Major Breeding Plumage Color Differences of Male Ruffs (Philomachus pugnax) Are Not Associated With Coding Sequence Variation in the MC1R Gene

PubMed Central

Küpper, Clemens; Burke, Terry; Lank, David B.

2015-01-01

Sequence variation in the melanocortin-1 receptor (MC1R) gene explains color morph variation in several species of birds and mammals. Ruffs (Philomachus pugnax) exhibit major dark/light color differences in melanin-based male breeding plumage which is closely associated with alternative reproductive behavior. A previous study identified a microsatellite marker (Ppu020) near the MC1R locus associated with the presence/absence of ornamental plumage. We investigated whether coding sequence variation in the MC1R gene explains major dark/light plumage color variation and/or the presence/absence of ornamental plumage in ruffs. Among 821bp of the MC1R coding region from 44 male ruffs we found 3 single nucleotide polymorphisms, representing 1 nonsynonymous and 2 synonymous amino acid substitutions. None were associated with major dark/light color differences or the presence/absence of ornamental plumage. At all amino acid sites known to be functionally important in other avian species with dark/light plumage color variation, ruffs were either monomorphic or the shared polymorphism did not coincide with color morph. Neither ornamental plumage color differences nor the presence/absence of ornamental plumage in ruffs are likely to be caused entirely by amino acid variation within the coding regions of the MC1R locus. Regulatory elements and structural variation at other loci may be involved in melanin expression and contribute to the extreme plumage polymorphism observed in this species. PMID:25534935

Prion gene haplotypes of U.S. cattle

PubMed Central

Clawson, Michael L; Heaton, Michael P; Keele, John W; Smith, Timothy PL; Harhay, Gregory P; Laegreid, William W

2006-01-01

Background Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. Characterizing linkage disequilibrium (LD) and haplotype networks within the bovine prion gene (PRNP) is important for 1) testing rare or common PRNP variation for an association with BSE and 2) interpreting any association of PRNP alleles with BSE susceptibility. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S. cattle genomes. Results A 25.2-kb genomic region containing PRNP was sequenced from 192 diverse U.S. beef and dairy cattle. Sequence analyses identified 388 total polymorphisms, of which 287 have not previously been reported. The polymorphism alleles define PRNP by regions of high and low LD. High LD is present between alleles in the promoter region through exon 2 (6.7 kb). PRNP alleles within the majority of intron 2, the entire coding sequence and the untranslated region of exon 3 are in low LD (18.0 kb). Two haplotype networks, one representing the region of high LD and the other the region of low LD yielded nineteen different combinations that represent haplotypes spanning PRNP. The haplotype combinations are tagged by 19 polymorphisms (htSNPS) which characterize variation within and across PRNP. Conclusion The number of polymorphisms in the prion gene region of U.S. cattle is nearly four times greater than previously described. These polymorphisms define PRNP haplotypes that may influence BSE susceptibility in cattle. PMID:17092337

Relationship between single nucleotide polymorphism of glycogen synthase gene of Pacific oyster Crassostrea gigas and its glycogen content

NASA Astrophysics Data System (ADS)

Liu, Siwei; Li, Qi; Yu, Hong; Kong, Lingfeng

2017-02-01

Glycogen is important not only for the energy supplementary of oysters, but also for human consumption. High glycogen content can improve the stress survival of oyster. A key enzyme in glycogenesis is glycogen synthase that is encoded by glycogen synthase gene GYS. In this study, the relationship between single nucleotide polymorphisms (SNPs) in coding regions of Crassostrea gigas GYS (Cg-GYS) and individual glycogen content was investigated with 321 individuals from five full-sib families. Single-strand conformation polymorphism (SSCP) procedure was combined with sequencing to confirm individual SNP genotypes of Cg-GYS. Least-square analysis of variance was performed to assess the relationship of variation in glycogen content of C. gigas with single SNP genotype and SNP haplotype. As a consequence, six SNPs were found in coding regions to be significantly associated with glycogen content ( P < 0.01), from which we constructed four main haplotypes due to linkage disequilibrium. Furthermore, the most effective haplotype H2 (GAGGAT) had extremely significant relationship with high glycogen content ( P < 0.0001). These findings revealed the potential influence of Cg-GYS polymorphism on the glycogen content and provided molecular biological information for the selective breeding of good quality traits of C. gigas.

Prion protein testis specific (PRNT) gene polymorphisms and transcript level in ovine spermatozoa: Implications in freezability, fertilization and embryo production.

PubMed

Pereira, R M; Mesquita, P; Pires, V M R; Baptista, M C; Barbas, J P; Pimenta, J; Horta, A E M; Prates, J A M; Marques, C C

2018-07-15

An essential role of prion protein testis specific (PRNT) and prion protein 2 dublet (PRND) genes in the male reproductive function has been highlighted, although a deeper knowledge for the mechanisms involved is still lacking. Our goal was to determine the importance of the PRNT haplotypic variants and mRNA expression levels in ovine spermatozoa freezability and ability for fertilization and embryo developmental processes. Their association with the PRND gene polymorphisms was also analyzed. DNA from rams belonging to three Portuguese sheep breeds (n = 28) was screened by single-strand conformation polymorphism (SSCP) analysis to identify the PRNT and PRND polymorphisms. Semen collected from these rams was cryopreserved and fertility traits evaluated. The SSCP analyses revealed polymorphisms in the codons 6, 38, 43 and 48 of the PRNT coding region - respectively c.17C > T (p.Ser6Phe, which disrupts a consensus arginine-X-X serine/threonine motif); c.112G > C (p.Gly38 > Arg); and synonymous c.129T > C and c.144A > G. The polymorphisms in codons 6, 38 and 48 occur simultaneously while the one in codon 43 occurs independently. Six haplotypes were identified in the PRNT coding region, resulting in three different amino acid polymorphic variants (6S-38G-43C-48V, S6F-G38R-43C-48V and 6F-38R-43C-48V). The PRNT gene mRNA transcript level in spermatozoa was related to the identified haplotypic variants, either considering the codons 6-38-48 (P ≤ 0.0001) or the codon 43 alone (P ≤ 0.0001) or altogether (P ≤ 0.0001). An interaction between PRNT haplotypes and PRND genotypes on PRNT transcript level was also identified (P = 0.0003). Rams carrying the 17C-112G-144A PRNT haplotype had sperm with the highest post-thawed individual motility (P ≤ 0.03). Combined PRNT and PRND polymorphic variation influenced the post-thawed individual motility (P = 0.01). The male PRNT haplotypic, either considering the codons 6-38-48 and 43 altogether or the codon 43 alone, interfered (P ≤ 0.04) in embryo production rates. In conclusion, our data confirm that the PRNT gene is highly polymorphic in sheep and that the PRNT and PRND genotypes are associated. The identified polymorphisms of PRNT coding region seems to interfere on the ram spermatozoa mRNA transcript level and on male fertility, specifically in sperm freezability and ability for embryo development. Copyright © 2018. Published by Elsevier Inc.

Differentiated evolutionary conservatism and lack of polymorphism of crucial sex determination genes (SRY and SOX9) in four species of the family Canidae.

PubMed

Nowacka-Woszuk, Joanna; Switonski, Marek

2009-01-01

The sex determination process is under the control of several genes of which two (SRY and SOX9), encoding transcription factors, play a crucial role. It is well-known that mutations at these genes may cause the development of an intersexual phenotype. The aim of this study was to conduct a comparative analysis of the coding sequence and 5'-flanking regions of both genes in four species of the family Canidae (the dog, red fox, arctic fox and Chinese raccoon dog). Similarity of the coding sequence of the SOX9 gene among the studied species was higher (99.7-99.9%) than in the case of the SRY gene (96.7-97.3%). Only single nucleotide changes were found in the compared coding sequences, whereas in the 5'-flanking region of both genes nucleotide substitutions, as well as insertions and deletions were observed. None of the changes detected in the 5'-flanking region occurred within the potential consensus sequences for transcription factors. No polymorphism was found for either of these genes in any of the analyzed species.

Mapping of the serotonin 5-HT{sub 1D{alpha}} autoreceptor gene (HTR1D) on chromosome 1 using a silent polymorphism in the coding region

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

Ozaki, N.; Lappalainen, J.; Linnoila, M.

Serotonin (5-HT){sub ID} receptors are 5-HT release-regulating autoreceptors in the human brain. Abnormalities in brain 5-HT function have been hypothesized in the pathophysiology of various psychiatric disorders, including obsessive-compulsive disorder, autism, mood disorders, eating disorders, impulsive violent behavior, and alcoholism. Thus, mutations occurring in 5-HT autoreceptors may cause or increase the vulnerability to any of these conditions. 5-HT{sub 1D{alpha}} and 5-HT{sub 1D{Beta}} subtypes have been previously localized to chromosomes 1p36.3-p34.3 and 6q13, respectively, using rodent-human hybrids and in situ localization. In this communication, we report the detection of a 5-HT{sub 1D{alpha}} receptor gene polymorphism by single strand conformation polymorphism (SSCP)more » analysis of the coding sequence. The polymorphism was used for fine scale linkage mapping of 5-HT{sub 1D{alpha}} on chromosome 1. This polymorphism should also be useful for linkage studies in populations and in families. Our analysis also demonstrates that functionally significant coding sequence variants of the 5-HT{sub 1D{alpha}} are probably not abundant either among alcoholics or in the general population. 14 refs., 1 fig., 1 tab.« less

Single nucleotide polymorphisms in the CXCR1 gene and its association with clinical mastitis incidence in Polish Holstein-Friesian cows.

PubMed

Pokorska, J; Dusza, M; Kułaj, D; Żukowski, K; Makulska, J

2016-04-28

The aim of this study was to identify the association between single nucleotide polymorphisms (SNPs) in the bovine chemokine receptor (CXCR1) gene and the resistance or susceptibility of cows to mastitis. The analysis of the CXCR1 polymorphism was carried out using polymerase chain reaction restriction fragment length polymorphism analysis for six SNP mutations (c.+291C>T, c.+365T>C, c.+816C>A, c.+819G>A, +1093C>T, and +1373C>A), of which four were located within the coding region and two in the 3'UTR region of the CXCR1 gene. Genetic material from 146 Polish Holstein-Friesian cows was analyzed after dividing into two groups depending on the incidence of clinical mastitis. Identified polymorphisms were in linkage disequilibrium and formed two linkage groups. Three haplotypes (CCCATA, TTAGCC, CTCGCC), forming six haplotype combinations, were detected. The logistic regression showed a significant association between the CC genotype at c.+365T>C and susceptibility of cows to clinical mastitis (P = 0.047). The frequency of haplotype combination 1/1 (CCCATA/CCCATA) was not significantly higher in cows susceptible to mastitis (P = 0.062). Of the identified SNP mutations, only c.+365T>C is a nonsynonymous mutation that induces a change in the coded protein [GCC (Ala) to GTC (Val) at the 122nd amino acid]. This amino acid change can result in changes in receptor function, which may be a reason for the increased mastitis incidence observed in cows with polymorphism at this site.

Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students.

PubMed

Hinney, Anke; Hoch, Anne; Geller, Frank; Schäfer, Helmut; Siegfried, Wolfgang; Goldschmidt, Hanspeter; Remschmidt, Helmut; Hebebrand, Johannes

2002-06-01

Ghrelin induces obesity via central and peripheral mechanisms. Administration of ghrelin leads to increased food intake and decreased fat utilisation in rodents. Ghrelin levels are decreased in obese individuals. Recently, a polymorphism (Arg-51-Gln) within the ghrelin gene (GHRL) was described to be associated with obesity. We screened the GHRL coding region in 215 extremely obese German Children and adolescents (study group 1) and 93 normal weight students (study group 2) by single strand conformation polymorphism analysis (SSCP). We found the two previously described single nucleotide polymorphisms (SNP: Arg-51-Gln and Leu-72-Met) in similar frequencies in study groups 1 and 2 (allele frequencies were: 0.019 and 0.016 for the 51-Gln allele and 0.091 and 0.086 for the 72-Met allele, respectively). Hence, we could not confirm the previous finding. Additionally, two novel variants were identified within the coding region: (1) We detected one healthy normal weight individual with a frameshift mutation (2bp deletion at codon 34). This frameshift mutation affects the coding region of the mature ghrelin. Hence, it is highly likely that the normal weight student is haplo-insufficient for ghrelin. (2) An A to T transversion leads to an amino acid exchange from Gln to Leu at amino acid position 90. The frequency of the 90-Leu allele was significantly higher in the extremely obese children and adolescents (0.063) than in the normal weight students (0.016; nominal p = 0.011). Additionally, we genotyped 134 underweight students and 44 normal weight adults for this SNP. Genotype frequencies were similar in extremely obese children and adolescents, underweight students and normal weight adults (p > 0.8). In conclusion, we identified four sequence variants in the coding region of the ghrelin gene in individuals belonging to different weight extremes. A frameshift mutation was detected in a normal weight individual. None of the variants seem to influence weight regulation.

Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci

PubMed Central

Brorsson, Caroline A.; Pociot, Flemming

2014-01-01

Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs. PMID:25144376

Forensic strategy to ensure the quality of sequencing data of mitochondrial DNA in highly degraded samples.

PubMed

Adachi, Noboru; Umetsu, Kazuo; Shojo, Hideki

2014-01-01

Mitochondrial DNA (mtDNA) is widely used for DNA analysis of highly degraded samples because of its polymorphic nature and high number of copies in a cell. However, as endogenous mtDNA in deteriorated samples is scarce and highly fragmented, it is not easy to obtain reliable data. In the current study, we report the risks of direct sequencing mtDNA in highly degraded material, and suggest a strategy to ensure the quality of sequencing data. It was observed that direct sequencing data of the hypervariable segment (HVS) 1 by using primer sets that generate an amplicon of 407 bp (long-primer sets) was different from results obtained by using newly designed primer sets that produce an amplicon of 120-139 bp (mini-primer sets). The data aligned with the results of mini-primer sets analysis in an amplicon length-dependent manner; the shorter the amplicon, the more evident the endogenous sequence became. Coding region analysis using multiplex amplified product-length polymorphisms revealed the incongruence of single nucleotide polymorphisms between the coding region and HVS 1 caused by contamination with exogenous mtDNA. Although the sequencing data obtained using long-primer sets turned out to be erroneous, it was unambiguous and reproducible. These findings suggest that PCR primers that produce amplicons shorter than those currently recognized should be used for mtDNA analysis in highly degraded samples. Haplogroup motif analysis of the coding region and HVS should also be performed to improve the reliability of forensic mtDNA data. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Single feature polymorphism (SFP)-based selective sweep identification and association mapping of growth-related metabolic traits in Arabidopsis thaliana

PubMed Central

2010-01-01

Background Natural accessions of Arabidopsis thaliana are characterized by a high level of phenotypic variation that can be used to investigate the extent and mode of selection on the primary metabolic traits. A collection of 54 A. thaliana natural accession-derived lines were subjected to deep genotyping through Single Feature Polymorphism (SFP) detection via genomic DNA hybridization to Arabidopsis Tiling 1.0 Arrays for the detection of selective sweeps, and identification of associations between sweep regions and growth-related metabolic traits. Results A total of 1,072,557 high-quality SFPs were detected and indications for 3,943 deletions and 1,007 duplications were obtained. A significantly lower than expected SFP frequency was observed in protein-, rRNA-, and tRNA-coding regions and in non-repetitive intergenic regions, while pseudogenes, transposons, and non-coding RNA genes are enriched with SFPs. Gene families involved in plant defence or in signalling were identified as highly polymorphic, while several other families including transcription factors are depleted of SFPs. 198 significant associations between metabolic genes and 9 metabolic and growth-related phenotypic traits were detected with annotation hinting at the nature of the relationship. Five significant selective sweep regions were also detected of which one associated significantly with a metabolic trait. Conclusions We generated a high density polymorphism map for 54 A. thaliana accessions that highlights the variability of resistance genes across geographic ranges and used it to identify selective sweeps and associations between metabolic genes and metabolic phenotypes. Several associations show a clear biological relationship, while many remain requiring further investigation. PMID:20302660

Identification and characterization of single nucleotide polymorphisms in 6 growth-correlated genes in porcine by denaturing high performance liquid chromatography.

PubMed

Liu, Dewu; Zhang, Yushan; Du, Yinjun; Yang, Guanfu; Zhang, Xiquan

2007-06-01

The growth-correlated genes that are part of the neuroendocrine growth axis play crucial roles in the regulation of growth and development of pig. The identification of genetic polymorphisms in these genes will enable the scientist to evaluate the biological relevance of such polymorphisms and to gain a better understanding of quantitative traits like growth. In the present study, seven pairs of primers were designed to obtain unknown sequences of growth-correlated genes, and other 25 pairs of primers were designed to identify single nucleotide polymorphisms (SNP) using the denaturing high-performance liquid chromatography (DHPLC) technology in four pig breeds (Duroc, Landrace, Lantang and Wuzhishan), significantly differing in growth and development characteristics. A total of 101 polymorphisms were discovered in 10,707 base pairs (bp) from six genes of the ghrelin (GHRL), leptin (LEP), insulin-like growth factor II (IGF-II), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and somatostatin (SS). The observed average distances between the SNP in the 5'UTR, coding regions, introns and 3'UTR were 134, 521, 81 and 92 bp, respectively. Four SNPs were found in the coding regions of IGF-II, IGFBP-2 and LEP, respectively. Two synonymous mutations were obtained in IGF-II and LEP genes respectively, and two non-synonymous were found in IGFBP-2 and LEP genes, respectively. Seven other mutations were also observed. Thirty-two PCR-RFLP markers were found among 101 polymorphisms of the six genes. The SNP discovered in this study would provide suitable markers for association studies of candidate genes with growth related traits in pig.

Norrie disease gene sequence variants in an ethnically diverse population with retinopathy of prematurity.

