubaidah; Lim, Phaik Eem; Tan, Tiong Kai; Lim, Yvonne A L; Chen, Chee Dhang; Norma-Rashid, Yusoff; Sofian-Azirun, Mohd

2014-01-01

The population genetic structure of Simulium tani was inferred from mitochondria-encoded sequences of cytochrome c oxidase subunits I (COI) and II (COII) along an elevational gradient in Cameron Highlands, Malaysia. A statistical parsimony network of 71 individuals revealed 71 haplotypes in the COI gene and 43 haplotypes in the COII gene; the concatenated sequences of the COI and COII genes revealed 71 haplotypes. High levels of genetic diversity but low levels of genetic differentiation were observed among populations of S. tani at five elevations. The degree of genetic diversity, however, was not in accordance with an altitudinal gradient, and a Mantel test indicated that elevation did not have a limiting effect on gene flow. No ancestral haplotype of S. tani was found among the populations. Pupae with unique structural characters at the highest elevation showed a tendency to form their own haplotype cluster, as revealed by the COII gene. Tajima's D, Fu's Fs, and mismatch distribution tests revealed population expansion of S. tani in Cameron Highlands. A strong correlation was found between nucleotide diversity and the levels of dissolved oxygen in the streams where S. tani was collected.

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.

PubMed

Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z

2016-10-01

The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.

[Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].

PubMed

Swarovskaya, M G; Stepanova, S K; Marussin, A V; Sukhomyasova, A L; Maximova, N R; Stepanov, V A

2015-06-01

The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.

Maternal and paternal genealogy of Eurasian taurine cattle (Bos taurus).

PubMed

Kantanen, J; Edwards, C J; Bradley, D G; Viinalass, H; Thessler, S; Ivanova, Z; Kiselyova, T; Cinkulov, M; Popov, R; Stojanović, S; Ammosov, I; Vilkki, J

2009-11-01

Maternally inherited mitochondrial DNA (mtDNA) has been used extensively to determine origin and diversity of taurine cattle (Bos taurus) but global surveys of paternally inherited Y-chromosome diversity are lacking. Here, we provide mtDNA information on previously uncharacterised Eurasian breeds and present the most comprehensive Y-chromosomal microsatellite data on domestic cattle to date. The mitochondrial haplogroup T3 was the most frequent, whereas T4 was detected only in the Yakutian cattle from Siberia. The mtDNA data indicates that the Ukrainian and Central Asian regions are zones where hybrids between taurine and zebu (B. indicus) cattle have existed. This zebu influence appears to have subsequently spread into southern and southeastern European breeds. The most common Y-chromosomal microsatellite haplotype, termed here as H11, showed an elevated frequency in the Eurasian sample set compared with that detected in Near Eastern and Anatolian breeds. The taurine Y-chromosomal microsatellite haplotypes were found to be structured in a network according to the Y-haplogroups Y1 and Y2. These data do not support the recent hypothesis on the origin of Y1 from the local European hybridization of cattle with male aurochsen. Compared with mtDNA, the intensive culling of breeding males and male-mediated crossbreeding of locally raised native breeds has accelerated loss of Y-chromosomal variation in domestic cattle, and affected the contribution of genetic drift to diversity. In conclusion, to maintain diversity, breeds showing rare Y-haplotypes should be prioritised in the conservation of cattle genetic resources.

The role of the JAK2 GGCC haplotype and the TET2 gene in familial myeloproliferative neoplasms

PubMed Central

Olcaydu, Damla; Rumi, Elisa; Harutyunyan, Ashot; Passamonti, Francesco; Pietra, Daniela; Pascutto, Cristiana; Berg, Tiina; Jäger, Roland; Hammond, Emma; Cazzola, Mario; Kralovics, Robert

2011-01-01

Background Myeloproliferative neoplasms constitute a group of diverse chronic myeloid malignancies that share pathogenic features such as acquired mutations in the JAK2, TET2, CBL and MPL genes. There are recent reports that a JAK2 gene haplotype (GGCC or 46/1) confers susceptibility to JAK2 mutation-positive myeloproliferative neoplasms. The aim of this study was to examine the role of the JAK2 GGCC haplotype and germline mutations of TET2, CBL and MPL in familial myeloproliferative neoplasms. Design and Methods We investigated patients with familial (n=88) or sporadic (n=684) myeloproliferative neoplasms, and a control population (n=203) from the same demographic area in Italy. Association analysis was performed using tagged single nucleotide polymorphisms (rs10974944 and rs12343867) of the JAK2 haplotype. Sequence analysis of TET2, CBL and MPL was conducted in the 88 patients with familial myeloproliferative neoplasms. Results Association analysis revealed no difference in haplotype frequency between familial and sporadic cases of myeloproliferative neoplasms (P=0.6529). No germline mutations in TET2, CBL or MPL that segregate with the disease phenotype were identified. As we observed variability in somatic mutations in the affected members of a pedigree with myeloproliferative neoplasms, we postulated that somatic mutagenesis is increased in familial myeloproliferative neoplasms. Accordingly, we compared the incidence of malignant disorders between sporadic and familial patients. Although the overall incidence of malignant disorders did not differ significantly between cases of familial and sporadic myeloproliferative neoplasms, malignancies were more frequent in patients with familial disease aged between 50 to 70 years (P=0.0198) than in patients in the same age range with sporadic myeloproliferative neoplasms. Conclusions We conclude that the JAK2 GGCC haplotype and germline mutations of TET2, CBL or MPL do not explain familial clustering of myeloproliferative neoplasms. As we observed an increased frequency of malignant disorders in patients with familial myeloproliferative neoplasms, we hypothesize that the germline genetic lesions that underlie familial clustering of myeloproliferative neoplasms predispose to somatic mutagenesis that is not restricted to myeloid hematopoietic cells but cause an increase in overall carcinogenesis. PMID:21173100

Mathematical properties and bounds on haplotyping populations by pure parsimony.

PubMed

Wang, I-Lin; Chang, Chia-Yuan

2011-06-01

Although the haplotype data can be used to analyze the function of DNA, due to the significant efforts required in collecting the haplotype data, usually the genotype data is collected and then the population haplotype inference (PHI) problem is solved to infer haplotype data from genotype data for a population. This paper investigates the PHI problem based on the pure parsimony criterion (HIPP), which seeks the minimum number of distinct haplotypes to infer a given genotype data. We analyze the mathematical structure and properties for the HIPP problem, propose techniques to reduce the given genotype data into an equivalent one of much smaller size, and analyze the relations of genotype data using a compatible graph. Based on the mathematical properties in the compatible graph, we propose a maximal clique heuristic to obtain an upper bound, and a new polynomial-sized integer linear programming formulation to obtain a lower bound for the HIPP problem. Copyright © 2011 Elsevier Inc. All rights reserved.

Highly Prevalent LIPH Founder Mutations Causing Autosomal Recessive Woolly Hair/Hypotrichosis in Japan and the Genotype/Phenotype Correlations

PubMed Central

Kono, Michihiro; Takama, Hiromichi; Hamajima, Nobuyuki; Akiyama, Masashi

2014-01-01

Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH), and the 2 missense mutations c.736T>A (p.Cys246Ser) and c.742C>A (p.His248Asn) are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016), and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024). In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH. PMID:24586639

16th IHIW: Global analysis of registry HLA haplotypes from 20 Million individuals: Report from the IHIW Registry Diversity Group

PubMed Central

Maiers, M; Gragert, L; Madbouly, A; Steiner, D; Marsh, S G E; Gourraud, P-A; Oudshoorn, M; Zanden, H; Schmidt, A H; Pingel, J; Hofmann, J; Müller, C; Eberhard, H-P

2013-01-01

This project has the goal to validate bioinformatics methods and tools for HLA haplotype frequency analysis specifically addressing unique issues of haematopoietic stem cell registry data sets. In addition to generating new methods and tools for the analysis of registry data sets, the intent is to produce a comprehensive analysis of HLA data from 20 million donors from the Bone Marrow Donors Worldwide (BMDW) database. This report summarizes the activity on this project as of the 16IHIW meeting in Liverpool. PMID:23280139

Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine.

PubMed

Olkhovych, N V; Gorovenko, N G

2016-01-01

The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W) and c.745C>T (R249W) in the HEXA gene, c.1726G>A (G576S) and c.2065G>A (E689K) in the GAA gene, c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease). The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes) was 10.3%. The frequency of c.739C>T (R247W) allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes) was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of pseudodeficiency may lead to serious diagnostic errors.

Haplotypic Background of a Private Allele at High Frequency in the Americas

PubMed Central

Schroeder, Kari B.; Jakobsson, Mattias; Crawford, Michael H.; Schurr, Theodore G.; Boca, Simina M.; Conrad, Donald F.; Tito, Raul Y.; Osipova, Ludmilla P.; Tarskaia, Larissa A.; Zhadanov, Sergey I.; Wall, Jeffrey D.; Pritchard, Jonathan K.; Malhi, Ripan S.; Smith, David G.; Rosenberg, Noah A.

2009-01-01

Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the “American Modal Haplotype” (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all modern Native Americans and Western Beringians trace a large portion of their ancestry to a single founding population that may have been isolated from other Asian populations prior to expanding into the Americas. PMID:19221006

Haplotype analysis of sucrose synthase gene family in three Saccharum species

PubMed Central

2013-01-01

Background Sugarcane is an economically important crop contributing about 80% and 40% to the world sugar and ethanol production, respectively. The complicated genetics consequential to its complex polyploid genome, however, have impeded efforts to improve sugar yield and related important agronomic traits. Modern sugarcane cultivars are complex hybrids derived mainly from crosses among its progenitor species, S. officinarum and S. spontanuem, and to a lesser degree, S. robustom. Atypical of higher plants, sugarcane stores its photoassimilates as sucrose rather than as starch in its parenchymous stalk cells. In the sugar biosynthesis pathway, sucrose synthase (SuSy, UDP-glucose: D-fructose 2-a-D-glucosyltransferase, EC 2.4.1.13) is a key enzyme in the regulation of sucrose accumulation and partitioning by catalyzing the reversible conversion of sucrose and UDP into UDP-glucose and fructose. However, little is known about the sugarcane SuSy gene family members and hence no definitive studies have been reported regarding allelic diversity of SuSy gene families in Saccharum species. Results We identified and characterized a total of five sucrose synthase genes in the three sugarcane progenitor species through gene annotation and PCR haplotype analysis by analyzing 70 to 119 PCR fragments amplified from intron-containing target regions. We detected all but one (i.e. ScSuSy5) of ScSuSy transcripts in five tissue types of three Saccharum species. The average SNP frequency was one SNP per 108 bp, 81 bp, and 72 bp in S. officinarum, S. robustom, and S. spontanuem respectively. The average shared SNP is 15 between S. officinarum and S. robustom, 7 between S. officinarum and S. spontanuem , and 11 between S. robustom and S. spontanuem. We identified 27, 35, and 32 haplotypes from the five ScSuSy genes in S. officinarum, S. robustom, and S. spontanuem respectively. Also, 12, 11, and 9 protein sequences were translated from the haplotypes in S. officinarum, S. robustom, S. spontanuem, respectively. Phylogenetic analysis showed three separate clusters composed of SbSuSy1 and SbSuSy2, SbSuSy3 and SbSuSy5, and SbSuSy4. Conclusions The five members of the SuSy gene family evolved before the divergence of the genera in the tribe Andropogoneae at least 12 MYA. Each ScSuSy gene showed at least one non-synonymous substitution in SNP haplotypes. The SNP frequency is the lowest in S. officinarum, intermediate in S. robustum, and the highest in S. spontaneum, which may reflect the timing of the two rounds of whole genome duplication in these octoploids. The higher rate of shared SNP frequency between S. officinarum and S. robustum than between S. officinarum and in S. spontaneum confirmed that the speciation event separating S. officinarum and S. robustum occurred after their common ancestor diverged from S. spontaneum. The SNP and haplotype frequencies in three Saccharum species provide fundamental information for designing strategies to sequence these autopolyploid genomes. PMID:23663250

Haplotype analysis of sucrose synthase gene family in three Saccharum species.

PubMed

Zhang, Jisen; Arro, Jie; Chen, Youqiang; Ming, Ray

2013-05-10

Sugarcane is an economically important crop contributing about 80% and 40% to the world sugar and ethanol production, respectively. The complicated genetics consequential to its complex polyploid genome, however, have impeded efforts to improve sugar yield and related important agronomic traits. Modern sugarcane cultivars are complex hybrids derived mainly from crosses among its progenitor species, S. officinarum and S. spontanuem, and to a lesser degree, S. robustom. Atypical of higher plants, sugarcane stores its photoassimilates as sucrose rather than as starch in its parenchymous stalk cells. In the sugar biosynthesis pathway, sucrose synthase (SuSy, UDP-glucose: D-fructose 2-a-D-glucosyltransferase, EC 2.4.1.13) is a key enzyme in the regulation of sucrose accumulation and partitioning by catalyzing the reversible conversion of sucrose and UDP into UDP-glucose and fructose. However, little is known about the sugarcane SuSy gene family members and hence no definitive studies have been reported regarding allelic diversity of SuSy gene families in Saccharum species. We identified and characterized a total of five sucrose synthase genes in the three sugarcane progenitor species through gene annotation and PCR haplotype analysis by analyzing 70 to 119 PCR fragments amplified from intron-containing target regions. We detected all but one (i.e. ScSuSy5) of ScSuSy transcripts in five tissue types of three Saccharum species. The average SNP frequency was one SNP per 108 bp, 81 bp, and 72 bp in S. officinarum, S. robustom, and S. spontanuem respectively. The average shared SNP is 15 between S. officinarum and S. robustom, 7 between S. officinarum and S. spontanuem , and 11 between S. robustom and S. spontanuem. We identified 27, 35, and 32 haplotypes from the five ScSuSy genes in S. officinarum, S. robustom, and S. spontanuem respectively. Also, 12, 11, and 9 protein sequences were translated from the haplotypes in S. officinarum, S. robustom, S. spontanuem, respectively. Phylogenetic analysis showed three separate clusters composed of SbSuSy1 and SbSuSy2, SbSuSy3 and SbSuSy5, and SbSuSy4. The five members of the SuSy gene family evolved before the divergence of the genera in the tribe Andropogoneae at least 12 MYA. Each ScSuSy gene showed at least one non-synonymous substitution in SNP haplotypes. The SNP frequency is the lowest in S. officinarum, intermediate in S. robustum, and the highest in S. spontaneum, which may reflect the timing of the two rounds of whole genome duplication in these octoploids. The higher rate of shared SNP frequency between S. officinarum and S. robustum than between S. officinarum and in S. spontaneum confirmed that the speciation event separating S. officinarum and S. robustum occurred after their common ancestor diverged from S. spontaneum. The SNP and haplotype frequencies in three Saccharum species provide fundamental information for designing strategies to sequence these autopolyploid genomes.

Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

PubMed Central

Lam, Tze Hau; Tay, Matthew Zirui; Wang, Bei; Xiao, Ziwei; Ren, Ee Chee

2015-01-01

Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, the nature of fine variations within their genomic structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation in two common Asian MHC haplotypes: A33-B58-DR3 and A2-B46-DR9. However, characterization of phase-resolved MHC haplotypes revealed unique intra-CEH patterns of variation and uncovered 127 single nucleotide variants (SNVs) which are missing from public databases. We further show that the strong linkage disequilibrium structure within the human MHC that typically confounds precise identification of genetic features can be resolved using intra-CEH variants, as evidenced by rs3129063 and rs448489, which affect expression of ZFP57, a gene important in methylation and epigenetic regulation. This study demonstrates an improved strategy that can be used towards genetic dissection of diseases. PMID:26593880

Genetic diversity and geographical structure of the pitcher plant Nepenthes vieillardii in New Caledonia: A chloroplast DNA haplotype analysis.

PubMed

Kurata, Kaoruko; Jaffré, Tanguy; Setoguchi, Hiroaki

2008-12-01

Among the many species that grow in New Caledonia, the pitcher plant Nepenthes vieillardii (Nepenthaceae) has a high degree of morphological variation. In this study, we present the patterns of genetic differentiation of pitcher plant populations based on chloroplast DNA haplotype analysis using the sequences of five spacers. We analyzed 294 samples from 16 populations covering the entire range of the species, using 4660 bp of sequence. Our analysis identified 17 haplotypes, including one that is widely distributed across the islands, as well as regional and private haplotypes. The greatest haplotype diversity was detected on the eastern coast of the largest island and included several private haplotypes, while haplotype diversity was low in the southern plains region. The parsimony network analysis of the 17 haplotypes suggested that the genetic divergence is the result of long-term isolation of individual populations. Results from a spatial analysis of molecular variance and a cluster analysis suggest that the plants once covered the entire serpentine area of New Caledonia and that subsequent regional fragmentation resulted in the isolation of each population and significantly restricted seed flow. This isolation may have been an important factor in the development of the morphological and genetic variation among pitcher plants in New Caledonia.

High Frequency of Haplotype HLA-DQ7 in Celiac Disease Patients from South Italy: Retrospective Evaluation of 5,535 Subjects at Risk of Celiac Disease

PubMed Central

Tinto, Nadia; Cola, Arturo; Piscopo, Chiara; Capuano, Marina; Galatola, Martina; Greco, Luigi; Sacchetti, Lucia

2015-01-01

Background Celiac disease (CD) has a strong genetic component mainly due to HLA DQ2/DQ8 encoding genes. However, a minority of CD patients are DQ2/DQ8-negative. To address this issue, we retrospectively characterized HLA haplotypes in 5,535 subjects at risk of CD (either relatives of CD patients or subjects with CD-like symptoms) referred to our center during a 10-year period. Methods We identified loci DQA1/DQB1/DRB1 by sequence-specific oligonucleotide-PCR and sequence-specific primer-PCR; anti-transglutaminase IgA/IgG and anti-endomysium IgA by ELISA and indirect immunofluorescence, respectively. Results We diagnosed CD in 666/5,535 individuals, 4.2% of whom were DQ2/DQ8-negative. Interestingly, DQ7 was one of the most abundant haplotypes in all CD patients and significantly more frequent in DQ2/DQ8-negative (38%) than in DQ2/DQ8-positive CD patients (24%) (p<0.05). Conclusion Our data lend support to the concept that DQ7 represents an additive or independent CD risk haplotype with respect to DQ2/DQ8 haplotypes but this finding should be verified in other large CD populations. PMID:26398634

Haplotype data for 23 Y-chromosome markers in a reference sample from Bosnia and Herzegovina.

PubMed

Kovačević, Lejla; Fatur-Cerić, Vera; Hadzic, Negra; Čakar, Jasmina; Primorac, Dragan; Marjanović, Damir

2013-06-01

To detect polymorphisms of 23 Y-chromosomal short tandem repeat (STR) loci, including 6 new loci, in a reference database of male population of Bosnia and Herzegovina, as well as to assess the importance of increasing the number of Y-STR loci utilized in forensic DNA analysis. The reference sample consisted of 100 healthy, unrelated men originating from Bosnia and Herzegovina. Sample collection using buccal swabs was performed in all geographical regions of Bosnia and Herzegovina in the period from 2010 to 2011. DNA samples were typed for 23 Y STR loci, including 6 new loci: DYS576, DYS481, DYS549, DYS533, DYS570, and DYS643, which are included in the new PowerPlex® Y 23 amplification kit. The absolute frequency of generated haplotypes was calculated and results showed that 98 samples had unique Y 23 haplotypes, and that only two samples shared the same haplotype. The most polymorphic locus was DYS418, with 14 detected alleles and the least polymorphic loci were DYS389I, DYS391, DYS437, and DYS393. This study showed that by increasing the number of highly polymorphic Y STR markers, to include those tested in our analysis, leads to a reduction of repeating haplotypes, which is very important in the application of forensic DNA analysis.

Cytokine polymorphisms in patients with pemphigus.

PubMed

Eberhard, Yanina; Burgos, Elisa; Gagliardi, Julio; Vullo, Carlos Maria; Borosky, Alicia; Pesoa, Susana; Serra, Horacio Marcelo

2005-01-01

The aim of this study was to assess whether tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1) and interleukin-10 (IL-10) polymorphisms are among the factors influencing the development of pemphigus. Whole blood from 20 patients with pemphigus and 24 control subjects was taken. Genomic DNA was obtained and cytokine genotyping for IL-10 (-1082 G/A; -819 C/T), TGFB1 (codon 10 C/T, codon 25 G/C) and TNFA (-308 G/A) was performed using the ARMS-PCR method. The distribution of IL-10 (-819) alleles was significantly different between the pemphigus and control groups (P=0.009). In particular, allele T was associated with the disease (OR 3.291, 95% CI 1.350-8.020). Similar results were observed when only pemphigus vulgaris (PV) patients were analyzed (P=0.012, OR 3.410, 95% CI 1.346-8.639). An increased frequency of the low producer IL-10 haplotype (-1082/-819 A/T) in patients with pemphigus compared with controls was observed (OR 2.714, 95% CI 1.102-6.685) and this association was also significant when only PV patients were considered (OR 2.667, 95% CI 1.043-6.816). There were no differences between patients and controls in the frequency of any other gene polymorphism analyzed. The increased frequency of the low producer IL-10 haplotype (-1082 /-819 A/T) suggest that the carriage of this haplotype might predispose to pemphigus or the high and intermediate producer haplotypes may be protective factors. The prevalence of the allele IL-10 (-819 T) in pemphigus patients cannot be explained by the current hypothesis, according to which a particular allele of the gene is associated with a different level of cytokine production and therefore affects the predisposition to a particular disease. However, this cytokine polymorphism might be linked to an unknown susceptibility factor.

Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a Dutch population.

PubMed

Bosch, T M; Doodeman, V D; Smits, P H M; Meijerman, I; Schellens, J H M; Beijnen, J H

2006-01-01

A possible explanation for the wide interindividual variability in toxicity and efficacy of drug therapy is variation in genes encoding drug-metabolizing enzymes and drug transporters. The allelic frequency of these genetic variants, linkage disequilibrium (LD), and haplotype of these polymorphisms are important parameters in determining the genetic differences between patients. The aim of this study was to explore the frequencies of polymorphisms in drug-metabolizing enzymes (CYP1A1, CYP2C9, CYP2C19, CYP3A4, CYP2D6, CYP3A5, DPYD, UGT1A1, GSTM1, GSTP1, GSTT1) and drug transporters (ABCB1[MDR1] and ABCC2[MRP2]), and to investigate the LD and perform haplotype analysis of these polymorphisms in a Dutch population. Blood samples were obtained from 100 healthy volunteers and genomic DNA was isolated and amplified by PCR. The amplification products were sequenced and analyzed for the presence of polymorphisms by sequence alignment. In the study population, we identified 13 new single nucleotide polymorphisms (SNPs) in Caucasians and three new SNPs in non-Caucasians, in addition to previously recognized SNPs. Three of the new SNPs were found within exons, of which two resulted in amino acid changes (A428T in CYP2C9 resulting in the amino acid substitution D143V; and C4461T in ABCC2 in a non-Caucasian producing the amino acid change T1476M). Several LDs and haplotypes were found in the Caucasian individuals. In this Dutch population, the frequencies of 16 new SNPs and those of previously recognized SNPs were determined in genes coding for drug-metabolizing enzymes and drug transporters. Several LDs and haplotypes were also inferred. These data are important for further research to help explain the interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy.

Restricted dog leucocyte antigen (DLA) class II haplotypes and genotypes in Beagles.

PubMed

Soutter, Francesca; Kennedy, Lorna J; Ollier, William E R; Solano-Gallego, Laia; Catchpole, Brian

2015-03-01

Beagles are commonly used in vaccine trials as part of the regulatory approval process. Genetic restriction within this breed and the impact this might have on vaccine responses are rarely considered. This study was designed to characterise diversity of dog leucocyte antigen (DLA) class II genes in a breeding colony of laboratory Beagles, whose offspring are used in vaccine studies. DLA haplotypes were determined by PCR and sequence-based typing from genomic DNA extracted from blood. Breeding colony Beagles had significantly different DLA haplotype frequencies in comparison with pet Beagles and both groups showed limited DLA diversity. Restricted DLA class II genetic variability within Beagles might result in selective antigen presentation and vaccine responses that are not necessarily representative of those seen in other dog breeds. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Determination of βS haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

PubMed Central

Cabral, Cynthia Hatsue Kitayama; Serafim, Édvis Santos Soares; de Medeiros, Waleska Rayane Dantas Bezerra; de Medeiros Fernandes, Thales Allyrio Araújo; Kimura, Elza Miyuki; Costa, Fernando Ferreira; de Fátima Sonati, Maria; Rebecchi, Ivanise Marina Moretti; de Medeiros, Tereza Maria Dantas

2011-01-01

βS haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5%) were identified with genotype CAR/CAR, 9 (19.1%) CAR/BEN, 6 (12.8%) CAR/CAM, 1 (2.1%) BEN/BEN, 2 (4.3%) CAR/Atp, 1 (2.1%) BEN/Atp and 1 (2.1%) with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte. PMID:21931513

Characterization of casein gene complex and genetic diversity analysis in Indian goats.

PubMed

Rout, P K; Kumar, A; Mandal, A; Laloe, D; Singh, S K; Roy, R

2010-04-01

Milk protein polymorphism plays an important role in genetic diversity analysis, phylogenetic studies, establishing geographical diversity, conservation decision, and improving breeding goals. Milk protein polymorphism in Indian goat breeds has not been well studied; therefore, an investigation was carried out to analyze the genetic structure of the casein gene and milk protein diversity at six milk protein loci in nine Indian goat breeds/genetic groups from varied agro-climatic zones. Milk protein genotyping was carried out in 1098 individual milk samples by SDS-PAGE at alphaS1-CN (CSN1S1), beta-CN (CSN2), alphaS2-CN (CSN1S2), kappa-CN (CSN3), beta-LG, and alpha-LA loci. Indian goats exhibited alphaS1-casein A allele in higher frequency in the majority of breeds except Ganjam and local goats. The alphaS1-casein A allele frequencies varied from 0.45 to 0.77. A total of 16 casein haplotypes were observed in seven breeds and breed specific haplotypes were observed with respect to geographic region. The average number of alleles was lowest in Ganjam (1.66 +/- 0.81) and highest in Sirohi goats (2.50 +/- 1.05). Expected heterozygosity at six different loci demonstrated genetic diversity and breed fragmentation. Neighbor-Joining tree was built basing on Nei's distance. There was about 16.95% variability due to differences between breeds, indicating a strong subdivision. Principal component analysis was carried out to highlight the relationship among breeds. The variability among goat breeds was contributed by alphaS2-CN, beta-LG and alphaS1-CN. The Indian goats exhibited alphaS1-CN (CSN1S1) A allele in higher frequency in all the breeds indicating the higher casein yield in their milk.

Association of HLA-DRB1 alleles and neuropsychological function in autism.

PubMed

Chien, Yi-Ling; Wu, Yu-Yu; Chen, Chia-Hsiang; Gau, Susan Shur-Fen; Huang, Yu-Shu; Chien, Wei-Hsien; Hu, Fu-Chang; Chao, Yu-Lin

2012-02-01

Evidence suggests an association between autism and immune dysfunction. The associations between human lymphocyte antigen (HLA)-A2, B44, DRβ1*04 (DR4), C4B, and haplotype B44-SC30-DR4 and autism have been reported in western countries but there is a lack of such information in Asian population. This study aimed to assess the association between HLA-DRB1 allele frequencies and the clinical phenomenology of autism. The sample included 141 participants (male, 87.2%), who were diagnosed with autistic disorder based on clinical assessments and structured interviews using the Chinese version of the Autism Diagnostic Interview-Revised, and 156 healthy controls (male, 38.6%). The HLA-DRB1 alleles were determined by sequencing-based typing method. A subsample of patients (n=39) were assessed for intelligence and neuropsychological functions. The results showed that the pattern of DRB1 allele frequencies was significantly different between patients with autism and the controls (P=0.047). After adjusting for sex by haplotype regression, the frequencies of DR4, DR11, and DR14 were significantly different between patients with autism and healthy controls. In addition, patients with autism and DR4, DR11, or DR14 had different performance on intelligence and neuropsychology tests. Despite a relatively small sample size and a case-control association design, the findings suggest HLA-DRB1 gene might be associated with autism in Han Chinese. The true functional variants associated with autism in our samples remain to be further clarified. It warrants a replication study of a larger family sample and to validate the HLA genetic association with autism and its influence on neuropsychological function.

Genetic Analysis of Snake River Sockeye Salmon (Oncorhynchus Nerka), 2003 Technical Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faler, Joyce; Powell, Madison

2003-12-01

A total of 1720 Oncorhynchus nerka tissue samples from 40 populations were characterized using mitochondrial DNA RFLPs (Restriction Fragment Length Polymorphisms). Analysis of anadromous sockeye populations indicated the historical presence of four major maternal lineages. Thirty-five composite mitochondrial haplotypes were observed from the 40 populations of O. nerka sampled throughout the Pacific Northwest. Six of these composite haplotypes ranged in frequency from 7-26% overall and were commonly observed in most populations. The six haplotypes together comprised 90% of the sampled O. nerka. An average of 4.6 composite haplotypes were observed per population. Genetic markers used were satisfactory in separating Redfishmore » Lake anadromous sockeye, residual sockeye and outmigrants from the sympatric kokanee population that spawns in the Fishhook Creek tributary. Outmigrants appear to be primarily composed of progeny from resident residual sockeye, and captively-reared progeny of the captive broodstock program. Thus, residual sockeye may be considered a suitable source of genetic variation to maintain genetic diversity among captive broodstocks of anadromous sockeye. Fishhook Creek kokanee are genetically diverse and during spawning, are temporally and spatially isolated from the residual sockeye population. Eleven composite haplotypes were observed in the kokanee population. The unusually high number of haplotypes is most likely a consequence of periodic stocking of Redfish Lake with kokanee from other sources. Genetic data from Redfish Lake creel samples taken during 1996-1999 putatively indicate the incidental take of a listed resident sockeye.« less

Cyclooxygenase 2 gene polymorphisms and chronic periodontitis in a North Indian population: a pilot study

PubMed Central

Daing, Anika; Singh, Sarvendra Vikram; Saimbi, Charanjeet Singh; Khan, Mohammad Akhlaq

2012-01-01

Purpose Cyclooxygenase (COX) enzyme catalyzes the production of prostaglandins, which are important mediators of tissue destruction in periodontitis. Single nucleotide polymorphisms of COX2 enzyme have been associated with increasing susceptibility to inflammatory diseases. The present study evaluates the association of two single nucleotide polymorphisms in COX2 gene (-1195G>A and 8473C>T) with chronic periodontitis in North Indians. Methods Both SNPs and their haplotypes were used to explore the associations between COX2 polymorphisms and chronic periodontitis in 56 patients and 60 controls. Genotyping was done by polymerase chain reaction followed by restriction fragment length polymorphism. Chi-square test and logistic regression analysis were performed for association analysis. Results By the individual genotype analysis, mutant genotypes (GA and AA) of COX2 -1195 showed more than a two fold risk (odds ratio [OR]>2) and COX2 8473 (TC and CC) showed a reduced risk for the disease, but the findings were not statistically significant. Haplotype analysis showed that the frequency of the haplotype AT was higher in the case group and a significant association was found for haplotype AT (OR, 1.79; 95% confidence interval, 1.03 to 3.11; P=0.0370) indicating an association between the AT haplotype of COX2 gene SNPs and chronic periodontitis. Conclusions Individual genotypes of both the SNPs were not associated while haplotype AT was found to be associated with chronic periodontitis in North Indians. PMID:23185695

µ-Calpain (CAPN1), calpastatin (CAST), and growth hormone receptor (GHR) genetic effects on Angus beef heifer performance traits and reproduction

USDA-ARS?s Scientific Manuscript database

Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to equalize CAPN1 haplotypes, CAST, and GHR genetic marker frequencies. The objective was t...