PubMed

Hutcheson, Kelly A; Paluru, Prasuna C; Bernstein, Steven L; Koh, Jamie; Rappaport, Eric F; Leach, Richard A; Young, Terri L

2005-07-14

Retinopathy of prematurity (ROP) is a leading cause of visual loss in the pediatric population. Mutations in the Norrie disease gene (NDP) are associated with heritable retinal vascular disorders, and have been found in a small subset of patients with severe retinopathy of prematurity. Varying rates of progression to threshold disease in different races may have a genetic basis, as recent studies suggest that the incidence of NDP mutations may vary in different groups. African Americans, for example, are less likely to develop severe degrees of ROP. We screened a large cohort of ethnically diverse patients for mutations in the entire NDP. A total of 143 subjects of different ethnic backgrounds were enrolled in the study. Fifty-four patients had severe ROP (Stage 3 or worse). Of these, 38 were threshold in at least one eye (with a mean gestational age of 26.1 weeks and mean birth weight of 788.4 g). There were 36 patients with mild or no ROP, 31 parents with no history of retinal disease or prematurity, and 22 wild type (normal) controls. There were 70 African American subjects, 55 Caucasians, and 18 of other races. Severe ROP was noted in 29 African American subjects, 17 Caucasians, and 8 of other races. Seven polymerase chain reaction primer pairs spanning the NDP were optimized for denaturing high performance liquid chromatography and direct sequencing. Three primer pairs covered the coding region, and the remaining four spanned the 3' and 5' untranslated regions (UTR). Six of 54 (11%) infants with severe ROP had polymorphisms in the NDP. Five of the infants were African American, and one was Caucasian. Two parents were heterozygous for the same polymorphism as their child. One parent-child pair had a single base pair (bp) insertion in the 3' UTR region. Another parent-child pair had two mutations: a 14 bp deletion in the 5' UTR region of exon 1 and a single nucleotide polymorphism in the 5' UTR region of exon 2. No coding region sequence changes were found. No polymorphisms were observed in infants with mild or no ROP, or in the wild type controls. Of the six sequence alterations found, five were novel nucleotide changes: One in the 5' UTR region of exon 2, and four in the 3' UTR region of exon 3. The extent of NDP polymorphisms in this large, racially diverse group of infants is moderate. NDP polymorphisms may play a role in the pathogenesis of ROP, but do not appear to be a major causative factor.

Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.

PubMed

Herrnstadt, Corinna; Elson, Joanna L; Fahy, Eoin; Preston, Gwen; Turnbull, Douglass M; Anderson, Christen; Ghosh, Soumitra S; Olefsky, Jerrold M; Beal, M Flint; Davis, Robert E; Howell, Neil

2002-05-01

The evolution of the human mitochondrial genome is characterized by the emergence of ethnically distinct lineages or haplogroups. Nine European, seven Asian (including Native American), and three African mitochondrial DNA (mtDNA) haplogroups have been identified previously on the basis of the presence or absence of a relatively small number of restriction-enzyme recognition sites or on the basis of nucleotide sequences of the D-loop region. We have used reduced-median-network approaches to analyze 560 complete European, Asian, and African mtDNA coding-region sequences from unrelated individuals to develop a more complete understanding of sequence diversity both within and between haplogroups. A total of 497 haplogroup-associated polymorphisms were identified, 323 (65%) of which were associated with one haplogroup and 174 (35%) of which were associated with two or more haplogroups. Approximately one-half of these polymorphisms are reported for the first time here. Our results confirm and substantially extend the phylogenetic relationships among mitochondrial genomes described elsewhere from the major human ethnic groups. Another important result is that there were numerous instances both of parallel mutations at the same site and of reversion (i.e., homoplasy). It is likely that homoplasy in the coding region will confound evolutionary analysis of small sequence sets. By a linkage-disequilibrium approach, additional evidence for the absence of human mtDNA recombination is presented here.

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase

PubMed Central

Hawkins, Vivian N; Auliff, Alyson; Prajapati, Surendra Kumar; Rungsihirunrat, Kanchana; Hapuarachchi, Hapuarachchige C; Maestre, Amanda; O'Neil, Michael T; Cheng, Qin; Joshi, Hema; Na-Bangchang, Kesara; Sibley, Carol Hopkins

2008-01-01

Background In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. Methods The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Results Synonymous and non-synonymous single nucleotide polymorphisms (SNPs) within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel). SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N) dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T) and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T) mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. Conclusion It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts sharply with the selective sweep of rare antifolate resistant alleles observed in the P. falciparum populations in Asia and Africa. The finding of multiple origins of resistance-conferring mutations has important implications for drug policy. PMID:18442404

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase.

PubMed

Hawkins, Vivian N; Auliff, Alyson; Prajapati, Surendra Kumar; Rungsihirunrat, Kanchana; Hapuarachchi, Hapuarachchige C; Maestre, Amanda; O'Neil, Michael T; Cheng, Qin; Joshi, Hema; Na-Bangchang, Kesara; Sibley, Carol Hopkins

2008-04-28

In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Synonymous and non-synonymous single nucleotide polymorphisms (SNPs) within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel). SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N) dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T) and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T) mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts sharply with the selective sweep of rare antifolate resistant alleles observed in the P. falciparum populations in Asia and Africa. The finding of multiple origins of resistance-conferring mutations has important implications for drug policy.

Mapping of the serotonin 5-HT{sub 1D{beta}} autoreceptor gene on chromosome 6 and direct analysis for sequence variants

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

Lappalainen, J.; Dean, M.; Virkkunen, M.

1995-04-24

Abnormal brain serotonin function may be characteristic of several neuropsychiatric disorders. Thus, it is important to identify polymorphic genes and screen for functional variants at loci coding for genes that control normal serotonin functions. 5-HT{sub 1D{beta}} is a terminal serotonin autoreceptor which may play a role in regulating serotonin synthesis and release. Using an SSCP technique we screened for 5-HT{sub 1D{beta}} coding sequence variants in psychiatrically interviewed populations, which included controls, alcoholics, and alcoholic arsonists and alcoholic violent offenders with low CSF concentrations of the main serotonin metabolite 5-HIAA. A common polymorphism was identified in the 5-HT{sub 1D{beta}} gene withmore » allele frequencies of 0.72 and 0.28. The SSCP variant was caused by a silent G to C substitution at nucleotide 861 of the coding region. This polymorphism could also be detected as a HincII RFLP of amplified DNA. DNAs from informative CEPH families were typed for the HincII RFLP and analyzed with respect to 20 linked markers on chromosome 6. Multipoint analysis placed the 5-HT{sub 1D{beta}} receptor gene between markers D6S286 and D6S275. A maximum two-point lod score of 10.90 was obtained to D6S26, which had been previously localized on 6q14-15. Chromosomal aberrations involving this region have been previously shown to cause retinal anomalies, developmental delay, and abnormal brain development. This region also contains the gene for North Carolina-type macular dystrophy. 34 refs., 3 figs., 1 tab.« less

Antigenic Diversity of the Plasmodium vivax Circumsporozoite Protein in Parasite Isolates of Western Colombia

PubMed Central

Hernández-Martínez, Miguel Ángel; Escalante, Ananías A.; Arévalo-Herrera, Myriam; Herrera, Sócrates

2011-01-01

Circumsporozoite (CS) protein is a malaria antigen involved in sporozoite invasion of hepatocytes, and thus considered to have good vaccine potential. We evaluated the polymorphism of the Plasmodium vivax CS gene in 24 parasite isolates collected from malaria-endemic areas of Colombia. We sequenced 27 alleles, most of which (25/27) corresponded to the VK247 genotype and the remainder to the VK210 type. All VK247 alleles presented a mutation (Gly → Asn) at position 28 in the N-terminal region, whereas the C-terminal presented three insertions: the ANKKAGDAG, which is common in all VK247 isolates; 12 alleles presented the insertion GAGGQAAGGNAANKKAGDAG; and 5 alleles presented the insertion GGNAGGNA. Both repeat regions were polymorphic in gene sequence and size. Sequences coding for B-, T-CD4+, and T-CD8+ cell epitopes were found to be conserved. This study confirms the high polymorphism of the repeat domain and the highly conserved nature of the flanking regions. PMID:21292878

Isozyme, ISSR and RAPD profiling of genotypes in marvel grass (Dichanthium annulatum).

PubMed

Saxena, Raghvendra; Chandra, Amaresh

2010-11-01

Genetic analysis of 30 accessions of marvel grass (Dichanthium annulatum Forsk.), a tropical range grass collected from grasslands and open fields of drier regions, was carried out with the objectives of identifying unique materials that could be used in developing the core germplasm for such regions as well as to explore gene (s) for drought tolerance. Five inter-simple sequence repeat (ISSR) primers [(CA)4, (AGAC), (GACA) 4; 27 random amplified polymorphic DNA (RAPD) and four enzyme systems were employed in the present study. In total, ISSR yielded 61 (52 polymorphic), RAPD 269 (253 polymorphic) and enzyme 55 isozymes (44 polymorphic) bands. The average polymorphic information content (PIC) and marker index (MI) across all polymorphic bands of 3 markers systems ranged from 0.419 to 0.480 and 4.34 to 5.25 respectively Dendrogram analysis revealed three main clusters with all three markers. Four enzymes namely esterase (EST), polyphenoloxidase (PPO), peroxidase (PRX) and superoxide dismutase (SOD) revealed 55 alleles from a total of 16 enzyme-coding loci. Of these, 14 loci and 44 alleles were polymorphic. The mean number of alleles per locus was 3.43. Mean heterozygosity observed among the polymorphic loci ranged from 0.406 (SOD) to 0.836 (EST) and accession wise from 0.679 (1G3108) to 0.743 (IGKMD-10). Though there was intermixing of few accessions of one agro-climatic region to another largely groupings of accessions were with their regions of collections. Bootstrap analysis at 1000 iterations also showed large numbers of nodes (11 to 17) having strong clustering (> 50 bootstrap values) in all three marker systems. The accessions of the arid and drier regions forming one cluster are assigned as distinct core collection of Dichanthium and can be targeted for isolation of gene (s) for drought tolerance. Variations in isozyme allele numbers and high PIC (0.48) and MI (4.98) as observed with ISSR markers indicated their usefulness for germplasm characterization.

Polymorphisms in the canine monoamine oxidase a (MAOA) gene: identification and variation among five broad dog breed groups.

PubMed

Sacco, James; Ruplin, Andrew; Skonieczny, Paul; Ohman, Michael

2017-01-01

In humans, reduced activity of the enzyme monoamine oxidase type A (MAOA) due to genetic polymorphisms within the MAOA gene leads to increased brain neurotransmitter levels associated with aggression. In order to study MAOA genetic diversity in dogs, we designed a preliminary study whose objectives were to identify novel alleles in functionally important regions of the canine MAOA gene, and to investigate whether the frequencies of these polymorphisms varied between five broad breed groups (ancient, herding, mastiff, modern European, and mountain). Fifty dogs representing these five breed groups were sequenced. A total of eleven polymorphisms were found. Seven were single nucleotide polymorphisms (SNPs; two exonic, two intronic and three in the promoter), while four were repeat intronic variations. The most polymorphic loci were repeat regions in introns 1, 2 (7 alleles) and 10 (3 alleles), while the exonic and the promoter regions were highly conserved. Comparison of the allele frequencies of certain microsatellite polymorphisms among the breed groups indicated a decreasing or increasing trend in the number of repeats at different microsatellite loci, as well as the highest genetic diversity for the ancient breeds and the lowest for the most recent mountain breeds, perhaps attributable to canine domestication and recent breed formation. While a specific promoter SNP (-212A > G) is rare in the dog, it is the major allele in wolves. Replacement of this ancestral allele in domestic dogs may lead to the deletion of heat shock factor binding sites on the MAOA promoter. Dogs exhibit significant variation in certain intronic regions of the MAOA gene, while the coding and promoter regions are well-conserved. Distinct genetic differences were observed between breed groups. Further studies are now required to establish whether such polymorphisms are associated in any way with MAOA level and canine behaviour including aggression.

Novel human CRYGD rare variant in a Brazilian family with congenital cataract

PubMed Central

Giordano, Gabriel Gorgone; Tavares, Anderson; da Silva, Márcio José; de Vasconcellos, José Paulo Cabral; Arieta, Carlos Eduardo Leite; de Melo, Mônica Barbosa

2011-01-01

Purpose To describe a novel polymorphism in the γD-crystallin (CRYGD) gene in a Brazilian family with congenital cataract. Methods A Brazilian four-generation family was analyzed. The proband had bilateral lamellar cataract and the phenotypes were classified by slit lamp examination. Genomic DNA was extracted from peripheral blood and coding regions and intron/exon boundaries of the αA-crystallin (CRYAA), γC-crystallin (CRYGC), and CRYGD genes were amplified by polymerase chain reaction and directly sequenced. Results Sequencing of the coding regions of CRYGD showed the presence of a heterozygous A→G transversion at c.401 position, which results in the substitution of a tyrosine to a cysteine (Y134C). The polymorphism was identified in three individuals, two affected and one unaffected. Conclusions A novel rare variant in CRYGD (Y134C) was detected in a Brazilian family with congenital cataract. Because there is no segregation between the substitution and the phenotypes in this family, other genetic alterations are likely to be present. PMID:21866214

Molecular Dissection of a Major Gene Effect on a Quantitative Trait: The Level of Alcohol Dehydrogenase Expression in Drosophila Melanogaster

PubMed Central

Stam, L. F.; Laurie, C. C.

1996-01-01

A molecular mapping experiment shows that a major gene effect on a quantitative trait, the level of alcohol dehydrogenase expression in Drosophila melanogaster, is due to multiple polymorphisms within the Adh gene. These polymorphisms are located in an intron, the coding sequence, and the 3' untranslated region. Because of nonrandom associations among polymorphisms at different sites, the individual effects combine (in some cases epistatically) to produce ``superalleles'' with large effect. These results have implications for the interpretation of major gene effects detected by quantitative trait locus mapping methods. They show that large effects due to a single locus may be due to multiple associated polymorphisms (or sequential fixations in isolated populations) rather than individual mutations of large effect. PMID:8978044

Sequence analysis of tau 3'untranslated region and saitohin gene in sporadic progressive supranuclear palsy

PubMed Central

Ezquerra, M; Campdelacreu, J; Munoz, E; Oliva, R; Tolosa, E

2004-01-01

Objectives: To search for genetic changes in the 3'untranslated region (3'UTR) of tau and adjacent sequence LOC147077, and in the coding region of STH in PSP patients. Methods: The study included 57 PSP patients and 83 healthy controls. The genetic analysis of each region was performed through sequencing. The Q7R polymorphism was studied through restriction enzyme and electrophoresis analysis. Results: No mutations were found in the regions analysed. The QQ genotype of the STH polymorphism was over-represented in participants with PSP (91.5%) compared with control subjects (47%) (p⩽0.00001). This genotype co-segregated with the H1/H1 haplotype in our PSP cases. Conclusions: Our results do not support a major role for the tau 3'UTR in PSP genetics. The QQ genotype of STH confers susceptibility for PSP and is in linkage disequilibrium with the H1/H1 haplotype. PMID:14707330

PSSRdb: a relational database of polymorphic simple sequence repeats extracted from prokaryotic genomes.

PubMed

Kumar, Pankaj; Chaitanya, Pasumarthy S; Nagarajaram, Hampapathalu A

2011-01-01

PSSRdb (Polymorphic Simple Sequence Repeats database) (http://www.cdfd.org.in/PSSRdb/) is a relational database of polymorphic simple sequence repeats (PSSRs) extracted from 85 different species of prokaryotes. Simple sequence repeats (SSRs) are the tandem repeats of nucleotide motifs of the sizes 1-6 bp and are highly polymorphic. SSR mutations in and around coding regions affect transcription and translation of genes. Such changes underpin phase variations and antigenic variations seen in some bacteria. Although SSR-mediated phase variation and antigenic variations have been well-studied in some bacteria there seems a lot of other species of prokaryotes yet to be investigated for SSR mediated adaptive and other evolutionary advantages. As a part of our on-going studies on SSR polymorphism in prokaryotes we compared the genome sequences of various strains and isolates available for 85 different species of prokaryotes and extracted a number of SSRs showing length variations and created a relational database called PSSRdb. This database gives useful information such as location of PSSRs in genomes, length variation across genomes, the regions harboring PSSRs, etc. The information provided in this database is very useful for further research and analysis of SSRs in prokaryotes.

Genomic DNA sequence and cytosine methylation changes of adult rice leaves after seeds space flight

NASA Astrophysics Data System (ADS)

Shi, Jinming

In this study, cytosine methylation on CCGG site and genomic DNA sequence changes of adult leaves of rice after seeds space flight were detected by methylation-sensitive amplification polymorphism (MSAP) and Amplified fragment length polymorphism (AFLP) technique respectively. Rice seeds were planted in the trial field after 4 days space flight on the shenzhou-6 Spaceship of China. Adult leaves of space-treated rice including 8 plants chosen randomly and 2 plants with phenotypic mutation were used for AFLP and MSAP analysis. Polymorphism of both DNA sequence and cytosine methylation were detected. For MSAP analysis, the average polymorphic frequency of the on-ground controls, space-treated plants and mutants are 1.3%, 3.1% and 11% respectively. For AFLP analysis, the average polymorphic frequencies are 1.4%, 2.9%and 8%respectively. Total 27 and 22 polymorphic fragments were cloned sequenced from MSAP and AFLP analysis respectively. Nine of the 27 fragments from MSAP analysis show homology to coding sequence. For the 22 polymorphic fragments from AFLP analysis, no one shows homology to mRNA sequence and eight fragments show homology to repeat region or retrotransposon sequence. These results suggest that although both genomic DNA sequence and cytosine methylation status can be effected by space flight, the genomic region homology to the fragments from genome DNA and cytosine methylation analysis were different.

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection.

PubMed

Mendes-Junior, C T; Castelli, E C; Meyer, D; Simões, A L; Donadi, E A

2013-12-01

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3'UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.

Genome-wide survey and analysis of microsatellites in giant panda (Ailuropoda melanoleuca), with a focus on the applications of a novel microsatellite marker system.

PubMed

Huang, Jie; Li, Yu-Zhi; Du, Lian-Ming; Yang, Bo; Shen, Fu-Jun; Zhang, He-Min; Zhang, Zhi-He; Zhang, Xiu-Yue; Yue, Bi-Song

2015-02-07

The giant panda (Ailuropoda melanoleuca) is a critically endangered species endemic to China. Microsatellites have been preferred as the most popular molecular markers and proven effective in estimating population size, paternity test, genetic diversity for the critically endangered species. The availability of the giant panda complete genome sequences provided the opportunity to carry out genome-wide scans for all types of microsatellites markers, which now opens the way for the analysis and development of microsatellites in giant panda. By screening the whole genome sequence of giant panda in silico mining, we identified microsatellites in the genome of giant panda and analyzed their frequency and distribution in different genomic regions. Based on our search criteria, a repertoire of 855,058 SSRs was detected, with mono-nucleotides being the most abundant. SSRs were found in all genomic regions and were more abundant in non-coding regions than coding regions. A total of 160 primer pairs were designed to screen for polymorphic microsatellites using the selected tetranucleotide microsatellite sequences. The 51 novel polymorphic tetranucleotide microsatellite loci were discovered based on genotyping blood DNA from 22 captive giant pandas in this study. Finally, a total of 15 markers, which showed good polymorphism, stability, and repetition in faecal samples, were used to establish the novel microsatellite marker system for giant panda. Meanwhile, a genotyping database for Chengdu captive giant pandas (n = 57) were set up using this standardized system. What's more, a universal individual identification method was established and the genetic diversity were analysed in this study as the applications of this marker system. The microsatellite abundance and diversity were characterized in giant panda genomes. A total of 154,677 tetranucleotide microsatellites were identified and 15 of them were discovered as the polymorphic and stable loci. The individual identification method and the genetic diversity analysis method in this study provided adequate material for the future study of giant panda.

Introgression from Domestic Goat Generated Variation at the Major Histocompatibility Complex of Alpine Ibex

PubMed Central

Grossen, Christine; Keller, Lukas; Biebach, Iris; Croll, Daniel

2014-01-01

The major histocompatibility complex (MHC) is a crucial component of the vertebrate immune system and shows extremely high levels of genetic polymorphism. The extraordinary genetic variation is thought to be ancient polymorphisms maintained by balancing selection. However, introgression from related species was recently proposed as an additional mechanism. Here we provide evidence for introgression at the MHC in Alpine ibex (Capra ibex ibex). At a usually very polymorphic MHC exon involved in pathogen recognition (DRB exon 2), Alpine ibex carried only two alleles. We found that one of these DRB alleles is identical to a DRB allele of domestic goats (Capra aegagrus hircus). We sequenced 2489 bp of the coding and non-coding regions of the DRB gene and found that Alpine ibex homozygous for the goat-type DRB exon 2 allele showed nearly identical sequences (99.8%) to a breed of domestic goats. Using Sanger and RAD sequencing, microsatellite and SNP chip data, we show that the chromosomal region containing the goat-type DRB allele has a signature of recent introgression in Alpine ibex. A region of approximately 750 kb including the DRB locus showed high rates of heterozygosity in individuals carrying one copy of the goat-type DRB allele. These individuals shared SNP alleles both with domestic goats and other Alpine ibex. In a survey of four Alpine ibex populations, we found that the region surrounding the DRB allele shows strong linkage disequilibria, strong sequence clustering and low diversity among haplotypes carrying the goat-type allele. Introgression at the MHC is likely adaptive and introgression critically increased MHC DRB diversity in the genetically impoverished Alpine ibex. Our finding contradicts the long-standing view that genetic variability at the MHC is solely a consequence of ancient trans-species polymorphism. Introgression is likely an underappreciated source of genetic diversity at the MHC and other loci under balancing selection. PMID:24945814

The evolution of small insertions and deletions in the coding genes of Drosophila melanogaster.

PubMed

Chong, Zechen; Zhai, Weiwei; Li, Chunyan; Gao, Min; Gong, Qiang; Ruan, Jue; Li, Juan; Jiang, Lan; Lv, Xuemei; Hungate, Eric; Wu, Chung-I

2013-12-01

Studies of protein evolution have focused on amino acid substitutions with much less systematic analysis on insertion and deletions (indels) in protein coding genes. We hence surveyed 7,500 genes between Drosophila melanogaster and D. simulans, using D. yakuba as an outgroup for this purpose. The evolutionary rate of coding indels is indeed low, at only 3% of that of nonsynonymous substitutions. As coding indels follow a geometric distribution in size and tend to fall in low-complexity regions of proteins, it is unclear whether selection or mutation underlies this low rate. To resolve the issue, we collected genomic sequences from an isogenic African line of D. melanogaster (ZS30) at a high coverage of 70× and analyzed indel polymorphism between ZS30 and the reference genome. In comparing polymorphism and divergence, we found that the divergence to polymorphism ratio (i.e., fixation index) for smaller indels (size ≤ 10 bp) is very similar to that for synonymous changes, suggesting that most of the within-species polymorphism and between-species divergence for indels are selectively neutral. Interestingly, deletions of larger sizes (size ≥ 11 bp and ≤ 30 bp) have a much higher fixation index than synonymous mutations and 44.4% of fixed middle-sized deletions are estimated to be adaptive. To our surprise, this pattern is not found for insertions. Protein indel evolution appear to be in a dynamic flux of neutrally driven expansion (insertions) together with adaptive-driven contraction (deletions), and these observations provide important insights for understanding the fitness of new mutations as well as the evolutionary driving forces for genomic evolution in Drosophila species.

Genetic Diversity in the Prion Protein Gene (PRNP) of Domestic Cattle and Water Buffaloes in Vietnam, Indonesia and Thailand

PubMed Central

UCHIDA, Leo; HERIYANTO, Agus; THONGCHAI, Chalermchaikit; HANH, Tran Thi; HORIUCHI, Motohiro; ISHIHARA, Kanako; TAMURA, Yutaka; MURAMATSU, Yasukazu

2014-01-01

ABSTRACT There has been an accumulation of information on frequencies of insertion/deletion (indel) polymorphisms within the bovine prion protein gene (PRNP) and on the number of octapeptide repeats and single nucleotide polymorphisms (SNPs) in the coding region of bovine PRNP related to bovine spongiform encephalopathy (BSE) susceptibility. We investigated the frequencies of 23-bp indel polymorphism in the promoter region (23indel) and 12-bp indel polymorphism in intron 1 region (12indel), octapeptide repeat polymorphisms and SNPs in the bovine PRNP of cattle and water buffaloes in Vietnam, Indonesia and Thailand. The frequency of the deletion allele in the 23indel site was significantly low in cattle of Indonesia and Thailand and water buffaloes. The deletion allele frequency in the 12indel site was significantly low in all of the cattle and buffaloes categorized in each subgroup. In both indel sites, the deletion allele has been reported to be associated with susceptibility to classical BSE. In some Indonesian local cattle breeds, the frequency of the allele with 5 octapeptide repeats was significantly high despite the fact that the allele with 6 octapeptide repeats has been reported to be most frequent in many breeds of cattle. Four SNPs observed in Indonesian local cattle have not been reported for domestic cattle. This study provided information on PRNP of livestock in these Southeast Asian countries. PMID:24705506

Association of Amine-Receptor DNA Sequence Variants with Associative Learning in the Honeybee.

PubMed

Lagisz, Malgorzata; Mercer, Alison R; de Mouzon, Charlotte; Santos, Luana L S; Nakagawa, Shinichi

2016-03-01

Octopamine- and dopamine-based neuromodulatory systems play a critical role in learning and learning-related behaviour in insects. To further our understanding of these systems and resulting phenotypes, we quantified DNA sequence variations at six loci coding octopamine-and dopamine-receptors and their association with aversive and appetitive learning traits in a population of honeybees. We identified 79 polymorphic sequence markers (mostly SNPs and a few insertions/deletions) located within or close to six candidate genes. Intriguingly, we found that levels of sequence variation in the protein-coding regions studied were low, indicating that sequence variation in the coding regions of receptor genes critical to learning and memory is strongly selected against. Non-coding and upstream regions of the same genes, however, were less conserved and sequence variations in these regions were weakly associated with between-individual differences in learning-related traits. While these associations do not directly imply a specific molecular mechanism, they suggest that the cross-talk between dopamine and octopamine signalling pathways may influence olfactory learning and memory in the honeybee.

Evaluation of genetic variations in miRNA-binding sites of BRCA1 and BRCA2 genes as risk factors for the development of early-onset and/or familial breast cancer.

PubMed

Erturk, Elif; Cecener, Gulsah; Polatkan, Volkan; Gokgoz, Sehsuvar; Egeli, Unal; Tunca, Berrin; Tezcan, Gulcin; Demirdogen, Elif; Ak, Secil; Tasdelen, Ismet

2014-01-01

Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intron- exon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3'UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/ BRCA2 and to identify specific 3'UTR variants that may be risk factors for cancer development. The 3'UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs c.*1287C>T (rs12516) (BRCA1) and c.*105A>C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3'UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism c.*1287C>T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP c.*1287C>T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population.

Dengue Virus Type 3 Adaptive Changes during Epidemics in São Jose de Rio Preto, Brazil, 2006–2007

PubMed Central

Bosch, Irene; Schimitt, Diane; Calzavara-Silva, Carlos E.; de A Zanotto, Paolo M.; Nogueira, Maurício L.

2013-01-01

Global dengue virus spread in tropical and sub-tropical regions has become a major international public health concern. It is evident that DENV genetic diversity plays a significant role in the immunopathology of the disease and that the identification of polymorphisms associated with adaptive responses is important for vaccine development. The investigation of naturally occurring genomic variants may play an important role in the comprehension of different adaptive strategies used by these mutants to evade the human immune system. In order to elucidate this role we sequenced the complete polyprotein-coding region of thirty-three DENV-3 isolates to characterize variants circulating under high endemicity in the city of São José de Rio Preto, Brazil, during the onset of the 2006-07 epidemic. By inferring the evolutionary history on a local-scale and estimating rates of synonymous (dS) and nonsynonimous (dN) substitutions, we have documented at least two different introductions of DENV-3 into the city and detected 10 polymorphic codon sites under significant positive selection (dN/dS > 1) and 8 under significant purifying selection (dN/dS < 1). We found several polymorphic amino acid coding sites in the envelope (15), NS1 (17), NS2A (11), and NS5 (24) genes, which suggests that these genes may be experiencing relatively recent adaptive changes. Furthermore, some polymorphisms correlated with changes in the immunogenicity of several epitopes. Our study highlights the existence of significant and informative DENV variability at the spatio-temporal scale of an urban outbreak. PMID:23667626

Brief Note Low diversity of the major histocompatibility complex class II DRA gene in domestic goats (Capra hircus) in Southern China.

PubMed

Chen, L P; E, G X; Zhao, Y J; Na, R S; Zhao, Z Q; Zhang, J H; Ma, Y H; Sun, Y W; Zhong, T; Zhang, H P; Huang, Y F

2015-06-18

DRA encodes the alpha chain of the DR heterodimer, is closely linked to DRB and is considered almost monomorphic in major histocompatibility complex region. In this study, we identified the exon 2 of DRA to evaluate the immunogenetic diversity of Chinese south indigenous goat. Two single nucleotide polymorphisms in an untranslated region and one synonymous substitution in coding region were identified. These data suggest that high immunodiversity in native Chinese population.

Phylogenetic Network for European mtDNA

PubMed Central

Finnilä, Saara; Lehtonen, Mervi S.; Majamaa, Kari

2001-01-01

The sequence in the first hypervariable segment (HVS-I) of the control region has been used as a source of evolutionary information in most phylogenetic analyses of mtDNA. Population genetic inference would benefit from a better understanding of the variation in the mtDNA coding region, but, thus far, complete mtDNA sequences have been rare. We determined the nucleotide sequence in the coding region of mtDNA from 121 Finns, by conformation-sensitive gel electrophoresis and subsequent sequencing and by direct sequencing of the D loop. Furthermore, 71 sequences from our previous reports were included, so that the samples represented all the mtDNA haplogroups present in the Finnish population. We found a total of 297 variable sites in the coding region, which allowed the compilation of unambiguous phylogenetic networks. The D loop harbored 104 variable sites, and, in most cases, these could be localized within the coding-region networks, without discrepancies. Interestingly, many homoplasies were detected in the coding region. Nucleotide variation in the rRNA and tRNA genes was 6%, and that in the third nucleotide positions of structural genes amounted to 22% of that in the HVS-I. The complete networks enabled the relationships between the mtDNA haplogroups to be analyzed. Phylogenetic networks based on the entire coding-region sequence in mtDNA provide a rich source for further population genetic studies, and complete sequences make it easier to differentiate between disease-causing mutations and rare polymorphisms. PMID:11349229

A novel TaqI polymorphism in the coding region of the ovine TNXB gene in the MHC class III region: morphostructural and physiological influences.

PubMed

Ajayi, Oyeyemi O; Adefenwa, Mufliat A; Agaviezor, Brilliant O; Ikeobi, Christian O N; Wheto, Matthew; Okpeku, Moses; Amusan, Samuel A; Yakubu, Abdulmojeed; De Donato, Marcos; Peters, Sunday O; Imumorin, Ikhide G

2014-02-01

The tenascin-XB (TNXB) gene has antiadhesive effects, functions in matrix maturation in connective tissues, and localizes to the major histocompatibility complex class III region. We hypothesized that it may influence adaptive physiological response through an effect on blood vessel function. We identified a novel g.1324 A→G polymorphism at a TaqI recognition site in a 454 bp fragment of ovine TNXB and genotyped it in 150 Nigerian sheep using PCR-RFLP. The missense mutation changes glutamic acid (GAA) to glycine (GGA). Among SNP genotypes, significant differences (P < 0.05) were observed in body weight and fore cannon bone length. Interaction effects of breed, SNP genotype, and geographic location had a significant effect (P < 0.05) on chest girth. The SNP genotype was significantly (P < 0.05) associated with physiological traits of pulse rate and skin temperature. The observed effect of this novel polymorphism may be mediated through its role in connective tissue biology, requiring further association and functional studies.

A new polymorphic and multicopy MHC gene family related to nonmammalian class I

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

Leelayuwat, C.; Degli-Esposti, M.A.; Abraham, L.J.

1994-12-31

The authors have used genomic analysis to characterize a region of the central major histocompatibility complex (MHC) spanning {approximately} 300 kilobases (kb) between TNF and HLA-B. This region has been suggested to carry genetic factors relevant to the development of autoimmune diseases such as myasthenia gravis (MG) and insulin dependent diabetes mellitus (IDDM). Genomic sequence was analyzed for coding potential, using two neural network programs, GRAIL and GeneParser. A genomic probe, JAB, containing putative coding sequences (PERB11) located 60 kb centromeric of HLA-B, was used for northern analysis of human tissues. Multiple transcripts were detected. Southern analysis of genomic DNAmore » and overlapping YAC clones, covering the region from BAT1 to HLA-F, indicated that there are at least five copies of PERB11, four of which are located within this region of the MHC. The partial cDNA sequence of PERB11 was obtained from poly-A RNA derived from skeletal muscle. The putative amino acid sequence of PERB11 shares {approximately} 30% identity to MHC class I molecules from various species, including reptiles, chickens, and frogs, as well as to other MHC class I-like molecules, such as the IgG FcR of the mouse and rat and the human Zn-{alpha}2-glycoprotein. From direct comparison of amino acid sequences, it is concluded that PERB11 is a distinct molecule more closely related to nonmammalian than known mammalian MHC class I molecules. Genomic sequence analysis of PERB11 from five MHC ancestral haplotypes (AH) indicated that the gene is polymorphic at both DNA and protein level. The results suggest that the authors have identified a novel polymorphic gene family with multiple copies within the MHC. 48 refs., 10 figs., 2 tabs.« less

Characterization and phylogenetic analysis of the swine leukocyte antigen 3 gene from Korean native pigs.

PubMed

Chung, H Y; Choi, Y C; Park, H N

2015-05-18

We investigated the phylogenetic relationships between pig breeds, compared the genetic similarity between humans and pigs, and provided basic genetic information on Korean native pigs (KNPs), using genetic variants of the swine leukocyte antigen 3 (SLA-3) gene. Primers were based on sequences from GenBank (accession Nos. AF464010 and AF464009). Polymerase chain reaction analysis amplified approximately 1727 bp of segments, which contained 1086 bp of coding regions and 641 bp of the 3'- and 5'-untranslated regions. Bacterial artificial chromosome clones of miniature pigs were used for sequencing the SLA-3 genomic region, which was 3114 bp in total length, including the coding (1086 bp) and non-coding (2028 bp) regions. Sequence analysis detected 53 single nucleotide polymorphisms (SNPs), based on a minor allele frequency greater than 0.01, which is low compared with other pig breeds, and the results suggest that there is low genetic variability in KNPs. Comparative analysis revealed that humans possess approximately three times more genetic variation than do pigs. Approximately 71% of SNPs in exons 2 and 3 were detected in KNPs, and exon 5 in humans is a highly polymorphic region. Newly identified sequences of SLA-3 using KNPs were submitted to GenBank (accession No. DQ992512-18). Cluster analysis revealed that KNPs were grouped according to three major alleles: SLA-3*0502 (DQ992518), SLA-3*0302 (DQ992513 and DQ992516), and SLA-3*0303 (DQ992512, DQ992514, DQ992515, and DQ992517). Alignments revealed that humans have a relatively close genetic relationship with pigs and chimpanzees. The information provided by this study may be useful in KNP management.