Vitamin D receptor gene polymorphisms and risk of polycystic ovary syndrome in South Indian women.

PubMed

Siddamalla, Swapna; Reddy, Tumu Venkat; Govatati, Suresh; Erram, Nagendram; Deenadayal, Mamata; Shivaji, Sisinthy; Bhanoori, Manjula

2018-02-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive age women. Emerging evidence suggests that Vitamin D Receptor (VDR) might be a causal factor for characteristics associated with PCOS such as obesity and type 2 diabetes. Present study investigated association between VDR gene BsmI A/G (rs1544410), ApaI A/C (rs7975232) and TaqI T/C (rs731236) single nucleotide polymorphisms and PCOS risk in South Indian women. Genotyping of VDR gene SNPs was carried out in PCOS patients (n = 95) and controls (n = 130) by PCR-RFLP method and confirmed by sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were assessed by Haploview software. Results showed significantly increased frequencies of BsmI G/G (p = .0197), ApaI C/C (p = .048), TaqI C/C (p = .044) genotypes and BsmI G (p = .0181), ApaI C (p = .0092), TaqI C (p = .0066) alleles in patients compared to controls. In addition, the frequency of the 'BsmI G, ApaI C, TaqI C' haplotype was also significantly elevated in patients (p = .0087). In conclusion, the VDR gene BsmI A/G ApaI A/C TaqI T/C and haplotype may constitute an inheritable risk factor for PCOS in South Indian women.

Association of swine leukocyte antigen class II haplotypes and immune-related traits in a swine line selected for resistance to mycoplasmal pneumonia.

PubMed

Ando, Asako; Shigenari, Atsuko; Kojima-Shibata, Chihiro; Nakajoh, Mitsuru; Suzuki, Keiichi; Kitagawa, Hitoshi; Shiina, Takashi; Inoko, Hidetoshi; Uenishi, Hirohide

2016-10-01

By selective breeding for five generations, a Landrace line has been recently established to improve resistance to mycoplasmal pneumonia of swine (MPS), daily gain (DG), back fat thickness (BF), and plasma cortisol concentrations (COR). To clarify the involvement of swine leukocyte antigen (SLA) polymorphisms in the selection process, we investigated possible associations of 11 SLA-class II haplotypes with selected traits or immune parameters. Pigs with the low-resolution SLA haplotype Lr-0.23 or Lr-0.13, which increased in frequency with the passage of generations, had less severe pathological lesions of MPS, increased leukocyte phagocytic activity, and higher white blood cell counts. In contrast, Lr-0.12 and Lr-0.2, which decreased in subsequent generations, were weakly associated with more severe pathological lesions of MPS. Therefore, in the studied Landrace line, the Lr-0.23 and Lr-0.13 haplotypes are potentially useful genetic markers for selecting and breeding animals with less severe pathological lesions of MPS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methylenetetrahydrofolate reductase gene haplotypes affect toxicity during maintenance therapy for childhood acute lymphoblastic leukemia in Japanese patients.

PubMed

Tanaka, Yoichi; Manabe, Atsushi; Nakadate, Hisaya; Kondoh, Kensuke; Nakamura, Kozue; Koh, Katsuyoshi; Kikuchi, Akira; Komiyama, Takako

2014-05-01

Abstract The aim of this study was to investigate the influence of daily 6-mercaptopurine (6-MP) and low-dose weekly methotrexate (MTX) combination treatment and methylenetetrahydrofolate reductase (MTHFR) haplotypes on toxicity during maintenance therapy in Japanese childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed the MTHFR C677T and A1298C polymorphisms and influence of haplotypes on toxicity in 73 patients. Patients with the MTHFR 677TT and 677CT + 1298AC were associated with severe liver toxicity (p = 0.014, odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.27-11.46) and more rapid onset of liver toxicity (p = 0.010). Patients with MTHFR 677TT and 677CT + 1298AC were associated with lower frequency of 6-MP and MTX dose reduction due to leukopenia (p < 0.05). No difference was observed in average drug doses in the MTHFR genotypes. In conclusion, the MTHFR C677T and A1298C haplotypes might be useful for monitoring adverse effects in childhood ALL maintenance therapy in Japanese patients.

Population genetic structure of critically endangered salamander (Hynobius amjiensis) in China: recommendations for conservation.

PubMed

Yang, J; Chen, C S; Chen, S H; Ding, P; Fan, Z Y; Lu, Y W; Yu, L P; Lin, H D

2016-06-10

Amji's salamander (Hynobius amjiensis) is a critically endangered species (IUCN Red List), which is endemic to mainland China. In the present study, five haplotypes were genotyped for the mtDNA cyt b gene in 45 specimens from three populations. Relatively low levels of haplotype diversity (h = 0.524) and nucleotide diversity (π = 0.00532) were detected. Analyses of the phylogenic structure of H. amjiensis showed no evidence of major geographic partitions or substantial barriers to historical gene flow throughout the species' range. Two major phylogenetic haplotype groups were revealed, and were estimated to have diverged about 1.262 million years ago. Mismatch distribution analysis, neutrality tests, and Bayesian skyline plots revealed no evidence of dramatic changes in the effective population size. According to the SAMOVA and STRUCTURE analyses, H. amjiensis should be regarded as two different management units.

Population genetic structure and conservation of marbled murrelets (Brachyramphus marmoratus)

USGS Publications Warehouse

Friesen, Vicki L.; Birt, T.P.; Piatt, John F.; Golightly, R.T.; Newman, S.H.; Hebert, P.N.; Congdon, B.C.; Gissing, G.

2005-01-01

Marbled murrelets (Brachyramphus marmoratus) are coastal seabirds that nest from California to the Aleutian Islands. They are declining and considered threatened in several regions. We compared variation in the mitochondrial control region, four nuclear introns and three microsatellite loci among 194 murrelets from throughout their range except Washington and Oregon. Significant population genetic structure was found: nine private control region haplotypes and three private intron alleles occurred at high frequency in the Aleutians and California; global estimates of FST or ??ST and most pairwise estimates involving the Aleutians and/or California were significant; and marked isolation-by-distance was found. Given the available samples, murrelets appear to comprise five genetic management units: (1) western Aleutian Islands, (2) central Aleutian Islands, (3) mainland Alaska and British Columbia, (4) northern California, and (5) central California.

Dynamics of Malaria Drug Resistance Patterns in the Amazon Basin Region following Changes in Peruvian National Treatment Policy for Uncomplicated Malaria▿ †

PubMed Central

Bacon, David J.; McCollum, Andrea M.; Griffing, Sean M.; Salas, Carola; Soberon, Valeria; Santolalla, Meddly; Haley, Ryan; Tsukayama, Pablo; Lucas, Carmen; Escalante, Ananias A.; Udhayakumar, Venkatachalam

2009-01-01

Monitoring changes in the frequencies of drug-resistant and -sensitive genotypes can facilitate in vivo clinical trials to assess the efficacy of drugs before complete failure occurs. Peru changed its national treatment policy for uncomplicated malaria to artesunate (ART)-plus-mefloquine (MQ) combination therapy in the Amazon basin in 2001. We genotyped isolates collected in 1999 and isolates collected in 2006 to 2007 for mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, multidrug resistance gene 1 (Pfmdr-1), the chloroquine (CQ) resistance transporter gene (Pfcrt), and the Ca2+ ATPase gene (PfATP6); these have been shown to be involved in resistance to sulfadoxine-pyrimethamine (SP), MQ, CQ, and possibly ART, respectively. Microsatellite haplotypes around the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr-1 loci were also determined. There was a significant decline in the highly SP resistant Pfdhfr and Pfdhps genotypes from 1999 to 2006. In contrast, a CQ-resistant Pfcrt genotype increased in frequency during the same period. Among five different Pfmdr-1 allelic forms noted in 1999, two genotypes increased in frequency while one genotype decreased by 2006. We also noted previously undescribed polymorphisms in the PfATP6 gene as well as an increase in the frequency of a deletion mutant during this period. In addition, microsatellite analysis revealed that the resistant Pfdhfr, Pfdhps, and Pfcrt genotypes have each evolved from a single founder haplotype, while Pfmdr-1 genotypes have evolved from at least two independent haplotypes. Importantly, this study demonstrates that the Peruvian triple mutant Pfdhps genotypes are very similar to those found in other parts of South America. PMID:19258269

Variants of transcription factor 7-like 2 (TCF7L2) gene and incident glucose intolerance in Japanese-Brazilians.

PubMed

Franco, L F; Crispim, F; Pereira, A C; Moisés, R S

2011-03-01

Common variants of the transcription factor 7-like 2 (TCF7L2) gene have been found to be associated with type 2 diabetes in different ethnic groups. The Japanese-Brazilian population has one of the highest prevalence rates of diabetes. Therefore, the aim of the present study was to assess whether two single-nucleotide polymorphisms (SNPs) of TCF7L2, rs7903146 and rs12255372, could predict the development of glucose intolerance in Japanese-Brazilians. In a population-based 7-year prospective study, we genotyped 222 individuals (72 males and 150 females, aged 56.2 ± 10.5 years) with normal glucose tolerance at baseline. In the study population, we found that the minor allele frequency was 0.05 for SNP rs7903146 and 0.03 for SNP rs12255372. No significant allele or genotype association with glucose intolerance incidence was found for either SNP. Haplotypes were constructed with these two SNPs and three haplotypes were defined: CG (frequency: 0.94), TT (frequency = 0.027) and TG (frequency = 0.026). None of the haplotypes provided evidence for association with the incidence of glucose intolerance. Despite no associations between incidence of glucose intolerance and SNPs of the TCF7L2 gene in Japanese-Brazilians, we found that carriers of the CT genotype for rs7903146 had significantly lower insulin levels 2 h after a 75-g glucose load than carriers of the CC genotype. In conclusion, in Japanese-Brazilians, a population with a high prevalence of type 2 diabetes, common TCF7L2 variants did not make major contributions to the incidence of glucose tolerance abnormalities.

Associations of ICOS and PD.1 Gene Variants with Colon Cancer Risk in The Iranian Population

PubMed

Shamsdin, Seyedeh Azra; Karimi, Mohammad Hossein; Hosseini, Seyed Vahid; Geramizadeh, Bita; Fattahi, Mohamad Reza; Mehrabani, Davood; Moravej, Ali

2018-03-27

Background: Positive and negative co-stimulatory molecules are important factors determining the outcome of immune responses to the presence of tumors. Since co-stimulatory molecule expression may be affected by gene polymorphisms, we aimed to investigate associations between variants of PD.1 and ICOS and susceptibility to colon cancer. Material and methods: ICOS (-693A/G), ICOS (+1720C/T) and PD.1 (-538G/A) gene polymorphisms were evaluated by the PCR-RFLP method in 76 colon cancer patients and 73 healthy controls. Results: The frequencies of the GG genotype and the G allele at position -693 of the ICOS gene were significantly higher in the patient group (P=0.014 and p=0.0002), while the AA genotype was significantly more common in controls (P=0.0016). At position -538 of PD.1, GG genotype and G allele frequencies were higher in the patient group (P<0.0001and P<0.0001). Again, AA and also AG genotypes significantly predominated in controls (P<0.0001 and P=0.012). Regarding genotypes and alleles of ICOS at position +1720. Frequencies of GCG and GTG haplotypes were higher in patients compared to those of controls (P=0.016 and P<0.0001), while, frequencies of GTA, ATA and ATG haplotypes were higher in controls (P=0.0017, P<0.0001 and P=0.015). GTG/GTG and GTG/GCG double haplotypes were more frequent in patients compared to controls (P=0.0147 and P=0.0071). Conclusion: Our study clarified that PD.1 (-538G/A) and ICOS (-693A/G) gene polymorphisms can be considered as genetic risk factors for the development of colon cancer among Iranian patients. Creative Commons Attribution License

HLA Class I and Genetic Susceptibility to Type 1 Diabetes

PubMed Central

Noble, Janelle A.; Valdes, Ana Maria; Varney, Michael D.; Carlson, Joyce A.; Moonsamy, Priscilla; Fear, Anna Lisa; Lane, Julie A.; Lavant, Eva; Rappner, Rebecca; Louey, Anthony; Concannon, Patrick; Mychaleckyj, Josyf C.; Erlich, Henry A.

2010-01-01

OBJECTIVE We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients. RESULTS Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes–associated alleles were B*5701 (odds ratio 0.19; P = 4 × 10−11) and B*3906 (10.31; P = 4 × 10−10). Other significantly type 1 diabetes–associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class II. Other class I type 1 diabetes associations appear to be specific to individual class II haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403). CONCLUSIONS These data indicate that HLA class I alleles, in addition to and independently from HLA class II alleles, are associated with type 1 diabetes. PMID:20798335

Genetic Population Structure of Dastarcus helophoroides (Coleoptera: Bothrideridae) From Different Long-Horned Beetle Hosts Based on Complete Sequences of Mitochondrial COI.

PubMed

Zhang, Zhengqing; Chang, Yong; Li, Menglou

2017-06-01

Dastarcus helophoroides (Fairmaire) (Coleoptera: Bothrideridae) is an important natural enemy of long-horned beetles in China, Japan, and Korea. In this study, the genetic sequence of cytochrome oxidase subunit Ι was used to investigate the genetics and relationships within and among D. helophoroides populations collected from five different geographic locations. We used principal component analysis, heatmap, and Venn diagram results to determine the relationship between haplotypes and populations. In total, 26 haplotypes with 51 nucleotide polymorphic sites were defined, and low genetic diversity was found among the different populations. Significant genetic variations were observed mainly within populations, and no correlation was found between genetic distribution and geographical distance. Low pairwise fixation index values (-0.01424 to 0.04896) and high gene flows show that there was high gene exchange between populations. The codistributed haplotype DH01 was suggested to be the most ancestral haplotype, and other haplotypes were thought to have evolved from it through several mutations. In four of the populations, both common haplotypes (DH01, DH03, and DH22) and unique haplotypes were found. Low genetic diversity among different populations is related to a relatively high flight capacity, host movement, and human-aided dispersal of D. helophoroides. The high gene exchange and typically weak population genetic structure among five populations, especially among populations of Anoplophora glabripennis (Motschulsky), Monochamus alternatus (Hope), and Massicus raddei (Blessig), may suggest that these populations cross naturally in the field. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lower frequency of the HLA-G UTR-4 haplotype in women with unexplained recurrent miscarriage.

PubMed

Meuleman, T; Drabbels, J; van Lith, J M M; Dekkers, O M; Rozemuller, E; Cretu-Stancu, M; Claas, F H J; Bloemenkamp, K W M; Eikmans, M

2018-04-01

HLA-G expressed by trophoblasts at the fetal-maternal interface and its soluble form have immunomodulatory effects. HLA-G expression depends on the combination of DNA polymorphisms. We hypothesized that combinations of specific single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of HLA-G play a role in unexplained recurrent miscarriage. In a case control design, 100 cases with at least three unexplained consecutive miscarriages prior to the 20th week of gestation were included. Cases were at time of the third miscarriage younger than 36 years, and they conceived all their pregnancies from the same partner. The control group included 89 women with an uneventful pregnancy. The association of HLA-G 3'UTR SNPs and specific HLA-G haplotype with recurrent miscarriage was studied with logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) were reported. Individual SNPs were not significantly associated with recurrent miscarriage after correction for multiple comparisons. However, the presence of the UTR-4 haplotype, which included +3003C, was significantly lower in women with recurrent miscarriage (OR 0.4, 95% CI 0.2-0.8, p = 0.015). In conclusion, this is the first study to perform a comprehensive analysis of HLA-G SNPs and HLA-G haplotypes in a well-defined group of women with recurrent miscarriage and women with uneventful pregnancy. The UTR-4 haplotype was less frequently observed in women with recurrent miscarriage, suggesting an immunoregulatory role of this haplotype for continuation of the pregnancy without complications. Thus, association of HLA-G with recurrent miscarriage is not related to single polymorphisms in the 3'UTR, but is rather dependent on haplotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

Phylogeographic study of Chinese seabuckthorn (Hippophae rhamnoides subsp. sinensis Rousi) reveals two distinct haplotype groups and multiple microrefugia on the Qinghai-Tibet Plateau

PubMed Central

Wang, Hongfang; Liu, Han; Yang, Mingbo; Bao, Lei; Ge, Jianping

2014-01-01

Historical climate change can shape the genetic pattern of a species. Studies on this phenomenon provide great advantage in predicting the response of species to current and future global climate change. Chinese seabuckthorn (Hippophae rhamnoides subsp. sinensis) is one of the most important cultivated plants in Northwest China. However, the subspecies history and the potential genetic resources within the subspecies range remain unclear. In this study, we utilized two intergenic chloroplast regions to characterize the spatial genetic distribution of the species. We found 19 haplotypes in total, 12 of which were unique to the Chinese seabuckthorn. The populations observed on the Qinghai-Tibet Plateau (QTP) consisted of most of the haplotypes, while in the northeast of the range of the subspecies, an area not on the QTP, only four haplotypes were detected. Our study also revealed two distinct haplotype groups of the subspecies with a sharp transition region located in the south of the Zoige Basin. 89.96% of the genetic variation located between the regions. Mismatch analysis indicated old expansions of these two haplotype groups, approximately around the early stage of Pleistocene. Additional morphological proofs from existing studies and habitat differentiation supported a long independent colonization history among the two regions. Potential adaptation probably occurred but needs more genome and morphology data in future. Chinese seabuckthorn have an older population expansion compared with subspecies in Europe. The lack of large land ice sheets and the heterogeneous landscape of the QTP could have provided extensive microrefugia for Chinese seabuckthorn during the glaciation period. Multiple localities sustaining high-frequency private haplotypes support this hypothesis. Our study gives clear insight into the distribution of genetic resources and the evolutionary history of Chinese seabuckthorn. PMID:25540697

[Association between the methylenetetrahydrofolate reductase gene polymorphisms and haplotype with toxicity response of high dose methotrexate chemotherapy].

PubMed

Liao, Qing-Chuan; Li, Xiao-Lei; Liu, Si-Ting; Zhang, Yong; Li, Tian-Yuan; Qiu, Jin-Chun

2012-07-01

To investigate the association between single nucleotide polymorphisms (SNP) and its haplotypes of methylenetetrahydrofolate reductase (MTHFR) gene with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL). HDMTX-treated children with ALL (1.2 to 14-years old) were selected from inpatient and followed for a retrospective study. The toxicity response of HDMTX chemotherapy was evaluated using WHO common toxicity criteria. Sixty-one patients with therapy-related toxicity and 36 patients without therapy-related toxicity were genotyped for 2 SNP (677C > T and 1298A > C) of the MTHFR gene by polymerase chain reaction-restriction fragment length polymorphism. Frequency of haplotypes and linkage disequilibrium of MTHFR gene were analyzed by SHEsis program. The distribution of MTHFR gene 677C > T polymorphism did not appeare different between groups with or without toxicity response (χ(2) = 4.609, P = 0.100), but the 1298A > C polymorphism was significantly different (χ(2) = 10.192, P = 0.006). Individuals who carried C allele (AC + CC genotype) had a decreased risk of toxicity response compared to AA genotype (OR = 0.245, 95%CI: 0.099 - 0.607, P = 0.002). 677C > T and 1298A > C polymorphisms showed strong linkage disequilibrium (D' = 0.895). The CC haplotype was significantly associated with decreased risk of toxicity response (OR = 0.338, 95%CI: 0.155 - 0.738, P = 0.005), while the TA haplotype was significantly associated with the increased risk of toxicity response (OR = 1.907, 95%CI: 1.045 - 3.482, P = 0.035). MTHFR gene 1298C allele and CC haplotype might serve as protective factors while TA haplotype as a risk factor for the susceptibility to toxicity response of HDMTX chemotherapy in children with ALL.

Global selection on sucrose synthase haplotypes during a century of wheat breeding.

PubMed

Hou, Jian; Jiang, Qiyan; Hao, Chenyang; Wang, Yuquan; Zhang, Hongna; Zhang, Xueyong

2014-04-01

Spike number per unit area, number of grains per spike, and thousand kernel weight (TKW) are important yield components. In China, increases in wheat (Triticum aestivum) yields are mainly due to increases in grain number per spike and TKW. TKW mainly depends on starch content, as starch accounts for about 70% of the grain endosperm. Sucrose synthase catalysis is the first step in the conversion of sucrose to starch, that is, the conversion of sucrose to fructose and UDP-glucose by the wheat sucrose synthase genes (TaSus1 and TaSus2) that are located on chromosomes 7A/7B/7D and 2A/2B/2D, respectively. A total of 1,520 wheat accessions were genotyped at the six loci. Two, two, five, and two haplotypes were identified at the TaSus2-2A, TaSus2-2B, TaSus1-7A, and TaSus1-7B loci, respectively. Their main variations were detected within the introns. Significant differences between the haplotypes correlated with TKW differences among 348 modern Chinese cultivars from the core collection. Frequency changes for favored haplotypes showed gradual increases in cultivars released since beginning of the last century in China, Europe, and North America. Geographic distributions and time changes of favored haplotypes were characterized in six major wheat production regions worldwide. Strong selection bottlenecks to haplotype variations occurred at polyploidization and domestication and during breeding of wheat. Genetic-effect differences between haplotypes at the same locus influence the selection time and intensity. This work shows that the endosperm starch synthesis pathway is a major target of indirect selection in global wheat breeding for higher yield.

Detecting disease-predisposing variants: the haplotype method.

PubMed Central

Valdes, A M; Thomson, G

1997-01-01

For many HLA-associated diseases, multiple alleles-- and, in some cases, multiple loci--have been suggested as the causative agents. The haplotype method for identifying disease-predisposing amino acids in a genetic region is a stratification analysis. We show that, for each haplotype combination containing all the amino acid sites involved in the disease process, the relative frequencies of amino acid variants at sites not involved in disease but in linkage disequilibrium with the disease-predisposing sites are expected to be the same in patients and controls. The haplotype method is robust to mode of inheritance and penetrance of the disease and can be used to determine unequivocally whether all amino acid sites involved in the disease have not been identified. Using a resampling technique, we developed a statistical test that takes account of the nonindependence of the sites sampled. Further, when multiple sites in the genetic region are involved in disease, the test statistic gives a closer fit to the null expectation when some--compared with none--of the true predisposing factors are included in the haplotype analysis. Although the haplotype method cannot distinguish between very highly correlated sites in one population, ethnic comparisons may help identify the true predisposing factors. The haplotype method was applied to insulin-dependent diabetes mellitus (IDDM) HLA class II DQA1-DQB1 data from Caucasian, African, and Japanese populations. Our results indicate that the combination DQA1#52 (Arg predisposing) DQB1#57 (Asp protective), which has been proposed as an important IDDM agent, does not include all the predisposing elements. With rheumatoid arthritis HLA class II DRB1 data, the results were consistent with the shared-epitope hypothesis. PMID:9042931

Toll-like receptor 4 polymorphisms and their haplotypes modulate the risk of developing diabetic retinopathy in type 2 diabetes patients

PubMed Central

Singh, Kanhaiya; Kant, Shri; Singh, Vivek Kumar; Agrawal, Neeraj K.; Gupta, Sanjeev K.

2014-01-01

Purpose Persistent inflammation and impaired neovascularization in type 2 diabetes mellitus (T2DM) patients may lead to development of macro- and microvascular complications. Diabetic retinopathy (DR) is one of the secondary microvascular complications of T2DM. Improper activation of the innate immune system may be an important contributor in the pathophysiology of DR. Toll-like receptor 4 (TLR4) is an important mediator of innate immunity, and genetic alterations in TLR4 support inflammation in the hyperglycemic condition. The present work was designed to investigate whether the TLR4 single nucleotide polymorphisms (SNPs) rs4986790, rs4986791, rs10759931, rs1927911, and rs1927914 are associated with DR in a north Indian population. Methods The study group of 698 individuals (128 DR, 250 T2DM, 320 controls) was genotyped by PCR-RFLP. Haplotype and linkage disequilibrium between SNPs were determined using Haploview software. Results Combined risk genotypes of TLR4 SNPs rs10759931 (odds ratio [OR] 1.50, p = 0.05) and rs1927914 (OR 1.48, p = 0.05) were found to be significantly associated with pathogenesis of DR. A total of 14 haplotypes with frequency >1% were obtained using Haploview software. Haplotypes ACATC (37.5%) and ACATT (14.8%) were the two most common haplotypes obtained. Conclusions Results of the present case-control study that included 698 north Indian subjects suggested that TLR4 SNPs rs10759931 and rs1927914 modulate the risk of DR in T2DM cases. Association analysis using haplotypes showed none of the haplotypes were associated with either susceptibility or resistance to DR in a north Indian population. PMID:24883015

[Association between aryl hydrocarbon receptor gene polymorphisms and chromosomal damage in coke-oven workers].

PubMed

Bin, Ping; Leng, Shuguang; Liang, Xuemiao; Cheng, Juan

2007-11-01

To investigate the association of single nucleotide polymorphisms (SNPs) or haplotypes of aryl hydrocarbon receptor (AHR) gene and chromosomal damage in peripheral blood lymphocytes among coke-oven workers. Eighty-nine coke-oven workers exposed to a high level of polycyclic aromatic hydrocarbons (PAHs) and sixty non-exposed workers were selected as the study subjects. Urinary 1-hydroxypyrene (1-OHPyr) levels were measured as the internal dose of PAHs exposure. The chromosomal damage in peripheral lymphocyte was measured by the cytokinesis-block micronucleus (CBMN) assay. Two SNPs in AHR gene, including rs6960165, rs2282885 were detected by PCR-RFLP. The AHR haplotypes were estimated by Bayesian statistical method with the software of PHASE Version 2.1. The associations between SNPs or haplotypes pairs and CBMN were assessed by analysis of covariance in the coke-oven workers and non-exposed workers. The level of 1-OHPyr among coke-oven workers was significantly higher than that among non-exposed workers (P < 0.01). The CBMN among coke-oven workers was significantly higher than that among non-exposed workers (P < 0.01). After adjusting the age and the level of 1-OHPyr, the different SNPs of AHR gene rs6960165 in coke-oven workers were related to the CBMN frequencies (P = 0.014), but no association between the different SNPs of AHR gene rs2282885 and the rates of CBMN was observed in coke-oven workers (P = 0.586), either in the controls (P = 0.308 and P = 0.415, respectively), the haplotypes in coke-oven workers were significantly related to the rates of CBMN (P = 0.007), while there was no significant association in non-exposed workers (P = 0.768). Our results suggested that SNPs rs6960165 or haplotypes of AHR were associated with the CBMN frequencies in coke-oven workers.

Recent selective sweeps in North American Drosophila melanogaster show signatures of soft sweeps.

PubMed

Garud, Nandita R; Messer, Philipp W; Buzbas, Erkan O; Petrov, Dmitri A

2015-02-01

Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps. In contrast to a hard selective sweep, in which a single adaptive haplotype rises to high population frequency, in a soft selective sweep multiple adaptive haplotypes sweep through the population simultaneously, producing distinct patterns of genetic variation in the vicinity of the adaptive site. Current statistical methods were expressly designed to detect hard sweeps and most lack power to detect soft sweeps. This is particularly unfortunate for the study of adaptation in species such as Drosophila melanogaster, where all three confirmed cases of recent adaptation resulted in soft selective sweeps and where there is evidence that the effective population size relevant for recent and strong adaptation is large enough to generate soft sweeps even when adaptation requires mutation at a specific single site at a locus. Here, we develop a statistical test based on a measure of haplotype homozygosity (H12) that is capable of detecting both hard and soft sweeps with similar power. We use H12 to identify multiple genomic regions that have undergone recent and strong adaptation in a large population sample of fully sequenced Drosophila melanogaster strains from the Drosophila Genetic Reference Panel (DGRP). Visual inspection of the top 50 candidates reveals that in all cases multiple haplotypes are present at high frequencies, consistent with signatures of soft sweeps. We further develop a second haplotype homozygosity statistic (H2/H1) that, in combination with H12, is capable of differentiating hard from soft sweeps. Surprisingly, we find that the H12 and H2/H1 values for all top 50 peaks are much more easily generated by soft rather than hard sweeps. We discuss the implications of these results for the study of adaptation in Drosophila and in species with large census population sizes.

Forensic data and microvariant sequence characterization of 27 Y-STR loci analyzed in four Eastern African countries.

PubMed

Iacovacci, Giuseppe; D'Atanasio, Eugenia; Marini, Ornella; Coppa, Alfredo; Sellitto, Daniele; Trombetta, Beniamino; Berti, Andrea; Cruciani, Fulvio

2017-03-01

By using the recently introduced 6-dye Yfiler ® Plus multiplex, we analyzed 462 males belonging to 20 ethnic groups from four eastern African countries (Eritrea, Ethiopia, Djibouti and Kenya). Through a Y-STR sequence analysis, combined with 62 SNP-based haplogroup information, we were able to classify observed microvariant alleles at four Y-STR loci as either monophyletic (DYF387S1 and DYS458) or recurrent (DYS449 and DYS627). We found evidence of non-allelic gene conversion among paralogous STRs of the two-copy locus DYF387S1. Twenty-two diallelic and triallelic patterns observed at 13 different loci were found to be significantly over-represented (p<10 -6 ) among profiles obtained from cell lines compared to those from blood and saliva. Most of the diallelic/triallelic patterns from cell lines involved recurrent mutations at rapidly mutating loci (RM Y-STRs) included in the multiplex (p<10 -2 ). At haplotype level, intra-population diversity indices were found to be among the lowest so far reported for the Yfiler ® Plus, while statistically significant differences among countries and ethnic groups were detected when considering haplotype frequencies alone (F ST ) or by using molecular distances among haplotypes (Φ ST ). The strong population subdivision observed is probably the consequence of the patrilineal social organization of most eastern African ethnic groups, and suggests caution in the use of country-based haplotype frequency distributions for forensic inferences in this region. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Molecular ecology of zebra mussel invasions.