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

PubMed Central

Imanishi, Tadashi; Itoh, Takeshi; Suzuki, Yutaka; O'Donovan, Claire; Fukuchi, Satoshi; Koyanagi, Kanako O; Barrero, Roberto A; Tamura, Takuro; Yamaguchi-Kabata, Yumi; Tanino, Motohiko; Yura, Kei; Miyazaki, Satoru; Ikeo, Kazuho; Homma, Keiichi; Kasprzyk, Arek; Nishikawa, Tetsuo; Hirakawa, Mika; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Ashurst, Jennifer; Jia, Libin; Nakao, Mitsuteru; Thomas, Michael A; Mulder, Nicola; Karavidopoulou, Youla; Jin, Lihua; Kim, Sangsoo; Yasuda, Tomohiro; Lenhard, Boris; Eveno, Eric; Suzuki, Yoshiyuki; Yamasaki, Chisato; Takeda, Jun-ichi; Gough, Craig; Hilton, Phillip; Fujii, Yasuyuki; Sakai, Hiroaki; Tanaka, Susumu; Amid, Clara; Bellgard, Matthew; Bonaldo, Maria de Fatima; Bono, Hidemasa; Bromberg, Susan K; Brookes, Anthony J; Bruford, Elspeth; Carninci, Piero; Chelala, Claude; Couillault, Christine; de Souza, Sandro J.; Debily, Marie-Anne; Devignes, Marie-Dominique; Dubchak, Inna; Endo, Toshinori; Estreicher, Anne; Eyras, Eduardo; Fukami-Kobayashi, Kaoru; R. Gopinath, Gopal; Graudens, Esther; Hahn, Yoonsoo; Han, Michael; Han, Ze-Guang; Hanada, Kousuke; Hanaoka, Hideki; Harada, Erimi; Hashimoto, Katsuyuki; Hinz, Ursula; Hirai, Momoki; Hishiki, Teruyoshi; Hopkinson, Ian; Imbeaud, Sandrine; Inoko, Hidetoshi; Kanapin, Alexander; Kaneko, Yayoi; Kasukawa, Takeya; Kelso, Janet; Kersey, Paul; Kikuno, Reiko; Kimura, Kouichi; Korn, Bernhard; Kuryshev, Vladimir; Makalowska, Izabela; Makino, Takashi; Mano, Shuhei; Mariage-Samson, Regine; Mashima, Jun; Matsuda, Hideo; Mewes, Hans-Werner; Minoshima, Shinsei; Nagai, Keiichi; Nagasaki, Hideki; Nagata, Naoki; Nigam, Rajni; Ogasawara, Osamu; Ohara, Osamu; Ohtsubo, Masafumi; Okada, Norihiro; Okido, Toshihisa; Oota, Satoshi; Ota, Motonori; Ota, Toshio; Otsuki, Tetsuji; Piatier-Tonneau, Dominique; Poustka, Annemarie; Ren, Shuang-Xi; Saitou, Naruya; Sakai, Katsunaga; Sakamoto, Shigetaka; Sakate, Ryuichi; Schupp, Ingo; Servant, Florence; Sherry, Stephen; Shiba, Rie; Shimizu, Nobuyoshi; Shimoyama, Mary; Simpson, Andrew J; Soares, Bento; Steward, Charles; Suwa, Makiko; Suzuki, Mami; Takahashi, Aiko; Tamiya, Gen; Tanaka, Hiroshi; Taylor, Todd; Terwilliger, Joseph D; Unneberg, Per; Veeramachaneni, Vamsi; Watanabe, Shinya; Wilming, Laurens; Yasuda, Norikazu; Yoo, Hyang-Sook; Stodolsky, Marvin; Makalowski, Wojciech; Go, Mitiko; Nakai, Kenta; Takagi, Toshihisa; Kanehisa, Minoru; Sakaki, Yoshiyuki; Quackenbush, John; Okazaki, Yasushi; Hayashizaki, Yoshihide; Hide, Winston; Chakraborty, Ranajit; Nishikawa, Ken; Sugawara, Hideaki; Tateno, Yoshio; Chen, Zhu; Oishi, Michio; Tonellato, Peter; Apweiler, Rolf; Okubo, Kousaku; Wagner, Lukas; Wiemann, Stefan; Strausberg, Robert L; Isogai, Takao; Auffray, Charles; Nomura, Nobuo; Sugano, Sumio

2004-01-01

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology. PMID:15103394

Toll-like receptor 2 gene polymorphisms in Chinese Holstein cattle and their associations with bovine tuberculosis.

PubMed

Zhao, Zhanqin; Xue, Yun; Hu, Zhigang; Zhou, Feng; Ma, Beibei; Long, Ta; Xue, Qiao; Liu, Huisheng

2017-04-01

This study evaluated whether there was an association between polymorphisms within the Toll-like receptor 2 gene (TLR2) of Chinese Holstein cattle and susceptibility to bovine tuberculosis (BTB). In a case-control study including 210 BTB cases and 237 control cattle, we found only two common single-nucleotide polymorphisms (SNPs) within the entire coding region of the TLR2 gene, A631G (rs95214857) and T1707C (rs1388116488). Additionally, the allele and genotype distributions of A631G and T1707C were not different between case and control groups, indicated that these SNPs were not associated with susceptibility to BTB. These results suggested that polymorphisms in the TLR2 gene might not play a significant role in the BTB risk in Chinese Holstein cattle. Copyright © 2017 Elsevier B.V. All rights reserved.

Ala397Asp mutation of myosin VIIA gene segregating in a Spanish family with type-Ib Usher syndrome.

PubMed

Espinós, C; Millán, J M; Sánchez, F; Beneyto, M; Nájera, C

1998-06-01

In the current study, 12 Spanish families affected by type-I Usher syndrome, that was previously linked to chromosome 11q, were screened for the presence of mutations in the N-terminal coding portion of the motor domain of the myosin VIIA gene by single-strand conformation polymorphism analysis of the first 14 exons. A mutation (Ala397Asp) segregating with the disease was identified, and several polymorphisms were also detected. It is presumed that the other USHIB mutations in these families could be located in the unscreened regions of the gene.

Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.

PubMed

Kim, S-J; Young, L J; Gonen, D; Veenstra-VanderWeele, J; Courchesne, R; Courchesne, E; Lord, C; Leventhal, B L; Cook, E H; Insel, T R

2002-01-01

Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

PubMed Central

Oh, Juliana J.; Koegel, Ashley; Phan, Diana T.; Razfar, Ali; Slamon, Dennis J.

2007-01-01

Summary Allele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour vs. adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected, instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC) whereas homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals. PMID:17606309

Polymorphisms in the phosducin (PDC) gene on chromosome 1q25-32

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

Humphries, P.; Mansergh, F.C.; Farrar, G.J.

1994-09-01

Phosducin (33 kDa protein or MEKA) is a principal water-soluble phosphoprotein in the rod and cone photoreceptor cells and pinealocytes. This protein modulates the phototransduction cascade by binding to the beta and gamma subunit complexes of transducin. The PDC gene has been mapped to 1q25-32, the region of linkage of two hereditary retinal degenerative disorders; autosomal dominant juvenile-onset open-angle glaucoma and one form of autosomal recessive RP. Using previously published sequence data, PCR primers were designed to amplify the coding and 5{prime} flanking regions of the PDC gene. Direct sequencing revealed three polymorphisms in the 5{prime} flanking region, two ofmore » which were in regions highly homologous between humans and mice. Analysis of the polymorphisms was then extended to larger population samples using SSCPE and denaturing gel analysis. The first polymorphism PDC1 resulted from an insertion of a G residue at position -653/4. Allele frequencies were determined to be 0.51 (insG) and 0.49 (normal) giving a PIC value of 0.50. A deletion of a T residue at position -488 was the basis of the PDC2 polymorphism with allele frequencies of 0.88 (normal) and 0.12 (delT) and a PIC value of 0.21. Interestingly, the allele with an inserted G residue in PDC1 always segregrated with the deleted T allele in PDC2. The third polymorphism PDC3 was caused by a T or G residue at position -1083. Allele frequencies of 0.26 (G residue) and 0.74 (T residue) were determined from an analysis of 80 individuals with an overall PIC value of 0.39. The identification of these three polymorphisms in the PDC gene will be useful for future genetic linkage studies of chromosome 1q in inherited retinopathies.« less

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

PubMed

Albrechtsen, A; Grarup, N; Li, Y; Sparsø, T; Tian, G; Cao, H; Jiang, T; Kim, S Y; Korneliussen, T; Li, Q; Nie, C; Wu, R; Skotte, L; Morris, A P; Ladenvall, C; Cauchi, S; Stančáková, A; Andersen, G; Astrup, A; Banasik, K; Bennett, A J; Bolund, L; Charpentier, G; Chen, Y; Dekker, J M; Doney, A S F; Dorkhan, M; Forsen, T; Frayling, T M; Groves, C J; Gui, Y; Hallmans, G; Hattersley, A T; He, K; Hitman, G A; Holmkvist, J; Huang, S; Jiang, H; Jin, X; Justesen, J M; Kristiansen, K; Kuusisto, J; Lajer, M; Lantieri, O; Li, W; Liang, H; Liao, Q; Liu, X; Ma, T; Ma, X; Manijak, M P; Marre, M; Mokrosiński, J; Morris, A D; Mu, B; Nielsen, A A; Nijpels, G; Nilsson, P; Palmer, C N A; Rayner, N W; Renström, F; Ribel-Madsen, R; Robertson, N; Rolandsson, O; Rossing, P; Schwartz, T W; Slagboom, P E; Sterner, M; Tang, M; Tarnow, L; Tuomi, T; van't Riet, E; van Leeuwen, N; Varga, T V; Vestmar, M A; Walker, M; Wang, B; Wang, Y; Wu, H; Xi, F; Yengo, L; Yu, C; Zhang, X; Zhang, J; Zhang, Q; Zhang, W; Zheng, H; Zhou, Y; Altshuler, D; 't Hart, L M; Franks, P W; Balkau, B; Froguel, P; McCarthy, M I; Laakso, M; Groop, L; Christensen, C; Brandslund, I; Lauritzen, T; Witte, D R; Linneberg, A; Jørgensen, T; Hansen, T; Wang, J; Nielsen, R; Pedersen, O

2013-02-01

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

[Genetic diversity analysis of Andrographis paniculata in China based on SRAP and SNP].

PubMed

Chen, Rong; Wang, Xiao-Yun; Song, Yu-Ning; Zhu, Yun-feng; Wang, Peng-liang; Li, Min; Zhong, Guo-Yue

2014-12-01

In order to reveal genetic diversity of domestic Andrographis paniculata and its impact on quality, genetic backgrounds of 103 samples from 7 provinces in China were analyzed using SRAP marker and SNP marker. Genetic structures of the A. paniculata populations were estimated with Powermarker V 3.25 and Mega 6.0 software, and polymorphic SNPs were identified with CodonCode Aligner software. The results showed that the genetic distances of domestic A. paniculata germplasm ranged from 0. 01 to 0.09, and no polymorphic SNPs were discovered in coding sequence fragments of ent-copalyl diphosphate synthase. A. paniculata germplasm from various regions in China had poor genetic diversity. This phenomenon was closely related to strict self-fertilization and earlier introduction from the same origin. Therefore, genetic background had little impact on variable qualities of A. paniculata in domestic market. Mutation breeding, polyploid breeding and molecular breeding were proposed as promising strategies in germplasm innovation.

Length and nucleotide sequence polymorphism at the trnL and trnF non-coding regions of chloroplast genomes among Saccharum and Erianthus species

USDA-ARS?s Scientific Manuscript database

The aneupolyploidy genome of sugarcane (Saccharum hybrids spp.) and lack of a classical genetic linkage map make genetics research most difficult for sugarcane. Whole genome sequencing and genetic characterization of sugarcane and related taxa are far behind other crops. In this study, universal PCR...

Selection signatures in four lignin genes from switchgrass populations divergently selected for in vitro dry matter digestibility

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

Chen, Shiyu; Kaeppler, Shawn M.; Vogel, Kenneth P.

Switchgrass is undergoing development as a dedicated cellulosic bioenergy crop. Fermentation of lignocellulosic biomass to ethanol in a bioenergy system or to volatile fatty acids in a livestock production system is strongly and negatively influenced by lignification of cell walls. This study detects specific loci that exhibit selection signatures across switchgrass breeding populations that differ in in vitro dry matter digestibility (IVDMD), ethanol yield, and lignin concentration. Allele frequency changes in candidate genes were used to detect loci under selection. Out of the 183 polymorphisms identified in the four candidate genes, twenty-five loci in the intron regions and four locimore » in coding regions were found to display a selection signature. All loci in the coding regions are synonymous substitutions. Selection in both directions were observed on polymorphisms that appeared to be under selection. Genetic diversity and linkage disequilibrium within the candidate genes were low. The recurrent divergent selection caused excessive moderate allele frequencies in the cycle 3 reduced lignin population as compared to the base population. As a result, this study provides valuable insight on genetic changes occurring in short-term selection in the polyploid populations, and discovered potential markers for breeding switchgrass with improved biomass quality.« less

Selection signatures in four lignin genes from switchgrass populations divergently selected for in vitro dry matter digestibility

DOE PAGES

Chen, Shiyu; Kaeppler, Shawn M.; Vogel, Kenneth P.; ...

2016-11-28

Switchgrass is undergoing development as a dedicated cellulosic bioenergy crop. Fermentation of lignocellulosic biomass to ethanol in a bioenergy system or to volatile fatty acids in a livestock production system is strongly and negatively influenced by lignification of cell walls. This study detects specific loci that exhibit selection signatures across switchgrass breeding populations that differ in in vitro dry matter digestibility (IVDMD), ethanol yield, and lignin concentration. Allele frequency changes in candidate genes were used to detect loci under selection. Out of the 183 polymorphisms identified in the four candidate genes, twenty-five loci in the intron regions and four locimore » in coding regions were found to display a selection signature. All loci in the coding regions are synonymous substitutions. Selection in both directions were observed on polymorphisms that appeared to be under selection. Genetic diversity and linkage disequilibrium within the candidate genes were low. The recurrent divergent selection caused excessive moderate allele frequencies in the cycle 3 reduced lignin population as compared to the base population. As a result, this study provides valuable insight on genetic changes occurring in short-term selection in the polyploid populations, and discovered potential markers for breeding switchgrass with improved biomass quality.« less

Variability and transmission by Aphis glycines of North American and Asian Soybean mosaic virus isolates.

PubMed

Domier, L L; Latorre, I J; Steinlage, T A; McCoppin, N; Hartman, G L

2003-10-01

The variability of North American and Asian strains and isolates of Soybean mosaic virus was investigated. First, polymerase chain reaction (PCR) products representing the coat protein (CP)-coding regions of 38 SMVs were analyzed for restriction fragment length polymorphisms (RFLP). Second, the nucleotide and predicted amino acid sequence variability of the P1-coding region of 18 SMVs and the helper component/protease (HC/Pro) and CP-coding regions of 25 SMVs were assessed. The CP nucleotide and predicted amino acid sequences were the most similar and predicted phylogenetic relationships similar to those obtained from RFLP analysis. Neither RFLP nor sequence analyses of the CP-coding regions grouped the SMVs by geographical origin. The P1 and HC/Pro sequences were more variable and separated the North American and Asian SMV isolates into two groups similar to previously reported differences in pathogenic diversity of the two sets of SMV isolates. The P1 region was the most informative of the three regions analyzed. To assess the biological relevance of the sequence differences in the HC/Pro and CP coding regions, the transmissibility of 14 SMV isolates by Aphis glycines was tested. All field isolates of SMV were transmitted efficiently by A. glycines, but the laboratory isolates analyzed were transmitted poorly. The amino acid sequences from most, but not all, of the poorly transmitted isolates contained mutations in the aphid transmission-associated DAG and/or KLSC amino acid sequence motifs of CP and HC/Pro, respectively.

Pool-based genome-wide association study identified novel candidate regions on BTA9 and 14 for oleic acid percentage in Japanese Black cattle.

PubMed

Kawaguchi, Fuki; Kigoshi, Hiroto; Nakajima, Ayaka; Matsumoto, Yuta; Uemoto, Yoshinobu; Fukushima, Moriyuki; Yoshida, Emi; Iwamoto, Eiji; Akiyama, Takayuki; Kohama, Namiko; Kobayashi, Eiji; Honda, Takeshi; Oyama, Kenji; Mannen, Hideyuki; Sasazaki, Shinji

2018-05-17

Fatty acid composition is an important indicator of beef quality. The objective of this study was to search the potential candidate region for fatty acid composition. We performed pool-based genome-wide association studies (GWAS) for oleic acid percentage (C18:1) in a Japanese Black cattle population from the Hyogo prefecture. GWAS analysis revealed two novel candidate regions on BTA9 and BTA14. The most significant single nucleotide polymorphisms (SNPs) in each region were genotyped in a population (n = 899) to verify their effect on C18:1. Statistical analysis revealed that both SNPs were significantly associated with C18:1 (p = .0080 and .0003), validating the quantitative trait loci (QTLs) detected in GWAS. We subsequently selected VNN1 and LYPLA1 genes as candidate genes from each region on BTA9 and BTA14, respectively. We sequenced full-length coding sequence (CDS) of these genes in eight individuals and identified a nonsynonymous SNP T66M on VNN1 gene as a putative candidate polymorphism. The polymorphism was also significantly associated with C18:1, but the p value (p = .0162) was higher than the most significant SNP on BTA9, suggesting that it would not be responsible for the QTL. Although further investigation will be needed to determine the responsible gene and polymorphism, our findings would contribute to development of selective markers for fatty acid composition in the Japanese Black cattle of Hyogo. © 2018 Japanese Society of Animal Science.

High throughput SNP discovery and genotyping in grapevine (Vitis vinifera L.) by combining a re-sequencing approach and SNPlex technology

PubMed Central

Lijavetzky, Diego; Cabezas, José Antonio; Ibáñez, Ana; Rodríguez, Virginia; Martínez-Zapater, José M

2007-01-01

Background Single-nucleotide polymorphisms (SNPs) are the most abundant type of DNA sequence polymorphisms. Their higher availability and stability when compared to simple sequence repeats (SSRs) provide enhanced possibilities for genetic and breeding applications such as cultivar identification, construction of genetic maps, the assessment of genetic diversity, the detection of genotype/phenotype associations, or marker-assisted breeding. In addition, the efficiency of these activities can be improved thanks to the ease with which SNP genotyping can be automated. Expressed sequence tags (EST) sequencing projects in grapevine are allowing for the in silico detection of multiple putative sequence polymorphisms within and among a reduced number of cultivars. In parallel, the sequence of the grapevine cultivar Pinot Noir is also providing thousands of polymorphisms present in this highly heterozygous genome. Still the general application of those SNPs requires further validation since their use could be restricted to those specific genotypes. Results In order to develop a large SNP set of wide application in grapevine we followed a systematic re-sequencing approach in a group of 11 grape genotypes corresponding to ancient unrelated cultivars as well as wild plants. Using this approach, we have sequenced 230 gene fragments, what represents the analysis of over 1 Mb of grape DNA sequence. This analysis has allowed the discovery of 1573 SNPs with an average of one SNP every 64 bp (one SNP every 47 bp in non-coding regions and every 69 bp in coding regions). Nucleotide diversity in grape (π = 0.0051) was found to be similar to values observed in highly polymorphic plant species such as maize. The average number of haplotypes per gene sequence was estimated as six, with three haplotypes representing over 83% of the analyzed sequences. Short-range linkage disequilibrium (LD) studies within the analyzed sequences indicate the existence of a rapid decay of LD within the selected grapevine genotypes. To validate the use of the detected polymorphisms in genetic mapping, cultivar identification and genetic diversity studies we have used the SNPlex™ genotyping technology in a sample of grapevine genotypes and segregating progenies. Conclusion These results provide accurate values for nucleotide diversity in coding sequences and a first estimate of short-range LD in grapevine. Using SNPlex™ genotyping we have shown the application of a set of discovered SNPs as molecular markers for cultivar identification, linkage mapping and genetic diversity studies. Thus, the combination a highly efficient re-sequencing approach and the SNPlex™ high throughput genotyping technology provide a powerful tool for grapevine genetic analysis. PMID:18021442

Identification of new polymorphic regions and differentiation of cultivated olives (Olea europaea L.) through plastome sequence comparison

PubMed Central

2010-01-01

Background The cultivated olive (Olea europaea L.) is the most agriculturally important species of the Oleaceae family. Although many studies have been performed on plastid polymorphisms to evaluate taxonomy, phylogeny and phylogeography of Olea subspecies, only few polymorphic regions discriminating among the agronomically and economically important olive cultivars have been identified. The objective of this study was to sequence the entire plastome of olive and analyze many potential polymorphic regions to develop new inter-cultivar genetic markers. Results The complete plastid genome of the olive cultivar Frantoio was determined by direct sequence analysis using universal and novel PCR primers designed to amplify all overlapping regions. The chloroplast genome of the olive has an organisation and gene order that is conserved among numerous Angiosperm species and do not contain any of the inversions, gene duplications, insertions, inverted repeat expansions and gene/intron losses that have been found in the chloroplast genomes of the genera Jasminum and Menodora, from the same family as Olea. The annotated sequence was used to evaluate the content of coding genes, the extent, and distribution of repeated and long dispersed sequences and the nucleotide composition pattern. These analyses provided essential information for structural, functional and comparative genomic studies in olive plastids. Furthermore, the alignment of the olive plastome sequence to those of other varieties and species identified 30 new organellar polymorphisms within the cultivated olive. Conclusions In addition to identifying mutations that may play a functional role in modifying the metabolism and adaptation of olive cultivars, the new chloroplast markers represent a valuable tool to assess the level of olive intercultivar plastome variation for use in population genetic analysis, phylogenesis, cultivar characterisation and DNA food tracking. PMID:20868482

Single-nucleotide polymorphisms in the SEPTIN12 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

PubMed

Miyakawa, Hiroe; Miyamoto, Toshinobu; Koh, Eitetsu; Tsujimura, Akira; Miyagawa, Yasushi; Saijo, Yasuaki; Namiki, Mikio; Sengoku, Kazuo

2012-01-01

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis, including human SEPTIN12, were identified by expression microarray analysis of human testicular tissue. Septin12 is a member of the septin family of conserved cytoskeletal GTPases that form heteropolymeric filamentous structures in interphase cells. It is expressed specifically in the testis. Therefore, we hypothesized that mutation or polymorphisms of SEPTIN12 participate in male infertility, especially Sertoli cell-only syndrome (SCOS). To investigate whether SEPTIN12 gene defects are associated with azoospermia caused by SCOS, mutational analysis was performed in 100 Japanese patients by direct sequencing of coding regions. Statistical analysis was performed in patients with SCOS and in 140 healthy control men. No mutations were found in SEPTIN12 ; however, 8 coding single-nucleotide polymorphisms (SNP1-SNP8) could be detected in the patients with SCOS. The genotype and allele frequencies in SNP3, SNP4, and SNP6 were notably higher in the SCOS group than in the control group (P < .001). These results suggest that SEPTIN12 might play a critical role in human spermatogenesis.