PubMed

May, Gemma E; Gelembiuk, Gregory W; Panov, Vadim E; Orlova, Marina I; Lee, Carol Eunmi

2006-04-01

The invasion of the zebra mussel, Dreissena polymorpha, into North American waters has resulted in profound ecological disturbances and large monetary losses. This study examined the invasion history and patterns of genetic diversity among endemic and invading populations of zebra mussels using DNA sequences from the mitochondrial cytochrome oxidase I (COI) gene. Patterns of haplotype frequency indicate that all invasive populations of zebra mussels from North America and Europe originated from the Ponto-Caspian Sea region. The distribution of haplotypes was consistent with invasive populations arising from the Black Sea drainage, but could not exclude the possibility of an origin from the Caspian Sea drainage. Similar haplotype frequencies among North American populations of D. polymorpha suggest colonization by a single founding population. There was no evidence of invasive populations arising from tectonic lakes in Turkey, while lakes in Greece and Macedonia contained only Dreissena stankovici. Populations in Turkey might be members of a sibling species complex of D. polymorpha. Ponto-Caspian derived populations of D. polymorpha (theta = 0.0011) and Dreissena bugensis (one haplotype) exhibited low levels of genetic diversity at the COI gene, perhaps as a result of repeated population bottlenecks. In contrast, geographically isolated tectonic lake populations exhibited relatively high levels of genetic diversity (theta = 0.0032 to 0.0134). It is possible that the fluctuating environment of the Ponto-Caspian basin facilitated the colonizing habit of invasive populations of D. polymorpha and D. bugensis. Our findings were concordant with the general trend of destructive freshwater invaders in the Great Lakes arising from the Ponto-Caspian Sea basin.

HLA polymorphisms in Sindhi community in Mumbai, India.

PubMed

Chhaya, S; Desai, S; Saranath, D

2010-10-01

Indian population is an amalgamation of various ethnicities, cultural and linguistic diversities, primarily due to marriages within a community. HLA-A, B and DRB1 alleles and haplotype frequencies were investigated in the Sindhi and compared with Marathi, Gujarati and North Indian population from Mumbai. This work is a part of a larger effort aimed at analysis of the HLA profile of diverse Indian ethnics to establish an umbilical cord stem cell panel in India. HLA polymorphisms at the HLA-A, B and DRB1 loci were determined in 413 cord blood samples by the molecular method of polymerase chain reaction using sequence-specific primer amplification. The most frequent alleles included A*01, A*02, A*11 and A*24 at A locus, B*35 and B*40 at B locus and DRB1*07 and DRB1*15 in all the four groups, although the frequency fluctuated in individual communities. HLA-DRB1*03 was significantly high (P < 0.05) in the Sindhi. Phylogenetic association using neighbour-joining tree, based on DA genetic distances for HLA-A and HLA-B alleles, indicated that the Sindhis cluster with North Indian and Pakistan Sindhi. The three locus haplotype analysis revealed that A*02-B*40-DRB1*15 and A*33-B*44-DRB1*07 were common haplotypes in all the groups. The three locus haplotypes found suggest an influence from Caucasian and Oriental populations. The data will be useful in developing an umbilical cord stem cell panel in India. The results will have clinical implications in unrelated umbilical cord stem cell for transplantation in India. © 2010 Blackwell Publishing Ltd.

Effects of methylenetetrahydrofolate reductase gene polymorphisms on toxicities during consolidation therapy in pediatric acute lymphoblastic leukemia in a Chinese population.

PubMed

Liu, Shu-Guang; Li, Zhi-Gang; Cui, Lei; Gao, Chao; Li, Wei-Jing; Zhao, Xiao-Xi

2011-06-01

This study aimed to investigate whether there was a correlation between the genotype or haplotype of the methylenetetrahydrofolate reductase gene (MTHFR) and toxicities during consolidation therapy or plasma methotrexate (MTX) levels at 48 h after the first dose of MTX infusion. We retrospectively genotyped 181 children with newly diagnosed acute lymphoblastic leukemia (ALL) who were treated with the Chinese Children's Leukemia Group protocol. In standard- and medium-risk treatment branches, the 677T carriers (CT + TT) had a higher risk of developing thrombocytopenia when compared with carriers of the CC genotype (odds ratio [OR] 5.21, 95% confidence interval [CI] 1.18-23.01, p = 0.017). The 1298AC/CC genotypes were associated with a decrease in skin toxicity, as compared with the common AA genotype (p = 0.037). An estimation of haplotype frequencies showed that there was no 677T-1298C haplotype in the population. A lower frequency of anemia (OR 0.44, 95% CI 0.21-0.90, p = 0.025) and lower MTX level (p = 0.044) were observed in patients with the 677C-1298C haplotype than in those without. High plasma MTX level was correlated with anemia (p = 0.011) and neutropenia (p = 0.044). In the high-risk group, the polymorphisms or plasma MTX levels were not correlated with any toxicity. Taken together, our data demonstrate that genotyping of MTHFR and measurement of plasma MTX levels might be useful to optimize MTX therapy.

JAK2 46/1 haplotype is associated with JAK2 V617F--positive myeloproliferative neoplasms in Brazilian patients.

PubMed

Macedo, L C; Santos, B C; Pagliarini-e-Silva, S; Pagnano, K B B; Rodrigues, C; Quintero, F C; Ferreira, M E; Baraldi, E C; Ambrosio-Albuquerque, E P; Sell, A M; Visentainer, J E L

2015-10-01

This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients. © 2015 John Wiley & Sons Ltd.

HLA class II susceptibility pattern for type 1 diabetes (T1D) in an Iranian population.

PubMed

Kiani, J; Hajilooi, M; Furst, D; Rezaei, H; Shahryari-Hesami, S; Kowsarifard, S; Zamani, A; Solgi, G

2015-08-01

This study aimed to determine the HLA-DRB1/HLA-DQB1 susceptibility and protection pattern for type 1 diabetes (T1D) in a population from Hamadan, north-west of Iran. A total of 133 patients with T1D were tested for HLA-DRB1 and HLA-DQB1 alleles using PCR-SSP compared to 100 ethnic-matched healthy controls. Alleles and haplotypes frequencies were compared between both groups. The most susceptible alleles for disease were HLA-DRB1*03:01, DRB1*04:02, DQB1*02:01 and DQB1*03:02, and protective alleles were HLA-DRB1*07:01, *11:01, *13:01, *14:01 and DRB1*15 and HLA-DQB1*06:01, *06:02 and *06:03. Haplotype analysis revealed that patients with T1D had higher frequencies of DRB1*03:01-DQB1*02:01 (OR = 4.86, P < 10(-7) ) and DRB1*04:02-DQB1*03:02 (OR = 9.93, P < 10(-7) ) and lower frequencies of DRB1*07:01-DQB1*02:01 (P = 0.0005), DRB1*11:01-DQB1*03:01 (P = 0.001), DRB1*13:01-DQB1*06:03 (P = 0.002) and DRB1*15-DQB1*06:01 (P = 0.001) haplotypes compared to healthy controls. Heterozygote combination of both susceptible haplotypes (DR3/DR4) confers the highest risk for T1D (RR = 18.80, P = 4 × 10(-5) ). Additionally, patients with homozygote diplotype, DR3/DR3 and DR4/DR4, showed a similar risk with less extent to heterozygote combination (P = 0.0004 and P = 0.01, respectively). Our findings not only confirm earlier reports from Iranians but also are in line with Caucasians and partly with Asians and some African patients with T1D. Remarkable differences were the identification of DRB1*04:01-DQB1*03:02, DRB1*07:01-DQB1*03:03 and DRB1*16-DQB1*05:02 as neutral and DRB1*13:01-DQB1*06:03 as the most protective haplotypes in this study. © 2015 John Wiley & Sons Ltd.

Mitochondrial phylogeography and subspecific variation in the red panda (Ailurus fulgens): implications for conservation.

PubMed

Li, Ming; Wei, Fuwen; Goossens, Benoît; Feng, Zuojian; Tamate, Hidetoshi B; Bruford, Michael W; Funk, Stephan M

2005-07-01

The red panda (Ailurus fulgens) is an endangered species and its present distribution is restricted to isolated mountain ranges in western China (Sichuan, Yunnan, and Tibet provinces) and the Himalayan Mountains chain of Nepal, India, Bhutan, and Burma. To examine the evolutionary history across its current range, and to assess the genetic divergence among current subspecies and population structure among different geographic locations, we sequenced mitochondrial DNA from the control region (CR) and cytochrome (cyt) b gene for 41 individuals in Sichuan, Yunnan, Tibet of China, and Burma. 25 CR haplotypes (10 for cyt b) were identified from 11 geographic locations. Only three haplotypes were shared among sample localities, including one among current subspecies. Nine haplotypes were shared with the study of Su et al. [Mol. Biol. Evol. 18 (2001) 1070]. CR haplotype diversity was high (0.95+/-0.02) and nucleotide diversity among all haplotypes was relatively low (0.018+/-0.009). Phylogenetic confirmed trees show a shallow pattern with very little structure or statistical robustness. The application of two coalescent-based tests for population growth allowed us to interpret this phylogeny as the result of a recent population expansion. Analysis of molecular variance and nested clade analysis failed to detect significant geographic structure in both data sets. The lack of significant differentiation between subspecies does not indicate the presence of evolutionary significant units. We suggest that the present population structure has resulted from habitat fragmentation and expansion from glacial refugia. Due to its habitat requirements it is likely that the red panda has undergone bottlenecks and population expansions several times in the recent past. The present population may exhibit a pattern reminiscent of a relatively recent population expansion.

Haplotype analysis of the apolipoprotein A5 gene in obese pediatric patients.

PubMed

Horvatovich, Katalin; Bokor, Szilvia; Baráth, Akos; Maász, Anita; Kisfali, Péter; Járomi, Luca; Polgár, Noémi; Tóth, Dénes; Répásy, Judit; Endreffy, Emoke; Molnár, Dénes; Melegh, Béla

2011-06-01

Apolipoprotein A5 (APOA5) gene variants have been shown to be associated with elevated TG levels; the T-1131C (rs662799) variant has been reported to confer risk for the metabolic syndrome in adult populations. Little is known about the APOA5 variants in pediatric population, no such information is available for pediatric obesity at all. Here we examined four haplotype-tagging polymorphisms (T-1131C, IVS3 + G476A [rs2072560], T1259C [rs2266788] and C56G [rs3135506]) and studied also the frequency of major naturally occurring haplotypes of APOA5 in obese children. The polymorphisms were analyzed in 232 obese children, and in 137 healthy, normal weight controls, using PCR-RFLP methods. In the pediatric patients we could confirm the already known adult subjects based association of -1131C, IVS3 + 476A and 1259C variants with elevated triglyceride concentrations, both in obese patients and in the controls. The prevalence of the APOA5*2 haplotype (containing the minor allele of T-1131C, IVS3 + G476A and T1259C SNPs together) was 15.5% in obese children, and 5.80% in the controls (p<0.001); multiple logistic regression analysis revealed that this haplotype confers susceptibility for development of obesity (OR=2.87; 95% CI: 1.29-6.37; p≤0.01). By contrast, the APOA5*4 haplotype (with -1131C alone) did not show similar associations. Our findings also suggest that the APOA5*5 haplotype (1259C alone) can be protective against obesity (OR=0.25; 95% CI: 0.07-0.80; p<0.05). While previous studies in adults demonstrated, that the APOA5 -1131C minor allele confers risk for adult metabolic syndrome, here we show, that the susceptibility nature of this SNP restricted to the APOA5*2 haplotype in pediatric obese subjects.

Mitochondrial DNA Markers Reveal High Genetic Diversity but Low Genetic Differentiation in the Black Fly Simulium tani Takaoka & Davies along an Elevational Gradient in Malaysia

PubMed Central

Low, Van Lun; Adler, Peter H.; Takaoka, Hiroyuki; Ya’cob, Zubaidah; Lim, Phaik Eem; Tan, Tiong Kai; Lim, Yvonne A. L.; Chen, Chee Dhang; Norma-Rashid, Yusoff; Sofian-Azirun, Mohd

2014-01-01

The population genetic structure of Simulium tani was inferred from mitochondria-encoded sequences of cytochrome c oxidase subunits I (COI) and II (COII) along an elevational gradient in Cameron Highlands, Malaysia. A statistical parsimony network of 71 individuals revealed 71 haplotypes in the COI gene and 43 haplotypes in the COII gene; the concatenated sequences of the COI and COII genes revealed 71 haplotypes. High levels of genetic diversity but low levels of genetic differentiation were observed among populations of S. tani at five elevations. The degree of genetic diversity, however, was not in accordance with an altitudinal gradient, and a Mantel test indicated that elevation did not have a limiting effect on gene flow. No ancestral haplotype of S. tani was found among the populations. Pupae with unique structural characters at the highest elevation showed a tendency to form their own haplotype cluster, as revealed by the COII gene. Tajima’s D, Fu’s Fs, and mismatch distribution tests revealed population expansion of S. tani in Cameron Highlands. A strong correlation was found between nucleotide diversity and the levels of dissolved oxygen in the streams where S. tani was collected. PMID:24941043

High Resolution Human Leukocyte Antigen Class I Allele Frequencies and HIV-1 Infection Associations in Chinese Han and Uyghur Cohorts

PubMed Central

Liu, Yanhou; Zhao, Zhongfang; Li, Tianyi; Liao, Qi; Kushner, Nicholas; Touzjian, Neal Y.; Shao, Yiming; Sun, Yongtao; Strong, Amie J.; Lu, Yichen

2012-01-01

Background Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort. Methodology/Principal Findings Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group. Conclusions At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates. PMID:23251376

Mechanisms of haplotype divergence at the RGA08 nucleotide-binding leucine-rich repeat gene locus in wild banana (Musa balbisiana)

PubMed Central

2010-01-01

Background Comparative sequence analysis of complex loci such as resistance gene analog clusters allows estimating the degree of sequence conservation and mechanisms of divergence at the intraspecies level. In banana (Musa sp.), two diploid wild species Musa acuminata (A genome) and Musa balbisiana (B genome) contribute to the polyploid genome of many cultivars. The M. balbisiana species is associated with vigour and tolerance to pests and disease and little is known on the genome structure and haplotype diversity within this species. Here, we compare two genomic sequences of 253 and 223 kb corresponding to two haplotypes of the RGA08 resistance gene analog locus in M. balbisiana "Pisang Klutuk Wulung" (PKW). Results Sequence comparison revealed two regions of contrasting features. The first is a highly colinear gene-rich region where the two haplotypes diverge only by single nucleotide polymorphisms and two repetitive element insertions. The second corresponds to a large cluster of RGA08 genes, with 13 and 18 predicted RGA genes and pseudogenes spread over 131 and 152 kb respectively on each haplotype. The RGA08 cluster is enriched in repetitive element insertions, in duplicated non-coding intergenic sequences including low complexity regions and shows structural variations between haplotypes. Although some allelic relationships are retained, a large diversity of RGA08 genes occurs in this single M. balbisiana genotype, with several RGA08 paralogs specific to each haplotype. The RGA08 gene family has evolved by mechanisms of unequal recombination, intragenic sequence exchange and diversifying selection. An unequal recombination event taking place between duplicated non-coding intergenic sequences resulted in a different RGA08 gene content between haplotypes pointing out the role of such duplicated regions in the evolution of RGA clusters. Based on the synonymous substitution rate in coding sequences, we estimated a 1 million year divergence time for these M. balbisiana haplotypes. Conclusions A large RGA08 gene cluster identified in wild banana corresponds to a highly variable genomic region between haplotypes surrounded by conserved flanking regions. High level of sequence identity (70 to 99%) of the genic and intergenic regions suggests a recent and rapid evolution of this cluster in M. balbisiana. PMID:20637079

Recent Advances in Experimental Whole Genome Haplotyping Methods

PubMed Central

Huang, Mengting; Lu, Zuhong

2017-01-01

Haplotype plays a vital role in diverse fields; however, the sequencing technologies cannot resolve haplotype directly. Pioneers demonstrated several approaches to resolve haplotype in the early years, which was extensively reviewed. Since then, numerous methods have been developed recently that have significantly improved phasing performance. Here, we review experimental methods that have emerged mainly over the past five years, and categorize them into five classes according to their maximum scale of contiguity: (i) encapsulation, (ii) 3D structure capture and construction, (iii) compartmentalization, (iv) fluorography, (v) long-read sequencing. Several subsections of certain methods are attached to each class as instances. We also discuss the relative advantages and disadvantages of different classes and make comparisons among representative methods of each class. PMID:28891974

Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map.

PubMed

N'Diaye, Amidou; Haile, Jemanesh K; Cory, Aron T; Clarke, Fran R; Clarke, John M; Knox, Ron E; Pozniak, Curtis J

2017-01-01

Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype-based analysis over single marker analysis to detect loci associated with colour traits in durum wheat.

Genetic diversity and population structure of Scottish Highland red deer (Cervus elaphus) populations: a mitochondrial survey.

PubMed

Pérez-Espona, S; Pérez-Barbería, F J; Goodall-Copestake, W P; Jiggins, C D; Gordon, I J; Pemberton, J M

2009-02-01

The largest population of red deer (Cervus elaphus) in Europe is found in Scotland. However, human impacts through hunting and introduction of foreign deer stock have disturbed the population's genetics to an unknown extent. In this study, we analysed mitochondrial control region sequences of 625 individuals to assess signatures of human and natural historical influence on the genetic diversity and population structure of red deer in the Scottish Highlands. Genetic diversity was high with 74 haplotypes found in our study area (115 x 87 km). Phylogenetic analyses revealed that none of the individuals had introgressed mtDNA from foreign species or subspecies of deer and only suggested a very few localized red deer translocations among British localities. A haplotype network and population analyses indicated significant genetic structure (Phi(ST)=0.3452, F(ST)=0.2478), largely concordant with the geographical location of the populations. Mismatch distribution analysis and neutrality tests indicated a significant population expansion for one of the main haplogroups found in the study area, approximately dated c. 8200 or 16 400 years ago when applying a fast or slow mutation rate, respectively. Contrary to general belief, our results strongly suggest that native Scottish red deer mtDNA haplotypes have persisted in the Scottish Highlands and that the population retains a largely natural haplotype diversity and structure in our study area.

Submegabase Clusters of Unstable Tandem Repeats Unique to the Tla Region of Mouse T Haplotypes

PubMed Central

Uehara, H.; Ebersole, T.; Bennett, D.; Artzt, K.

1990-01-01

We describe here the identification and genomic organization of mouse t haplotype-specific elements (TSEs) 7.8 and 5.8 kb in length. The TSEs exist as submegabase-long clusters of tandem repeats localized in the Tla region of the major histocompatibility complex of all t haplotype chromosomes examined. In contrast, no such clusters were detected among 12 inbred strains of Mus musculus and other Mus species; thus, clusters of TSEs represent the first absolutely qualitative difference between t haplotypes and wild-type chromosomes. Pulsed field gel electrophoresis shows that the number of clusters, and the number of repeats in each cluster are extremely variable. Dramatic quantitative differences of TSEs uniquely distinguish every independent t haplotype from any other. The complete nucleotide sequence of one 7.8-kb TSE reveals significant homology to the ETn (a major transcript in the early embryo of the mouse), and some homologies to intracisternal A-particles and the mammary tumor virus env gene. Apart from the diagnostic relevance to t haplotypes, evolutionary and functional significances are discussed with respect to chromosome structure and genetic recombination. PMID:2076812

Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru

PubMed Central

Akinyi, Sheila; Hayden, Tonya; Gamboa, Dionicia; Torres, Katherine; Bendezu, Jorge; Abdallah, Joseph F.; Griffing, Sean M.; Quezada, Wilmer Marquiño; Arrospide, Nancy; De Oliveira, Alexandre Macedo; Lucas, Carmen; Magill, Alan J.; Bacon, David J.; Barnwell, John W.; Udhayakumar, Venkatachalam

2013-01-01

The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. PMID:24077522

Genetic structure of Octopus vulgaris (Cephalopoda, Octopodidae) in the central Mediterranean Sea inferred from the mitochondrial COIII gene.

PubMed

Fadhlaoui-Zid, Karima; Knittweis, Leyla; Aurelle, Didier; Nafkha, Chaala; Ezzeddine, Soufia; Fiorentino, Fabio; Ghmati, Hisham; Ceriola, Luca; Jarboui, Othman; Maltagliati, Ferruccio

2012-01-01

The polymorphism of the mitochondrial gene cytochrome oxidase III was studied in the Mediterranean octopus, Octopus vulgaris Cuvier, 1797. A total of 202 specimens from seven sampling sites were analysed with the aim of elucidating patterns of genetic structure in the central Mediterranean Sea and to give an insight into the phylogeny of the Octopus genus. Phylogenetic analyses showed that individuals from the central Mediterranean belong to the O. vulgaris species whose limits should nevertheless be clarified. Concerning genetic structure, two high-frequency haplotypes were present in all locations. The overall genetic divergence (Φ(ST)=0.05, P<0.05) indicated a significant genetic structuring in the study area and an AMOVA highlighted a significant break between western and eastern Mediterranean basins (Φ(CT)=0.094, P<0.05). Possible explanations for the observed patterns of genetic structuring are discussed with reference to their relevance for fisheries management. Copyright © 2012. Published by Elsevier SAS.

Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

PubMed Central

Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

2016-01-01

Background: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Methods: Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. Results: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10−3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10−7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Conclusions: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID:27364786

[Association between CETP polymorphisms and haplotypes with dyslipidemia in Xinjiang Uygur and Kazak residents].

PubMed

Hu, Y H; Liu, J M; Zhang, M; He, J; Yan, Y Z; Ma, J L; Ma, R L; Guo, H; Rui, D S; Sun, F; Mu, L L; Niu, Q; Ding, Y S; Zhang, J Y; Li, S G; Guo, S X

2016-08-24

To explore the relationship between the polymorphisms and haplotypes in the CETP gene and dyslipidemia among Xinjiang Kazak and Uygur residents. A population status survey was performed from 2010 to 2011 in Kashgar Xinjiang Uygur and Kazak residents, stratified cluster sampling method was used to select Uygur, Kazak residents with abnormal blood lipid values (n=367 and 345, respectively) as the dyslipidemia groups, and to select residents with normal lipid values as control group from the same area (n=374 and 390, respectively). SNaPshot technology was applied to detect the DNA of CETP gene rs3764261, rs1800775, rs708272 and rs5882 loci in all selected residents, and linkage disequilibrium analysis and haplotype construction were performed. (1) In Uygur residents, the dyslipidemia risk of rs708272 CT (OR=0.64, 95%CI 0.46-0.91, P=0.01) and TT genotype (OR=0.60, 95%CI 0.40-0.91, P=0.02) was significantly lower than CC genotype. Dyslipidemia risk of rs3764261 GT (OR=0.55, 95%CI 0.40-0.74, P=0.00) and TT genotype (OR=0.47, 95%CI 0.28-0.78, P<0.01) was significantly lower than GG genetype. Dyslipidemia risk of the rs1800775 CC genotype was higher than AA genotype (OR=1.79, 95%CI 1.17-2.74, P=0.01). There was no statistical significance in CETP gene of the 4 genotype and allele frequency between the dyslipidemia and normal lipid groups in Kazak residents (all P>0.05). (2) In Uighur residents with dyslipidemia, HDL-C level was significantly higher in rs708272 TT genotype carriers than in CC and CT genotypes (all P<0.05) and in rs3764261 TT genotype carriers than in GG genotype carriers (P=0.008), while was significantly lower in rs1800775 CC genotype carriers with AA genotype carriers (P=0.008). (3) Linkage disequilibrium analysis showed that there was strong linkage disequilibrium between rs3764261 and rs708272 (D'=0.869, r(2)=0.869), rs1800775 and rs708272 (D'=0.845, r(2)=0.446) in Uighur residents, and there was strong linkage disequilibrium between rs3764261 and rs708272 (D'=0.963, r(2)=0.963), rs1800775 and rs708272 (D'=0.988, r(2)=0.630) in Kazak residents. (4) Significant differences were observed in frequency distribution of haplotype GACA(OR=0.579, 95%CI 0.388-0.864, P=0.006), GATA (OR=2.183, 95%CI 1.231-3.873, P=0.006), GCCA (OR=0.723, 95%CI 0.549-0.954, P=0.001), TATA (OR=0.723, 95%CI 0.549-0.954, P=0.021) and TATG (OR=0.601, 95%CI 0.429-0.841, P=0.002) in Uighur residents with normal or abnormal lipid profiles, while significant difference was observed in frequency distribution of haplotype GCCG (OR=1.961, 95%CI 1.207-3.188, P=0.005) in Kazak residents with normal or abnormal lipid profiles. CETP genotype rs708272, rs3764261 and rs1800775 polymorphism is closely related to dyslipidemia and haplotype GACA, TATA and TATG will reduce the risk of dyslipidemia, while haplotype GATA, GCCA will increase the risk of dyslipidemia in Uygur residents. The four CETP polymorphisms are not related to the risk of dyslipidemia, but haplotype GCCG is related to increased risk of dyslipidemia in Kazakhs residents.

Mapping human genetic diversity in Asia.

PubMed

Abdulla, Mahmood Ameen; Ahmed, Ikhlak; Assawamakin, Anunchai; Bhak, Jong; Brahmachari, Samir K; Calacal, Gayvelline C; Chaurasia, Amit; Chen, Chien-Hsiun; Chen, Jieming; Chen, Yuan-Tsong; Chu, Jiayou; Cutiongco-de la Paz, Eva Maria C; De Ungria, Maria Corazon A; Delfin, Frederick C; Edo, Juli; Fuchareon, Suthat; Ghang, Ho; Gojobori, Takashi; Han, Junsong; Ho, Sheng-Feng; Hoh, Boon Peng; Huang, Wei; Inoko, Hidetoshi; Jha, Pankaj; Jinam, Timothy A; Jin, Li; Jung, Jongsun; Kangwanpong, Daoroong; Kampuansai, Jatupol; Kennedy, Giulia C; Khurana, Preeti; Kim, Hyung-Lae; Kim, Kwangjoong; Kim, Sangsoo; Kim, Woo-Yeon; Kimm, Kuchan; Kimura, Ryosuke; Koike, Tomohiro; Kulawonganunchai, Supasak; Kumar, Vikrant; Lai, Poh San; Lee, Jong-Young; Lee, Sunghoon; Liu, Edison T; Majumder, Partha P; Mandapati, Kiran Kumar; Marzuki, Sangkot; Mitchell, Wayne; Mukerji, Mitali; Naritomi, Kenji; Ngamphiw, Chumpol; Niikawa, Norio; Nishida, Nao; Oh, Bermseok; Oh, Sangho; Ohashi, Jun; Oka, Akira; Ong, Rick; Padilla, Carmencita D; Palittapongarnpim, Prasit; Perdigon, Henry B; Phipps, Maude Elvira; Png, Eileen; Sakaki, Yoshiyuki; Salvador, Jazelyn M; Sandraling, Yuliana; Scaria, Vinod; Seielstad, Mark; Sidek, Mohd Ros; Sinha, Amit; Srikummool, Metawee; Sudoyo, Herawati; Sugano, Sumio; Suryadi, Helena; Suzuki, Yoshiyuki; Tabbada, Kristina A; Tan, Adrian; Tokunaga, Katsushi; Tongsima, Sissades; Villamor, Lilian P; Wang, Eric; Wang, Ying; Wang, Haifeng; Wu, Jer-Yuarn; Xiao, Huasheng; Xu, Shuhua; Yang, Jin Ok; Shugart, Yin Yao; Yoo, Hyang-Sook; Yuan, Wentao; Zhao, Guoping; Zilfalil, Bin Alwi

2009-12-11

Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations.

A prospective study of the APOA1 XmnI and APOC3 SstI polymorphisms in the APOA1/C3/A4 gene cluster and risk of incident myocardial infarction in men.

PubMed

Liu, Simin; Song, Yiqing; Hu, Frank B; Niu, Tianhua; Ma, Jing; Gaziano, Michael; Stampfer, Meir J

2004-11-01

Apolipoproteins AI/CIII/AIV play important roles in the metabolism of triglycerides (TG) and high-density lipoprotein (HDL) cholesterol. However, whether genetic variations in the APOA1/C3/A4 gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain and prospective data are sparse. In a prospective nested case-control study of 385 incident cases of MI and 373 age- and smoking-matched controls from the Physicians' Health Study, we examined the relationship between 2 common single nucleotide polymorphisms (APOA1 XmnI and APOC3 SstI) in the APOA1/C3/A4 gene cluster and haplotypes defined by these SNPs and risk of incident MI. No significant differences in allele or genotype frequency for the APOA1 XmnI and APOC3 SstI polymorphisms were detected between cases and controls. After adjusting for non-lipid coronary risk factors, the relative risks for incident MI were 1.00 (95% CI 0.68-1.47) for men carrying the X2 allele compared with those homozygous for the X1 allele in the APOA1 XmnI site and 1.07 (95% CI 0.69-1.64) for men carrying the S2 versus those homozygous for the S1 allele in the APOC3 SstI site. Moreover, we did not observe any effect modification by HDL or TG levels for the associations of these APOA1 and APOC3 genotypes with MI risk. There were significant differences in TG levels among men carrying different haplotypes (P=0.01) and men carrying the X1-S2 haplotype had higher levels of TG than those carrying the X2-S1 haplotype (202 mg/dl versus 157 mg/dl, P=0.03); however, haplotype frequencies defined by these two polymorphisms did not differ significantly between cases and controls. In this prospective study of apparently healthy middle-aged US men, carriers of the X1-S2 haplotype in the APOA1 XmnI and APOC3 SstI variants across the APOA1/C3/A4 gene cluster had higher TG levels, but there was no evidence for significant associations between these two common variants or haplotypes defined by them and risk of incident MI in this cohort.

Accelerating next generation sequencing data analysis with system level optimizations.

PubMed

Kathiresan, Nagarajan; Temanni, Ramzi; Almabrazi, Hakeem; Syed, Najeeb; Jithesh, Puthen V; Al-Ali, Rashid

2017-08-22

Next generation sequencing (NGS) data analysis is highly compute intensive. In-memory computing, vectorization, bulk data transfer, CPU frequency scaling are some of the hardware features in the modern computing architectures. To get the best execution time and utilize these hardware features, it is necessary to tune the system level parameters before running the application. We studied the GATK-HaplotypeCaller which is part of common NGS workflows, that consume more than 43% of the total execution time. Multiple GATK 3.x versions were benchmarked and the execution time of HaplotypeCaller was optimized by various system level parameters which included: (i) tuning the parallel garbage collection and kernel shared memory to simulate in-memory computing, (ii) architecture-specific tuning in the PairHMM library for vectorization, (iii) including Java 1.8 features through GATK source code compilation and building a runtime environment for parallel sorting and bulk data transfer (iv) the default 'on-demand' mode of CPU frequency is over-clocked by using 'performance-mode' to accelerate the Java multi-threads. As a result, the HaplotypeCaller execution time was reduced by 82.66% in GATK 3.3 and 42.61% in GATK 3.7. Overall, the execution time of NGS pipeline was reduced to 70.60% and 34.14% for GATK 3.3 and GATK 3.7 respectively.

Variation in mitochondrial DNA and allozymes discriminates early and late forms of Chinook salmon Oncorhynchus tshawytscha in the Kenai and Kasilof Rivers, AK

USGS Publications Warehouse

Adams, Noah S.; Spearman, William J.; Burger, Carl V.; Currens, Kenneth P.; Schreck, Carl B.; Li, Hiram W.

1994-01-01

Genetic differences between early and late forms of Alaskan chinook salmon (Oncorhynchus tshawytscha) were identified using two genetic approaches: mitochondrial DNA (mtDNA) analysis, and protein electrophoresis. Study populations consisted of early and late runs in each of the Kenai and Kasilof rivers in Alaska, and a population from the Minam River, Oregon. Two segments of mtDNA were amplified using the polymerase chain reaction (PCR) and digested with 14–16 restriction enzymes. Results showed that early runs were genetically similar to each other but different from the late runs. The late runs were different from each other based on the frequency of the common haplotypes. Frequency differences in shared haplotypes together with the presence of a unique haplotype separated the Minam River stock from those in Alaska. In the protein analysis, each population was examined at 30 allozyme loci. Based on 14 polymorphic loci, Minam River salmon were genetically distinct from the Alaskan populations. Within the Alaskan populations, early runs were most similar to each other but different from the late runs; the late runs were also genetically most similar to each other. Both mtDNA and allozyme analysis suggest that chinook salmon may segregate into genetically different early and late forms within a drainage.

The effect of polyandry on a distorter system with differential viabilities in the sexes.

PubMed

Manser, Andri; Lindholm, Anna K; König, Barbara; Bagheri, Homayoun C

2012-11-01

The presence of selfish genetic elements can have fatal consequences for populations that harbor them. In the well known t haplotype in wild house mice, large proportions of the population die from t/t recessive lethal effects. Due to strong advantages at the gamete level (drive), t haplotypes nevertheless occur at substantial frequencies. The stable presence of a lethal is not the only effect of the t. It also distorts the fate of mutations that differentially affect male and female survival and reproduction (such as in sexual conflict), by giving male selective effects a strong advantage over female selective effects. In a recent study, we proposed polyandry as a potential counterstrategy against t deleterious effects. Here, we show that (1) the efficiency of polyandry in reducing the t frequency strongly depends on the selective context and (2) polyandry helps to reduce male-biased leverage in sex dependent selection.

LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants.

PubMed

Machiela, Mitchell J; Chanock, Stephen J

2015-11-01

Assessing linkage disequilibrium (LD) across ancestral populations is a powerful approach for investigating population-specific genetic structure as well as functionally mapping regions of disease susceptibility. Here, we present LDlink, a web-based collection of bioinformatic modules that query single nucleotide polymorphisms (SNPs) in population groups of interest to generate haplotype tables and interactive plots. Modules are designed with an emphasis on ease of use, query flexibility, and interactive visualization of results. Phase 3 haplotype data from the 1000 Genomes Project are referenced for calculating pairwise metrics of LD, searching for proxies in high LD, and enumerating all observed haplotypes. LDlink is tailored for investigators interested in mapping common and uncommon disease susceptibility loci by focusing on output linking correlated alleles and highlighting putative functional variants. LDlink is a free and publically available web tool which can be accessed at http://analysistools.nci.nih.gov/LDlink/. mitchell.machiela@nih.gov. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.

Paleogenetical study of pre-Columbian samples from Pampa Grande (Salta, Argentina).

PubMed

Carnese, Fransisco R; Mendisco, Fanny; Keyser, Christine; Dejean, Cristina B; Dugoujon, Jean-Michel; Bravi, Claudio M; Ludes, Bertrand; Crubézy, Eric

2010-03-01

Ancient DNA recovered from 21 individuals excavated from burial sites in the Pampa Grande (PG) region (Salta province) of North-Western Argentina (NWA) was analyzed using various genetic markers (mitochondrial DNA, autosomal STRs, and Y chromosomal STRs). The results were compared to ancient and modern DNA from various populations in the Andean and North Argentinean regions, with the aim of establishing their relationships with PG. The mitochondrial haplogroup frequencies described (11% A, 47% B, and 42% D) presented values comparable to those found for the ancient Andean populations from Peru and San Pedro de Atacama. On the other hand, mitochondrial and Y chromosomal haplotypes were specific to PG, as they did not match any other of the South American populations studied. The described genetic diversity indicates homogeneity in the genetic structure of the ancient Andean populations, which was probably facilitated by the intense exchange network in the Andean zone, in particular among Tiwanaku, San Pedro de Atacama, and NWA. The discovery of haplotypes unique to PG could be due to a loss of genetic diversity caused by recent events affecting the autochthonous populations (establishment of the Inca Empire in the region, colonization by the Europeans).

Evaluation of the Association Between Common Genetic Variants Near the ABCA1 Gene and Primary Angle Closure Glaucoma in a Han Chinese Population.

PubMed

Luo, Huaichao; Chen, Yuhong; Ye, Zimeng; Sun, Xinghuai; Shi, Yi; Luo, Qian; Gong, Bo; Shuai, Ping; Yang, Jiyun; Zhou, Yu; Liu, Xiaoqi; Zhang, Kaijiong; Tan, Chang; Li, Yuanfeng; Lin, Ying; Yang, Zhenglin

2015-10-01

Recently, three large genome-wide association studies have identified multiple variants associated with primary open angle glaucoma (POAG) near the ABCA1 gene. Considering that POAG and primary angle closure glaucoma (PACG) share many similar clinical manifestations, the present study was conducted to investigate whether these genetic variants were also associated with PACG in a Han Chinese population. A case-control association study of 1122 cases (PACG/PAC) and 1311 normal, matched controls was undertaken. Seven single-nucleotide polymorphisms (SNPs) near the ABCA1 gene, including rs2422493, rs2487042, rs2472496, rs2472493, rs2487032, rs2472459, and rs2472519, were genotyped. Genotype and allele frequencies were assessed using χ² tests. Linkage disequilibrium (LD) structure was analyzed by computer software. Among the SNPs genotyped, no association was observed between these SNPs and PACG. However, we discovered that two haplotypes, CATTTAC (corrected P = 0.048) and CGCCCGC (corrected P = 0.048), remained significantly associated with PACG/PAC after Bonferroni correction. Subjects with the CATTTAC haplotype have a 1.71-fold increased possibility of having PACG/PAC, whereas subjects with the CGCCCGC haplotype have 0.47-fold decreased possibility of developing PACG. Our findings suggest that the genetic backgrounds of PACG and POAG might be different. However, whether or not ABCA1 plays a role in the development of PACG is still not made certain by this study. Thus, further research is needed to find the role of ABCA1 in the progress of PACG.

Positive selection of lactase persistence among people of Southern Arabia.

PubMed

Bayoumi, Riad; De Fanti, Sara; Sazzini, Marco; Giuliani, Cristina; Quagliariello, Andrea; Bortolini, Eugenio; Boattini, Alessio; Al-Habori, Molham; Al-Zubairi, Adel Sharaf; Rose, Jeffrey I; Romeo, Giovanni; Al-Abri, Abdulrahim; Luiselli, Donata

2016-12-01

Frequency patterns of the lactase persistence (LP)-associated -13,915 G allele and archaeological records pointing to substantial role played by southern regions in the peopling and domestication processes that involved the Arabian Peninsula suggest that Southern Arabia plausibly represented the center of diffusion of such adaptive variant. Nevertheless, a well-defined scenario for evolution of Arabian LP is still to be elucidated and the burgeoning archaeological picture of complex human migrations occurred through the peninsula is not matched by an equivalent high-resolution description of genetic variation underlying this adaptive trait. To fill this gap, we investigated diversity at a wide genomic interval surrounding the LCT gene in different Southern Arabian populations. 40 SNPs were genotyped to characterize LCT profiles of 630 Omani and Yemeni individuals to perform population structure, linkage disequilibrium, population differentiation-based and haplotype-based analyses. Typical Arabian LP-related variation was found in Dhofaris and Yemenis, being characterized by private haplotypes carrying the -13,915 G allele, unusual differentiation with respect to northern groups and conserved homozygous haplotype-blocks, suggesting that the adaptive allele was likely introduced in the Arabian gene pool in southern populations and was then subjected to prolonged selective pressure. By pointing to Yemen as one of the best candidate centers of diffusion of the Arabian-specific adaptive variant, obtained results indicate the spread of indigenous groups as the main process underlying dispersal of LP along the Arabian Peninsula, supporting a refugia model for Arabian demic movements occurred during the Terminal Pleistocene and Early Holocene. © 2016 Wiley Periodicals, Inc.

Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle

PubMed Central

Huson, Heather J.; Kim, Eui-Soo; Godfrey, Robert W.; Olson, Timothy A.; McClure, Matthew C.; Chase, Chad C.; Rizzi, Rita; O'Brien, Ana M. P.; Van Tassell, Curt P.; Garcia, José F.; Sonstegard, Tad S.

2014-01-01

The slick hair coat (SLICK) is a dominantly inherited trait typically associated with tropically adapted cattle that are from Criollo descent through Spanish colonization of cattle into the New World. The trait is of interest relative to climate change, due to its association with improved thermo-tolerance and subsequent increased productivity. Previous studies localized the SLICK locus to a 4 cM region on chromosome (BTA) 20 and identified signatures of selection in this region derived from Senepol cattle. The current study compares three slick-haired Criollo-derived breeds including Senepol, Carora, and Romosinuano and three additional slick-haired cross-bred lineages to non-slick ancestral breeds. Genome-wide association (GWA), haplotype analysis, signatures of selection, runs of homozygosity (ROH), and identity by state (IBS) calculations were used to identify a 0.8 Mb (37.7–38.5 Mb) consensus region for the SLICK locus on BTA20 in which contains SKP2 and SPEF2 as possible candidate genes. Three specific haplotype patterns are identified in slick individuals, all with zero frequency in non-slick individuals. Admixture analysis identified common genetic patterns between the three slick breeds at the SLICK locus. Principal component analysis (PCA) and admixture results show Senepol and Romosinuano sharing a higher degree of genetic similarity to one another with a much lesser degree of similarity to Carora. Variation in GWA, haplotype analysis, and IBS calculations with accompanying population structure information supports potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus. PMID:24808908

Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle.

PubMed

Huson, Heather J; Kim, Eui-Soo; Godfrey, Robert W; Olson, Timothy A; McClure, Matthew C; Chase, Chad C; Rizzi, Rita; O'Brien, Ana M P; Van Tassell, Curt P; Garcia, José F; Sonstegard, Tad S

2014-01-01

The slick hair coat (SLICK) is a dominantly inherited trait typically associated with tropically adapted cattle that are from Criollo descent through Spanish colonization of cattle into the New World. The trait is of interest relative to climate change, due to its association with improved thermo-tolerance and subsequent increased productivity. Previous studies localized the SLICK locus to a 4 cM region on chromosome (BTA) 20 and identified signatures of selection in this region derived from Senepol cattle. The current study compares three slick-haired Criollo-derived breeds including Senepol, Carora, and Romosinuano and three additional slick-haired cross-bred lineages to non-slick ancestral breeds. Genome-wide association (GWA), haplotype analysis, signatures of selection, runs of homozygosity (ROH), and identity by state (IBS) calculations were used to identify a 0.8 Mb (37.7-38.5 Mb) consensus region for the SLICK locus on BTA20 in which contains SKP2 and SPEF2 as possible candidate genes. Three specific haplotype patterns are identified in slick individuals, all with zero frequency in non-slick individuals. Admixture analysis identified common genetic patterns between the three slick breeds at the SLICK locus. Principal component analysis (PCA) and admixture results show Senepol and Romosinuano sharing a higher degree of genetic similarity to one another with a much lesser degree of similarity to Carora. Variation in GWA, haplotype analysis, and IBS calculations with accompanying population structure information supports potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus.

Demographic collapse and low genetic diversity of the Irrawaddy dolphin population inhabiting the Mekong River

PubMed Central

Beasley, Isabel; Ackermann, Corinne Y.; Lieckfeldt, Dietmar; Ludwig, Arne; Ryan, Gerard E.; Bejder, Lars; Parra, Guido J.; Wolfensberger, Rebekka; Spencer, Peter B. S.

2018-01-01

In threatened wildlife populations, it is important to determine whether observed low genetic diversity may be due to recent anthropogenic pressure or the consequence of historic events. Historical size of the Irrawaddy dolphin (Orcaella brevirostris) population inhabiting the Mekong River is unknown and there is significant concern for long-term survival of the remaining population as a result of low abundance, slow reproduction rate, high neonatal mortality, and continuing anthropogenic threats. We investigated population structure and reconstructed the demographic history based on 60 Irrawaddy dolphins samples collected between 2001 and 2009. The phylogenetic analysis indicated reciprocal monophyly of Mekong River Orcaella haplotypes with respect to haplotypes from other populations, suggesting long-standing isolation of the Mekong dolphin population from other Orcaella populations. We found that at least 85% of all individuals in the two main study areas: Kratie and Stung Treng, bore the same mitochondrial haplotype. Out of the 21 microsatellite loci tested, only ten were polymorphic and exhibited very low levels of genetic diversity. Both individual and frequency-based approaches suggest very low and non-significant genetic differentiation of the Mekong dolphin population. Evidence for recent bottlenecks was equivocal. Some results suggested a recent exponential decline in the Mekong dolphin population, with the current size being only 5.2% of the ancestral population. In order for the Mekong dolphin population to have any potential for long-term survival, it is imperative that management priorities focus on preventing any further population fragmentation or genetic loss, reducing or eliminating anthropogenic threats, and promoting connectivity between all subpopulations. PMID:29298312

Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson's disease susceptibility in Chinese Han population.

PubMed

Dai, Yi; Wu, Yuquan; Li, Yansheng

2015-01-01

The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson's disease (PD) susceptibility in Chinese Han population. The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ(2) test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.

Patterns of haplotypes for 92 cystic fibrosis mutations: Variability, association and recurrence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morral, N.; Llevadot, R.; Estivill, X.

1994-09-01

Most CFTR mutations are very uncommon among the cystic fibrosis population, with frequencies of less than 1%, and many are found only in specific areas. We have analyzed 92 CF mutations for several markers (4 microsatellites and 3 other polymorphisms) scattered in the CFTR gene. Haplotypes associated with these mutations can be used as a framework in the screening of chromosomes carrying unknown mutations. The association between mutation and haplotype reduces the number of mutations it is necessary to search for to a maximum of 16 for the same haplotype. Only mutations {triangle}F508, G542X and N1303K are associated with moremore » than one haplotype as a result of slippage at more than one microsatellite loci, suggesting that these three are the most ancient CF mutations. Recurrence has been found for at least 7 mutations: H199Y, R347P, L558S, R553X, 2184insA, 3272-26A{r_arrow}G, 3849+10kbC{r_arrow}T and R1162X. Also microsatellite analysis of chromosomes of several ethnic origins (Czech, Italian, Russian, Slovac and Spanish) suggested that possibility of three or more independent origins for mutations R334W, R347P, R1162X, and 3849+10kbC{r_arrow}T, which was confirmed by analysis of markers flanking these mutations.« less

Haplotype data for 23 Y-chromosome markers in a reference sample from Bosnia and Herzegovina

PubMed Central

Kovačević, Lejla; Fatur-Cerić, Vera; Hadžić, Negra; Čakar, Jasmina; Primorac, Dragan; Marjanović, Damir

2013-01-01

Aim To detect polymorphisms of 23 Y-chromosomal short tandem repeat (STR) loci, including 6 new loci, in a reference database of male population of Bosnia and Herzegovina, as well as to assess the importance of increasing the number of Y-STR loci utilized in forensic DNA analysis. Methods The reference sample consisted of 100 healthy, unrelated men originating from Bosnia and Herzegovina. Sample collection using buccal swabs was performed in all geographical regions of Bosnia and Herzegovina in the period from 2010 to 2011. DNA samples were typed for 23 Y STR loci, including 6 new loci: DYS576, DYS481, DYS549, DYS533, DYS570, and DYS643, which are included in the new PowerPlex® Y 23 amplification kit. Results The absolute frequency of generated haplotypes was calculated and results showed that 98 samples had unique Y 23 haplotypes, and that only two samples shared the same haplotype. The most polymorphic locus was DYS418, with 14 detected alleles and the least polymorphic loci were DYS389I, DYS391, DYS437, and DYS393. Conclusion This study showed that by increasing the number of highly polymorphic Y STR markers, to include those tested in our analysis, leads to a reduction of repeating haplotypes, which is very important in the application of forensic DNA analysis. PMID:23771760

No evidence for MHC class II-based non-random mating at the gametic haplotype in Atlantic salmon.

PubMed

Promerová, M; Alavioon, G; Tusso, S; Burri, R; Immler, S

2017-06-01

Genes of the major histocompatibility complex (MHC) are a likely target of mate choice because of their role in inbreeding avoidance and potential benefits for offspring immunocompetence. Evidence for female choice for complementary MHC alleles among competing males exists both for the pre- and the postmating stages. However, it remains unclear whether the latter may involve non-random fusion of gametes depending on gametic haplotypes resulting in transmission ratio distortion or non-random sequence divergence among fused gametes. We tested whether non-random gametic fusion of MHC-II haplotypes occurs in Atlantic salmon Salmo salar. We performed in vitro fertilizations that excluded interindividual sperm competition using a split family design with large clutch sample sizes to test for a possible role of the gametic haplotype in mate choice. We sequenced two MHC-II loci in 50 embryos per clutch to assess allelic frequencies and sequence divergence. We found no evidence for transmission ratio distortion at two linked MHC-II loci, nor for non-random gamete fusion with respect to MHC-II alleles. Our findings suggest that the gametic MHC-II haplotypes play no role in gamete association in Atlantic salmon and that earlier findings of MHC-based mate choice most likely reflect choice among diploid genotypes. We discuss possible explanations for these findings and how they differ from findings in mammals.

A Primary Assembly of a Bovine Haplotype Block Map Based on a 15,036-Single-Nucleotide Polymorphism Panel Genotyped in Holstein–Friesian Cattle

PubMed Central

Khatkar, Mehar S.; Zenger, Kyall R.; Hobbs, Matthew; Hawken, Rachel J.; Cavanagh, Julie A. L.; Barris, Wes; McClintock, Alexander E.; McClintock, Sara; Thomson, Peter C.; Tier, Bruce; Nicholas, Frank W.; Raadsma, Herman W.

2007-01-01

Analysis of data on 1000 Holstein–Friesian bulls genotyped for 15,036 single-nucleotide polymorphisms (SNPs) has enabled genomewide identification of haplotype blocks and tag SNPs. A final subset of 9195 SNPs in Hardy–Weinberg equilibrium and mapped on autosomes on the bovine sequence assembly (release Btau 3.1) was used in this study. The average intermarker spacing was 251.8 kb. The average minor allele frequency (MAF) was 0.29 (0.05–0.5). Following recent precedents in human HapMap studies, a haplotype block was defined where 95% of combinations of SNPs within a region are in very high linkage disequilibrium. A total of 727 haplotype blocks consisting of ≥3 SNPs were identified. The average block length was 69.7 ± 7.7 kb, which is ∼5–10 times larger than in humans. These blocks comprised a total of 2964 SNPs and covered 50,638 kb of the sequence map, which constitutes 2.18% of the length of all autosomes. A set of tag SNPs, which will be useful for further fine-mapping studies, has been identified. Overall, the results suggest that as many as 75,000–100,000 tag SNPs would be needed to track all important haplotype blocks in the bovine genome. This would require ∼250,000 SNPs in the discovery phase. PMID:17435229

Unraveling Haplotype Diversity of the Apical Membrane Antigen-1 Gene in Plasmodium falciparum Populations in Thailand

PubMed Central

Lumkul, Lalita; Sawaswong, Vorthon; Simpalipan, Phumin; Kaewthamasorn, Morakot; Harnyuttanakorn, Pongchai; Pattaradilokrat, Sittiporn

2018-01-01

Development of an effective vaccine is critically needed for the prevention of malaria. One of the key antigens for malaria vaccines is the apical membrane antigen 1 (AMA-1) of the human malaria parasite Plasmodium falciparum, the surface protein for erythrocyte invasion of the parasite. The gene encoding AMA-1 has been sequenced from populations of P. falciparum worldwide, but the haplotype diversity of the gene in P. falciparum populations in the Greater Mekong Subregion (GMS), including Thailand, remains to be characterized. In the present study, the AMA-1 gene was PCR amplified and sequenced from the genomic DNA of 65 P. falciparum isolates from 5 endemic areas in Thailand. The nearly full-length 1,848 nucleotide sequence of AMA-1 was subjected to molecular analyses, including nucleotide sequence diversity, haplotype diversity and deduced amino acid sequence diversity and neutrality tests. Phylogenetic analysis and pairwise population differentiation (Fst indices) were performed to infer the population structure. The analyses identified 60 single nucleotide polymorphic loci, predominately located in domain I of AMA-1. A total of 31 unique AMA-1 haplotypes were identified, which included 11 novel ones. The phylogenetic tree of the AMA-1 haplotypes revealed multiple clades of AMA-1, each of which contained parasites of multiple geographical origins, consistent with the Fst indices indicating genetic homogeneity or gene flow among geographically distinct populations of P. falciparum in Thailand’s borders with Myanmar, Laos and Cambodia. In summary, the study revealed novel haplotypes and population structure needed for the further advancement of AMA-1-based malaria vaccines in the GMS. PMID:29742870

Unexpected absence of genetic separation of a highly diverse population of hookworms from geographically isolated hosts.

PubMed

Haynes, Benjamin T; Marcus, Alan D; Higgins, Damien P; Gongora, Jaime; Gray, Rachael; Šlapeta, Jan

2014-12-01

The high natal site fidelity of endangered Australian sea lions (Neophoca cinerea) along the southern Australian coast suggests that their maternally transmitted parasitic species, such as hookworms, will have restricted potential for dispersal. If this is the case, we would expect to find a hookworm haplotype structure corresponding to that of the host mtDNA haplotype structure; that is, restricted among geographically separated colonies. In this study, we used a fragment of the cytochrome c oxidase I mitochondrial DNA (mtDNA) gene to investigate the diversity of hookworms (Uncinaria sanguinis) in N. cinerea to assess the importance of host distribution and ecology on the evolutionary history of the parasite. High haplotype (h=0.986) and nucleotide diversity (π=0.013) were seen, with 45 unique hookworm mtDNA haplotypes across N. cinerea colonies; with most of the variation (78%) arising from variability within hookworms from individual colonies. This is supported by the low genetic differentiation co-efficient (GST=0.007) and a high gene flow (Nm=35.25) indicating a high migration rate between the populations of hookworms. The haplotype network demonstrated no clear distribution and delineation of haplotypes according to geographical location. Our data rejects the vicariance hypothesis; that female host natal site fidelity and the transmammary route of infection restrict hookworm gene flow between N. cinerea populations and highlights the value of studies of parasite diversity and dispersal to challenge our understanding of parasite and host ecology. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Population Genetics of Human CYP3A Locus: Signatures of Positive Selection and Implications for Evolutionary Environmental Medicine

PubMed Central

Chen, Xiaoping; Wang, Haijian; Zhou, Gangqiao; Zhang, Xiumei; Dong, Xiaojia; Zhi, Lianteng; Jin, Li; He, Fuchu

2009-01-01

Background The human CYP3A gene cluster codes for cytochrome P450 (CYP) subfamily enzymes that catalyze the metabolism of various exogenous and endogenous chemicals and is an obvious candidate for evolutionary and environmental genomic study. Functional variants in the CYP3A locus may have undergone a selective sweep in response to various environmental conditions. Objective The goal of this study was to profile the allelic structure across the human CYP3A locus and investigate natural selection on that locus. Methods From the CYP3A locus spanning 231 kb, we resequenced 54 genomic DNA fragments (a total of 43,675 bases) spanning four genes (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) and two pseudogenes (CYP3AP1 and CYP3AP2), and randomly selected intergenic regions at the CYP3A locus in Africans (24 individuals), Caucasians (24 individuals), and Chinese (29 individuals). We comprehensively investigated the nucleotide diversity and haplotype structure and examined the possible role of natural selection in shaping the sequence variation throughout the gene cluster. Results Neutrality tests with Tajima’s D, Fu and Li’s D* and F*, and Fay and Wu’s H indicated possible roles of positive selection on the entire CYP3A locus in non-Africans. Sliding-window analyses of nucleotide diversity and frequency spectrum, as well as haplotype diversity and phylogenetically inferred haplotype structure, revealed that CYP3A4 and CYP3A7 had recently undergone or were undergoing a selective sweep in all three populations, whereas CYP3A43 and CYP3A5 were undergoing a selective sweep in non-Africans and Caucasians, respectively. Conclusion The refined allelic architecture and selection spectrum for the human CYP3A locus highlight that evolutionary dynamics of molecular adaptation may underlie the phenotypic variation of the xenobiotic disposition system and varied predisposition to complex disorders in which xenobiotics play a role. PMID:20019904

The association of 22 Y chromosome short tandem repeat loci with initiative-aggressive behavior.

PubMed

Yang, Chun; Ba, Huajie; Zhang, Wei; Zhang, Shuyou; Zhao, Hanqing; Yu, Haiying; Gao, Zhiqin; Wang, Binbin

2018-05-15

Aggressive behavior represents an important public concern and a clinical challenge to behaviorists and psychiatrists. Aggression in humans is known to have an important genetic basis, so to investigate the association of Y chromosome short tandem repeat (Y-STR) loci with initiative-aggressive behavior, we compared allelic and haplotypic distributions of 22 Y-STRs in a group of Chinese males convicted of premeditated extremely violent crimes (n = 271) with a normal control group (n = 492). Allelic distributions of DYS533 and DYS437 loci differed significantly between the two groups (P < 0.05). The case group had higher frequencies of DYS533 allele 14, DYS437 allele 14, and haplotypes 11-14 of DYS533-DYS437 compared with the control group. Additionally, the DYS437 allele 15 frequency was significantly lower in cases than controls. No frequency differences were observed in the other 20 Y-STR loci between these two groups. Our results indicate a genetic role for Y-STR loci in the development of initiative aggression in non-psychiatric subjects. Copyright © 2018 Elsevier B.V. All rights reserved.

HLA diversity among Nadars, a primitive Dravidian caste of South India.

PubMed

Shankarkumar, U; Sridharan, B; Pitchappan, R M

2003-12-01

South India is one of the oldest geophysical regions mainly occupied by Dravidian language-speaking people. Here a random panel of 61 unrelated Nadar healthy individual from Tamil Nadu State were analyzed and compared with other populations of India and the world. HLA-A, B and C alleles frequencies and their haplotype frequencies were determined by high-resolution typing of genomic DNA. The analysis revealed that the Nadar caste of South India have several characters shared with East Asian populations consistent with the demographic history of South India, as well as specific features including several unique alleles such as A*03011, A*31011, B*15011, B*3501, B*51011, Cw*02022. In addition, haplotypes such as A*31011-Cw*02022-B*3501, A*03011-Cw*04011-B*4406 and A*2402101-Cw*04011-B*51011 are of high frequency in both these populations but are rare or absent in other populations of India and the world. The study suggests that a comparatively lesser degree of genetic admixture occurred between the South Indian and North Indian racial groups than that between South Indian and East Asian groups.

Association study between BDNF gene variants and Mexican patients with obsessive-compulsive disorder.

PubMed

Márquez, Lidia; Camarena, Beatriz; Hernández, Sandra; Lóyzaga, Cristina; Vargas, Luis; Nicolini, Humberto

2013-11-01

Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We investigate the role of three variants of the BDNF gene (rs6265, rs1519480 and rs7124442) by single SNP and haplotype analysis in OCD Mexican patients using a case-control and family-based association design. BDNF gene variants were genotyped in 283 control subjects, 232 OCD patients and first degree relatives of 111 OCD subjects. Single SNP analysis in case-control study showed an association between rs6265 and OCD with a high frequency of Val/Val genotype and Val allele (p=0.0001 and p=0.0001, respectively). Also, genotype and allele analysis of rs1519480 showed significant differences (p=0.0001, p=0.0001; respectively) between OCD and control groups. Haplotype analysis showed a high frequency of A-T (rs6265-rs1519480) in OCD patients compared with the control group (OR=2.06 [1.18-3.59], p=0.0093) and a low frequency of haplotype A-C in the OCD patients (OR=0.04 [0.01-0.16], p=0.000002). The family-based association study showed no significant differences in the transmission of any variant. Our study replicated the association between BDNF Val66Met gene polymorphism and OCD. Also, we found a significant association of rs1519480 in OCD patients compared with a control group, region that has never been analyzed in OCD. In conclusion, our findings suggest that BDNF gene could be related to the development of OCD. © 2013 Elsevier B.V. and ECNP. All rights reserved.

Phylogeographic history of grey wolves in Europe

PubMed Central

2010-01-01

Background While it is generally accepted that patterns of intra-specific genetic differentiation are substantially affected by glacial history, population genetic processes occurring during Pleistocene glaciations are still poorly understood. In this study, we address the question of the genetic consequences of Pleistocene glaciations for European grey wolves. Combining our data with data from published studies, we analysed phylogenetic relationships and geographic distribution of mitochondrial DNA haplotypes for 947 contemporary European wolves. We also compared the contemporary wolf sequences with published sequences of 24 ancient European wolves. Results We found that haplotypes representing two haplogroups, 1 and 2, overlap geographically, but substantially differ in frequency between populations from south-western and eastern Europe. A comparison between haplotypes from Europe and other continents showed that both haplogroups are spread throughout Eurasia, while only haplogroup 1 occurs in contemporary North American wolves. All ancient wolf samples from western Europe that dated from between 44,000 and 1,200 years B.P. belonged to haplogroup 2, suggesting the long-term predominance of this haplogroup in this region. Moreover, a comparison of current and past frequencies and distributions of the two haplogroups in Europe suggested that haplogroup 2 became outnumbered by haplogroup 1 during the last several thousand years. Conclusions Parallel haplogroup replacement, with haplogroup 2 being totally replaced by haplogroup 1, has been reported for North American grey wolves. Taking into account the similarity of diets reported for the late Pleistocene wolves from Europe and North America, the correspondence between these haplogroup frequency changes may suggest that they were associated with ecological changes occurring after the Last Glacial Maximum. PMID:20409299

[Correlation analysis of surnames and Y-chromosome genetic heritage in 3 provinces of southwestern Colombia].

PubMed

Gómez, Alberto; Avila, Sandra J; Briceño, Ignacio

2008-09-01

In Colombia, surnames are characters usually passed to the children by the father, and they have been compared to neutral alleles associated with the Y-chromosome. Population frequencies were determined for 17 short tandem repeats (STR) DNA markers on the Y-chromosome to compare the two identity codes and define the correlation between haplotypes and surnames in each individual. DNA was extracted from blood samples from 308 male individuals in provinces of Valle del Cauca, Cauca and Nariño, all in southwestern Colombia. Sample DNA was analyzed with the commercial kit AmpFLSTR Yfiler (Applied Biosystems) and examined for the following 17 Y-chromosome STR markers: DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y-GATA-H4. The frequencies of molecular haplotypes were associated with the surname reported by each individual, and a correlation table was constructed. Amerindian and European surnames were associated with the presence of allele DYS19/13, a characteristic of Amerindian populations. Allele frequencies were reported for each of the 17 STR markers in the southwestern region of Colombia-high genetic and haplotypic diversities were obtained. Approximately 40% of lineage inconsistencies were found when the molecular genotype was compared with the European or Amerindian surnames. Surnames must be used as population markers with reservation. The genetic evidence indicates that traditional genealogies based on surnames with or without documental support, may be inconsistant with their biological provenance.