Assessment of FAE1 polymorphisms in three Brassica species using EcoTILLING and their association with differences in seed erucic acid contents

PubMed Central

2010-01-01

Background FAE1 (fatty acid elongase1) is the key gene in the control of erucic acid synthesis in seeds of Brassica species. Due to oil with low erucic acid (LEA) content is essential for human health and not enough LEA resource could be available, thus new LEA genetic resources are being sought for Brassica breeding. EcoTILLING, a powerful genotyping method, can readily be used to identify polymorphisms in Brassica. Results Seven B. rapa, nine B. oleracea and 101 B. napus accessions were collected for identification of FAE1 polymorphisms. Three polymorphisms were detected in the two FAE1 paralogues of B. napus using EcoTILLING and were found to be strongly associated with differences in the erucic acid contents of seeds. In genomic FAE1 sequences obtained from seven B. rapa accessions, one SNP in the coding region was deduced to cause loss of gene function. Molecular evolution analysis of FAE1 homologues showed that the relationship between the Brassica A and C genomes is closer than that between the A/C genomes and Arabidopsis genome. Alignment of the coding sequences of these FAE1 homologues indicated that 18 SNPs differed between the A and C genomes and could be used as genome-specific markers in Brassica. Conclusion This study showed the applicability of EcoTILLING for detecting gene polymorphisms in Brassica. The association between B. napus FAE1 polymorphisms and the erucic acid contents of seeds may provide useful guidance for LEA breeding. The discovery of the LEA resource in B. rapa can be exploited in Brasscia cultivation. PMID:20594317

Assessment of FAE1 polymorphisms in three Brassica species using EcoTILLING and their association with differences in seed erucic acid contents.

PubMed

Wang, Nian; Shi, Lei; Tian, Fang; Ning, Huicai; Wu, Xiaoming; Long, Yan; Meng, Jinling

2010-07-01

FAE1 (fatty acid elongase1) is the key gene in the control of erucic acid synthesis in seeds of Brassica species. Due to oil with low erucic acid (LEA) content is essential for human health and not enough LEA resource could be available, thus new LEA genetic resources are being sought for Brassica breeding. EcoTILLING, a powerful genotyping method, can readily be used to identify polymorphisms in Brassica. Seven B. rapa, nine B. oleracea and 101 B. napus accessions were collected for identification of FAE1 polymorphisms. Three polymorphisms were detected in the two FAE1 paralogues of B. napus using EcoTILLING and were found to be strongly associated with differences in the erucic acid contents of seeds. In genomic FAE1 sequences obtained from seven B. rapa accessions, one SNP in the coding region was deduced to cause loss of gene function. Molecular evolution analysis of FAE1 homologues showed that the relationship between the Brassica A and C genomes is closer than that between the A/C genomes and Arabidopsis genome. Alignment of the coding sequences of these FAE1 homologues indicated that 18 SNPs differed between the A and C genomes and could be used as genome-specific markers in Brassica. This study showed the applicability of EcoTILLING for detecting gene polymorphisms in Brassica. The association between B. napus FAE1 polymorphisms and the erucic acid contents of seeds may provide useful guidance for LEA breeding. The discovery of the LEA resource in B. rapa can be exploited in Brasscia cultivation.

Serum amyloid A1: Structure, function and gene polymorphism

PubMed Central

Sun, Lei; Ye, Richard D.

2017-01-01

Inducible expression of serum amyloid A (SAA) is a hallmark of the acute-phase response, which is a conserved reaction of vertebrates to environmental challenges such as tissue injury, infection and surgery. Human SAA1 is encoded by one of the four SAA genes and is the best-characterized SAA protein. Initially known as a major precursor of amyloid A (AA), SAA1 has been found to play an important role in lipid metabolism and contributes to bacterial clearance, the regulation of inflammation and tumor pathogenesis. SAA1 has five polymorphic coding alleles (SAA1.1 – SAA1.5) that encode distinct proteins with minor amino acid substitutions. Single nucleotide polymorphism (SNP) has been identified in both the coding and non-coding regions of human SAA1. Despite high levels of sequence homology among these variants, SAA1 polymorphisms have been reported as risk factors of cardiovascular diseases and several types of cancer. A recently solved crystal structure of SAA1.1 reveals a hexameric bundle with each of the SAA1 subunits assuming a 4-helix structure stabilized by the C-terminal tail. Analysis of the native SAA1.1 structure has led to the identification of a competing site for high-density lipoprotein (HDL) and heparin, thus providing the structural basis for a role of heparin and heparan sulfate in the conversion of SAA1 to AA. In this brief review, we compares human SAA1 with other forms of human and mouse SAAs, and discuss how structural and genetic studies of SAA1 have advanced our understanding of the physiological functions of the SAA proteins. PMID:26945629

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.

Detection of 98. 5% of the mutations in 200 Belgian cystic fibrosis alleles by reverse dot-blot and sequencing of the complete coding region and exon/intron junctions of the CFTR gene

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

Cuppens, H.; Marynen, P.; Cassiman, J.J.

1993-12-01

The authors have previously shown that about 85% of the mutations in 194 Belgian cystic fibrosis alleles could be detected by a reverse dot-blot assay. In the present study, 50 Belgian chromosomes were analyzed for mutations in the cystic fibrosis transmembrane conductance regulator gene by means of direct solid phase automatic sequencing of PCR products of individual exons. Twenty-six disease mutations and 14 polymorphisms were found. Twelve of these mutations and 3 polymorphisms were not described before. With the exception of one mutant allele carrying two mutations, these mutations were the only mutations found in the complete coding region andmore » their exon/intron boundaries. The total sensitivity of mutant CF alleles that could be identified was 98.5%. Given the heterogeneity of these mutations, most of them very rare, CFTR mutation screening still remains rather complex in the population, and population screening, whether desirable or not, does not appear to be technically feasible with the methods currently available. 24 refs., 1 fig., 2 tabs.« less

Different evolutionary patterns of SNPs between domains and unassigned regions in human protein-coding sequences.

PubMed

Pang, Erli; Wu, Xiaomei; Lin, Kui

2016-06-01

Protein evolution plays an important role in the evolution of each genome. Because of their functional nature, in general, most of their parts or sites are differently constrained selectively, particularly by purifying selection. Most previous studies on protein evolution considered individual proteins in their entirety or compared protein-coding sequences with non-coding sequences. Less attention has been paid to the evolution of different parts within each protein of a given genome. To this end, based on PfamA annotation of all human proteins, each protein sequence can be split into two parts: domains or unassigned regions. Using this rationale, single nucleotide polymorphisms (SNPs) in protein-coding sequences from the 1000 Genomes Project were mapped according to two classifications: SNPs occurring within protein domains and those within unassigned regions. With these classifications, we found: the density of synonymous SNPs within domains is significantly greater than that of synonymous SNPs within unassigned regions; however, the density of non-synonymous SNPs shows the opposite pattern. We also found there are signatures of purifying selection on both the domain and unassigned regions. Furthermore, the selective strength on domains is significantly greater than that on unassigned regions. In addition, among all of the human protein sequences, there are 117 PfamA domains in which no SNPs are found. Our results highlight an important aspect of protein domains and may contribute to our understanding of protein evolution.

[Genomics of type I diabetes mellitus and its late complications].

PubMed

Nosikov, V V

2004-01-01

In ethnic Russians, MHC (HLA) was shown to be the major locus determining the predisposition to type 1 diabetes mellitus (T1DM). To map the regions linked to T1DM, families with concordant or discordant sib pairs were selected from the Russian population of Moscow. With these families, linkage to T1DM was demonstrated for CTLA4 (IDDM12, 2q32.1-q33), which codes for a T-cell surface antigen, and PDCD2 (IDDM8, 6q25-q27), which is homologous to the mouse programmed cell death activator gene. With polymorphic microsatellites, regions 3q21-q25 (IDDM9) and 10p12.2 (IDDM10) were also linked to T1DM. Case/control and family studies of the polymorphic markers from region 11p13 revealed a new T1DM-associated locus in the vicinity of the catalase gene (CAT); linkage to this locus was not reported earlier for other populations. Diabetic polyneuropathy (DPN) proved to be associated with single-nucleotide polymorphisms Ala(-9)Val (SOD2), Arg213Gly (SOD3), and T(-262)C (CAT) and with a polymorphic microsatellite of the NOS2 promoter. Hence oxidative stress, which results from hyperglycemia, increased mitochondrial production of superoxide radicals, and insufficient activities of antioxidative enzymes, was assumed to play an important part in DPN development in T1DM. Diabetic nephropathy (DN) showed no association with the antioxidative enzyme genes. However, the association was observed for the insertion/deletion (I/D) polymorphism of ACE and the ecNOS34a/4b polymorphism of NOS3, two genes involved in controlling vascular tonicity, and for the I/D polymorphism of APOB and the epsilon 2/epsilon 3/epsilon 4 polymorphism of APOE, two genes involved in lipid transport. In addition, polymorphic microsatellites of chromosome 3q21-q25 proved to be closely associated with DN. The tightest association was established for D3S1550, carriers of allele 12 or genotype 12/14 having high risk of DN (OR = 4.85 and 6.25, respectively). Region 3q21-q25 was assumed to contain a major gene determining DN development, while the other DN-associated genes mostly affect the progression of DN.

PRKAG3 and CAST genetic polymorphisms and quality traits of dry-cured hams--I. Associations in Spanish dry-cured ham Jamón Serrano.

PubMed

Gou, P; Zhen, Z Y; Hortós, M; Arnau, J; Diestre, A; Robert, N; Claret, A; Čandek-Potokar, M; Santé-Lhoutellier, V

2012-12-01

The functional single polymorphisms identified in the calpastatin (CAST) gene have been related to the rate of meat tenderization and the protein turnover after slaughter, and the Ile199Val polymorphism identified in the coding region of the protein kinase AMP-activated (PRKAG3) gene has been proven to affect ultimate pH in muscle. The aim of the present study was to show the effects of these genetic polymorphisms on the quality traits of Spanish dry-cured ham Jamón Serrano. A tissue sample from 665 crossbreed pigs were genotyped for PRKAG3 Ile199Val, CAST Arg249Lys and CAST Ser638Arg polymorphisms, and a subsample of 120 dry cured hams was selected to perform physico-chemical, rheological, instrumental colour and sensory analyses. Associations between the polymorphisms and several quality traits of dry-cured ham, mainly related to flavour and texture, were found. The genotypes PRKAG3 Ile/Ile, CAST249 Arg/Arg and CAST638 Arg/Arg, and the haplotype CAST 249Arg-638Arg were the most favourable for Jamón Serrano production. Copyright © 2012 Elsevier Ltd. All rights reserved.

Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin 1 locus.

PubMed

Lakshmikumaran, M S; D'Ambrosio, E; Laimins, L A; Lin, D T; Furano, A V

1985-09-01

The insulin 1, but not the insulin 2, locus is polymorphic (i.e., exhibits allelic variation) in rats. Restriction enzyme analysis and hybridization studies showed that the polymorphic region is 2.2 kilobases upstream of the insulin 1 coding region and is due to the presence or absence of an approximately 2.7-kilobase repeated DNA element. DNA sequence determination showed that this DNA element is a member of a long interspersed repeated DNA family (LINE) that is highly repeated (greater than 50,000 copies) and highly transcribed in the rat. Although the presence or absence of LINE sequences at the insulin 1 locus occurs in both the homozygous and heterozygous states, LINE-containing insulin 1 alleles are more prevalent in the rat population than are alleles without LINEs. Restriction enzyme analysis of the LINE-containing alleles indicated that at least two versions of the LINE sequence may be present at the insulin 1 locus in different rats. Either repeated transposition of LINE sequences or gene conversion between the resident insulin 1 LINE and other sequences in the genome are possible explanations for this.

Genetic variations in the MCT1 (SLC16A1) gene in the Chinese population of Singapore.

PubMed

Lean, Choo Bee; Lee, Edmund Jon Deoon

2009-01-01

MCT1(SLC16A1) is the first member of the monocarboxylate transporter (MCT) and its family is involved in the transportation of metabolically important monocarboxylates such as lactate, pyruvate, acetate and ketone bodies. This study identifies genetic variations in SLC16A1 in the ethnic Chinese group of the Singaporean population (n=95). The promoter, coding region and exon-intron junctions of the SLC16A1 gene encoding the MCT1 transporter were screened for genetic variation in the study population by DNA sequencing. Seven genetic variations of SLC16A1, including 4 novel ones, were found: 2 in the promoter region, 2 in the coding exons (both nonsynonymous variations), 2 in the 3' untranslated region (3'UTR) and 1 in the intron. Of the two mutations detected in the promoter region, the -363-855T>C is a novel mutation. The 1282G>A (Val(428)Ile) is a novel SNP and was found as heterozygotic in 4 subjects. The 1470T>A (Asp(490)Glu) was found to be a common polymorphism in this study. Lastly, IVS3-17A>C in intron 3 and 2258 (755)A>G in 3'UTR are novel mutations found to be common polymorphisms in the local Chinese population. To our knowledge, this is the first report of a comprehensive analysis on the MCT1 gene in any population.

Genetic Variation Linked to Lung Cancer Survival in White Smokers | Center for Cancer Research

Cancer.gov

CCR investigators have discovered evidence that links lung cancer survival with genetic variations (called single nucleotide polymorphisms) in the MBL2 gene, a key player in innate immunity. The variations in the gene, which codes for a protein called the mannose-binding lectin, occur in its promoter region, where the RNA polymerase molecule binds to start transcription, and

Catalog of MicroRNA Seed Polymorphisms in Vertebrates

PubMed Central

Calin, George Adrian; Horvat, Simon; Jiang, Zhihua; Dovc, Peter; Kunej, Tanja

2012-01-01

MicroRNAs (miRNAs) are a class of non-coding RNA that plays an important role in posttranscriptional regulation of mRNA. Evidence has shown that miRNA gene variability might interfere with its function resulting in phenotypic variation and disease susceptibility. A major role in miRNA target recognition is ascribed to complementarity with the miRNA seed region that can be affected by polymorphisms. In the present study, we developed an online tool for the detection of miRNA polymorphisms (miRNA SNiPer) in vertebrates (http://www.integratomics-time.com/miRNA-SNiPer) and generated a catalog of miRNA seed region polymorphisms (miR-seed-SNPs) consisting of 149 SNPs in six species. Although a majority of detected polymorphisms were due to point mutations, two consecutive nucleotide substitutions (double nucleotide polymorphisms, DNPs) were also identified in nine miRNAs. We determined that miR-SNPs are frequently located within the quantitative trait loci (QTL), chromosome fragile sites, and cancer susceptibility loci, indicating their potential role in the genetic control of various complex traits. To test this further, we performed an association analysis between the mmu-miR-717 seed SNP rs30372501, which is polymorphic in a large number of standard inbred strains, and all phenotypic traits in these strains deposited in the Mouse Phenome Database. Analysis showed a significant association between the mmu-miR-717 seed SNP and a diverse array of traits including behavior, blood-clinical chemistry, body weight size and growth, and immune system suggesting that seed SNPs can indeed have major pleiotropic effects. The bioinformatics analyses, data and tools developed in the present study can serve researchers as a starting point in testing more targeted hypotheses and designing experiments using optimal species or strains for further mechanistic studies. PMID:22303453

High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes.

PubMed

Splendore, A; Silva, E O; Alonso, L G; Richieri-Costa, A; Alonso, N; Rosa, A; Carakushanky, G; Cavalcanti, D P; Brunoni, D; Passos-Bueno, M R

2000-10-01

Twenty-eight families with a clinical diagnosis of Treacher Collins syndrome were screened for mutations in the 25 coding exons of TCOF1 and their adjacent splice junctions through SSCP and direct sequencing. Pathogenic mutations were detected in 26 patients, yielding the highest detection rate reported so far for this disease (93%) and bringing the number of known disease-causing mutations from 35 to 51. This is the first report to describe clustering of pathogenic mutations. Thirteen novel polymorphic alterations were characterized, confirming previous reports that TCOF1 has an unusually high rate of single-nucleotide polymorphisms (SNPs) within its coding region. We suggest a possible different mechanism leading to TCS or genetic heterogeneity for this condition, as we identified two families with no apparent pathogenic mutation in the gene. Furthermore, our data confirm the absence of genotype-phenotype correlation and reinforce that the apparent anticipation often observed in TCS families is due to ascertainment bias. Copyright 2000 Wiley-Liss, Inc.