The methylenetetrahydrofolate reductase 677T-1298C haplotype is a risk factor for acute lymphoblastic leukemia in children.

PubMed

Kałużna, Ewelina Maria; Strauss, Ewa; Świątek-Kościelna, Bogna; Zając-Spychała, Olga; Gowin, Ewelina; Nowak, Jerzy S; Rembowska, Jolanta; Januszkiewicz-Lewandowska, Danuta

2017-12-01

The etiology of acute lymphoblastic leukemia (ALL) is complex, linked with both environmental exposures and genetic factors. Functional variants of the methylenetetrahydrofolate reductase (MTHFR) gene result in disturbance in folate metabolism and may affect susceptibility to cancer. The study was performed to evaluate whether MTHFR C677T and A1298C polymorphisms, analyzed separately and together, are associated with the development of ALL in a population under 18 years of age of Caucasian ancestry.The study included 117 pediatric patients (59% males, mean age at diagnosis 7.4 ± 5.2 years) with ALL, confirmed by conventional immunophenotyping surface-marker analysis and 404 healthy control subjects (48.5% men, mean age 37.7 ± 11.3 years). The MTHFR C677T and A1298C genotypes were analyzed using allele discrimination tests with Taq-Man fluorescent probes.The MTHFR 677TT genotype was related to a 2-fold increase in risk of ALL (P = .014). The 677T-1298C haplotype was found in ALL patients but not in controls (frequency 0.598%; P <.0001). The observed frequency of carriers of this rare haplotype was 12%, including 677CT/1298CC (1.7%), 677TT/1298AC (6.0%), and 677CT/1298AC (4.3%) genotypes.The MTHFR 677T allele alone or in combination with the MTHFR 1298C allele significantly increases the risk of development of ALL in Polish population under 18 years of age. Further studies of haplotype composition in subjects with the 677CT/1298AC genotype are necessary to assess the risk of childhood ALL. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

The methylenetetrahydrofolate reductase 677T-1298C haplotype is a risk factor for acute lymphoblastic leukemia in children

PubMed Central

Kałużna, Ewelina Maria; Strauss, Ewa; Świątek-Kościelna, Bogna; Zając-Spychała, Olga; Gowin, Ewelina; Nowak, Jerzy S.; Rembowska, Jolanta; Januszkiewicz-Lewandowska, Danuta

2017-01-01

Abstract The etiology of acute lymphoblastic leukemia (ALL) is complex, linked with both environmental exposures and genetic factors. Functional variants of the methylenetetrahydrofolate reductase (MTHFR) gene result in disturbance in folate metabolism and may affect susceptibility to cancer. The study was performed to evaluate whether MTHFR C677T and A1298C polymorphisms, analyzed separately and together, are associated with the development of ALL in a population under 18 years of age of Caucasian ancestry. The study included 117 pediatric patients (59% males, mean age at diagnosis 7.4 ± 5.2 years) with ALL, confirmed by conventional immunophenotyping surface-marker analysis and 404 healthy control subjects (48.5% men, mean age 37.7 ± 11.3 years). The MTHFR C677T and A1298C genotypes were analyzed using allele discrimination tests with Taq-Man fluorescent probes. The MTHFR 677TT genotype was related to a 2-fold increase in risk of ALL (P = .014). The 677T-1298C haplotype was found in ALL patients but not in controls (frequency 0.598%; P <.0001). The observed frequency of carriers of this rare haplotype was 12%, including 677CT/1298CC (1.7%), 677TT/1298AC (6.0%), and 677CT/1298AC (4.3%) genotypes. The MTHFR 677T allele alone or in combination with the MTHFR 1298C allele significantly increases the risk of development of ALL in Polish population under 18 years of age. Further studies of haplotype composition in subjects with the 677CT/1298AC genotype are necessary to assess the risk of childhood ALL. PMID:29390492

Association of an MHC Class II Haplotype with Increased Risk of Polymyositis in Hungarian Vizsla Dogs

PubMed Central

Massey, Jonathan; Rothwell, Simon; Rusbridge, Clare; Tauro, Anna; Addicott, Diane; Chinoy, Hector; Cooper, Robert G.; Ollier, William E. R.; Kennedy, Lorna J.

2013-01-01

A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 “graded” controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis. PMID:23457575

Identification of Genetic Variation on the Horse Y Chromosome and the Tracing of Male Founder Lineages in Modern Breeds

PubMed Central

Wallner, Barbara; Vogl, Claus; Shukla, Priyank; Burgstaller, Joerg P.; Druml, Thomas; Brem, Gottfried

2013-01-01

The paternally inherited Y chromosome displays the population genetic history of males. While modern domestic horses (Equus caballus) exhibit abundant diversity within maternally inherited mitochondrial DNA, no significant Y-chromosomal sequence diversity has been detected. We used high throughput sequencing technology to identify the first polymorphic Y-chromosomal markers useful for tracing paternal lines. The nucleotide variability of the modern horse Y chromosome is extremely low, resulting in six haplotypes (HT), all clearly distinct from the Przewalski horse (E. przewalskii). The most widespread HT1 is ancestral and the other five haplotypes apparently arose on the background of HT1 by mutation or gene conversion after domestication. Two haplotypes (HT2 and HT3) are widely distributed at high frequencies among modern European horse breeds. Using pedigree information, we trace the distribution of Y-haplotype diversity to particular founders. The mutation leading to HT3 occurred in the germline of the famous English Thoroughbred stallion “Eclipse” or his son or grandson and its prevalence demonstrates the influence of this popular paternal line on modern sport horse breeds. The pervasive introgression of Thoroughbred stallions during the last 200 years to refine autochthonous breeds has strongly affected the distribution of Y-chromosomal variation in modern horse breeds and has led to the replacement of autochthonous Y chromosomes. Only a few northern European breeds bear unique variants at high frequencies or fixed within but not shared among breeds. Our Y-chromosomal data complement the well established mtDNA lineages and document the male side of the genetic history of modern horse breeds and breeding practices. PMID:23573227

Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms

PubMed Central

NurWaliyuddin, Hanis Z. A.; Norazmi, Mohd N.; Edinur, Hisham A.; Chambers, Geoffrey K.; Panneerchelvam, Sundararajulu; Zafarina, Zainuddin

2015-01-01

The aboriginal populations of Peninsular Malaysia, also known as Orang Asli (OA), comprise three major groups; Semang, Senoi and Proto-Malays. Here, we analyzed for the first time KIR gene polymorphisms for 167 OA individuals, including those from four smallest OA subgroups (Che Wong, Orang Kanaq, Lanoh and Kensiu) using polymerase chain reaction-sequence specific primer (PCR-SSP) analyses. The observed distribution of KIR profiles of OA is heterogenous; Haplotype B is the most frequent in the Semang subgroups (especially Batek) while Haplotype A is the most common type in the Senoi. The Semang subgroups were clustered together with the Africans, Indians, Papuans and Australian Aborigines in a principal component analysis (PCA) plot and shared many common genotypes (AB6, BB71, BB73 and BB159) observed in these other populations. Given that these populations also display high frequencies of Haplotype B, it is interesting to speculate that Haplotype B may be generally more frequent in ancient populations. In contrast, the two Senoi subgroups, Che Wong and Semai are displaced toward Southeast Asian and African populations in the PCA scatter plot, respectively. Orang Kanaq, the smallest and the most endangered of all OA subgroups, has lost some degree of genetic variation, as shown by their relatively high frequency of the AB2 genotype (0.73) and a total absence of KIR2DL2 and KIR2DS2 genes. Orang Kanaq tradition that strictly prohibits intermarriage with outsiders seems to have posed a serious threat to their survival. This present survey is a demonstration of the value of KIR polymorphisms in elucidating genetic relationships among human populations. PMID:26565719

Temporal fluctuation in North East Baltic Sea region cattle population revealed by mitochondrial and Y-chromosomal DNA analyses.

PubMed

Niemi, Marianna; Bläuer, Auli; Iso-Touru, Terhi; Harjula, Janne; Nyström Edmark, Veronica; Rannamäe, Eve; Lõugas, Lembi; Sajantila, Antti; Lidén, Kerstin; Taavitsainen, Jussi-Pekka

2015-01-01

Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y chromosomal haplotypes by new types of cattle.

Temporal Fluctuation in North East Baltic Sea Region Cattle Population Revealed by Mitochondrial and Y-Chromosomal DNA Analyses

PubMed Central

Niemi, Marianna; Bläuer, Auli; Iso-Touru, Terhi; Harjula, Janne; Nyström Edmark, Veronica; Rannamäe, Eve; Lõugas, Lembi; Sajantila, Antti; Lidén, Kerstin; Taavitsainen, Jussi-Pekka

2015-01-01

Background Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Results Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). Conclusions The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y chromosomal haplotypes by new types of cattle. PMID:25992976

Association of methylenetetrahydrofolate reductase (MTHFR 677C>T) and thymidylate synthase (TSER and TS 1494del6) polymorphisms with premature ovarian failure in Korean women.

PubMed

Rah, HyungChul; Jeon, Young Joo; Choi, Youngsok; Shim, Sung Han; Yoon, Tae Ki; Choi, Dong Hee; Cha, Sun Hee; Kim, Nam Keun

2012-11-01

The aim of our study was to investigate whether methylenetetrahydrofolate reductase (MTHFR) gene variant (MTHFR 677C>T) and thymidylate synthase (TS) gene variants (TS enhancer region [TSER] and TS 1494del6) confer a risk for premature ovarian failure (POF). We genotyped 136 POF patients and 236 controls among Korean women for the three single nucleotide polymorphism sites using polymerase chain reaction restriction fragment length polymorphism analysis. Differences in the MTHFR 677C>T, TSER, and TS 1494del6 genotype frequencies between POF patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as a measure of the strength of the association between genotypes and POF. The MTHFR 677CT and CT + TT variant genotypes were more frequent in POF patients than in controls (OR, 2.249; 95% CI, 1.317-3.843; and OR, 2.132; 95% CI, 1.268-3.585, respectively). The combined genotype frequencies of MTHFR 677CT + TT/TSER 3R3R and 677CT + TT/TS 1494del6 del6/del6 were higher in patients than in controls (OR, 2.300; 95% CI, 1.219-4.337; and OR, 3.314; 95% CI, 1.623-6.767, respectively). The T-3R-del6 and T-2R-del6 (MTHFR 677C>T/TSER/TS 1494del6) haplotypes were more frequent in patients (OR, 1.450; 95% CI, 1.050-2.002; and OR, 2.911; 95% CI, 1.191-7.117, respectively), whereas the C-2R-del6 haplotype was less frequent in patients (OR, 0.372; 95% CI, 0.152-0.912). The T-del6 (MTHFR 677/TS 1494del6) haplotype frequency was higher among patients (OR, 1.653; 95% CI, 1.206-2.266), whereas the C-del6 haplotype frequency was lower among patients (OR, 0.700; 95% CI, 0.516-0.950). We did not find an association between TSER or TS 1494del6 polymorphisms and POF. Our data suggest that the MTHFR 677T allele may increase the risk for POF, which could lead to the development of novel genetic markers for predicting the risk of POF in patients.

An Increased Frequency in HLA Class I Alleles and Haplotypes Suggests Genetic Susceptibility to Influenza A (H1N1) 2009 Pandemic: A Case-Control Study

PubMed Central

Narayanankutty, Arun; Reséndiz-Hernández, Juan M.; Nava-Quiroz, Karol J.; Bautista-Félix, Nora E.; Castillejos-López, Manuel D. J.

2018-01-01

Background The influenza A H1N1/09 pandemic infected a small number of exposed individuals, which suggests the involvement of genetic factors. There are scarce data available on classical HLA class I association with the influenza A H1N1/09 pandemic. Methods We analyzed the frequency of classical HLA class I alleles and haplotypes in A H1N1/09 influenza in a case-control study including 138 influenza patients (INF-P) and 225 asymptomatic healthy contacts (INF-C) simultaneously recruited. HLA class I typing was performed by high-resolution sequence-based typing method. Results Our analysis revealed higher frequency of C∗07:02:01, B∗39:06:02, C∗03:02:01, B∗44:03:01, B∗51:01:05, and B∗73:01 (p < 0.05; OR = 1.84–9.98) and of two haplotypes—A∗68:01:02-C∗07:02:01 (p = 1.05E − 05; OR = 23.99) and B∗35:01:01-C∗07:02.01 (p = 4.15E − 04, OR = 2.15)—in A H1N1/09 influenza subjects. A∗68:01:01 was exclusively present only in the INF-P group (5/138). A decrease in the frequency of C∗03:03:01, A∗11:01:01, B∗39:01:01, A∗24:02:01, C∗03:04:01, B∗51:01:01, and C∗07:01:01 (p < 0.05; OR = 0.12–0.52) and of haplotypes A∗02:01:01-B∗35:01:01-C∗04:01:01, A∗24:02:01-B∗35:01:01, B∗39:01:01-C∗07:02:01, and B∗40:02:01-C∗03:04:01 (p < 0.05; OR = 0.08–0.22) were observed in INF-P group. Conclusion Selective classical HLA class I allele and haplotype combinations predispose individuals towards susceptibility or protection against the influenza A H1N1/09 pandemic. This work has significant implications for accessing population transmission risk for A H1N1/09 or a similar strain breakout in the future. PMID:29682588

Insight into the Migration Routes of Plutella xylostella in China Using mtCOI and ISSR Markers

PubMed Central

Tian, Lixia; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Wang, Xiangjing; Wu, Qingjun

2015-01-01

The larvae of the diamondback moth, Plutella xylostella, cause major economic losses to cruciferous crops, including cabbage, which is an important vegetable crop in China. In this study, we used the mitochondrial COI gene and 11 ISSR markers to characterize the genetic structure and seasonal migration routes of 23 P. xylostella populations in China. Both the mitochondrial and nuclear markers revealed high haplotype diversity and gene flow among the populations, although some degree of genetic isolation was evident between the populations of Hainan Island and other sampling sites. The dominant haplotypes, LX1 and LX2, differed significantly from all other haplotypes both in terms of the number of individuals with those haplotypes and their distributions. Haplotypes that were shared among populations revealed that P. xylostella migrates from the lower reaches of the Yangtze River to northern China and then to northeastern China. Our results also revealed another potential migration route for P. xylostella, i.e., from southwestern China to both northwestern and southern China. PMID:26098353

CAPN1, CAST, and DGAT1 genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in a beef cattle population selected for haplotype and allele equalization

USDA-ARS?s Scientific Manuscript database

Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC III) was subjected to marker assisted selection for multiple years to equalize specific marker frequencies to 1) estimate effect size an...

Haplotype combination of the bovine INSIG1 gene sequence variants and association with growth traits in Nanyang cattle.

PubMed

Sun, Jiajie; Gao, Yuan; Liu, Dong; Ma, Wei; Xue, Jing; Zhang, Chunlei; Lan, Xianyong; Lei, Chuzhao; Chen, Hong

2012-06-01

The insulin-induced gene 1 (INSIG1) gene encodes a protein that blocks proteolytic activation of sterol regulatory element binding proteins, which are transcription factors that activate genes that regulate cholesterol, fatty acid, and glucose metabolism. However, similar research for the bovine INSIG1 gene is lacking. Therefore, in this study, polymorphisms of the bovine INSIG1 gene were detected in 643 individuals from four cattle breeds by DNA pooling, forced PCR-RFLP, PCR-SSCP, and DNA sequencing methods. Only 10 novel SNPs were identified, which included four mutations in the coding region and the others in the introns. In Nanyang individuals, seven common haplotypes were identified based on four coding region SNPs. The haplotype GACT, with a frequency of 75.4%, was the most prevalent haplotypes and SNPs formed two linkage disequilibrium blocks with strong multi-allelic D' (D' = 1). Additionally, association analysis between mutations of the bovine INSIG1 gene and growth traits in Nanyang cattle at 6, 12, 18, and 24 months old was performed, and the results indicated that the polymorphisms were not significantly associated with body mass.

Haplotypes and effects on growth traits of bovine Wnt7a gene in Chinese Qinchuan cattle.

PubMed

Xue, Jing; Sun, Yujia; Guo, Wenjiao; Yang, Ziqi; Tian, Huibin; Zhang, Chunlei; Lei, Chuzhao; Lan, Xianyong; Chen, Hong

2013-07-25

Wnt7a is a member of the WNT gene family, which encodes secreted signaling proteins and responds to many biological processes. Specifically Wnt7a influences satellite stem cells and regulates the regenerative potential of the muscle. However, similar researches about the bovine Wnt7a gene are lacking. Therefore, in this study, polymorphisms of the bovine Wnt7a gene were detected in 488 individuals from Chinese Qinchuan cattle by DNA pooling, forced PCR-RFLP, and DNA sequencing methods. 3 novel SNPs were identified, two SNPs (g.T4926C and g.A21943G) were in the intron and the last one (g.C63777T) was in the exon. Five haplotypes involved in these three variant sites in the Wnt7a gene were identified and their effects on growth traits were analyzed. The results revealed that haplotype 1 had the highest haplotype frequencies and was highly significantly associated with body height (P<0.01), body weight (P<0.05), chest width (P<0.05) and height at hip cross (P<0.01) respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetic variability of populations of Nyssomyia neivai in the Northern State of Paraná, Brazil

PubMed Central

Gasparotto, Jaqueline de Carvalho; da Costa-Ribeiro, Magda Clara Vieira; Thomaz-Soccol, Vanete; Liebel, Sandra Mara Rodrigues da Silva; Neitzke-Abreu, Herintha Coeto; Reinhold-Castro, Kárin Rosi; Cristovão, Edilson Colhera; Teodoro, Ueslei

2017-01-01

ABSTRACT The genetic study of sandfly populations needs to be further explored given the importance of these insects for public health. Were sequenced the NDH4 mitochondrial gene from populations of Nyssomyia neivai from Doutor Camargo, Lobato, Japira, and Porto Rico, municipalities in the State of Paraná, Brazil, to understand the genetic structure and gene flow. Eighty specimens of Ny. Neivai were sequenced, 20 from each municipality, and 269 base pairs were obtained. A total of 27 haplotypes and 28 polymorphic sites were found, along with a haplotypic diversity of 0.80696 and a nucleotide diversity of 0.00567. Haplotype H5, with 33 specimens, was the most common among the four populations. Only haplotypes H5 and H7 were present in all four populations. The population from Doutor Camargo showed the highest genetic diversity, and only this population shared haplotypes with those from the other municipalities. The highest number of haplotypes was sheared with Lobato which also had the highest number of unique haplotypes. This probably occurred because of constant anthropic changes that happened in the environment during the first half of the twentieth century, mainly after 1998. There was no significant correlation between genetic and geographical distances regarding these populations. However, the highest genetic and geographical distances, and the lowest gene flow were observed between Japira and Porto Rico. Geographical distance is a possible barrier between these municipalities through the blocking of haplotype sharing. PMID:28380111

Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map

PubMed Central

Haile, Jemanesh K.; Cory, Aron T.; Clarke, Fran R.; Clarke, John M.; Knox, Ron E.; Pozniak, Curtis J.

2017-01-01

Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype-based analysis over single marker analysis to detect loci associated with colour traits in durum wheat. PMID:28135299

Age at cancer onset in germline TP53 mutation carriers: association with polymorphisms in predicted G-quadruplex structures

PubMed Central

Hainaut, Pierre

2014-01-01

Germline TP53 mutations predispose to multiple cancers defining Li-Fraumeni/Li-Fraumeni-like syndrome (LFS/LFL), a disease with large individual disparities in cancer profiles and age of onset. G-quadruplexes (G4s) are secondary structural motifs occurring in guanine tracks, with regulatory effects on DNA and RNA. We analyzed 85 polymorphisms within or near five predicted G4s in TP53 in search of modifiers of penetrance of LFS/LFL in Brazilian cancer families with (n = 35) or without (n = 110) TP53 mutations. Statistical analyses stratified on family structure showed that cancer tended to occur ~15 years later in mutation carriers who also carried the variant alleles of two polymorphisms within predicted G4-forming regions, rs17878362 (TP53 PIN3, 16 bp duplication in intron 3; P = 0.082) and rs17880560 (6 bp duplication in 3′ flanking region; P = 0.067). Haplotype analysis showed that this inverse association was driven by the polymorphic status of the remaining wild-type (WT) haplotype in mutation carriers: in carriers with a WT haplotype containing at least one variant allele of rs17878362 or rs17880560, cancer occurred ~15 years later than in carriers with other WT haplotypes (P = 0.019). No effect on age of cancer onset was observed in subjects without a TP53 mutation. The G4 in intron 3 has been shown to regulate alternative p53 messenger RNA splicing, whereas the biological roles of predicted G4s in the 3′ flanking region remain to be elucidated. In conclusion, this study demonstrates that G4 polymorphisms in haplotypes of the WT TP53 allele have an impact on LFS/LFL penetrance in germline TP53 mutation carriers. PMID:24336192

The Genetic Integrity of the Ex Situ Population of the European Wildcat (Felis silvestris silvestris) Is Seriously Threatened by Introgression from Domestic Cats (Felis silvestris catus)

PubMed Central

Witzenberger, Kathrin A.; Hochkirch, Axel

2014-01-01

Studies on the genetic diversity and relatedness of zoo populations are crucial for implementing successful breeding programmes. The European wildcat, Felis s. silvestris, is subject to intensive conservation measures, including captive breeding and reintroduction. We here present the first systematic genetic analysis of the captive population of Felis s. silvestris in comparison with a natural wild population. We used microsatellites and mtDNA sequencing to assess genetic diversity, structure and integrity of the ex situ population. Our results show that the ex situ population of the European wildcat is highly structured and that it has a higher genetic diversity than the studied wild population. Some genetic clusters matched the breeding lines of certain zoos or groups of zoos that often exchanged individuals. Two mitochondrial haplotype groups were detected in the in situ populations, one of which was closely related to the most common haplotype found in domestic cats, suggesting past introgression in the wild. Although native haplotypes were also found in the captive population, the majority (68%) of captive individuals shared a common mtDNA haplotype with the domestic cat (Felis s. catus). Only six captive individuals (7.7%) were assigned as wildcats in the STRUCTURE analysis (at K = 2), two of which had domestic cat mtDNA haplotypes and only two captive individuals were assigned as purebred wildcats by NewHybrids. These results suggest that the high genetic diversity of the captive population has been caused by admixture with domestic cats. Therefore, the captive population cannot be recommended for further breeding and reintroduction. PMID:25162450

Population Genetic Structure of Rock Bream (Oplegnathus fasciatus Temminck & Schlegel, 1884) Revealed by mtDNA COI Sequence in Korea and China

NASA Astrophysics Data System (ADS)

Park, Hyun Suk; Kim, Choong-Gon; Kim, Sung; Park, Yong-Joo; Choi, Hee-Jung; Xiao, Zhizhong; Li, Jun; Xiao, Yongshuang; Lee, Youn-Ho

2018-04-01

The rock bream, Oplegnathus fasciatus, is a common rocky reef game fish in East Asia and recently has become an aquaculture species. Despite its commercial importance, the population genetic structure of this fish species remains poorly understood. In this study, 163 specimens were collected from 6 localities along the coastal waters of Korea and China and their genetic variation was analyzed with mtDNA COI sequences. A total of 34 polymorphic sites were detected which determined 30 haplotypes. The genetic pattern reveals a low level of nucleotide diversity (0.04 ± 0.003) but a high level of haplotype diversity (0.83 ± 0.02). The 30 haplotypes are divided into two major genealogical clades: one that consists of only Zhoushan (ZS, East China Sea) specific haplotypes from the southern East China Sea and the other that consists of the remaining haplotypes from the northern East China Sea, Yellow Sea, Korea Strait, and East Sea/Sea of Japan. The two clades are separated by approximately 330 435 kyBP. Analyses of AMOVA and F st show a significant population differentiation between the ZS sample and the other ones, corroborating separation of the two genealogical clades. Larval dispersal and the fresh Yangtze River plume are invoked as the main determining factors for this population genetic structure of O. fasciatus. Neutrality tests and mismatch distribution analyses indicate late Pleistocene population expansion along the coastal waters of Korea and China approximately 133-183 kyBP during which there were periodic cycles of glaciations and deglaciations. Such population information needs to be taken into account when stock enhancement and conservation measures are implemented for this fisheries species.

HLA-A, B and DRB1 allele and haplotype frequencies in volunteer bone marrow donors from the north of Parana State.

PubMed

Bardi, Marlene Silva; Jarduli, Luciana Ribeiro; Jorge, Adylson Justino; Camargo, Rossana Batista Oliveira Godoy; Carneiro, Fernando Pagotto; Gelinski, Jair Roberto; Silva, Roseclei Assunção Feliciano; Lavado, Edson Lopes

2012-01-01

Knowledge of allele and haplotype frequencies of the human leukocyte antigen (HLA) system is important in the search for unrelated bone marrow donors. The Brazilian population is very heterogeneous and the HLA system is highly informative of populations because of the high level of polymorphisms. The aim of this study was to characterize the immunogenetic profile of ethnic groups (Caucasians, Afro-Brazilians and Asians) in the north of Parana State. A study was carried out of 3978 voluntary bone marrow donors registered in the Brazilian National Bone Marrow Donor Registry and typed for the HLA-A, B and DRB1 (low resolution) loci. The alleles were characterized by the polymerase chain reaction sequence-specific oligonucleotides method using the LabType SSO kit (One Lambda, CA, USA). The ARLEQUIN v.3.11 computer program was used to calculate allele and haplotype frequencies The most common alleles found in Caucasians were HLA-A*02, 24, 01; HLA-B*35, 44, 51; DRB1*11, 13, 07; for Afro-Brazilians they were HLA-A*02, 03, 30; HLA-B*35, 15, 44; DRB1*13, 11, 03; and for Asians they were: HLA-A*24, 02, 26; HLA-B*40, 51, 52; DRB1*04, 15, 09. The most common haplotype combinations were: HLA-A*01, B*08, DRB1*03 and HLA-A*29, B*44, DRB1*07 for Caucasians; HLA-A*29, B*44, DRB1*07 and HLA-A*01, B*08 and DRB1*03 for Afro-Brazilians; and HLA-A*24, B*52, DRB1*15 and HLA-A*24, B*40 and DRB1*09 for Asians. There is a need to target and expand bone marrow donor campaigns in the north of Parana State. The data of this study may be used as a reference by the Instituto Nacional de Cancer/Brazilian National Bone Marrow Donor Registry to evaluate the immunogenetic profile of populations in specific regions and in the selection of bone marrow donors.

HLA-A, B and DRB1 allele and haplotype frequencies in volunteer bone marrow donors from the north of Parana State

PubMed Central

Bardi, Marlene Silva; Jarduli, Luciana Ribeiro; Jorge, Adylson Justino; Camargo, Rossana Batista Oliveira Godoy; Carneiro, Fernando Pagotto; Gelinski, Jair Roberto; Silva, Roseclei Assunção Feliciano; Lavado, Edson Lopes

2012-01-01

Background Knowledge of allele and haplotype frequencies of the human leukocyte antigen (HLA) system is important in the search for unrelated bone marrow donors. The Brazilian population is very heterogeneous and the HLA system is highly informative of populations because of the high level of polymorphisms. Aim The aim of this study was to characterize the immunogenetic profile of ethnic groups (Caucasians, Afro-Brazilians and Asians) in the north of Parana State. Methods A study was carried out of 3978 voluntary bone marrow donors registered in the Brazilian National Bone Marrow Donor Registry and typed for the HLA-A, B and DRB1 (low resolution) loci. The alleles were characterized by the polymerase chain reaction sequence-specific oligonucleotides method using the LabType SSO kit (One Lambda, CA, USA). The ARLEQUIN v.3.11 computer program was used to calculate allele and haplotype frequencies Results The most common alleles found in Caucasians were HLA-A*02, 24, 01; HLA-B*35, 44, 51; DRB1*11, 13, 07; for Afro-Brazilians they were HLA-A*02, 03, 30; HLA-B*35, 15, 44; DRB1*13, 11, 03; and for Asians they were: HLA-A*24, 02, 26; HLA-B*40, 51, 52; DRB1*04, 15, 09. The most common haplotype combinations were: HLA-A*01, B*08, DRB1*03 and HLA-A*29, B*44, DRB1*07 for Caucasians; HLA-A*29, B*44, DRB1*07 and HLA-A*01, B*08 and DRB1*03 for Afro-Brazilians; and HLA-A*24, B*52, DRB1*15 and HLA-A*24, B*40 and DRB1*09 for Asians. Conclusion There is a need to target and expand bone marrow donor campaigns in the north of Parana State. The data of this study may be used as a reference by the Instituto Nacional de Cancer/Brazilian National Bone Marrow Donor Registry to evaluate the immunogenetic profile of populations in specific regions and in the selection of bone marrow donors PMID:23049380

Genetic Affiliation of Pre-Hispanic and Contemporary Mayas Through Maternal Linage.

PubMed

Ochoa-Lugo, Mirna Isabel; Muñoz, María de Lourdes; Pérez-Ramírez, Gerardo; Beaty, Kristine G; López-Armenta, Mauro; Cervini-Silva, Javiera; Moreno-Galeana, Miguel; Meza, Adrián Martínez; Ramos, Eduardo; Crawford, Michael H; Romano-Pacheco, Arturo

2016-04-01

Maya civilization developed in Mesoamerica and encompassed the Yucatan Peninsula, Guatemala, Belize, part of the Mexican states of Tabasco and Chiapas, and the western parts of Honduras and El Salvador. This civilization persisted approximately 3,000 years and was one of the most advanced of its time, possessing the only known full writing system at the time, as well as art, sophisticated architecture, and mathematical and astronomical systems. This civilization reached the apex of its power and influence during the Preclassic period, from 2000 BCE to 250 CE. Genetic variation in the pre-Hispanic Mayas from archaeological sites in the Mexican states of Yucatan, Chiapas, Quintana Roo, and Tabasco and their relationship with the contemporary communities in these regions have not been previously studied. Consequently, the principal aim of this study was to determine mitochondrial DNA (mtDNA) variation in the pre-Hispanic Maya population and to assess the relationship of these individuals with contemporary Mesoamerican Maya and populations from Asia, Beringia, and North, Central, and South America. Our results revealed interactions and gene flow between populations in the different archaeological sites assessed in this study. The mtDNA haplogroup frequency in the pre-Hispanic Maya population (60.53%, 34.21%, and 5.26% for haplogroups A, C, and D, respectively) was similar to that of most Mexican and Guatemalan Maya populations, with haplogroup A exhibiting the highest frequency. Haplogroup B most likely arrived independently and mixed with populations carrying haplogroups A and C based on its absence in the pre-Hispanic Mexican Maya populations and low frequencies in most Mexican and Guatemalan Maya populations, although this also may be due to drift. Maya and Ciboneys sharing haplotype H10 belonged to haplogroup C1 and haplotype H4 of haplogroup D, suggesting shared regional haplotypes. This may indicate a shared genetic ancestry, suggesting more regional interaction between populations in the circum-Caribbean region than previously demonstrated. Haplotype sharing between the pre-Hispanic Maya and the indigenous populations from Asia, the Aleutian Islands, and North, Central, and South America provides evidence for gene flow from the ancestral Amerindian population of the pre-Hispanic Maya to Central and South America.