Differentiation of Populus species using chloroplast single nucleotide polymorphism (SNP) markers--essential for comprehensible and reliable poplar breeding.

PubMed

Schroeder, H; Hoeltken, A M; Fladung, M

2012-03-01

Within the genus Populus several species belonging to different sections are cross-compatible. Hence, high numbers of interspecies hybrids occur naturally and, additionally, have been artificially produced in huge breeding programmes during the last 100 years. Therefore, determination of a single poplar species, used for the production of 'multi-species hybrids' is often difficult, and represents a great challenge for the use of molecular markers in species identification. Within this study, over 20 chloroplast regions, both intergenic spacers and coding regions, have been tested for their ability to differentiate different poplar species using 23 already published barcoding primer combinations and 17 newly designed primer combinations. About half of the published barcoding primers yielded amplification products, whereas the new primers designed on the basis of the total sequenced cpDNA genome of Populus trichocarpa Torr. & Gray yielded much higher amplification success. Intergenic spacers were found to be more variable than coding regions within the genus Populus. The highest discrimination power of Populus species was found in the combination of two intergenic spacers (trnG-psbK, psbK-psbl) and the coding region rpoC. In barcoding projects, the coding regions matK and rbcL are often recommended, but within the genus Populus they only show moderate variability and are not efficient in species discrimination. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

Wheat CBF gene family: identification of polymorphisms in the CBF coding sequence.

PubMed

Mohseni, Sara; Che, Hua; Djillali, Zakia; Dumont, Estelle; Nankeu, Joseph; Danyluk, Jean

2012-12-01

Expression of cold-regulated genes needed for protection against freezing stress is mediated, in part, by the CBF transcription factor family. Previous studies with temperate cereals suggested that the CBF gene family in wheat was large, and that CBF genes were at the base of an important low temperature tolerance trait. Therefore, the goal of our study was to identify the CBF repertoire in the freezing-tolerant hexaploid wheat cultivar Norstar, and then to examine if the coding region of CBF genes in two spring cultivars contain polymorphisms that could affect the protein sequence and structure. Our analyses reveal that hexaploid wheat contains a complex CBF family consisting of at least 65 CBF genes of which 60 are known to be expressed in the cultivar Norstar. They represent 27 paralogous genes with 1-3 homeologous copies for the A, B, and D genomes. The cultivar Norstar contains two pseudogenes and at least 24 additional proteins having sequences and (or) structures that deviate from the consensus in the conserved AP2 DNA-binding and (or) C-terminal activation-domains. This suggests that in cultivars such as Norstar, low temperature tolerance may be increased through breeding of additional optimal alleles. The examination of the CBF repertoire present in the two spring cultivars, Chinese Spring and Manitou, reveals that they have additional polymorphisms affecting conserved positions in these domains. Understanding the effects of these polymorphisms will provide additional information for the selection of optimum CBF alleles in Triticeae breeding programs.

Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population.

PubMed

Munshi, Anjana; Rajeshwar, K; Kaul, Subhash; Al-Hazzani, Amal; Alshatwi, Ali A; Sai Babu, M; Usha, A; Jyothy, A

2010-12-01

Within the past few years there has been increasing evidence that the genetic variation in the genes coding pro- and anti-inflammatory markers may play an important role in the pathogenesis of various human diseases, including stroke. The aim of the study was to evaluate the association of Interleukin-10 (IL-10)-1082 G/A, promoter polymorphism (rs1800896) with ischemic stroke in a South Indian population from Andhra Pradesh. In this study 480 ischemic stroke patients and 470 age and sex matched healthy controls were included. The ischemic stroke patients were classified according to TOAST classification. The region of interest in the IL-10 gene was amplified by polymerase chain reaction with the use of allele specific oligonucleotide primers flanking the polymorphic region. Association between genotypes and stroke was examined by Odds Ratio (OR) with 95% confidence interval (CI) and Chi-square analysis. Significant difference was observed between the patients and healthy controls, in genotypic distribution as well as allelic frequency (p<0.05). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and IL-10 gene variant revealed that -1082 G/A polymorphism in the promoter region of IL-10 gene is significantly [adjusted OR=2.26; 95% C.I. (1.24-4.15), p<0.001] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We found significant association of this polymorphism with stroke of undetermined etiology (p<0.001). Moreover, hypertensive and diabetic individuals bearing A allele of IL-10 gene in high frequency were found to be more predisposed to stroke. Copyright © 2010 Elsevier Ltd. All rights reserved.

An Efficient Strategy Combining SSR Markers- and Advanced QTL-seq-driven QTL Mapping Unravels Candidate Genes Regulating Grain Weight in Rice

PubMed Central

Daware, Anurag; Das, Sweta; Srivastava, Rishi; Badoni, Saurabh; Singh, Ashok K.; Agarwal, Pinky; Parida, Swarup K.; Tyagi, Akhilesh K.

2016-01-01

Development and use of genome-wide informative simple sequence repeat (SSR) markers and novel integrated genomic strategies are vital to drive genomics-assisted breeding applications and for efficient dissection of quantitative trait loci (QTLs) underlying complex traits in rice. The present study developed 6244 genome-wide informative SSR markers exhibiting in silico fragment length polymorphism based on repeat-unit variations among genomic sequences of 11 indica, japonica, aus, and wild rice accessions. These markers were mapped on diverse coding and non-coding sequence components of known cloned/candidate genes annotated from 12 chromosomes and revealed a much higher amplification (97%) and polymorphic potential (88%) along with wider genetic/functional diversity level (16–74% with a mean 53%) especially among accessions belonging to indica cultivar group, suggesting their utility in large-scale genomics-assisted breeding applications in rice. A high-density 3791 SSR markers-anchored genetic linkage map (IR 64 × Sonasal) spanning 2060 cM total map-length with an average inter-marker distance of 0.54 cM was generated. This reference genetic map identified six major genomic regions harboring robust QTLs (31% combined phenotypic variation explained with a 5.7–8.7 LOD) governing grain weight on six rice chromosomes. One strong grain weight major QTL region (OsqGW5.1) was narrowed-down by integrating traditional QTL mapping with high-resolution QTL region-specific integrated SSR and single nucleotide polymorphism markers-based QTL-seq analysis and differential expression profiling. This led us to delineate two natural allelic variants in two known cis-regulatory elements (RAV1AAT and CARGCW8GAT) of glycosyl hydrolase and serine carboxypeptidase genes exhibiting pronounced seed-specific differential regulation in low (Sonasal) and high (IR 64) grain weight mapping parental accessions. Our genome-wide SSR marker resource (polymorphic within/between diverse cultivar groups) and integrated genomic strategy can efficiently scan functionally relevant potential molecular tags (markers, candidate genes and alleles) regulating complex agronomic traits (grain weight) and expedite marker-assisted genetic enhancement in rice. PMID:27833617

Variation in the coding and 3’ untranslated regions of the porcine prolactin receptor short form modifies protein expression and function

USDA-ARS?s Scientific Manuscript database

The actions of prolactin (PRL) are mediated by both long (LF) and short isoforms (SF) of the PRL receptor (PRLR). Here, we report on a genetic and functional analysis of the porcine PRLR (pPRLR) SF. Three single nucleotide polymorphisms (SNPs) within exon 11 of the pPRLR-SF give rise to four amino a...

Distribution and localization of microsatellites in the Perigord black truffle genome and identification of new molecular markers (2010) Fungal Genetics and Biology

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

Murat, Claude; Riccioni, C; Belfiori, B

The level of genetic diversity and genetic structure in the Perigord black truffle (Tuber melanosporum Vittad.) has been debated for several years, mainly due to the lack of appropriate genetic markers. Microsatellites or simple sequence repeats (SSRs) are important for the genome organisation, phenotypic diversity and are one of the most popular molecular markers. In this study, we surveyed the T. melanosporum genome (1) to characterise its SSR pattern; (2) to compare it with SSR patterns found in 48 other fungal and three oomycetes genomes and (3) to identify new polymorphic SSR markers for population genetics. The T. melanosporum genomemore » is rich in SSRs with 22,425 SSRs with mono-nucleotides being the most frequent motifs. SSRs were found in all genomic regions although they are more frequent in non-coding regions (introns and intergenic regions). Sixty out of 135 PCR-amplified mono-, di-, tri-, tetra, penta, and hexanucleotides were polymorphic (44%) within black truffle populations and 27 were randomly selected and analysed on 139 T. melanosporum isolates from France, Italy and Spain. The number of alleles varied from 2 to 18 and the expected heterozygosity from 0.124 to 0.815. One hundred and thirty-two different multilocus genotypes out of the 139 T. melanosporum isolates were identified and the genotypic diversity was high (0.999). Polymorphic SSRs were found in UTR regulatory regions of fruiting bodies and ectomycorrhiza regulated genes, suggesting that they may play a role in phenotypic variation. In conclusion, SSRs developed in this study were highly polymorphic and our results showed that T. melanosporum is a species with an important genetic diversity, which is in agreement with its recently uncovered heterothallic mating system.« less

Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region.

PubMed

Jiang, Yong-Hui; Wauki, Kekio; Liu, Qian; Bressler, Jan; Pan, Yanzhen; Kashork, Catherine D; Shaffer, Lisa G; Beaudet, Arthur L

2008-01-28

Prader-Willi syndrome (PWS) is a neurobehavioral disorder characterized by neonatal hypotonia, childhood obesity, dysmorphic features, hypogonadism, mental retardation, and behavioral problems. Although PWS is most often caused by a paternal interstitial deletion of a 6-Mb region of chromosome 15q11-q13, the identity of the exact protein coding or noncoding RNAs whose deficiency produces the PWS phenotype is uncertain. There are also reports describing a PWS-like phenotype in a subset of patients with full mutations in the FMR1 (fragile X mental retardation 1) gene. Taking advantage of the human genome sequence, we have performed extensive sequence analysis and molecular studies for the PWS candidate region. We have characterized transcripts for the first time for two UCSC Genome Browser predicted protein-coding genes, GOLGA8E (golgin subfamily a, 8E) and WHDC1L1 (WAS protein homology region containing 1-like 1) and have further characterized two previously reported genes, CYF1P1 and NIPA2; all four genes are in the region close to the proximal/centromeric deletion breakpoint (BP1). GOLGA8E belongs to the golgin subfamily of coiled-coil proteins associated with the Golgi apparatus. Six out of 16 golgin subfamily proteins in the human genome have been mapped in the chromosome 15q11-q13 and 15q24-q26 regions. We have also identified more than 38 copies of GOLGA8E-like sequence in the 15q11-q14 and 15q23-q26 regions which supports the presence of a GOLGA8E-associated low copy repeat (LCR). Analysis of the 15q11-q13 region by PFGE also revealed a polymorphic region between BP1 and BP2. WHDC1L1 is a novel gene with similarity to mouse Whdc1 (WAS protein homology region 2 domain containing 1) and human JMY protein (junction-mediating and regulatory protein). Expression analysis of cultured human cells and brain tissues from PWS patients indicates that CYFIP1 and NIPA2 are biallelically expressed. However, we were not able to determine the allele-specific expression pattern for GOLGA8E and WHDC1L1 because these two genes have highly related sequences that might also be expressed. We have presented an updated version of a sequence-based physical map for a complex chromosomal region, and we raise the possibility of polymorphism in the genomic orientation of the BP1 to BP2 region. The identification of two new proteins GOLGA8E and WHDC1L1 encoded by genes in the 15q11-q13 region may extend our understanding of the molecular basis of PWS. In terms of copy number variation and gene organization, this is one of the most polymorphic regions of the human genome, and perhaps the single most polymorphic region of this type.

Genetic Diversity and Natural Selection in 42 kDa Region of Plasmodium vivax Merozoite Surface Protein-1 from China-Myanmar Endemic Border.

PubMed

Zhou, Xia; Tambo, Ernest; Su, Jing; Fang, Qiang; Ruan, Wei; Chen, Jun-Hu; Yin, Ming-Bo; Zhou, Xiao-Nong

2017-10-01

Plasmodium vivax merozoite surface protein-1 (PvMSP1) gene codes for a major malaria vaccine candidate antigen. However, its polymorphic nature represents an obstacle to the design of a protective vaccine. In this study, we analyzed the genetic polymorphism and natural selection of the C-terminal 42 kDa fragment within PvMSP1 gene (Pv MSP142) from 77 P. vivax isolates, collected from imported cases of China-Myanmar border (CMB) areas in Yunnan province and the inland cases from Anhui, Yunnan, and Zhejiang province in China during 2009-2012. Totally, 41 haplotypes were identified and 30 of them were new haplotypes. The differences between the rates of non-synonymous and synonymous mutations suggest that PvMSP142 has evolved under natural selection, and a high selective pressure preferentially acted on regions identified of PvMSP133. Our results also demonstrated that PvMSP142 of P. vivax isolates collected on China-Myanmar border areas display higher genetic polymorphisms than those collected from inland of China. Such results have significant implications for understanding the dynamic of the P. vivax population and may be useful information towards China malaria elimination campaign strategies.

Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin 1 locus.

PubMed Central

Lakshmikumaran, M S; D'Ambrosio, E; Laimins, L A; Lin, D T; Furano, A V

1985-01-01

The insulin 1, but not the insulin 2, locus is polymorphic (i.e., exhibits allelic variation) in rats. Restriction enzyme analysis and hybridization studies showed that the polymorphic region is 2.2 kilobases upstream of the insulin 1 coding region and is due to the presence or absence of an approximately 2.7-kilobase repeated DNA element. DNA sequence determination showed that this DNA element is a member of a long interspersed repeated DNA family (LINE) that is highly repeated (greater than 50,000 copies) and highly transcribed in the rat. Although the presence or absence of LINE sequences at the insulin 1 locus occurs in both the homozygous and heterozygous states, LINE-containing insulin 1 alleles are more prevalent in the rat population than are alleles without LINEs. Restriction enzyme analysis of the LINE-containing alleles indicated that at least two versions of the LINE sequence may be present at the insulin 1 locus in different rats. Either repeated transposition of LINE sequences or gene conversion between the resident insulin 1 LINE and other sequences in the genome are possible explanations for this. Images PMID:3016521

Polymorphism of the Pv200L Fragment of Merozoite Surface Protein-1 of Plasmodium vivax in Clinical Isolates from the Pacific Coast of Colombia

PubMed Central

Valderrama-Aguirre, Augusto; Zúñiga-Soto, Evelin; Mariño-Ramírez, Leonardo; Moreno, Luz Ángela; Escalante, Ananías A.; Arévalo-Herrera, Myriam; Herrera, Sócrates

2011-01-01

Merozoite surface protein 1 (MSP-1) is a polymorphic malaria protein with functional domains involved in parasite erythrocyte interaction. Plasmodium vivax MSP-1 has a fragment (Pv200L) that has been identified as a potential subunit vaccine because it is highly immunogenic and induces partial protection against infectious parasite challenge in vaccinated monkeys. To determine the extent of genetic polymorphism and its effect on the translated protein, we sequenced the Pv200L coding region from isolates of 26 P. vivax-infected patients in a malaria-endemic area of Colombia. The extent of nucleotide diversity (π) in these isolates (0.061 ± 0.004) was significantly lower (P ≤ 0.001) than that observed in Thai and Brazilian isolates; 0.083 ± 0.006 and 0.090 ± 0.006, respectively. We found two new alleles and several previously unidentified dimorphic substitutions and significant size polymorphism. The presence of highly conserved blocks in this fragment has important implications for the development of Pv200L as a subunit vaccine candidate. PMID:21292880

Leptin and leptin receptor gene polymorphisms are correlated with production performance in the Arctic fox.

PubMed

Zhang, M; Bai, X J

2015-05-25

The polymerase chain reaction-single-strand conformation polymorphism technique was employed to measure mononucleotide diversity in the coding region of the leptin and leptin receptor genes in the Arctic fox. The relationships between specific genetic mutations and reproductive performance in Arctic foxes were determined to im-prove breeding strategies. We found that a leptin gene polymorphism was significantly associated with body weight (P < 0.01), abdominal circumference (P < 0.01), and fur length (P < 0.01). Furthermore, a polymorphism in the leptin receptor gene was associated with carcass weight and guard hair length (P < 0.01). Leptin and leptin receptor gene combinatorial genotypes were significantly associated with abdominal circumference, fur length (P < 0.01), and body weight (P < 0.05). The leptin gene is thus a key gene affecting body weight, abdominal circumference, and fur length in Arctic foxes, whereas variations in the leptin receptor mainly affect carcass weight and guard hair. The marker loci identified in this study can be used to assist in the selection of Arctic foxes for breeding to raise the production performance of this species.

Mitochondrial haplotypes are not associated with mice selectively bred for high voluntary wheel running.

PubMed

Wone, Bernard W M; Yim, Won C; Schutz, Heidi; Meek, Thomas H; Garland, Theodore

2018-04-04

Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNA Arg gene and is associated with mitochondrial densities and number of mtDNA copies. We hypothesized that the capacity for high levels of voluntary wheel-running behavior would be associated with mitochondrial haplotype. Here, we analyzed the mtDNA polymorphic region in mice from each of four replicate lines selectively bred for 54 generations for high voluntary wheel running (HR) and from four control lines (Control) randomly bred for 54 generations. Sequencing the polymorphic region revealed a variable number of adenine repeats. Single nucleotide polymorphisms (SNPs) varied from 2 to 3 adenine insertions, resulting in three haplotypes. We found significant genetic differentiations between the HR and Control groups (F st  = 0.779, p ≤ 0.0001), as well as among the replicate lines of mice within groups (F sc  = 0.757, p ≤ 0.0001). Haplotypes, however, were not strongly associated with voluntary wheel running (revolutions run per day), nor with either body mass or litter size. This system provides a useful experimental model to dissect the physiological processes linking mitochondrial, genomic SNPs, epigenetics, or nuclear-mitochondrial cross-talk to exercise activity. Copyright © 2018. Published by Elsevier B.V.

Genetic polymorphisms of the drug-metabolizing enzyme cytochrome P450 3A5 in a Uyghur Chinese population.

PubMed

Chen, Zhengshuai; Li, Jingjie; Chen, Peng; Wang, Fengjiao; Zhang, Ning; Yang, Min; Jin, Tianbo; Chen, Chao

2016-09-01

1.  Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in Uyghur ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. 2. We used DNA sequencing to investigate the promoter, exons and surrounding introns, and 3'-untranslated region of the CYP3A5 gene in 96 unrelated healthy Uyghur individuals. We also used SIFT and PolyPhen-2 to predict the protein function of the novel non-synonymous mutation in CYP3A5 coding regions. 3. We found 24 different CYP3A5 polymorphisms in the Uyghur population, three of which were novel: the synonymous mutation 43C > T in exon 1, two mutations 32120C > G and 32245T > C in 3'-untranslated region, and we detected the allele frequencies of CYP3A5*1 and *3 as 64.58% and 35.42%, respectively. While no subjects with CYP3A5*6 were identified. Other identified genotypes included the heterozygous genotype 1A/3A (59.38%) and 1A/3E (11.46%), which lead to decreased enzyme activity. In addition, the frequency of haplotype "TTAGGT" was the most prevalent with 0.781. 4. Our data provide new information regarding CYP3A5 genetic polymorphisms in Uyghur individuals, which may help to improve individualization of drug therapy and offer a preliminary basis for more rational use of drugs.

Gene network polymorphism is the raw material of natural selection: the selfish gene network hypothesis.

PubMed

Boldogköi, Zsolt

2004-09-01

Population genetics, the mathematical theory of modern evolutionary biology, defines evolution as the alteration of the frequency of distinct gene variants (alleles) differing in fitness over the time. The major problem with this view is that in gene and protein sequences we can find little evidence concerning the molecular basis of phenotypic variance, especially those that would confer adaptive benefit to the bearers. Some novel data, however, suggest that a large amount of genetic variation exists in the regulatory region of genes within populations. In addition, comparison of homologous DNA sequences of various species shows that evolution appears to depend more strongly on gene expression than on the genes themselves. Furthermore, it has been demonstrated in several systems that genes form functional networks, whose products exhibit interrelated expression profiles. Finally, it has been found that regulatory circuits of development behave as evolutionary units. These data demonstrate that our view of evolution calls for a new synthesis. In this article I propose a novel concept, termed the selfish gene network hypothesis, which is based on an overall consideration of the above findings. The major statements of this hypothesis are as follows. (1) Instead of individual genes, gene networks (GNs) are responsible for the determination of traits and behaviors. (2) The primary source of microevolution is the intraspecific polymorphism in GNs and not the allelic variation in either the coding or the regulatory sequences of individual genes. (3) GN polymorphism is generated by the variation in the regulatory regions of the component genes and not by the variance in their coding sequences. (4) Evolution proceeds through continuous restructuring of the composition of GNs rather than fixing of specific alleles or GN variants.

Genomic Correlates of Relationship QTL Involved in Fore- versus Hind Limb Divergence in Mice

PubMed Central

Pavlicev, Mihaela; Wagner, Günter P.; Noonan, James P.; Hallgrímsson, Benedikt; Cheverud, James M.

2013-01-01

Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here, we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore- and hind limb long bone lengths (loci affecting the relationship between traits, relationship quantitative trait loci [rQTL]). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due to pleiotropic mutations. Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside. We find that these two classes of QTL intervals harbor different kinds of molecular variation. SNPs in rQTL intervals more frequently reside in limb-specific cis-regulatory regions than SNPs in intQTL intervals. The intQTL loci modified by the rQTL, in contrast, show the signature of protein-coding variation. This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms. For both types of QTL intervals, the underlying candidate genes are enriched for genes involved in protein binding. This finding suggests that rQTL effects are caused by local interactions among the products of the causal genes harbored in rQTL and intQTL intervals. This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation. PMID:24065733

Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk

PubMed Central

Pattison, Jillian M.; Posternak, Valeriya; Cole, Michael D.

2016-01-01

It is well established that environmental toxins, such as exposure to arsenic, are risk factors in the development of urinary bladder cancer, yet recent genome-wide association studies (GWAS) provide compelling evidence that there is a strong genetic component associated with disease predisposition. A single nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12, residing 6 kb upstream of the important cell cycle regulator and proto-oncogene, Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer predisposition has been unclear since it lies within a non-coding region of the genome. Here, it is demonstrated that bladder cancer cells heterozygous for this SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription occurring from the risk allele. Furthermore, using chromatin immunoprecipitation assays, a novel enhancer element was identified within the first intron of CCNE1 that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP in high linkage disequilibrium with rs8102137 residing in the center of a KLF5 motif, alters KLF5 binding to this genomic region. Through luciferase assays and CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element controlling CCNE1 transcription is characterized. These studies uncover how a cancer-associated polymorphism mechanistically contributes to an increased predisposition for bladder cancer development. Implications A polymorphic KLF5 binding site near the CCNE1 gene explains genetic risk identified through genome wide association studies. PMID:27514407

Evidence for a functional genetic polymorphism of the human thiosulfate sulfurtransferase (Rhodanese), a cyanide and H2S detoxification enzyme.

PubMed

Billaut-Laden, Ingrid; Allorge, Delphine; Crunelle-Thibaut, Aurélie; Rat, Emmanuel; Cauffiez, Christelle; Chevalier, Dany; Houdret, Nicole; Lo-Guidice, Jean-Marc; Broly, Franck

2006-08-01

Rhodanese or thiosulfate sulfurtransferase (TST) is a mitochondrial matrix enzyme that plays roles in cyanide detoxification, the formation of iron-sulfur proteins and the modification of sulfur-containing enzymes. Transsulfuration reaction catalyzed by TST is also involved in H(2)S detoxification. To date, no polymorphism of the human TST gene had been reported. We developed a screening strategy based on a PCR-SSCP method to search for mutations in the 3 exons of TST and their proximal flanking regions. This strategy has been applied to DNA samples from 50 unrelated French individuals of Caucasian origin. Eleven polymorphisms consisting in seven nucleotide substitutions in non-coding regions, two silent mutations and two missense mutations were characterized. The functional consequences of the identified mutations were assessed in vivo by measurement of erythrocyte TST activity and/or in vitro using heterologous expression in Saccharomyces cerevisiae or transient transfection assay in HT29 and Caco-2 cell lines. The P(285)A variant appears to encode a protein with a 50% decrease of in vitro intrinsic clearance compared to the wild-type enzyme. Additionally, the six polymorphisms located upstream the ATG initiation codon are responsible for a significant decrease (ranging from 40% to 73%) in promoter activity of a reporter gene compared to the corresponding wild-type sequence. This work constitutes the first report of the existence of a functional genetic polymorphism affecting TST activity and should be of great help to investigate certain disorders for which impairment of CN(-) or H(2)S detoxification have been suggested to be involved.

HLA-F polymorphisms in a Euro-Brazilian population from Southern Brazil.

PubMed

Manvailer, L F S; Wowk, P F; Mattar, S B; da Siva, J S; da Graça Bicalho, M; Roxo, V M M S

2014-12-01

HLA-F is a non-classical major histocompatibility complex (MHC) gene. It codes class Ib MHC molecules with restricted distribution and less nucleotide variations than MHC class Ia genes. Of the 22 alleles registered on the IMGT database only four alleles encode for proteins that differ in their primary structure. To estimate genotype and allele frequencies, this study targeted on known protein coding regions of the HLA-F gene. Genotyping was performed by Sequence Base Typing (SBT). The sample was composed by 199-unrelated bone marrow donors from the Brazilian Bone Marrow Donor Registry (REDOME), Euro-Brazilians, from Southern Brazil. About 1673 bp were analyzed. The most frequent allele was HLA-F*01:01 (87.19%), followed by HLA-F*01:03 (12.31%), HLA-F*01:02 (0.25%) and HLA-F*01:04 (0.25%). Significant linkage disequilibrium (LD) was verified between HLA-F and HLA classes I and II alleles. This is the first study regarding HLA-F polymorphisms in a Euro-Brazilian population contributing to the Southern Brazilian genetic characterization. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The complete chloroplast DNA sequence of Eleutherococcus senticosus (Araliaceae); comparative evolutionary analyses with other three asterids.

PubMed

Yi, Dong-Keun; Lee, Hae-Lim; Sun, Byung-Yun; Chung, Mi Yoon; Kim, Ki-Joong

2012-05-01

This study reports the complete chloroplast (cp) DNA sequence of Eleutherococcus senticosus (GenBank: JN 637765), an endangered endemic species. The genome is 156,768 bp in length, and contains a pair of inverted repeat (IR) regions of 25,930 bp each, a large single copy (LSC) region of 86,755 bp and a small single copy (SSC) region of 18,153 bp. The structural organization, gene and intron contents, gene order, AT content, codon usage, and transcription units of the E. senticosus chloroplast genome are similar to that of typical land plant cp DNA. We aligned and analyzed the sequences of 86 coding genes, 19 introns and 113 intergenic spacers (IGS) in three different taxonomic hierarchies; Eleutherococcus vs. Panax, Eleutherococcus vs. Daucus, and Eleutherococcus vs. Nicotiana. The distribution of indels, the number of polymorphic sites and nucleotide diversity indicate that positional constraint is more important than functional constraint for the evolution of cp genome sequences in Asterids. For example, the intron sequences in the LSC region exhibited base substitution rates 5-11-times higher than that of the IR regions, while the intron sequences in the SSC region evolved 7-14-times faster than those in the IR region. Furthermore, the Ka/Ks ratio of the gene coding sequences supports a stronger evolutionary constraint in the IR region than in the LSC or SSC regions. Therefore, our data suggest that selective sweeps by base collection mechanisms more frequently eliminate polymorphisms in the IR region than in other regions. Chloroplast genome regions that have high levels of base substitutions also show higher incidences of indels. Thirty-five simple sequence repeat (SSR) loci were identified in the Eleutherococcus chloroplast genome. Of these, 27 are homopolymers, while six are di-polymers and two are tri-polymers. In addition to the SSR loci, we also identified 18 medium size repeat units ranging from 22 to 79 bp, 11 of which are distributed in the IGS or intron regions. These medium size repeats may contribute to developing a cp genome-specific gene introduction vector because the region may use for specific recombination sites.

Promoter variants of Xa23 alleles affect bacterial blight resistance and evolutionary pattern

PubMed Central

Xu, Feifei; Tang, Yongchao; Gao, Ying

2017-01-01

Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is the most important bacterial disease in rice (Oryza sativa L.). Our previous studies have revealed that the bacterial blight resistance gene Xa23 from wild rice O. rufipogon Griff. confers the broadest-spectrum resistance against all the naturally occurring Xoo races. As a novel executor R gene, Xa23 is transcriptionally activated by the bacterial avirulence (Avr) protein AvrXa23 via binding to a 28-bp DNA element (EBEAvrXa23) in the promoter region. So far, the evolutionary mechanism of Xa23 remains to be illustrated. Here, a rice germplasm collection of 97 accessions, including 29 rice cultivars (indica and japonica) and 68 wild relatives, was used to analyze the evolution, phylogeographic relationship and association of Xa23 alleles with bacterial blight resistance. All the ~ 473 bp DNA fragments consisting of promoter and coding regions of Xa23 alleles in the germplasm accessions were PCR-amplified and sequenced, and nine single nucleotide polymorphisms (SNPs) were detected in the promoter regions (~131 bp sequence upstream from the start codon ATG) of Xa23/xa23 alleles while only two SNPs were found in the coding regions. The SNPs in the promoter regions formed 5 haplotypes (Pro-A, B, C, D, E) which showed no significant difference in geographic distribution among these 97 rice accessions. However, haplotype association analysis indicated that Pro-A is the most favored haplotype for bacterial blight resistance. Moreover, SNP changes among the 5 haplotypes mostly located in the EBE/ebe regions (EBEAvrXa23 and corresponding ebes located in promoters of xa23 alleles), confirming that the EBE region is the key factor to confer bacterial blight resistance by altering gene expression. Polymorphism analysis and neutral test implied that Xa23 had undergone a bottleneck effect, and selection process of Xa23 was not detected in cultivated rice. In addition, the Xa23 coding region was found highly conserved in the Oryza genus but absent in other plant species by searching the plant database, suggesting that Xa23 originated along with the diversification of the Oryza genus from the grass family during evolution. This research offers a potential for flexible use of novel Xa23 alleles in rice breeding programs and provide a model for evolution analysis of other executor R genes. PMID:28982185

Promoter variants of Xa23 alleles affect bacterial blight resistance and evolutionary pattern.

PubMed

Cui, Hua; Wang, Chunlian; Qin, Tengfei; Xu, Feifei; Tang, Yongchao; Gao, Ying; Zhao, Kaijun

2017-01-01

Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is the most important bacterial disease in rice (Oryza sativa L.). Our previous studies have revealed that the bacterial blight resistance gene Xa23 from wild rice O. rufipogon Griff. confers the broadest-spectrum resistance against all the naturally occurring Xoo races. As a novel executor R gene, Xa23 is transcriptionally activated by the bacterial avirulence (Avr) protein AvrXa23 via binding to a 28-bp DNA element (EBEAvrXa23) in the promoter region. So far, the evolutionary mechanism of Xa23 remains to be illustrated. Here, a rice germplasm collection of 97 accessions, including 29 rice cultivars (indica and japonica) and 68 wild relatives, was used to analyze the evolution, phylogeographic relationship and association of Xa23 alleles with bacterial blight resistance. All the ~ 473 bp DNA fragments consisting of promoter and coding regions of Xa23 alleles in the germplasm accessions were PCR-amplified and sequenced, and nine single nucleotide polymorphisms (SNPs) were detected in the promoter regions (~131 bp sequence upstream from the start codon ATG) of Xa23/xa23 alleles while only two SNPs were found in the coding regions. The SNPs in the promoter regions formed 5 haplotypes (Pro-A, B, C, D, E) which showed no significant difference in geographic distribution among these 97 rice accessions. However, haplotype association analysis indicated that Pro-A is the most favored haplotype for bacterial blight resistance. Moreover, SNP changes among the 5 haplotypes mostly located in the EBE/ebe regions (EBEAvrXa23 and corresponding ebes located in promoters of xa23 alleles), confirming that the EBE region is the key factor to confer bacterial blight resistance by altering gene expression. Polymorphism analysis and neutral test implied that Xa23 had undergone a bottleneck effect, and selection process of Xa23 was not detected in cultivated rice. In addition, the Xa23 coding region was found highly conserved in the Oryza genus but absent in other plant species by searching the plant database, suggesting that Xa23 originated along with the diversification of the Oryza genus from the grass family during evolution. This research offers a potential for flexible use of novel Xa23 alleles in rice breeding programs and provide a model for evolution analysis of other executor R genes.

Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

PubMed

Miyamoto, T; Koh, E; Tsujimura, A; Miyagawa, Y; Saijo, Y; Namiki, M; Sengoku, K

2014-04-01

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, ten novel genes involved in human spermatogenesis, including human LRWD1, have been identified by expression microarray analysis of human testictissue. The human LRWD1 protein mediates the origin recognition complex in chromatin, which is critical for the initiation of pre-replication complex assembly in G1 and chromatin organization in post-G1 cells. The Lrwd1 gene expression is specific to the testis in mice. Therefore, we hypothesized that mutation or polymorphisms of LRWD1 participate in male infertility, especially azoospermia. To investigate whether LRWD1 gene defects are associated with azoospermia caused by SCOS and meiotic arrest (MA), mutational analysis was performed in 100 and 30 Japanese patients by direct sequencing of the coding regions, respectively. Statistical analysis was performed for patients with SCOS and MA and in 100 healthy control men. No mutations were found in LRWD1; however, three coding single-nucleotide polymorphisms (SNP1-SNP3) could be detected in the patients. The genotype and allele frequencies in SNP1 and SNP2 were notably higher in the SCOS group than in the control group (P < 0.05). These results suggest the critical role of LRWD1 in human spermatogenesis. © 2013 Blackwell Verlag GmbH.

Multiplexed direct genomic selection (MDiGS): a pooled BAC capture approach for highly accurate CNV and SNP/INDEL detection.

PubMed

Alvarado, David M; Yang, Ping; Druley, Todd E; Lovett, Michael; Gurnett, Christina A

2014-06-01

Despite declining sequencing costs, few methods are available for cost-effective single-nucleotide polymorphism (SNP), insertion/deletion (INDEL) and copy number variation (CNV) discovery in a single assay. Commercially available methods require a high investment to a specific region and are only cost-effective for large samples. Here, we introduce a novel, flexible approach for multiplexed targeted sequencing and CNV analysis of large genomic regions called multiplexed direct genomic selection (MDiGS). MDiGS combines biotinylated bacterial artificial chromosome (BAC) capture and multiplexed pooled capture for SNP/INDEL and CNV detection of 96 multiplexed samples on a single MiSeq run. MDiGS is advantageous over other methods for CNV detection because pooled sample capture and hybridization to large contiguous BAC baits reduces sample and probe hybridization variability inherent in other methods. We performed MDiGS capture for three chromosomal regions consisting of ∼ 550 kb of coding and non-coding sequence with DNA from 253 patients with congenital lower limb disorders. PITX1 nonsense and HOXC11 S191F missense mutations were identified that segregate in clubfoot families. Using a novel pooled-capture reference strategy, we identified recurrent chromosome chr17q23.1q23.2 duplications and small HOXC 5' cluster deletions (51 kb and 12 kb). Given the current interest in coding and non-coding variants in human disease, MDiGS fulfills a niche for comprehensive and low-cost evaluation of CNVs, coding, and non-coding variants across candidate regions of interest. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Single nucleotide polymorphism of FSHβ gene associated with reproductive traits in Japanese flounder ( Paralichthys olivaceus)

NASA Astrophysics Data System (ADS)

He, Feng; Wen, Haishen; Yu, Dahui; Li, Jifang; Shi, Bao; Chen, Caifang; Zhang, Jiaren; Jin, Guoxiong; Chen, Xiaoyan; Shi, Dan; Yang, Yanping

2010-12-01

Follicle stimulating hormone β (FSHβ) of Japanese flounder ( Paralichthys olivaceus) plays a key role in the regulation of gonadal development. This study aimed to investigate molecular genetic characteristics of the FSHβ gene and elucidate the effects of single nucleotide polymorphisms (SNPs) of FSHβ on reproductive traits in Japanese flounder. We used polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and sequencing of the FSHβ gene in 60 individuals. We identified only an SNP (T/C) in the coding region of exon3 of FSHβ. The SNP (T/C) did not lead to amino acid changes at the position 340 bp of FSHβ gene. Statistical analysis showed that the SNP was significantly associated with testosterone (T) level and gonadosomatic index (GSI) ( P < 0.05). Individuals with genotype TC of the SNP had significantly higher serum T levels and GSI ( P < 0.05) than that of genotype CC. Therefore, FSHβ gene could be a useful molecular marker in selection for prominent reproductive trait in Japanese Flounder.