Predictive value of interleukin-10 promoter genotypes and haplotypes in determining the susceptibility to nephropathy in type 2 diabetes patients.

PubMed

Mtiraoui, Nabil; Ezzidi, Intissar; Kacem, Maha; Ben Hadj Mohamed, Manel; Chaieb, Molka; Haj Jilani, Aoutef Bel; Mahjoub, Touhami; Almawi, Wassim Y

2009-01-01

The IL-10 promoter polymorphisms -1082G/A, -819C/T, and -592C/A have been consistently associated with type 2 diabetes (T2DM). We examined whether these polymorphisms variants are also associated with progression of diabetic nephropathy (DN). These promoter variants were genotyped in 917 T2DM patients comprising 515 DN patients and 402 control patients without nephropathy (DWN), together with 748 non-diabetic control subjects. Haplotype analysis and multivariate regression analysis were employed in assessing the contribution of IL-10 haplotypes to DN risk, using genotype, clinical and biochemical profile, and their interactions as predictors of DN. Carriers of mutant -592A and -819T alleles, and -819T/T, -592A/A, and -819C/T genotypes were more frequent in T2DM. However, the -819C/T genotype appeared to be protective of DN, since lower frequency -819T allele and -819C/T genotype were seen in DN patients. Regression analysis identified -1082G/-819T/-592A (GTA) and -1082G/-819T/-592C (GTC) haplotypes as DN-protective haplotypes. Relative to the -1082G/-819C/-592C haplotype, GTA [P = 0.044; odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.30-0.98] and GTC (P = 0.045; OR = 0.56, 95% CI: 0.31-0.99) haplotypes were associated with decreased odds ratio (OR) for DN, after controlling for a number of covariates (age, sex, body mass index (BMI), hypertension, glucose, HbA(1c), DN duration, total cholesterol). Our results indicate that genetic variations at the IL-10 promoter influence the risk of nephropathy in T2DM patients and thus represent a potential DN genetic-susceptibility locus worthy of replication. Copyright 2009 John Wiley & Sons, Ltd.

Common polymorphisms of calpain-10 and the risk of Type 2 Diabetes in a Tunisian Arab population: a case-control study

PubMed Central

2010-01-01

Background Genetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D). Methods We examined the association of CAPN10 UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) SNPs with T2D in 917 Tunisian T2D patients and 748 non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP. Results Enrichment of UCSNP-19 2R (minor) allele and 2R/2R genotype was found in T2D patients; the allele and genotype distribution of UCSNP-43 and UCSNP-63 alleles and genotypes were not significantly different between patient groups and non-diabetic control subjects. Regression analysis demonstrated progressive increases in T2D risk in 3R/2R [OR (95% CI) = 1.35 (1.08 - 1.68)] and 2R/2R [OR (95% CI) = 1.61 (1.20 - 2.18)] genotypes. Of the six haplotypes detected, enrichment of haplotype 111 (UCSNP-43/UCSNP-19/UCSNP-63) was seen in patients (Pc = 0.034); the distribution of the other haplotypes was comparable between patients and control subjects; neither haplotype 211 nor haplotype 212 was observed. Furthermore, the frequency of all CAPN10 diplotypes identified, including the "high-risk diplotype (112/121) reported for Mexican-Americans and Northern Europeans, were comparable between patients and controls. Conclusions CAPN10 UCSNP-19 variant, and the 111 haplotype contribute to the risk of T2D in Tunisian subjects; no significant associations between CAPN10 diplotypes and T2D were demonstrated for Tunisians. PMID:20470430

Genetic epidemiology of the beta s gene.

PubMed

Nagel, R L; Fleming, A F

1992-04-01

The beta s gene arose at least four times in Africa, with three of these mutations expanding through diverse ethnic groups, but limited to definite geographical areas: Atlantic west Africa for the Senegal haplotype linked beta s; central west Africa for the Benin haplotype; and equatorial, eastern and southern Africa for the Bantu haplotype. The fourth mutation (linked to the Cameroon haplotype) is restricted to a single ethnic group, the Eton of central Cameroon. The Benin haplotype linked beta s gene was spread by gene flow to the Mediterranean (north, south and east) and to the western portions of Saudi Arabia. An independent mutation linked to a fifth haplotype, Arab-India, is found among the tribals of India (independent from their geographical origin) and in the eastern oases of Saudi Arabia. It is also suspected of being associated with the beta s gene found in Afghanistan, Iran, Transcaucasia and central Asia. The selective force involved in the expansion of the gene was most likely P. falciparum malaria, and the time of the gene frequency increase was likely to have been during the expansion of agriculture about 4000 or more years ago in India and about 3000 years ago in Africa. The partial protection against severe and life-threatening malaria is through the limitation of P. falciparum parasitaemia. This is a complex process which involves at least two mechanisms: early intraerythrocyte parasite forms are in a suicidal position through increasing the tendency of HbAS cell to sickle and then be destroyed by the spleen; intraerythrocyte growth is inhibited during deep vascular schizogony. Although there is evidence that P. falciparum (and P. malariae) parasitaemias are limited in HbSS red cells, malaria is a major trigger to haemolytic and infarctive crises in sickle-cell disease, and a common cause of morbidity and mortality.

Genetic deviation in geographically close populations of the dengue vector Aedes aegypti (Diptera: Culicidae): influence of environmental barriers in South India.

PubMed

Vadivalagan, Chithravel; Karthika, Pushparaj; Murugan, Kadarkarai; Panneerselvam, Chellasamy; Paulpandi, Manickam; Madhiyazhagan, Pari; Wei, Hui; Aziz, Al Thabiani; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Nicoletti, Marcello; Paramasivan, Rajaiah; Dinesh, Devakumar; Benelli, Giovanni

2016-03-01

Mosquitoes are vectors of devastating pathogens and parasites, causing millions of deaths every year. Dengue is a mosquito-borne viral infection found in tropical and subtropical regions around the world. Recently, dengue transmission has strongly increased in urban and semiurban areas, becoming a major international public health concern. Aedes aegypti (Diptera: Culicidae) is a primary vector of dengue. Shedding light on genetic deviation in A. aegypti populations is of crucial importance to fully understand their molecular ecology and evolution. In this research, haplotype and genetic analyses were conducted using individuals of A. aegypti from 31 localities in the north, southeast, northeast and central regions of Tamil Nadu (South India). The mitochondrial DNA region of cytochrome c oxidase 1 (CO1) gene was used as marker for the analyses. Thirty-one haplotypes sequences were submitted to GenBank and authenticated. The complete haplotype set included 64 haplotypes from various geographical regions clustered into three groups (lineages) separated by three fixed mutational steps, suggesting that the South Indian Ae. aegypti populations were pooled and are linked with West Africa, Columbian and Southeast Asian lineages. The genetic and haplotype diversity was low, indicating reduced gene flow among close populations of the vector, due to geographical barriers such as water bodies. Lastly, the negative values for neutrality tests indicated a bottle-neck effect and supported for low frequency of polymorphism among the haplotypes. Overall, our results add basic knowledge to molecular ecology of the dengue vector A. aegypti, providing the first evidence for multiple introductions of Ae. aegypti populations from Columbia and West Africa in South India.

Genetic analysis of autoimmune regulator haplotypes in alopecia areata.

PubMed

Wengraf, D A; McDonagh, A J G; Lovewell, T R J; Vasilopoulos, Y; Macdonald-Hull, S P; Cork, M J; Messenger, A G; Tazi-Ahnini, R

2008-03-01

Alopecia areata is an immune-mediated disorder, occurring with the highest observed frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected association between alopecia areata and a single nucleotide polymorphism (SNP) in the AIRE gene in patients without APECED, and we now report the findings of an extended examination of the association of alopecia areata with haplotype analysis including six SNPs in the AIRE gene: C-103T, C4144G, T5238C, G6528A, T7215C and T11787C. In Caucasian groups of 295 patients and 363 controls, we found strong association between the AIRE 7215C allele and AA [P = 3.8 x 10(-8), OR (95% CI): 2.69 (1.8-4.0)]. The previously reported association between AA and the AIRE 4144G allele was no longer significant on correction for multiple testing. The AIRE haplotypes CCTGCT and CGTGCC showed a highly significant association with AA [P = 6.05 x 10(-6), 9.47 (2.91-30.8) and P = 0.001, 3.51 (1.55-7.95), respectively]. To select the haplotypes most informative for analysis, we tagged the polymorphisms using SNPTag software. Employing AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, two haplotypes were associated with AA; AIRE CGCT and AIRE CGCC [P = 3.84 x 10(-7), 11.40 (3.53-36.9) and P = 3.94 x 10(-4), 2.13 (1.39-3.24) respectively]. The AIRE risk haplotypes identified in this study potentially account for a major component of the genetic risk of developing alopecia areata.

Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank.

PubMed

Howard, David M; Adams, Mark J; Clarke, Toni-Kim; Wigmore, Eleanor M; Zeng, Yanni; Hagenaars, Saskia P; Lyall, Donald M; Thomson, Pippa A; Evans, Kathryn L; Porteous, David J; Nagy, Reka; Hayward, Caroline; Haley, Chris S; Smith, Blair H; Murray, Alison D; Batty, G David; Deary, Ian J; McIntosh, Andrew M

2017-01-01

Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. In the present analysis, three cohort studies (n total = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P -value overlapped with the D-amino acid oxidase activator ( DAOA ) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer's disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10 -7 ), was the butyrylcholinesterase ( BCHE ) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer's disease and its role in cognitive ability merits further investigation. Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect.

Genetic structure of the Caribbean giant barrel sponge Xestospongia muta using the I3-M11 partition of COI

NASA Astrophysics Data System (ADS)

López-Legentil, S.; Pawlik, J. R.

2009-03-01

In recent years, reports of sponge bleaching, disease, and subsequent mortality have increased alarmingly. Population recovery may depend strongly on colonization capabilities of the affected species. The giant barrel sponge Xestospongia muta is a dominant reef constituent in the Caribbean. However, little is known about its population structure and gene flow. The 5'-end fragment of the mitochondrial gene cytochrome oxidase subunit I is often used to address these kinds of questions, but it presents very low intraspecific nucleotide variability in sponges. In this study, the usefulness of the I3-M11 partition of COI to determine the genetic structure of X. muta was tested for seven populations from Florida, the Bahamas and Belize. A total of 116 sequences of 544 bp were obtained for the I3-M11 partition corresponding to four haplotypes. In order to make a comparison with the 5'-end partition, 10 sequences per haplotype were analyzed for this fragment. The 40 resulting sequences were of 569 bp and corresponded to two haplotypes. The nucleotide diversity of the I3-M11 partition (π = 0.00386) was higher than that of the 5'-end partition (π = 0.00058), indicating better resolution at the intraspecific level. Sponges with the most divergent external morphologies (smooth vs. digitate surface) had different haplotypes, while those with the most common external morphology (rough surface) presented a mixture of haplotypes. Pairwise tests for genetic differentiation among geographic locations based on F ST values showed significant genetic divergence between most populations, but this genetic differentiation was not due to isolation by distance. While limited larval dispersal may have led to differentiation among some of the populations, the patterns of genetic structure appear to be most strongly related to patterns of ocean currents. Therefore, hydrological features may play a major role in sponge colonization and need to be considered in future plans for management and conservation of these important components of coral reef ecosystems.

Population structure of the large Japanese field mouse, Apodemus speciosus (Rodentia: Muridae), in suburban landscape, based on mitochondrial D-loop sequences.

PubMed

Hirota, Tadao; Hirohata, Tetsuo; Mashima, Hiroshi; Satoh, Toshiyuki; Obara, Yoshiaki

2004-11-01

Genetic structure of the large Japanese field mouse populations in suburban landscape of West Tokyo, Japan was determined using mitochondrial DNA control region sequence. Samples were collected from six habitats linked by forests and green tract along the Tama River, and from two forests segregated by urban areas from those continuous habitats. Thirty-five haplotypes were detected in 221 animals. Four to eight haplotypes were found within each local population belonging to the continuous landscape. Some haplotypes were shared by two or three adjacent local populations. On the other hand, two isolated habitats were occupied by one or two indigenous haplotypes. Significant genetic differentiation between all pairs of local populations, except for one pair in the continuous habitats, was found by analysis of molecular variance (amova). The geographical distance between habitats did not explain the large variance of pairwise F(ST)-values among local populations. F(ST)-values between local populations segregated by urban areas were higher than those between local populations in the continuous habitat, regardless of geographical distance. The results of this study demonstrated quantitatively that urban areas inhibit the migration of Apodemus speciosus, whereas a linear green tract along a river functions as a corridor. Moreover, it preserves the metapopulation structure of A. speciosus as well as the corridors in suburban landscape.

Comparison of phasing strategies for whole human genomes

PubMed Central

Kirkness, Ewen; Schork, Nicholas J.

2018-01-01

Humans are a diploid species that inherit one set of chromosomes paternally and one homologous set of chromosomes maternally. Unfortunately, most human sequencing initiatives ignore this fact in that they do not directly delineate the nucleotide content of the maternal and paternal copies of the 23 chromosomes individuals possess (i.e., they do not ‘phase’ the genome) often because of the costs and complexities of doing so. We compared 11 different widely-used approaches to phasing human genomes using the publicly available ‘Genome-In-A-Bottle’ (GIAB) phased version of the NA12878 genome as a gold standard. The phasing strategies we compared included laboratory-based assays that prepare DNA in unique ways to facilitate phasing as well as purely computational approaches that seek to reconstruct phase information from general sequencing reads and constructs or population-level haplotype frequency information obtained through a reference panel of haplotypes. To assess the performance of the 11 approaches, we used metrics that included, among others, switch error rates, haplotype block lengths, the proportion of fully phase-resolved genes, phasing accuracy and yield between pairs of SNVs. Our comparisons suggest that a hybrid or combined approach that leverages: 1. population-based phasing using the SHAPEIT software suite, 2. either genome-wide sequencing read data or parental genotypes, and 3. a large reference panel of variant and haplotype frequencies, provides a fast and efficient way to produce highly accurate phase-resolved individual human genomes. We found that for population-based approaches, phasing performance is enhanced with the addition of genome-wide read data; e.g., whole genome shotgun and/or RNA sequencing reads. Further, we found that the inclusion of parental genotype data within a population-based phasing strategy can provide as much as a ten-fold reduction in phasing errors. We also considered a majority voting scheme for the construction of a consensus haplotype combining multiple predictions for enhanced performance and site coverage. Finally, we also identified DNA sequence signatures associated with the genomic regions harboring phasing switch errors, which included regions of low polymorphism or SNV density. PMID:29621242

Molecular characterization of swine leukocyte antigen gene diversity in purebred Pietrain pigs.

PubMed

Essler, Sabine E; Ertl, Werner; Deutsch, Julia; Ruetgen, Barbara C; Groiss, Sandra; Stadler, Maria; Wysoudil, Bhuma; Gerner, Wilhelm; Ho, Chak-Sum; Saalmueller, Armin

2013-04-01

The porcine major histocompatibility complex (MHC) harbors the highly polymorphic swine leukocyte antigen (SLA) class I and II gene clusters encoding glycoproteins that present antigenic peptides to T cells in the adaptive immune response. In Austria, the majority of commercial pigs are F 2 descendants of F 1 Large White/Landrace hybrids paired with Pietrain boars. Therefore, the repertoire of SLA alleles and haplotypes present in Pietrain pigs has an important influence on that of their descendants. In this study, we characterized the SLA class I ( SLA-1 , SLA-2 , SLA-3 ) and class II ( SLA-DRB1 , SLA-DQB1 , SLA-DQA ) genes of 27 purebred Pietrain pigs using a combination of the high-resolution sequence-based typing (SBT) method and a low-resolution (Lr) PCR-based method using allele-group, sequence-specific primers (PCR-SSP). A total of 15 class I and 13 class II haplotypes were identified in the studied cohort. The most common SLA class I haplotype Lr-43.0 ( SLA-1 *11XX- SLA-3 *04XX- SLA-2 *04XX) was identified in 11 animals with a frequency of 20%. For SLA class II, the most prevalent haplotype, Lr-0.14 [ SLA-DRB1 *0901- SLA-DQB1 *0801- SLA-DQA *03XX], was found in 14 animals with a frequency of 26%. Two class II haplotypes, tentatively designated as Lr-Pie-0.1 [ SLA-DRB1 *01XX/be01/ha04- SLA-DQB1 *05XX- SLA - DQA*blank] and Lr-Pie-0.2 [ SLA-DRB1 *06XX- SLA-DQB1 *03XX- SLA-DQA *03XX], appeared to be novel and have never been reported so far in other pig populations. We showed that SLA genotyping using PCR-SSP-based assays represents a rapid and cost-effective way to study SLA diversity in outbred commercial pigs and may facilitate the development of more effective vaccines or identification of disease-resistant pigs in the context of SLA antigens to improve overall swine health. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

PubMed

do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

2014-06-01

Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

PubMed Central

do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

2014-01-01

Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45–4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

Haplotypes in SLC24A5 Gene as Ancestry Informative Markers in Different Populations

PubMed Central

Giardina, Emiliano; Pietrangeli, Ilenia; Martínez-Labarga, Cristina; Martone, Claudia; de Angelis, Flavio; Spinella, Aldo; De Stefano, Gianfranco; Rickards, Olga; Novelli, Giuseppe

2008-01-01

Ancestry informative markers (AIMs) are human polymorphisms that exhibit substantially allele frequency differences among populations. These markers can be useful to provide information about ancestry of samples which may be useful in predicting a perpetrator’s ethnic origin to aid criminal investigations. Variations in human pigmentation are the most obvious phenotypes to distinguish individuals. It has been recently shown that the variation of a G in an A allele of the coding single-nucleotide polymorphism (SNP) rs1426654 within SLC24A5 gene varies in frequency among several population samples according to skin pigmentation. Because of these observations, the SLC24A5 locus has been evaluated as Ancestry Informative Region (AIR) by typing rs1426654 together with two additional intragenic markers (rs2555364 and rs16960620) in 471 unrelated individuals originating from three different continents (Africa, Asia and Europe). This study further supports the role of human SLC24A5 gene in skin pigmentation suggesting that variations in SLC24A5 haplotypes can correlate with human migration and ancestry. Furthermore, our data do reveal the utility of haplotype and combined unphased genotype analysis of SLC24A5 in predicting ancestry and provide a good example of usefulness of genetic characterization of larger regions, in addition to single polymorphisms, as candidates for population-specific sweeps in the ancestral population. PMID:19440451

Divergent evolution of life span associated with mitochondrial DNA evolution.

PubMed

Stojković, Biljana; Sayadi, Ahmed; Đorđević, Mirko; Jović, Jelena; Savković, Uroš; Arnqvist, Göran

2017-01-01

Mitochondria play a key role in ageing. The pursuit of genes that regulate variation in life span and ageing have shown that several nuclear-encoded mitochondrial genes are important. However, the role of mitochondrial encoded genes (mtDNA) is more controversial and our appreciation of the role of mtDNA for the evolution of life span is limited. We use replicated lines of seed beetles that have been artificially selected for long or short life for >190 generations, now showing dramatic phenotypic differences, to test for a possible role of mtDNA in the divergent evolution of ageing and life span. We show that these divergent selection regimes led to the evolution of significantly different mtDNA haplotype frequencies. Selection for a long life and late reproduction generated positive selection for one specific haplotype, which was fixed in most such lines. In contrast, selection for reproduction early in life led to both positive selection as well as negative frequency-dependent selection on two different haplotypes, which were both present in all such lines. Our findings suggest that the evolution of life span was in part mediated by mtDNA, providing support for the emerging general tenet that adaptive evolution of life-history syndromes may involve mtDNA. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease.

PubMed

Alshiekh, S; Zhao, L P; Lernmark, Å; Geraghty, D E; Naluai, Å T; Agardh, D

2017-08-01

Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value < .0001). In a subpopulation analysis, DRB3*01:01:02-DQA1*05:01-DQB1*02:01 remained the most significant in patients with Scandinavian ethnicity (RR = 4.63; P < .0001) whereas DRB1*07:01:01-DRB4*01:03:01-DQA1*02:01-DQB1*02:02:01 presented the highest risk of celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Phylogeography, post-glacial gene flow, and population history of North American goshawks (Accipeter gentilis)

USGS Publications Warehouse

Bayard De Volo, Shelley; Reynolds, Richard T.; Sonsthagen, Sarah A.; Talbot, Sandra; Antolin, Michael F.

2013-01-01

Climate cycling during the Quaternary played a critical role in the diversification of avian lineages in North America, greatly influencing the genetic characteristics of contemporary populations. To test the hypothesis that North American Northern Goshawks (Accipitergentilis) were historically isolated within multiple Late Pleistocene refugia, we assessed diversity and population genetic structure as well as migration rates and signatures of historical demography using mitochondrial control-region data. On the basis of sampling from 24 locales, we found that Northern Goshawks were genetically structured across a large portion of their North American range. Long-term population stability, combined with strong genetic differentiation, suggests that Northern Goshawks were historically isolated within at least three refugial populations representing two regions: the Pacific (CascadesSierra-Vancouver Island) and the Southwest (Colorado Plateau and Jemez Mountains). By contrast, populations experiencing significant growth were located in the Southeast Alaska-British Columbia, Arizona Sky Islands, Rocky Mountains, Great Lakes, and Appalachian bioregions. In the case of Southeast Alaska-British Columbia, Arizona Sky Islands, and Rocky Mountains, Northern Goshawks likely colonized these regions from surrounding refugia. The near fixation for several endemic haplotypes in the Arizona Sky Island Northern Goshawks (A. g apache) suggests long-term isolation subsequent to colonization. Likewise, Great Lakes and Appalachian Northern Goshawks differed significantly in haplotype frequencies from most Western Northern Goshawks, which suggests that they, too, experienced long-term isolation prior to a more recent recolonization of eastern U.S. forests.

Reemergence of chloroquine-sensitive pfcrt K76 Plasmodium falciparum genotype in southeastern Cameroon.

PubMed

Ndam, Nicaise Tuikue; Basco, Leonardo K; Ngane, Vincent Foumane; Ayouba, Ahidjo; Ngolle, Eitel Mpoudi; Deloron, Philippe; Peeters, Martine; Tahar, Rachida

2017-03-27

Chloroquine had been used extensively during the last five decades in Cameroon. Its decreasing clinical effectiveness, supported by high proportions of clinical isolates carrying the mutant pfcrt haplotype (CVIET), led the health authorities to resort to amodiaquine monotherapy in 2002 and artemisinin-based combination therapy (ACT) in 2004 (artesunate-amodiaquine, with artemether-lumefantrine as an alternative since 2006) as the first-line treatment of uncomplicated malaria. The aim of the present study was to investigate whether the withdrawal of chloroquine was associated with a reduction in pfcrt mutant parasite population and reemergence of chloroquine-sensitive parasites in southeastern Cameroon between 2003 and 2012. The frequency of pfcrt haplotypes at positions 72-76 in Plasmodium falciparum isolates collected from individuals in 2003 and 2012 in southeastern Cameroon was determined by sequence specific oligonucleotide probes-enzyme linked immunosorbent assay (SSOP-ELISA). The proportions of parasites carrying the mutant haplotype CVIET and the wild-type CVMNK were 53.0 and 28.0% in 2003, respectively. The proportion of the mutant haplotype in samples collected 9 years later decreased to 25.3% whereas the proportion of parasites carrying the wild-type CVMNK haplotype was 53.7%. Even though the proportion of chloroquine-sensitive parasites seems to be increasing in southeastern Cameroon, a reintroduction of chloroquine cannot be recommended at present in Cameroon. The current national anti-malarial drug policy should be implemented and reinforced to combat drug-resistant malaria.

Dominant Sequences of Human Major Histocompatibility Complex Conserved Extended Haplotypes from HLA-DQA2 to DAXX

PubMed Central

Larsen, Charles E.; Alford, Dennis R.; Trautwein, Michael R.; Jalloh, Yanoh K.; Tarnacki, Jennifer L.; Kunnenkeri, Sushruta K.; Fici, Dolores A.; Yunis, Edmond J.; Awdeh, Zuheir L.; Alper, Chester A.

2014-01-01

We resequenced and phased 27 kb of DNA within 580 kb of the MHC class II region in 158 population chromosomes, most of which were conserved extended haplotypes (CEHs) of European descent or contained their centromeric fragments. We determined the single nucleotide polymorphism and deletion-insertion polymorphism alleles of the dominant sequences from HLA-DQA2 to DAXX for these CEHs. Nine of 13 CEHs remained sufficiently intact to possess a dominant sequence extending at least to DAXX, 230 kb centromeric to HLA-DPB1. We identified the regions centromeric to HLA-DQB1 within which single instances of eight “common” European MHC haplotypes previously sequenced by the MHC Haplotype Project (MHP) were representative of those dominant CEH sequences. Only two MHP haplotypes had a dominant CEH sequence throughout the centromeric and extended class II region and one MHP haplotype did not represent a known European CEH anywhere in the region. We identified the centromeric recombination transition points of other MHP sequences from CEH representation to non-representation. Several CEH pairs or groups shared sequence identity in small blocks but had significantly different (although still conserved for each separate CEH) sequences in surrounding regions. These patterns partly explain strong calculated linkage disequilibrium over only short (tens to hundreds of kilobases) distances in the context of a finite number of observed megabase-length CEHs comprising half a population's haplotypes. Our results provide a clearer picture of European CEH class II allelic structure and population haplotype architecture, improved regional CEH markers, and raise questions concerning regional recombination hotspots. PMID:25299700

Association of HLA haplotype with alopecia areata in Chinese Hans.

PubMed

Xiao, F-L; Ye, D-Q; Yang, S; Zhou, F-S; Zhou, S-M; Zhu, Y-G; Liang, Y-H; Ren, Y-Q; Zhang, X-J

2006-11-01

Some studies have shown discrepancies in human leucocyte antigen (HLA) associated with alopecia areata (AA) between different ethnic populations. To investigate whether HLA-I, -DQA1 and -DQB1 alleles and the HLA haplotype are associated with AA, and the correlation between the HLA haplotype profile, age of onset and severity of AA in Chinese Hans. The polymerase chain reaction-sequence specific primer (PCR-SSP) method was used to analyse the frequencies of HLA class I, -DQA1 and -DQB1 alleles in 192 patients with AA and 252 controls in Chinese Hans. The linkage disequilibrium was calculated using the 2 x 2 table. The 24 two-locus haplotypes [including A*02-B*18, A*02-B*27, A*02-B*52, A*02-Cw*0704, A*02-DQA1*0104, A*02-DQB1*0604, A*02-DQB1*0606, B*18-Cw*0704, B*18-DQA1*0104, B*18-DQA1*0302, B*18-DQB1*0606, B*27-Cw*0704, B*27-DQA1*0104, B*27-DQA1*0302, B*52-Cw*0704, B*52-DQA1*0104, B*52-DQA1*0302, B52-DQB1*0606, Cw*0704-DQA1*0104, Cw*0704-DQA1*0302, Cw*0704-DQB1*0606, DQA1*0104-DQB1*0604, DQA1*0104-DQB1*0606, DQA1*0302-DQB1*0606 (P<0.05)] were associated with AA, while eight extended haplotypes (A*02-B*18-DQA1*0104, A*02-B*27-DQA1*0104, A*02-B*52-DQA1*0104, A*02-B*52-DQA1*0302, A*02-B*52-DQB1*0606, B*52-Cw*0704-DQA1*0104, B*52-Cw*0704-DQA1*0302, A*02-B*52-DQA1*0302-DQB1*0606) were found to be related to AA in Chinese Hans. Through stratified analysis, we found that the extended haplotype B*52-Cw*0704-DQA1*0302 was related to early onset of AA, and no haplotype was only associated with severe AA. This is the first detailed report to elucidate HLA haplotypes associated with AA and that demonstrates the significant HLA haplotypes in Chinese Hans AA. The haplotype B*52-Cw*0704-DQA1*0302 was identified to be related to early onset of AA. Our results provide some information for future research on predisposing genes in HLA regions in Chinese Hans.

Nucleotide-binding oligomerization domain containing 1 (NOD1) haplotypes and single nucleotide polymorphisms modify susceptibility to inflammatory bowel diseases in a New Zealand caucasian population: a case-control study

PubMed Central

Huebner, Claudia; Ferguson, Lynnette R; Han, Dug Yeo; Philpott, Martin; Barclay, Murray L; Gearry, Richard B; McCulloch, Alan; Demmers, Pieter S; Browning, Brian L

2009-01-01

Background The nucleotide-binding oligomerization domain containing 1 (NOD1) gene encodes a pattern recognition receptor that senses pathogens, leading to downstream responses characteristic of innate immunity. We investigated the role of NOD1 single nucleotide polymorphisms (SNPs) on IBD risk in a New Zealand Caucasian population, and studied Nod1 expression in response to bacterial invasion in the Caco2 cell line. Findings DNA samples from 388 Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis patients and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in NOD1, using the MassARRAY® iPLEX Gold assay. Transcriptional activation of the protein produced by NOD1 (Nod1) was studied after infection of Caco2 cells with Escherichia coli LF82. Carrying the rs2075818 G allele decreased the risk of CD (OR = 0.66, 95% CI = 0.50–0.88, p < 0.002) but not UC. There was an increased frequency of the three SNP (rs2075818, rs2075822, rs2907748) haplotype, CTG (p = 0.004) and a decreased frequency of the GTG haplotype (p = 0.02).in CD. The rs2075822 CT or TT genotypes were at an increased frequency (genotype p value = 0.02), while the rs2907748 AA or AG genotypes showed decreased frequencies in UC (p = 0.04), but not in CD. Functional assays showed that Nod1 is produced 6 hours after bacterial invasion of the Caco2 cell line. Conclusion The NOD1 gene is important in signalling invasion of colonic cells by pathogenic bacteria, indicative of its' key role in innate immunity. Carrying specific SNPs in this gene significantly modifies the risk of CD and/or UC in a New Zealand Caucasian population. PMID:19327158

TAS2R38 and CA6 genetic polymorphisms, frequency of bitter food intake, and blood biomarkers among elderly woman.

PubMed

Mikołajczyk-Stecyna, Joanna; Malinowska, Anna M; Chmurzynska, Agata

2017-09-01

Taste sensitivity is one of the most important biological determinants of food choice. Three SNPs of the TAS2R38 gene (rs713598, rs1726866, and rs10246939) give rise to two common haplotypes: PAV and AVI. These haplotypes, as well as an SNP within the CA6 gene (rs2274333) that encodes carbonic anhydrase VI (CA6), correlate with bitterness perception. The extent of consumption of bitter food may influence some health outcomes. The aim of this study is thus to investigate the impact of the TAS2R38 and CA6 genetic polymorphisms on the choice of bitter food, BMI, blood lipoprotein, and glucose concentrations as well as systemic inflammation in elderly women. The associations between the TAS2R38 diplotype, CA6 genotype, and the intake of bitter-tasting foods were studied in a group of 118 Polish women over 60 years of age. The intake of Brassica vegetables, grapefruit, and coffee was assessed using a food frequency questionnaire. Biochemical parameters were measured using the spectrophotometric method. Genotyping was performed using the high resolution melting method. We found a correlation between lipid profile, glucose and CRP levels, and frequency of bitter food intake. The AVI/AVI subjects drank coffee more frequently than did the PAV/PAV homozygotes, as did the A carriers of CA6 in comparison with the GG homozygotes. We also observed that simultaneous carriers of the PAV haplotype and A allele of TAS2R38 and CA6, respectively, choose white cabbage more frequent and had lower plasma levels of CRP and glucose than did AVI/AVI and GG homozygotes. In elderly women, the TAS2R38 and CA6 polymorphisms may affect the frequency of consumption of coffee and white cabbage, but not of other bitter-tasting foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of HLA class I alleles with aloplecia areata in Chinese Hans.

PubMed

Xiao, Feng-Li; Yang, Sen; Yan, Kai-lin; Cui, Yong; Liang, Yan-Hua; Zhou, Fu-Sheng; Du, Wen-Hui; Gao, Min; Sun, Liang-Dan; Fan, Xing; Chen, Jian-Jun; Wang, Pei-Guang; Zhu, Ya-Gang; Zhou, Shun-Ming; Zhang, Xue-Jun

2006-02-01

Some studies suggested that human HLA status may potentiate development of the AA phenotype and exists ethic differences. No report has been published about HLA class I alleles associated with AA in Chinese Hans. To study the distribution of HLA class I alleles and haplotypes in Chinese Hans AA patients and the relation of HLA class I profile with age of onset, severity, duration of current attack, past history and family history. The polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA class I alleles in 192 patients with AA and 252 healthy controls in Chinese Hans. The frequencies of HLA-A*02, -A*03, -B*18, -B*27, -B*52 and -Cw*0704 were significantly higher in patients than in controls. The A*2-B*18, A*2-B*27, A*2-B*52, A*2-Cw*0704, B*18-Cw*0704, B*27-Cw*0704, B*52-Cw*0704 were found as high-risk haplotypes in developing AA in this study. The HLA-A*02 and -A*03 were observed increased frequencies in patients less than 50% hair loss, and HLA-B*27 equally in patients of 50-99% hair loss, alopecia totalis and alopecia universalis. The frequencies of HLA-A*02 and -B*27 were significantly raised in recurrent patients, and ones of HLA-A*02, -A*03 and -B*27 similarly in patients without a positive family history. This study demonstrated the positive association of HLA class I alleles and haplotypes with AA. There may be differences in genetic background in patients with different age of onset, grade of scalp hair loss, duration of current attack, a past history and a family history.

An EPAS1 haplotype is associated with high altitude polycythemia in male Han Chinese at the Qinghai-Tibetan plateau.

PubMed

Chen, Yu; Jiang, Chunhua; Luo, Yongjun; Liu, Fuyu; Gao, Yuqi

2014-12-01

Hemoglobin concentration at high altitude is considered an important marker of high altitude adaptation, and native Tibetans in the Qinghai-Tibetan plateau show lower hemoglobin concentrations than Han people who have emigrated from plains areas. Genetic studies revealed that EPAS1 plays a key role in high altitude adaptation and is associated with the low hemoglobin concentration in Tibetans. Three single nucleotide polymorphisms (rs13419896, rs4953354, rs1868092) of noncoding regions in EPAS1 exhibited significantly different allele frequencies in the Tibetan and Han populations and were associated with low hemoglobin concentrations in Tibetans. To explore the hereditary basis of high altitude polycythemia (HAPC) and investigate the association between EPAS1 and HAPC in the Han population, these 3 single nucleotide polymorphisms were assessed in 318 male Han Chinese HAPC patients and 316 control subjects. Genotyping was performed by high resolution melting curve analysis. The G-G-G haplotype of rs13419896, rs4953354, and rs1868092 was significantly more frequent in HAPC patients than in control subjects, whereas no differences in the allele or genotype frequencies of the 3 single nucleotide polymorphisms were found between HAPC patients and control subjects. Moreover, genotypes of rs1868092 (AA) and rs4953354 (GG) that were not observed in the Chinese Han in the Beijing population were found at frequencies of 1.6% and 0.9%, respectively, in our study population of HAPC patients and control subjects. Carriers of this EPAS1 haplotype (G-G-G, rs13419896, rs4953354, and rs1868092) may have a higher risk for HAPC. These results may contribute to a better understanding of the pathogenesis of HAPC in the Han population. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Regional differences in the distribution of the sub-Saharan, West Eurasian, and South Asian mtDNA lineages in Yemen.

PubMed

Cerný, Viktor; Mulligan, Connie J; Rídl, Jakub; Zaloudková, Martina; Edens, Christopher M; Hájek, Martin; Pereira, Luísa

2008-06-01

Despite its key location for population movements out of and back into Africa, Yemen has not yet been sampled on a regional level for an investigation of sub-Saharan, West Eurasian, and South Asian genetic contributions. In this study, we present mitochondrial DNA (mtDNA) data for regionally distinct Yemeni populations that reveal different distributions of mtDNA lineages. An extensive database of mtDNA sequences from North and East African, Middle Eastern and Indian populations was analyzed to provide a context for the regional Yemeni mtDNA datasets. The groups of western Yemen appear to be most closely related to Middle Eastern and North African populations, while the eastern Yemeni population from Hadramawt is most closely related to East Africa. Furthermore, haplotype matches with Africa are almost exclusively confined to West Eurasian R0a haplogroup in southwestern Yemen, although more sub-Saharan L-type matches appear in more northern Yemeni populations. In fact, Yemeni populations have the highest frequency of R0a haplotypes detected to date, thus Yemen or southern Arabia may be the site of the initial expansion of this haplogroup. Whereas two variants of the sub-Saharan haplogroup M1 were detected only in southwestern Yemen close to the Bab el-Mandeb Strait, different non-African M haplotypes were detected at low frequencies (approximately 2%) in western parts of the country and at a higher frequency (7.5%) in the Hadramawt. We conclude that the Yemeni gene pool is highly stratified both regionally and temporally and that it has received West Eurasian, Northeast African, and South Asian gene flow. Copyright 2008 Wiley-Liss, Inc.

HLA Diversity in the 1000 Genomes Dataset

PubMed Central

Gourraud, Pierre-Antoine; Khankhanian, Pouya; Cereb, Nezih; Yang, Soo Young; Feolo, Michael; Maiers, Martin; D. Rioux, John; Hauser, Stephen; Oksenberg, Jorge

2014-01-01

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC), only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD) decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies. PMID:24988075

HLA diversity in the 1000 genomes dataset.

PubMed

Gourraud, Pierre-Antoine; Khankhanian, Pouya; Cereb, Nezih; Yang, Soo Young; Feolo, Michael; Maiers, Martin; Rioux, John D; Hauser, Stephen; Oksenberg, Jorge

2014-01-01

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC), only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD) decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies.

Copy number variation of human AMY1 is a minor contributor to variation in salivary amylase expression and activity.

PubMed

Carpenter, Danielle; Mitchell, Laura M; Armour, John A L

2017-02-20

Salivary amylase in humans is encoded by the copy variable gene AMY1 in the amylase gene cluster on chromosome 1. Although the role of salivary amylase is well established, the consequences of the copy number variation (CNV) at AMY1 on salivary amylase protein production are less well understood. The amylase gene cluster is highly structured with a fundamental difference between odd and even AMY1 copy number haplotypes. In this study, we aimed to explore, in samples from 119 unrelated individuals, not only the effects of AMY1 CNV on salivary amylase protein expression and amylase enzyme activity but also whether there is any evidence for underlying difference between the common haplotypes containing odd numbers of AMY1 and even copy number haplotypes. AMY1 copy number was significantly correlated with the variation observed in salivary amylase production (11.7% of variance, P < 0.0005) and enzyme activity (13.6% of variance, P < 0.0005) but did not explain the majority of observed variation between individuals. AMY1-odd and AMY1-even haplotypes showed a different relationship between copy number and expression levels, but the difference was not statistically significant (P = 0.052). Production of salivary amylase is correlated with AMY1 CNV, but the majority of interindividual variation comes from other sources. Long-range haplotype structure may affect expression, but this was not significant in our data.

Genetic relationships among some subspecies of the Peregrine Falcon (Falco peregrinus L.), inferred from mitochondrial DNA control-region sequences

USGS Publications Warehouse

White, Clayton M.; Sonsthagen, Sarah A.; Sage, George K.; Anderson, Clifford; Talbot, Sandra L.

2013-01-01

The ability to successfully colonize and persist in diverse environments likely requires broad morphological and behavioral plasticity and adaptability, and this may partly explain why the Peregrine Falcon (Falco peregrinus) exhibits a large range of morphological characteristics across their global distribution. Regional and local differences within Peregrine Falcons were sufficiently variable that ∼75 subspecies have been described; many were subsumed, and currently 19 are generally recognized. We used sequence information from the control region of the mitochondrial genome to test for concordance between genetic structure and representatives of 12 current subspecies and from two areas where subspecies distributions overlap. Haplotypes were broadly shared among subspecies, and all geographic locales shared a widely distributed common haplotype (FalconCR2). Haplotypes were distributed in a star-like phylogeny, consistent with rapid expansion of a recently derived species, with observed genetic patterns congruent with incomplete lineage sorting and/or differential rates of evolution on morphology and neutral genetic characters. Hierarchical analyses of molecular variance did not uncover genetic partitioning at the continental level, despite strong population-level structure (FST = 0.228). Similar analyses found weak partitioning, albeit significant, among subspecies (FCT = 0.138). All reconstructions placed the hierofalcons' (Gyrfalcon [F. rusticolus] and Saker Falcon [F. cherrug]) haplotypes in a well-supported clade either basal or unresolved with respect to the Peregrine Falcon. In addition, haplotypes representing Taita Falcon (F. fasciinucha) were placed within the Peregrine Falcon clade.

Mitochondrial cytochrome b sequence variations and population structure of Siberian chipmunk (Tamias sibiricus) in Northeastern Asia and population substructure in South Korea.

PubMed

Lee, Mu-Yeong; Lissovsky, Andrey A; Park, Sun-Kyung; Obolenskaya, Ekaterina V; Dokuchaev, Nikolay E; Zhang, Ya-Ping; Yu, Li; Kim, Young-Jun; Voloshina, Inna; Myslenkov, Alexander; Choi, Tae-Young; Min, Mi-Sook; Lee, Hang

2008-12-31

Twenty-five chipmunk species occur in the world, of which only the Siberian chipmunk, Tamias sibiricus, inhabits Asia. To investigate mitochondrial cytochrome b sequence variations and population structure of the Siberian chipmunk in northeastern Asia, we examined mitochondrial cytochrome b sequences (1140 bp) from 3 countries. Analyses of 41 individuals from South Korea and 33 individuals from Russia and northeast China resulted in 37 haplotypes and 27 haplotypes, respectively. There were no shared haplotypes between South Korea and Russia--northeast China. Phylogenetic trees and network analysis showed 2 major maternal lineages for haplotypes, referred to as the S and R lineages. Haplotype grouping in each cluster was nearly coincident with its geographic affinity. In particular, 3 distinct groups were found that mostly clustered in the northern, central and southern parts of South Korea. Nucleotide diversity of the S lineage was twice that of lineage R. The divergence between S and R lineages was estimated to be 2.98-0.98 Myr. During the ice age, there may have been at least 2 refuges in South Korea and Russia--northeast China. The sequence variation between the S and R lineages was 11.3% (K2P), which is indicative of specific recognition in rodents. These results suggest that T. sibiricus from South Korea could be considered a separate species. However, additional information, such as details of distribution, nuclear genes data or morphology, is required to strengthen this hypothesis.

Use of massively parallel pyrosequencing to evaluate the diversity of and selection on Plasmodium falciparum csp T-cell epitopes in Lilongwe, Malawi.

PubMed

Bailey, Jeffrey A; Mvalo, Tisungane; Aragam, Nagesh; Weiser, Matthew; Congdon, Seth; Kamwendo, Debbie; Martinson, Francis; Hoffman, Irving; Meshnick, Steven R; Juliano, Jonathan J

2012-08-15

The development of an effective malaria vaccine has been hampered by the genetic diversity of commonly used target antigens. This diversity has led to concerns about allele-specific immunity limiting the effectiveness of vaccines. Despite extensive genetic diversity of circumsporozoite protein (CS), the most successful malaria vaccine is RTS/S, a monovalent CS vaccine. By use of massively parallel pyrosequencing, we evaluated the diversity of CS haplotypes across the T-cell epitopes in parasites from Lilongwe, Malawi. We identified 57 unique parasite haplotypes from 100 participants. By use of ecological and molecular indexes of diversity, we saw no difference in the diversity of CS haplotypes between adults and children. We saw evidence of weak variant-specific selection within this region of CS, suggesting naturally acquired immunity does induce variant-specific selection on CS. Therefore, the impact of CS vaccines on variant frequencies with widespread implementation of vaccination requires further study.

Phylogeography of the West Indian manatee (Trichechus manatus): How many populations and how many taxa?

USGS Publications Warehouse

Garcia-Rodriguez, A. I.; Bowen, B.W.; Domning, D.; Mignucci-Giannoni, A. A.; Marmontel, M.; Montoya-Ospina, R. A.; Morales-Vela, B.; Rudin, M.; Bonde, R.K.; McGuire, P.M.

1998-01-01

To resolve the population genetic structure and phylogeography of the West Indian manatee (Trichechus manatus), mitochondrial (mt) DNA control region sequences were compared among eight locations across the western Atlantic region. Fifteen haplotypes were identified among 86 individuals from Florida, Puerto Rico, the Dominican Republic, Mexico, Colombia, Venezuela, Guyana and Brazil. Despite the manatee's ability to move thousands of kilometres along continental margins, strong population separations between most locations were demonstrated with significant haplotype frequency shifts. These findings are consistent with tagging studies which indicate that stretches of open water and unsuitable coastal habitats constitute substantial barriers to gene flow and colonization. Low levels of genetic diversity within Florida and Brazilian samples might be explained by recent colonization into high latitudes or bottleneck effects. Three distinctive mtDNA lineages were observed in an intraspecific phylogeny of T. manatus, corresponding approximately to: (i) Florida and the West Indies; (ii) the Gulf of Mexico to the Caribbean rivers of South America; and (iii) the northeast Atlantic coast of South America. These lineages, which are not concordant with previous subspecies designations, are separated by sequence divergence estimates of d = 0.04-0.07, approximately the same level of divergence observed between T. manatus and the Amazonian manatee (T. inunguis, n = 16). Three individuals from Guyana, identified as T. manatus, had mtDNA haplotypes which are affiliated with the endemic Amazon form T. inunguis. The three primary T. manatus lineages and the T. inunguis lineage may represent relatively deep phylogeographic partitions which have been bridged recently due to changes in habitat availability (after the Wisconsin glacial period, 10 000 BP), natural colonization, and human-mediated transplantation.

Mixed-stock analysis reveals the migrations of juvenile hawksbill turtles (Eretmochelys imbricata) in the Caribbean Sea.

PubMed

Bowen, B W; Grant, W S; Hillis-Starr, Z; Shaver, D J; Bjorndal, K A; Bolten, A B; Bass, A L

2007-01-01

Hawksbill turtles (Eretmochelys imbricata) migrate between nesting beaches and feeding habitats that are often associated with tropical reefs, but it is uncertain which nesting colonies supply which feeding habitats. To address this gap in hawksbill biology, we compile previously published and new mitochondrial DNA (mtDNA) haplotype data for 10 nesting colonies (N = 347) in the western Atlantic and compare these profiles to four feeding populations and four previously published feeding samples (N = 626). Nesting colonies differ significantly in mtDNA haplotype frequencies (Phi(ST) = 0.588, P < 0.001), corroborating earlier conclusions of nesting site fidelity and setting the stage for mixed-stock analysis. Feeding aggregations show lower but significant structure (Phi(ST) = 0.089, P < 0.001), indicating that foraging populations are not homogenous across the Caribbean Sea. Bayesian mixed-stock estimates of the origins of juveniles in foraging areas show a highly significant, but shallow, correlation with nesting population size (r = 0.378, P = 0.004), supporting the premise that larger rookeries contribute more juveniles to feeding areas. A significant correlation between the estimated contribution and geographical distance from nesting areas (r = -0.394, P = 0.003) demonstrates the influence of proximity on recruitment to feeding areas. The influence of oceanic currents is illustrated by pelagic stage juveniles stranded in Texas, which are assigned primarily (93%) to the upstream rookery in Yucatan. One juvenile had a haplotype previously identified only in the eastern Atlantic, invoking rare trans-oceanic migrations. The mixed-stock analysis demonstrates that harvests in feeding habitats will impact nesting colonies throughout the region, with the greatest detriment to nearby nesting populations.

A CT-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer’s disease and affects SNCA expression

PubMed Central

Lutz, Michael W.; Saul, Robert; Linnertz, Colton; Glenn, Omolara-Chinue; Roses, Allen D.; Chiba-Falek, Ornit

2015-01-01

INTRODUCTION We recently showed that tagging-SNPs across the SNCA locus were significantly associated with increased risk for LB pathology in AD cases. However, the actual genetic variant(s) that underlie the observed associations remain elusive. METHODS We used a bioinformatics algorithm to catalogue Structural-Variants in a region of SNCA-intron4, followed by phased-sequencing. We performed a genetic-association analysis in autopsy series of LBV/AD cases compared with AD-only controls. We investigated the biological functions by expression analysis using temporal-cortex samples. RESULTS We identified four distinct haplotypes within a highly-polymorphic-low-complexity CT-rich region. We showed that a specific haplotype conferred risk to develop LBV/AD. We demonstrated that the CT-rich site acts as an enhancer element, where the risk haplotype was significantly associated with elevated levels of SNCA-mRNA. DISCUSSION We have discovered a novel haplotype in a CT-rich region in SNCA that contributes to LB pathology in AD patients, possibly via cis-regulation of the gene expression. PMID:26079410

Population Genetic Structure of the Magnificent Frigatebird Fregata magnificens (Aves, Suliformes) Breeding Colonies in the Western Atlantic Ocean

PubMed Central

Nuss, Andressa; Carlos, Caio J.; Moreno, Ignacio B.; Fagundes, Nelson J. R.

2016-01-01

The Magnificent Frigatebird Fregata magnificens has a pantropical distribution, nesting on islands along the Atlantic and Pacific coasts. In the Caribbean, there is little genetic structure among colonies; however, the genetic structure among the colonies off Brazil and its relationship with those in the Caribbean are unknown. In this study, we used mtDNA and microsatellite markers to infer population structure and evolutionary history in a sample of F. magnificens individuals collected in Brazil, Grand Connétable (French Guyana), and Barbuda. Virtually all Brazilian individuals had the same mtDNA haplotype. There was no haplotype sharing between Brazil and the Caribbean, though Grand Connétable shared haplotypes with both regions. A Bayesian clustering analysis using microsatellite data found two genetic clusters: one associated with Barbuda and the other with the Brazilian populations. Grand Connétable was more similar to Barbuda but had ancestry from both clusters, corroborating its “intermediate” position. The Caribbean and Grand Connétable populations showed higher genetic diversity and effective population size compared to the Brazilian population. Overall, our results are in good agreement with an effect of marine winds in isolating the Brazilian meta-population. PMID:26901878

Integration of genotoxicity and population genetic analyses in kangaroo rats (Dipodomys merriami) exposed to radionuclide contamination at the Nevada Test Site, USA

USGS Publications Warehouse

Theodorakis, Christopher W.; Bickham, John W.; Lamb, Trip; Medica, Philip A.; Lyne, T. Barrett

2001-01-01

We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotype individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.

Computational intelligence in bioinformatics: SNP/haplotype data in genetic association study for common diseases.

PubMed

Kelemen, Arpad; Vasilakos, Athanasios V; Liang, Yulan

2009-09-01

Comprehensive evaluation of common genetic variations through association of single-nucleotide polymorphism (SNP) structure with common complex disease in the genome-wide scale is currently a hot area in human genome research due to the recent development of the Human Genome Project and HapMap Project. Computational science, which includes computational intelligence (CI), has recently become the third method of scientific enquiry besides theory and experimentation. There have been fast growing interests in developing and applying CI in disease mapping using SNP and haplotype data. Some of the recent studies have demonstrated the promise and importance of CI for common complex diseases in genomic association study using SNP/haplotype data, especially for tackling challenges, such as gene-gene and gene-environment interactions, and the notorious "curse of dimensionality" problem. This review provides coverage of recent developments of CI approaches for complex diseases in genetic association study with SNP/haplotype data.

Genetic profile of scrapie codons 146, 211 and 222 in the PRNP gene locus in three breeds of dairy goats.

PubMed

Vouraki, Sotiria; Gelasakis, Athanasios I; Alexandri, Panoraia; Boukouvala, Evridiki; Ekateriniadou, Loukia V; Banos, Georgios; Arsenos, Georgios

2018-01-01

Polymorphisms at PRNP gene locus have been associated with resistance against classical scrapie in goats. Genetic selection on this gene within appropriate breeding programs may contribute to the control of the disease. The present study characterized the genetic profile of codons 146, 211 and 222 in three dairy goat breeds in Greece. A total of 766 dairy goats from seven farms were used. Animals belonged to two indigenous Greek, Eghoria (n = 264) and Skopelos (n = 287) and a foreign breed, Damascus (n = 215). Genomic DNA was extracted from blood samples from individual animals. Polymorphisms were detected in these codons using Real-Time PCR analysis and four different Custom TaqMan® SNP Genotyping Assays. Genotypic, allelic and haplotypic frequencies were calculated based on individual animal genotypes. Chi-square tests were used to examine Hardy-Weinberg equilibrium state and compare genotypic distribution across breeds. Genetic distances among the three breeds, and between these and 30 breeds reared in other countries were estimated based on haplotypic frequencies using fixation index FST with Arlequin v3.1 software; a Neighbor-Joining tree was created using PHYLIP package v3.695. Level of statistical significance was set at P = 0.01. All scrapie resistance-associated alleles (146S, 146D, 211Q and 222K) were detected in the studied population. Significant frequency differences were observed between the indigenous Greek and Damascus breeds. Alleles 222K and 146S had the highest frequency in the two indigenous and the Damascus breed, respectively (ca. 6.0%). The studied breeds shared similar haplotypic frequencies with most South Italian and Turkish breeds but differed significantly from North-Western European, Far East and some USA goat breeds. Results suggest there is adequate variation in the PRNP gene locus to support breeding programs for enhanced scrapie resistance in goats reared in Greece. Genetic comparisons among goat breeds indicate that separate breeding programs should apply to the two indigenous and the imported Damascus breeds.

A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain.

PubMed

Callén, Elsa; Casado, José A; Tischkowitz, Marc D; Bueren, Juan A; Creus, Amadeu; Marcos, Ricard; Dasí, Angeles; Estella, Jesús M; Muñoz, Arturo; Ortega, Juan J; de Winter, Johan; Joenje, Hans; Schindler, Detlev; Hanenberg, Helmut; Hodgson, Shirley V; Mathew, Christopher G; Surrallés, Jordi

2005-03-01

Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure and cancer predisposition. Here we have identified Spanish Gypsies as the ethnic group with the world's highest prevalence of FA (carrier frequency of 1/64-1/70). DNA sequencing of the FANCA gene in 8 unrelated Spanish Gypsy FA families after retroviral subtyping revealed a homozygous FANCA mutation (295C>T) leading to FANCA truncation and FA pathway disruption. This mutation appeared specific for Spanish Gypsies as it is not found in other Gypsy patients with FA from Hungary, Germany, Slovakia, and Ireland. Haplotype analysis showed that Spanish Gypsy patients all share the same haplotype. Our data thus suggest that the high incidence of FA among Spanish Gypsies is due to an ancestral founder mutation in FANCA that originated in Spain less than 600 years ago. The high carrier frequency makes the Spanish Gypsies a population model to study FA heterozygote mutations in cancer.

Two distinct mtDNA lineages of the blue crab reveal large-scale population structure in its native Atlantic distribution

NASA Astrophysics Data System (ADS)

Alaniz Rodrigues, Marcos; Dumont, Luiz Felipe Cestari; dos Santos, Cléverson Rannieri Meira; D'Incao, Fernando; Weiss, Steven; Froufe, Elsa

2017-10-01

For the first time, a molecular approach was used to evaluate the phylogenetic structure of the disjunct native American distribution of the blue crab Callinectes sapidus. Population structure was investigated by sequencing 648bp of the Cytochrome oxidase subunit 1 (COI), in a total of 138 sequences stemming from individual samples from both the northern and southern hemispheres of the Western Atlantic distribution of the species. A Bayesian approach was used to construct a phylogenetic tree for all samples, and a 95% confidence parsimony network was created to depict the relationship among haplotypes. Results revealed two highly distinct lineages, one containing all samples from the United States and some from Brazil (lineage 1) and the second restricted to Brazil (lineage 2). In addition, gene flow (at least for females) was detected among estuaries at local scales and there is evidence for shared haplotypes in the south. Furthermore, the findings of this investigation support the contemporary introduction of haplotypes that have apparently spread from the south to the north Atlantic.

Polymorphisms of the resistin gene and their association with obesity and resistin levels in Malaysian Malays.

PubMed

Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Su, Tin Tin; Majid, Hazreen Abdul; Bulgiba, Awang; Mohamed, Zahurin

2015-06-01

Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers.

Association of human leukocyte antigen class II allele and haplotypes in chikungunya viral infection in a western Indian population.

PubMed

Thanapati, Subrat; Hande, Aparna; Das, Rumki; Gurav, Yogesh; Tripathy, Anuradha S

2014-05-01

Genes coding for human leukocyte antigen (HLA) class II molecules are polymorphic and have been shown to influence susceptibility to viral diseases. One hundred patients with acute chikungunya with and without viral load and 250 chikungunya negative controls from western India were studied for the distribution of HLA class II alleles by PCR with sequence-specific primer (SSP) method. Frequency of DRB1*11 allele group (patients vs controls: p=0.002, Pc=0.036, OR=0.21) and haplotype DRB1*11/DQB1*03 (patients vs controls: p=0.007, OR=0.15) were significantly low, while haplotype DRB1*04/DQB1*03 (patients vs controls: p=0.042, OR=1.94) was significantly high in the patient population. HLA DQB1*04 allele was found only in the patient group with viral load (n=17), suggesting possible involvement of the same with chikungunya virus (CHIKV) replication. Association of HLA-DRB1*11 and the emergence of DRB1*11/DQB1*03 & DRB1*04/DQB1*03 as resistant and susceptible haplotypes towards CHIKV infection is being reported for the first time. Our results suggest that genetic susceptibility and/or resistance to chikungunya infection may be modulated by HLA class II alleles.

Following the footprints of polymorphic inversions on SNP data: from detection to association tests

PubMed Central

Cáceres, Alejandro; González, Juan R.

2015-01-01

Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease. PMID:25672393

The Phylogeographical Pattern and Conservation of the Chinese Cobra (Naja atra) across Its Range Based on Mitochondrial Control Region Sequences

PubMed Central

Lin, Long-Hui; Hua, Lei; Qu, Yan-Fu; Gao, Jian-Fang; Ji, Xiang

2014-01-01

The vulnerable Chinese cobra (Naja atra) ranges from southeastern China south of the Yangtze River to northern Vietnam and Laos. Large mountain ranges and water bodies may influence the pattern of genetic diversity of this species. We sequenced the mitochondrial DNA control region (1029 bp) using 285 individuals collected from 23 localities across the species' range and obtained 18 sequences unique to Taiwan from GenBank for phylogenetic and population analysis. Two distinct clades were identified, one including haplotypes from the two westernmost localities (Hekou and Miyi) and the other including haplotypes from all sampling sites except Miyi. A strong population structure was found (Φst = 0.76, P<0.0001) with high haplotype diversity (h = 1.00) and low nucleotide diversity (π = 0.0049). The Luoxiao and Nanling Mountains act as historical geographical barriers limiting gene exchange. In the haplotype network there were two “star” clusters. Haplotypes from populations east of the Luoxiao Mountains were represented within one cluster and haplotypes from populations west of the mountain range within the other, with haplotypes from populations south of the Nanling Mountains in between. Lineage sorting between mainland and island populations is incomplete. It remains unknown as to how much adaptive differentiation there is between population groups or within each group. We caution against long-distance transfers within any group, especially when environmental differences are apparent. PMID:25184236

The phylogeographical pattern and conservation of the Chinese cobra (Naja atra) across its range based on mitochondrial control region sequences.

PubMed

Lin, Long-Hui; Hua, Lei; Qu, Yan-Fu; Gao, Jian-Fang; Ji, Xiang

2014-01-01

The vulnerable Chinese cobra (Naja atra) ranges from southeastern China south of the Yangtze River to northern Vietnam and Laos. Large mountain ranges and water bodies may influence the pattern of genetic diversity of this species. We sequenced the mitochondrial DNA control region (1029 bp) using 285 individuals collected from 23 localities across the species' range and obtained 18 sequences unique to Taiwan from GenBank for phylogenetic and population analysis. Two distinct clades were identified, one including haplotypes from the two westernmost localities (Hekou and Miyi) and the other including haplotypes from all sampling sites except Miyi. A strong population structure was found (Φst = 0.76, P<0.0001) with high haplotype diversity (h = 1.00) and low nucleotide diversity (π = 0.0049). The Luoxiao and Nanling Mountains act as historical geographical barriers limiting gene exchange. In the haplotype network there were two "star" clusters. Haplotypes from populations east of the Luoxiao Mountains were represented within one cluster and haplotypes from populations west of the mountain range within the other, with haplotypes from populations south of the Nanling Mountains in between. Lineage sorting between mainland and island populations is incomplete. It remains unknown as to how much adaptive differentiation there is between population groups or within each group. We caution against long-distance transfers within any group, especially when environmental differences are apparent.

Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family.

PubMed

Redondo, Rodrigo A F; de Vladar, Harold P; Włodarski, Tomasz; Bollback, Jonathan P

2017-01-01

Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima. © 2017 The Authors.

Hierarchical spatial genetic structure in a distinct population segment of greater sage-grouse

USGS Publications Warehouse

Oyler-McCance, Sara J.; Casazza, Michael L.; Fike, Jennifer A.; Coates, Peter S.

2014-01-01

Greater sage-grouse (Centrocercus urophasianus) within the Bi-State Management Zone (area along the border between Nevada and California) are geographically isolated on the southwestern edge of the species’ range. Previous research demonstrated that this population is genetically unique, with a high proportion of unique mitochondrial DNA (mtDNA) haplotypes and with significant differences in microsatellite allele frequencies compared to populations across the species’ range. As a result, this population was considered a distinct population segment (DPS) and was recently proposed for listing as threatened under the U.S. Endangered Species Act. A more comprehensive understanding of the boundaries of this genetically unique population (where the Bi-State population begins) and an examination of genetic structure within the Bi-State is needed to help guide effective management decisions. We collected DNA from eight sampling locales within the Bi-State (N = 181) and compared those samples to previously collected DNA from the two most proximal populations outside of the Bi-State DPS, generating mtDNA sequence data and amplifying 15 nuclear microsatellites. Both mtDNA and microsatellite analyses support the idea that the Bi-State DPS represents a genetically unique population, which has likely been separated for thousands of years. Seven mtDNA haplotypes were found exclusively in the Bi-State population and represented 73 % of individuals, while three haplotypes were shared with neighboring populations. In the microsatellite analyses both STRUCTURE and FCA separate the Bi-State from the neighboring populations. We also found genetic structure within the Bi-State as both types of data revealed differences between the northern and southern part of the Bi-State and there was evidence of isolation-by-distance. STRUCTURE revealed three subpopulations within the Bi-State consisting of the northern Pine Nut Mountains (PNa), mid Bi-State, and White Mountains (WM) following a north–south gradient. This genetic subdivision within the Bi-State is likely the result of habitat loss and fragmentation that has been exacerbated by recent human activities and the encroachment of singleleaf pinyon (Pinus monophylla) and juniper (Juniperus spp.) trees. While genetic concerns may be only one of many priorities for the conservation and management of the Bi-State greater sage-grouse, we believe that they warrant attention along with other issues (e.g., quality of sagebrush habitat, preventing future loss of habitat). Management actions that promote genetic connectivity, especially with respect to WM and PNa, may be critical to the long-term viability of the Bi-State DPS.

Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation.

PubMed

Mishra, Anshuman; Nizammuddin, Sheikh; Mallick, Chandana Basu; Singh, Sakshi; Prakash, Satya; Siddiqui, Niyamat Ali; Rai, Niraj; Carlus, S Justin; Sudhakar, Digumarthi V S; Tripathi, Vishnu P; Möls, Märt; Kim-Howard, Xana; Dewangan, Hemlata; Mishra, Abhishek; Reddy, Alla G; Roy, Biswajit; Pandey, Krishna; Chaubey, Gyaneshwer; Das, Pradeep; Nath, Swapan K; Singh, Lalji; Thangaraj, Kumarasamy

2017-03-01

Our understanding of the genetics of skin pigmentation has been largely skewed towards populations of European ancestry, imparting less attention to South Asian populations, who behold huge pigmentation diversity. Here, we investigate skin pigmentation variation in a cohort of 1,167 individuals in the Middle Gangetic Plain of the Indian subcontinent. Our data confirm the association of rs1426654 with skin pigmentation among South Asians, consistent with previous studies, and also show association for rs2470102 single nucleotide polymorphism. Our haplotype analyses further help us delineate the haplotype distribution across social categories and skin color. Taken together, our findings suggest that the social structure defined by the caste system in India has a profound influence on the skin pigmentation patterns of the subcontinent. In particular, social category and associated single nucleotide polymorphisms explain about 32% and 6.4%, respectively, of the total phenotypic variance. Phylogeography of the associated single nucleotide polymorphisms studied across 52 diverse populations of the Indian subcontinent shows wide presence of the derived alleles, although their frequencies vary across populations. Our results show that both polymorphisms (rs1426654 and rs2470102) play an important role in the skin pigmentation diversity of South Asians. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Genetic Evidence for Modifying Oceanic Boundaries Relative to Fiji.

PubMed

Shipley, Gerhard P; Taylor, Diana A; N'Yeurt, Antoine D R; Tyagi, Anand; Tiwari, Geetanjali; Redd, Alan J

2016-07-01

We present the most comprehensive genetic characterization to date of five Fijian island populations: Viti Levu, Vanua Levu, Kadavu, the Lau Islands, and Rotuma, including nonrecombinant Y (NRY) chromosome and mitochondrial DNA (mtDNA) haplotypes and haplogroups. As a whole, Fijians are genetically intermediate between Melanesians and Polynesians, but the individual Fijian island populations exhibit significant genetic structure reflecting different settlement experiences in which the Rotumans and the Lau Islanders were more influenced by Polynesians, and the other Fijian island populations were more influenced by Melanesians. In particular, Rotuman and Lau Islander NRY chromosomal and mtDNA haplogroup frequencies and Rotuman mtDNA hypervariable segment 1 region haplotypes more closely resemble those of Polynesians, while genetic markers of the other populations more closely resemble those of the Near Oceanic Melanesians. Our findings provide genetic evidence supportive of modifying regional boundaries relative to Fiji, as has been suggested by others based on a variety of nongenetic evidence. Specifically, for the traditional Melanesia/Polynesia/Micronesia scheme, our findings support moving the Melanesia-Polynesia boundary to include Rotuma and the Lau Islands in Polynesia. For the newer Near/Remote Oceania scheme, our findings support keeping Rotuma and the Lau Islands in Remote Oceania and locating the other Fijian island populations in an intermediate or "Central Oceania" region to better reflect the great diversity of Oceania.

Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population.

PubMed

Liu, Xiaoxi; Kawamura, Yoshiya; Shimada, Takafumi; Otowa, Takeshi; Koishi, Shinko; Sugiyama, Toshiro; Nishida, Hisami; Hashimoto, Ohiko; Nakagami, Ryoichi; Tochigi, Mamoru; Umekage, Tadashi; Kano, Yukiko; Miyagawa, Taku; Kato, Nobumasa; Tokunaga, Katsushi; Sasaki, Tsukasa

2010-03-01

The oxytocin receptor (OXTR) gene, which is located on chromosome 3p25.3, has been implicated as a candidate gene for susceptibility of autism spectrum disorder (ASD). Positive associations between OXTR and ASD have been reported in earlier studies. However, the results were inconsistent and demand further studies. In this study, we investigated the associations between OXTR and ASD in a Japanese population by analyzing 11 single-nucleotide polymorphisms (SNPs) using both family-based association test (FBAT) and population-based case-control test. No significant signal was detected in the FBAT test. However, significant differences were observed in allelic frequencies of four SNPs, including rs2254298 between patients and controls. The risk allele of rs2254298 was 'A', which was consistent with the previous study in Chinese, and not with the observations in Caucasian. The difference in the risk allele of this SNP in previous studies might be attributable to an ethnic difference in the linkage disequilibrium structure between the Asians and Caucasians. In addition, haplotype analysis exhibits a significant association between a five-SNP haplotype and ASD, including rs22542898. In conclusion, our study might support that OXTR has a significant role in conferring the risk of ASD in the Japanese population.

Inclusion of Population-specific Reference Panel from India to the 1000 Genomes Phase 3 Panel Improves Imputation Accuracy.

PubMed

Ahmad, Meraj; Sinha, Anubhav; Ghosh, Sreya; Kumar, Vikrant; Davila, Sonia; Yajnik, Chittaranjan S; Chandak, Giriraj R

2017-07-27

Imputation is a computational method based on the principle of haplotype sharing allowing enrichment of genome-wide association study datasets. It depends on the haplotype structure of the population and density of the genotype data. The 1000 Genomes Project led to the generation of imputation reference panels which have been used globally. However, recent studies have shown that population-specific panels provide better enrichment of genome-wide variants. We compared the imputation accuracy using 1000 Genomes phase 3 reference panel and a panel generated from genome-wide data on 407 individuals from Western India (WIP). The concordance of imputed variants was cross-checked with next-generation re-sequencing data on a subset of genomic regions. Further, using the genome-wide data from 1880 individuals, we demonstrate that WIP works better than the 1000 Genomes phase 3 panel and when merged with it, significantly improves the imputation accuracy throughout the minor allele frequency range. We also show that imputation using only South Asian component of the 1000 Genomes phase 3 panel works as good as the merged panel, making it computationally less intensive job. Thus, our study stresses that imputation accuracy using 1000 Genomes phase 3 panel can be further improved by including population-specific reference panels from South Asia.

Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.

PubMed

Peñaloza-Espinosa, Rosenda I; Arenas-Aranda, Diego; Cerda-Flores, Ricardo M; Buentello-Malo, Leonor; González-Valencia, Gerardo; Torres, Javier; Alvarez, Berenice; Mendoza, Irma; Flores, Mario; Sandoval, Lucila; Loeza, Francisco; Ramos, Irma; Muñoz, Leopoldo; Salamanca, Fabio

2007-06-01

In this descriptive study we investigated the genetic structure of 513 Mexican indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi, Purépecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua-Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua-Coyolillo) based on mtDNA haplogroups. These communities are geographically and culturally isolated; parents and grandparents were born in the community. Our data show that 98.6% of the mtDNA was distributed in haplogroups A1, A2, B1, B2, C1, C2, D1, and D2. Haplotype X6 was present in the Tarahumara (1/53) and Huichol (3/15), and haplotype L was present in the Nahua-Coyolillo (3/38). The first two principal components accounted for 95.9% of the total variation in the sample. The mtDNA haplogroup frequencies in the Purépecha and Zitlala were intermediate to cluster 1 (Otomi, Nahua-Ixhuatlancillo, Nahua-Xochimilco, Mixteca-Baja, and Tzeltal) and cluster 2 (Nahua-Necoxtla, Nahua-Atocpan, and Nahua-Chilacachapa). The Huichol, Tarahumara, Mixteca-Alta, and Nahua-Coyolillo were separated from the rest of the populations. According to these findings, the distribution of mtDNA haplogroups found in Mexican indigenous groups is similar to other Amerindian haplogroups, except for the African haplogroup found in one population.

Genome-Wide Divergence and Linkage Disequilibrium Analyses for Capsicum baccatum Revealed by Genome-Anchored Single Nucleotide Polymorphisms

PubMed Central

Nimmakayala, Padma; Abburi, Venkata L.; Saminathan, Thangasamy; Almeida, Aldo; Davenport, Brittany; Davidson, Joshua; Reddy, C. V. Chandra Mohan; Hankins, Gerald; Ebert, Andreas; Choi, Doil; Stommel, John; Reddy, Umesh K.

2016-01-01

Principal component analysis (PCA) with 36,621 polymorphic genome-anchored single nucleotide polymorphisms (SNPs) identified collectively for Capsicum annuum and Capsicum baccatum was used to characterize population structure and species domestication of these two important incompatible cultivated pepper species. Estimated mean nucleotide diversity (π) and Tajima's D across various chromosomes revealed biased distribution toward negative values on all chromosomes (except for chromosome 4) in cultivated C. baccatum, indicating a population bottleneck during domestication of C. baccatum. In contrast, C. annuum chromosomes showed positive π and Tajima's D on all chromosomes except chromosome 8, which may be because of domestication at multiple sites contributing to wider genetic diversity. For C. baccatum, 13,129 SNPs were available, with minor allele frequency (MAF) ≥0.05; PCA of the SNPs revealed 283 C. baccatum accessions grouped into 3 distinct clusters, for strong population structure. The fixation index (FST) between domesticated C. annuum and C. baccatum was 0.78, which indicates genome-wide divergence. We conducted extensive linkage disequilibrium (LD) analysis of C. baccatum var. pendulum cultivars on all adjacent SNP pairs within a chromosome to identify regions of high and low LD interspersed with a genome-wide average LD block size of 99.1 kb. We characterized 1742 haplotypes containing 4420 SNPs (range 9–2 SNPs per haplotype). Genome-wide association study (GWAS) of peduncle length, a trait that differentiates wild and domesticated C. baccatum types, revealed 36 significantly associated genome-wide SNPs. Population structure, identity by state (IBS) and LD patterns across the genome will be of potential use for future GWAS of economically important traits in C. baccatum peppers. PMID:27857720

Genome-Wide Divergence and Linkage Disequilibrium Analyses for Capsicum baccatum Revealed by Genome-Anchored Single Nucleotide Polymorphisms.

PubMed

Nimmakayala, Padma; Abburi, Venkata L; Saminathan, Thangasamy; Almeida, Aldo; Davenport, Brittany; Davidson, Joshua; Reddy, C V Chandra Mohan; Hankins, Gerald; Ebert, Andreas; Choi, Doil; Stommel, John; Reddy, Umesh K

2016-01-01

Principal component analysis (PCA) with 36,621 polymorphic genome-anchored single nucleotide polymorphisms (SNPs) identified collectively for Capsicum annuum and Capsicum baccatum was used to characterize population structure and species domestication of these two important incompatible cultivated pepper species. Estimated mean nucleotide diversity (π) and Tajima's D across various chromosomes revealed biased distribution toward negative values on all chromosomes (except for chromosome 4) in cultivated C. baccatum , indicating a population bottleneck during domestication of C. baccatum . In contrast, C. annuum chromosomes showed positive π and Tajima's D on all chromosomes except chromosome 8, which may be because of domestication at multiple sites contributing to wider genetic diversity. For C. baccatum , 13,129 SNPs were available, with minor allele frequency (MAF) ≥0.05; PCA of the SNPs revealed 283 C. baccatum accessions grouped into 3 distinct clusters, for strong population structure. The fixation index ( F ST ) between domesticated C. annuum and C. baccatum was 0.78, which indicates genome-wide divergence. We conducted extensive linkage disequilibrium (LD) analysis of C. baccatum var. pendulum cultivars on all adjacent SNP pairs within a chromosome to identify regions of high and low LD interspersed with a genome-wide average LD block size of 99.1 kb. We characterized 1742 haplotypes containing 4420 SNPs (range 9-2 SNPs per haplotype). Genome-wide association study (GWAS) of peduncle length, a trait that differentiates wild and domesticated C. baccatum types, revealed 36 significantly associated genome-wide SNPs. Population structure, identity by state (IBS) and LD patterns across the genome will be of potential use for future GWAS of economically important traits in C. baccatum peppers.

A Haplotype Information Theory Method Reveals Genes of Evolutionary Interest in European vs. Asian Pigs.

PubMed

Hudson, Nicholas J; Naval-Sánchez, Marina; Porto-Neto, Laercio; Pérez-Enciso, Miguel; Reverter, Antonio

2018-06-05

Asian and European wild boars were independently domesticated ca. 10,000 years ago. Since the 17th century, Chinese breeds have been imported to Europe to improve the genetics of European animals by introgression of favourable alleles, resulting in a complex mosaic of haplotypes. To interrogate the structure of these haplotypes further, we have run a new haplotype segregation analysis based on information theory, namely compression efficiency (CE). We applied the approach to sequence data from individuals from each phylogeographic region (n = 23 from Asia and Europe) including a number of major pig breeds. Our genome-wide CE is able to discriminate the breeds in a manner reflecting phylogeography. Furthermore, 24,956 non-overlapping sliding windows (each comprising 1,000 consecutive SNP) were quantified for extent of haplotype sharing within and between Asia and Europe. The genome-wide distribution of extent of haplotype sharing was quite different between groups. Unlike European pigs, Asian pigs haplotype sharing approximates a normal distribution. In line with this, we found the European breeds possessed a number of genomic windows of dramatically higher haplotype sharing than the Asian breeds. Our CE analysis of sliding windows capture some of the genomic regions reported to contain signatures of selection in domestic pigs. Prominent among these regions, we highlight the role of a gene encoding the mitochondrial enzyme LACTB which has been associated with obesity, and the gene encoding MYOG a fundamental transcriptional regulator of myogenesis. The origin of these regions likely reflects either a population bottleneck in European animals, or selective targets on commercial phenotypes reducing allelic diversity in particular genes and/or regulatory regions.

Absence of population genetic structure in Heterakis gallinarum of chicken from Sichuan, inferred from mitochondrial cytochrome c oxidase subunit I gene.

PubMed

Gu, Xiaobin; Zhu, Jun-Yang; Jian, Ke-Ling; Wang, Bao-Jian; Peng, Xue-Rong; Yang, Guang-You; Wang, Tao; Zhong, Zhi-Jun; Peng, Ke-Yun

2016-09-01

Population genetics information provides a foundation for understanding the transmission and epidemiology of parasite and, therefore, may be used to assist in the control of parasitosis. However, limited available sequence information in Heterakis gallinarum has greatly impeded the study in this area. In this study, we first investigated the genetic variability and genetic structure of H. gallinarum. The 1325 bp fragments of the mitochondrial COX1 gene were amplified in 56 isolates of H. gallinarum from seven different geographical regions in Sichuan province, China. The 56 sequences were classified into 22 haplotypes (H1-H22). The values of haplotype diversity (0.712) and nucleotide diversity (0.00158) in Sichuan population indicate a rapid expansion occurred from a relatively small, short-term effective population in the past. The haplotype network formed a distribution around H1 in a star-like topology, and the haplotypes did not cluster according to their geographical location. Similar conclusions could be made from MP phylogenetic tree. The Fst value (Fst<0.16965) and AMOVA analysis revealed that no significant genetic differentiation was observed among the seven different geographical populations. Neutrality tests (Tajima's D and Fu's Fs) and mismatch analysis indicated that H. gallinarum experienced a population expansion in the past. Our results indicated that H. gallinarum experienced a rapid population expansion in the past, and there was a low genetic diversity and an absence of population structure across the population.

High diversity and no significant selection signal of human ADH1B gene in Tibet

PubMed Central

2012-01-01

Background ADH1B is one of the most studied human genes with many polymorphic sites. One of the single nucleotide polymorphism (SNP), rs1229984, coding for the Arg48His substitution, have been associated with many serious diseases including alcoholism and cancers of the digestive system. The derived allele, ADH1B*48His, reaches high frequency only in East Asia and Southwest Asia, and is highly associated with agriculture. Micro-evolutionary study has defined seven haplogroups for ADH1B based on seven SNPs encompassing the gene. Three of those haplogroups, H5, H6, and H7, contain the ADH1B*48His allele. H5 occurs in Southwest Asia and the other two are found in East Asia. H7 is derived from H6 by the derived allele of rs3811801. The H7 haplotype has been shown to have undergone significant positive selection in Han Chinese, Hmong, Koreans, Japanese, Khazak, Mongols, and so on. Methods In the present study, we tested whether Tibetans also showed evidence for selection by typing 23 SNPs in the region covering the ADH1B gene in 1,175 individuals from 12 Tibetan populations representing all districts of the Tibet Autonomous Region. Multiple statistics were estimated to examine the gene diversities and positive selection signals among the Tibetans and other populations in East Asia. Results The larger Tibetan populations (Qamdo, Lhasa, Nagqu, Nyingchi, Shannan, and Shigatse) comprised mostly farmers, have around 12% of H7, and 2% of H6. The smaller populations, living on hunting or recently switched to farming, have lower H7 frequencies (Tingri 9%, Gongbo 8%, Monba and Sherpa 6%). Luoba (2%) and Deng (0%) have even lower frequencies. Long-range haplotype analyses revealed very weak signals of positive selection for H7 among Tibetans. Interestingly, the haplotype diversity of H7 is higher in Tibetans than in any other populations studied, indicating a longer diversification history for that haplogroup in Tibetans. Network analysis on the long-range haplotypes revealed that H7 in the Han Chinese did not come from the Tibetans but from a common ancestor of the two populations. Conclusions We argue that H7 of ADH1B originated in the ancestors of Sino-Tibetan populations and flowed to Tibetans very early. However, as Tibetans depend less on crops, and therefore were not significantly affected by selection. Thus, H7 has not risen to a high frequency, whereas the diversity of the haplogroup has accumulated to a very high level. PMID:23176670

Genetic structure of Phytophthora infestans populations in China indicates multiple migration events.

PubMed

Guo, Liyun; Zhu, Xiao-Qiong; Hu, Chia-Hui; Ristaino, Jean Beagle

2010-10-01

One hundred isolates of Phytophthora infestans collected from 10 provinces in China between 1998 and 2004 were analyzed for mating type, metalaxyl resistance, mitochondrial DNA (mtDNA) haplotype, allozyme genotype, and restriction fragment length polymorphism (RFLP) with the RG-57 probe. In addition, herbarium samples collected in China, Russia, Australia, and other Asian countries were also typed for mtDNA haplotype. The Ia haplotype was found during the first outbreaks of the disease in China (1938 and 1940), Japan (1901, 1930, and 1931), India (1913), Peninsular Malaysia (1950), Nepal (1954), The Philippines (1910), Australia (1917), Russia (1917), and Latvia (1935). In contrast, the Ib haplotype was found after 1950 in China on both potato and tomato (1952, 1954, 1956, and 1982) and in India (1968 and 1974). Another migration of a genotype found in Siberia called SIB-1 (Glucose-6-phosphate isomerase [Gpi] 100/100, Peptidase [Pep] 100/100, IIa mtDNA haplotype) was identified using RFLP fingerprints among 72% of the isolates and was widely distributed in the north and south of China and has also been reported in Japan. A new genotype named CN-11 (Gpi 100/111, Pep 100/100, IIb mtDNA haplotype), found only in the south of China, and two additional genotypes (Gpi 100/100, Pep 100/100, Ia mtDNA haplotype) named CN-9 and CN-10 were identified. There were more diverse genotypes among isolates from Yunnan province than elsewhere. The SIB-1 (IIa) genotype is identical to those from Siberia, suggesting later migration of this genotype from either Russia or Japan into China. The widespread predominance of SIB-1 suggests that this genotype has enhanced fitness compared with other genotypes found. Movement of the pathogen into China via infected seed from several sources most likely accounts for the distribution of pathogen genotypes observed. MtDNA haplotype evidence and RFLP data suggest multiple migrations of the pathogen into China after the initial introduction of the Ia haplotype in the 1930s.

Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors

PubMed Central

Dannemann, Michael; Andrés, Aida M.; Kelso, Janet

2016-01-01

Pathogens and the diseases they cause have been among the most important selective forces experienced by humans during their evolutionary history. Although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. Archaic humans, who lived in Europe and Western Asia for more than 200,000 years, were probably well adapted to this environment and its local pathogens. It is therefore conceivable that modern humans entering Europe and Western Asia who admixed with them obtained a substantial immune advantage from the introgression of archaic alleles. Here we document a cluster of three Toll-like receptors (TLR6-TLR1-TLR10) in modern humans that carries three distinct archaic haplotypes, indicating repeated introgression from archaic humans. Two of these haplotypes are most similar to the Neandertal genome, and the third haplotype is most similar to the Denisovan genome. The Toll-like receptors are key components of innate immunity and provide an important first line of immune defense against bacteria, fungi, and parasites. The unusually high allele frequencies and unexpected levels of population differentiation indicate that there has been local positive selection on multiple haplotypes at this locus. We show that the introgressed alleles have clear functional effects in modern humans; archaic-like alleles underlie differences in the expression of the TLR genes and are associated with reduced microbial resistance and increased allergic disease in large cohorts. This provides strong evidence for recurrent adaptive introgression at the TLR6-TLR1-TLR10 locus, resulting in differences in disease phenotypes in modern humans. PMID:26748514

The autoimmune regulator gene (AIRE) is strongly associated with vitiligo.

PubMed

Tazi-Ahnini, R; McDonagh, A J G; Wengraf, D A; Lovewell, T R J; Vasilopoulos, Y; Messenger, A G; Cork, M J; Gawkrodger, D J

2008-09-01

Vitiligo is an autoimmune disorder that occurs with greatly increased frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected an association between alopecia areata and single nucleotide polymorphisms (SNPs) in the AIRE gene. To report the findings of an extended study including haplotype analysis on six AIRE polymorphisms (AIRE C-103T, C4144G, T5238C, G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease. A case-control analysis was performed. Results showed a strong association between AIRE 7215C and vitiligo [P = 1.36 x 10(-5), odds ratio (OR) 3.12, 95% confidence interval (CI) 1.87-5.46]. We found no significant association with the other polymorphisms individually. However, haplotype analysis revealed that the AIRE haplotype CCTGCC showed a highly significant association with vitiligo (P = 4.14 x 10(-4), OR 3.00, 95% CI 1.70-5.28). To select the most informative minimal haplotypes, we tagged the polymorphisms using SNP tag software. Using AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, the haplotype AIRE CGCC was associated with vitiligo (P = 0.003, OR 2.49, 95% CI 1.45-4.26). The link between vitiligo and AIRE raises the possibility that defective skin peripheral antigen selection in the thymus is involved in the changes that result in melanocyte destruction in this disorder.

Association of gene polymorphisms in ABO blood group chromosomal regions and menstrual disorders

PubMed Central

SU, YONG; KONG, GUI-LIAN; SU, YA-LI; ZHOU, YAN; LV, LI-FANG; WANG, QIONG; HUANG, BAO-PING; ZHENG, RUI-ZHI; LI, QUAN-ZHONG; YUAN, HUI-JUAN; ZHAO, ZHI-GANG

2015-01-01

This study aimed to investigate whether single nucleotide polymorphisms (SNPs) located near the gene of the ABO blood group play an important role in the genetic aetiology of menstrual disorders (MDs). Polymerase chain reaction-ligase detection reaction technology was used to detect eight SNPs near the ABO gene location on the chromosomes in 250 cases of MD and 250 cases of normal menstruation. The differences in the distribution of each genotype, as well as the allele frequency in the normal and control groups, were analysed using Pearson's χ2 test to search for disease-associated loci. SHEsis software was used to analyse the linkage disequilibrium and haplotype frequencies and to inspect the correlation between haplotypes and the disease. Compared with the control group, the experimental group exhibited statistically significant differences in the genotype distribution frequencies of the rs657152 locus of the ABO blood group gene and the rs17250673 locus of the tumour necrosis factor cofactor 2 (TRAF2) gene, which is located downstream of the ABO gene. The allele distribution frequencies of rs657152 and rs495828 loci in the ABO blood group gene exhibited significant differences between the groups. Dominant and recessive genetic model analysis of each locus revealed that the experimental group exhibited statistically significant differences from the control group in the genotype distribution frequencies of rs657152 and rs495828 loci, respectively. These results indicate that the ABO blood group gene and TRAF2 gene may be a cause of MDs. PMID:26136981

Specific, non-nutritional association between an ascomycete fungus and Allomerus plant-ants.

PubMed

Ruiz-González, Mario X; Malé, Pierre-Jean G; Leroy, Céline; Dejean, Alain; Gryta, Hervé; Jargeat, Patricia; Quilichini, Angélique; Orivel, Jérôme

2011-06-23

Ant-fungus associations are well known from attine ants, whose nutrition is based on a symbiosis with basidiomycete fungi. Otherwise, only a few non-nutritional ant-fungus associations have been recorded to date. Here we focus on one of these associations involving Allomerus plant-ants that build galleried structures on their myrmecophytic hosts in order to ambush prey. We show that this association is not opportunistic because the ants select from a monophyletic group of closely related fungal haplotypes of an ascomycete species from the order Chaetothyriales that consistently grows on and has been isolated from the galleries. Both the ants' behaviour and an analysis of the genetic population structure of the ants and the fungus argue for host specificity in this interaction. The ants' behaviour reveals a major investment in manipulating, growing and cleaning the fungus. A molecular analysis of the fungus demonstrates the widespread occurrence of one haplotype and many other haplotypes with a lower occurrence, as well as significant variation in the presence of these fungal haplotypes between areas and ant species. Altogether, these results suggest that such an interaction might represent an as-yet undescribed type of specific association between ants and fungus in which the ants cultivate fungal mycelia to strengthen their hunting galleries.

Geographic variation, genetic structure and conservation unit designation in the larch mountain salamander( Plethodon larselli)

USGS Publications Warehouse

Wagner, R.S.; Miller, Mark P.; Crisafulli, Charles; Haig, Susan M.

2005-01-01

The Larch Mountain salamander (Plethodon larselli Burns, 1954) is an endemic species in the Pacific northwestern United States facing threats related to habitat destruction. To facilitate development of conservation strategies, we used DNA sequences and RAPDs (random amplified polymorphic DNA) to examine differences among populations of this species. Phylogenetic analyses of cytochrome b revealed a clade of haplotypes from populations north of the Columbia River derived from a clade containing haplotypes from the river's southwestern region. Haplotypes from southeastern populations formed a separate clade. Nucleotide diversity was reduced in northern populations relative to southern populations. These results were corroborated by analyses of RAPD loci, which revealed similar patterns of clustering and diversity. Network analyses suggested that northern populations were colonized following a range expansion mediated by individuals from populations located southwest of the river. Changes in the Columbia River's location during the Pliocene and Pleistocene likely released distributional constraints on this species, permitting their northern range expansion. Based on the barrier presented by the Columbia River's present location and differences in haplotype diversity and population structure observed between northern and southern populations, we suggest that designation of separate management units encompassing each region may assist with mitigating different threats to this species.

Genetic structure and evolution of natural populations of viruses causing the tomato yellow leaf curl disease in Spain.

PubMed

Font, María Isabel; Rubio, Luis; Martínez-Culebras, Pedro Vicente; Jordá, Concepción

2007-09-01

The population structure and genetic variation of two begomoviruses: tomato yellow leaf curl Sardinia virus (TYLCSV) and tomato yellow leaf curl virus (TYLCV) in tomato crops of Spain were studied from 1997 until 2001. Restriction digestion of a genomic region comprised of the CP coat protein gene (CPR) of 358 TYLC virus isolates enabled us to classify them into 14 haplotypes. Nucleotide sequences of two genomic regions: CPR, and the surrounding intergenic region (SIR) were determined for at least two isolates per haplotype. SIR was more variable than CPR and showed multiple recombination events whereas no recombination was detected within CPR. In all geographic regions except Murcia, the population was, or evolved to be composed of one predominant haplotype with a low genetic diversity (<0.0180). In Murcia, two successive changes of the predominant haplotype were observed in the best studied population. Phylogenetic analysis showed that the TYLCSV sequences determined clustered with sequences obtained from the GenBank of other TYLCSV Spanish isolates which were clearly separated from TYLCSV Italian isolates. Most of our TYLCV sequences were similar to those of isolates from Japan and Portugal, and the sequences obtained from TYLCV isolates from the Canary island of Lanzarote were similar to those of Caribbean TYLCV isolates.

Contrasting patterns of historical colonization in white oaks (Quercus spp.) in California and Europe.

PubMed

Grivet, Delphine; Deguilloux, Marie-France; Petit, Remy J; Sork, Victoria L

2006-11-01

Phylogeography allows the inference of evolutionary processes that have shaped the current distribution of genealogical lineages across a landscape. In this perspective, comparative phylogeographical analyses are useful in detecting common historical patterns by either comparing different species within the same area within a continent or by comparing similar species in different areas. Here, we analyse one taxon (the white oak, genus Quercus, subgenus Quercus, section Quercus) that is widespread worldwide, and we evaluate its phylogeographical pattern on two different continents: western North America and Western Europe. The goals of the present study are: (i) to compare the chloroplast genetic diversity found in one California oak species vs. that found in the extensively studied European oak species (in France and the Iberian Peninsula); (ii) to contrast the geographical structure of haplotypes between these two taxa and test for a phylogeographical structure for the California species. For this purpose, we used the same six maternally inherited chloroplast microsatellite markers and a similar sampling strategy. The haplotype diversity within site as well as the differentiation among sites was alike in both taxa, but the Californian species has higher allelic richness with a greater number of haplotypes (39 vs. 11 in the European white oak complex). Furthermore, in California these 39 haplotypes are distributed locally in patches while in the European oaks haplotypes are distributed into lineages partitioned longitudinally. These contrasted patterns could indicate that gene movement in California oak populations have been more stable in response to past climatic and geological events, in contrast to their European counterparts.

Phenotypic expression of partial AZFc deletions is independent of the variations in DAZL and BOULE in a Han population.

PubMed

Chen, Pu; Ma, Mingyi; Li, Lei; Zhang, Sizhong; Su, Dan; Ma, Yongxin; Liu, Yunqiang; Tao, Dachang; Lin, Li; Yang, Yuan

2010-01-01

DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.