Polymorphism of prion protein gene in Arctic fox (Vulpes lagopus).

PubMed

Wan, Jiayu; Bai, Xue; Liu, Wensen; Xu, Jing; Xu, Ming; Gao, Hongwei

2009-07-01

Prion diseases are fatal neurodegenerative disorders of humans and certain other mammals. Prion protein gene (Prnp) is associated with susceptibility and species barrier to prion diseases. No natural and experimental prion diseases have been documented to date in Arctic fox. In the present study, coding region of Prnp from 135 Arctic foxes were cloned and screened for polymorphisms. Our results indicated that the Arctic fox Prnp open reading frame (ORF) contains 771 nucleotides encoding 257 amino acids. Four single nucleotide polymorphisms (SNPs) (G312C, A337G, C541T, and A723G) were identified. SNPs G312C and A723G produced silent mutations, but SNPs A337G and C541T resulted in a M-V change at codon 113 and R-C at codon 181, respectively. The Arctic fox Prnp amino acid sequence was similar to that of the dog (XM 542906). In short, this study provides preliminary information about genotypes of Prnp in Arctic fox.

Next-generation genomic shotgun sequencing indicates greater genetic variability in the mitochondria of Hypophthalmichthys molitrix relative to H. nobilis from the Mississippi River, USA and provides tools for research and detection

USGS Publications Warehouse

Miller, John J; Eackles, Michael S.; Stauffer, Jay R; King, Timothy L.

2015-01-01

We characterized variation within the mitochondrial genomes of the invasive silver carp (Hypophthalmichthys molitrix) and bighead carp (H. nobilis) from the Mississippi River drainage by mapping our Next-Generation sequences to their publicly available genomes. Variant detection resulted in 338 single-nucleotide polymorphisms for H. molitrix and 39 for H. nobilis. The much greater genetic variation in H. molitrix mitochondria relative to H. nobilis may be indicative of a greater North American female effective population size of the former. When variation was quantified by gene, many tRNA loci appear to have little or no variability based on our results whereas protein-coding regions were more frequently polymorphic. These results provide biologists with additional regions of DNA to be used as markers to study the invasion dynamics of these species.

Choline dehydrogenase polymorphism rs12676 is a functional variation and is associated with changes in human sperm cell function.

PubMed

Johnson, Amy R; Lao, Sai; Wang, Tongwen; Galanko, Joseph A; Zeisel, Steven H

2012-01-01

Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh(-/-) males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm.

Choline Dehydrogenase Polymorphism rs12676 Is a Functional Variation and Is Associated with Changes in Human Sperm Cell Function

PubMed Central

Johnson, Amy R.; Lao, Sai; Wang, Tongwen; Galanko, Joseph A.; Zeisel, Steven H.

2012-01-01

Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh−/− males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm. PMID:22558321

Polymorphism at codon 36 of the p53 gene.

PubMed

Felix, C A; Brown, D L; Mitsudomi, T; Ikagaki, N; Wong, A; Wasserman, R; Womer, R B; Biegel, J A

1994-01-01

A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

In the nose of the beholder: are olfactory influences on human mate choice driven by variation in immune system genes or sex hormone levels?

PubMed

Roberts, Thomas; Roiser, Jonathan P

2010-11-01

The human leukocyte antigen (HLA) is the most polymorphic region of the genome, coding for proteins that mediate human immune response. This polymorphism may be maintained by balancing selection and certain populations show deviations from expected gene frequencies. Supporting this hypothesis, studies into olfactory preferences have suggested that females prefer the scent of males with dissimilar HLA to their own. However, it has also been proposed that androstenones play a role in female mate choice, and as these molecules inhibit the immune system, this has implications for the theory of HLA-driven mate preference. This review will critically analyze the findings of studies investigating olfactory preference in humans, and their implications for these two contrasting theories of mate choice.

The genetics of folate metabolism and maternal risk of birth of a child with Down syndrome and associated congenital heart defects

PubMed Central

Coppedè, Fabio

2015-01-01

Almost 15 years ago it was hypothesized that polymorphisms of genes encoding enzymes involved in folate metabolism could lead to aberrant methylation of peri-centromeric regions of chromosome 21, favoring its abnormal segregation during maternal meiosis. Subsequently, more than 50 small case-control studies investigated whether or not maternal polymorphisms of folate pathway genes could be risk factors for the birth of a child with Down syndrome (DS), yielding conflicting and inconclusive results. However, recent meta-analyses of those studies suggest that at least three of those polymorphisms, namely MTHFR 677C>T, MTRR 66A>G, and RFC1 80G>A, are likely to act as maternal risk factors for the birth of a child with trisomy 21, revealing also complex gene-nutrient interactions. A large-cohort study also revealed that lack of maternal folic acid supplementation at peri-conception resulted in increased risk for a DS birth due to errors occurred at maternal meiosis II in the aging oocyte, and it was shown that the methylation status of chromosome 21 peri-centromeric regions could favor recombination errors during meiosis leading to its malsegregation. In this regard, two recent case-control studies revealed association of maternal polymorphisms or haplotypes of the DNMT3B gene, coding for an enzyme required for the regulation of DNA methylation at centromeric and peri-centromeric regions of human chromosomes, with risk of having a birth with DS. Furthermore, congenital heart defects (CHD) are found in almost a half of DS births, and increasing evidence points to a possible contribution of lack of folic acid supplementation at peri-conception, maternal polymorphisms of folate pathway genes, and resulting epigenetic modifications of several genes, at the basis of their occurrence. This review summarizes available case-control studies and literature meta-analyses in order to provide a critical and up to date overview of what we currently know in this field. PMID:26161087

Distribution of HLA-G extended haplotypes and one HLA-E polymorphism in a large-scale study of mother-child dyads with and without severe preeclampsia and eclampsia.

PubMed

Nilsson, L L; Djurisic, S; Andersen, A-M N; Melbye, M; Bjerre, D; Ferrero-Miliani, L; Hackmon, R; Geraghty, D E; Hviid, T V F

2016-10-01

The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants. Most nucleotide variations are clustered in the 5'-upstream regulatory region (5'URR) and 3'-untranslated regulatory region (3'UTR) of HLA-G and reflect a stringent expressional control. Based on genotyping and full gene sequencing of HLA-G in a large number of cases and controls (n > 900), the present study, which to our knowledge is the largest and most comprehensive performed, investigated the association between the HLA-G 14-bp ins/del (rs66554220) and HLA-E polymorphisms in mother and newborn dyads from pregnancies complicated by severe preeclampsia/eclampsia and from uncomplicated pregnancies. Furthermore, results from extended HLA-G haplotyping in the newborns are presented in order to assess whether a combined contribution of nucleotide variations spanning the 5'URR, coding region, and 3'UTR of HLA-G describes the genetic association with severe preeclampsia more closely. In contrast to earlier findings, the HLA-G 14-bp ins/del polymorphism was not associated with severe preeclampsia. Furthermore, the polymorphism (rs1264457) defining the two nonsynonymous HLA-E alleles, HLA-E*01:01:xx:xx and HLA-E*01:03:xx:xx, were not associated with severe preeclampsia. Finally, no specific HLA-G haplotypes were significantly associated with increased risk of developing severe preeclampsia/eclampsia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Junk DNA and the long non-coding RNA twist in cancer genetics

PubMed Central

Ling, Hui; Vincent, Kimberly; Pichler, Martin; Fodde, Riccardo; Berindan-Neagoe, Ioana; Slack, Frank J.; Calin, George A

2015-01-01

The central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs (lncRNAs) have attracted much attention due to their large number and biological significance. Many lncRNAs have been identified as mapping to regulatory elements including gene promoters and enhancers, ultraconserved regions, and intergenic regions of protein-coding genes. Yet, the biological function and molecular mechanisms of lncRNA in human diseases in general and cancer in particular remain largely unknown. Data from the literature suggest that lncRNA, often via interaction with proteins, functions in specific genomic loci or use their own transcription loci for regulatory activity. In this review, we summarize recent findings supporting the importance of DNA loci in lncRNA function, and the underlying molecular mechanisms via cis or trans regulation, and discuss their implications in cancer. In addition, we use the 8q24 genomic locus, a region containing interactive SNPs, DNA regulatory elements and lncRNAs, as an example to illustrate how single nucleotide polymorphism (SNP) located within lncRNAs may be functionally associated with the individual’s susceptibility to cancer. PMID:25619839

Mitochondrial sequence analysis for forensic identification using pyrosequencing technology.

PubMed

Andréasson, H; Asp, A; Alderborn, A; Gyllensten, U; Allen, M

2002-01-01

Over recent years, requests for mtDNA analysis in the field of forensic medicine have notably increased, and the results of such analyses have proved to be very useful in forensic cases where nuclear DNA analysis cannot be performed. Traditionally, mtDNA has been analyzed by DNA sequencing of the two hypervariable regions, HVI and HVII, in the D-loop. DNA sequence analysis using the conventional Sanger sequencing is very robust but time consuming and labor intensive. By contrast, mtDNA analysis based on the pyrosequencing technology provides fast and accurate results from the human mtDNA present in many types of evidence materials in forensic casework. The assay has been developed to determine polymorphic sites in the mitochondrial D-loop as well as the coding region to further increase the discrimination power of mtDNA analysis. The pyrosequencing technology for analysis of mtDNA polymorphisms has been tested with regard to sensitivity, reproducibility, and success rate when applied to control samples and actual casework materials. The results show that the method is very accurate and sensitive; the results are easily interpreted and provide a high success rate on casework samples. The panel of pyrosequencing reactions for the mtDNA polymorphisms were chosen to result in an optimal discrimination power in relation to the number of bases determined.

Single nucleotide polymorphism-specific regulation of matrix metalloproteinase-9 by multiple miRNAs targeting the coding exon

PubMed Central

Duellman, Tyler; Warren, Christopher; Yang, Jay

2014-01-01

Microribonucleic acids (miRNAs) work with exquisite specificity and are able to distinguish a target from a non-target based on a single nucleotide mismatch in the core nucleotide domain. We questioned whether miRNA regulation of gene expression could occur in a single nucleotide polymorphism (SNP)-specific manner, manifesting as a post-transcriptional control of expression of genetic polymorphisms. In our recent study of the functional consequences of matrix metalloproteinase (MMP)-9 SNPs, we discovered that expression of a coding exon SNP in the pro-domain of the protein resulted in a profound decrease in the secreted protein. This missense SNP results in the N38S amino acid change and a loss of an N-glycosylation site. A systematic study demonstrated that the loss of secreted protein was due not to the loss of an N-glycosylation site, but rather an SNP-specific targeting by miR-671-3p and miR-657. Bioinformatics analysis identified 41 SNP-specific miRNA targeting MMP-9 SNPs, mostly in the coding exon and an extension of the analysis to chromosome 20, where the MMP-9 gene is located, suggesting that SNP-specific miRNAs targeting the coding exon are prevalent. This selective post-transcriptional regulation of a target messenger RNA harboring genetic polymorphisms by miRNAs offers an SNP-dependent post-transcriptional regulatory mechanism, allowing for polymorphic-specific differential gene regulation. PMID:24627221

Development of a set of SNP markers present in expressed genes of the apple.

PubMed

Chagné, David; Gasic, Ksenija; Crowhurst, Ross N; Han, Yuepeng; Bassett, Heather C; Bowatte, Deepa R; Lawrence, Timothy J; Rikkerink, Erik H A; Gardiner, Susan E; Korban, Schuyler S

2008-11-01

Molecular markers associated with gene coding regions are useful tools for bridging functional and structural genomics. Due to their high abundance in plant genomes, single nucleotide polymorphisms (SNPs) are present within virtually all genomic regions, including most coding sequences. The objective of this study was to develop a set of SNPs for the apple by taking advantage of the wealth of genomics resources available for the apple, including a large collection of expressed sequenced tags (ESTs). Using bioinformatics tools, a search for SNPs within an EST database of approximately 350,000 sequences developed from a variety of apple accessions was conducted. This resulted in the identification of a total of 71,482 putative SNPs. As the apple genome is reported to be an ancient polyploid, attempts were made to verify whether those SNPs detected in silico were attributable either to allelic polymorphisms or to gene duplication or paralogous or homeologous sequence variations. To this end, a set of 464 PCR primer pairs was designed, PCR was amplified using two subsets of plants, and the PCR products were sequenced. The SNPs retrieved from these sequences were then mapped onto apple genetic maps, including a newly constructed map of a Royal Gala x A689-24 cross and a Malling 9 x Robusta 5, map using a bin mapping strategy. The SNP genotyping was performed using the high-resolution melting (HRM) technique. A total of 93 new markers containing 210 coding SNPs were successfully mapped. This new set of SNP markers for the apple offers new opportunities for understanding the genetic control of important horticultural traits using quantitative trait loci (QTL) or linkage disequilibrium analysis. These also serve as useful markers for aligning physical and genetic maps, and as potential transferable markers across the Rosaceae family.

Association of α-, β-, and γ-Synuclein With Diffuse Lewy Body Disease

PubMed Central

Nishioka, Kenya; Wider, Christian; Vilariño-Güell, Carles; Soto-Ortolaza, Alexandra I.; Lincoln, Sarah J.; Kachergus, Jennifer M.; Jasinska-Myga, Barbara; Ross, Owen A.; Rajput, Alex; Robinson, Christopher A.; Ferman, Tanis J.; Wszolek, Zbigniew K.; Dickson, Dennis W.; Farrer, Matthew J.

2016-01-01

Objective To determine the association of the genes that encode α-, β-, and γ-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD). Design Case-control study. Subjects A total of 172 patients with DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia with Lewy bodies and 350 clinically and 97 pathologically normal controls. Interventions Sequencing of SNCA, SNCB, and SNCG and genotyping of single-nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer and a Sequenom MassArray pLEX platform, respectively. Associations were determined using χ2 or Fisher exact tests. Results Initial sequencing studies of the coding regions of each gene in 89 patients with DLBD did not detect any pathogenic substitutions. Nevertheless, genotyping of known polymorphic variability in sequence-conserved regions detected several single-nucleotide polymorphisms in the SNCA and SNCG genes that were significantly associated with disease (P=.05 to <.001). Significant association was also observed for 3 single-nucleotide polymorphisms located in SNCB when comparing DLBD cases and pathologically confirmed normal controls (P=.03-.01); however, this association was not significant for the clinical controls alone or the combined clinical and pathological controls (P>.05). After correction for multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823) remained significant in all of the analyses (P=.05-.009). Conclusion These findings suggest that variants in all 3 members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing DLBD and warrant further investigation in larger, pathologically defined data sets as well as clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control series. PMID:20697047

Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene

PubMed Central

2008-01-01

Background The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two ~350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)25 microsatellite; the second block, DupB, has a complex (CT)4-(TT)-(CT)8-(GT)24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Results Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (Pan troglodytes) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. Conclusion There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a unique opportunity to assess the functional role of this duplication in contributing to variation in social behavior in primates. While our initial studies show no signs of directional selection on this locus in chimps, pharmacological and genetic association studies support a potential role for this region in influencing V1aR expression and social behavior. PMID:18573213

Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene.

PubMed

Donaldson, Zoe R; Kondrashov, Fyodor A; Putnam, Andrea; Bai, Yaohui; Stoinski, Tara L; Hammock, Elizabeth A D; Young, Larry J

2008-06-23

The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two approximately 350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)25 microsatellite; the second block, DupB, has a complex (CT)4-(TT)-(CT)8-(GT)24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (Pan troglodytes) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a unique opportunity to assess the functional role of this duplication in contributing to variation in social behavior in primates. While our initial studies show no signs of directional selection on this locus in chimps, pharmacological and genetic association studies support a potential role for this region in influencing V1aR expression and social behavior.

Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population.

PubMed

Solus, Joseph F; Arietta, Brenda J; Harris, James R; Sexton, David P; Steward, John Q; McMunn, Chara; Ihrie, Patrick; Mehall, Janelle M; Edwards, Todd L; Dawson, Elliott P

2004-10-01

The extent of genetic variation found in drug metabolism genes and its contribution to interindividual variation in response to medication remains incompletely understood. To better determine the identity and frequency of variation in 11 phase I drug metabolism genes, the exons and flanking intronic regions of the cytochrome P450 (CYP) isoenzyme genes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5 were amplified from genomic DNA and sequenced. A total of 60 kb of bi-directional sequence was generated from each of 93 human DNAs, which included Caucasian, African-American and Asian samples. There were 388 different polymorphisms identified. These included 269 non-coding, 45 synonymous and 74 non-synonymous polymorphisms. Of these, 54% were novel and included 176 non-coding, 14 synonymous and 21 non-synonymous polymorphisms. Of the novel variants observed, 85 were represented by single occurrences of the minor allele in the sample set. Much of the variation observed was from low-frequency alleles. Comparatively, these genes are variation-rich. Calculations measuring genetic diversity revealed that while the values for the individual genes are widely variable, the overall nucleotide diversity of 7.7 x 10(-4) and polymorphism parameter of 11.5 x 10(-4) are higher than those previously reported for other gene sets. Several independent measurements indicate that these genes are under selective pressure, particularly for polymorphisms corresponding to non-synonymous amino acid changes. There is relatively little difference in measurements of diversity among the ethnic groups, but there are large differences among the genes and gene subfamilies themselves. Of the three CYP subfamilies involved in phase I drug metabolism (1, 2, and 3), subfamily 2 displays the highest levels of genetic diversity.

Investigation of genes coding for inflammatory components in Parkinson's disease.

PubMed

Håkansson, Anna; Westberg, Lars; Nilsson, Staffan; Buervenich, Silvia; Carmine, Andrea; Holmberg, Björn; Sydow, Olof; Olson, Lars; Johnels, Bo; Eriksson, Elias; Nissbrandt, Hans

2005-05-01

Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD. Copyright 2005 Movement Disorder Society.

Investigation of QTL regions on Chromosome 17 for genes associated with meat color in the pig.

PubMed

Fan, B; Glenn, K L; Geiger, B; Mileham, A; Rothschild, M F

2008-08-01

Previous studies have uncovered several significant quantitative trait loci (QTL) relevant to meat colour traits mapped at the end of SSC17 in the pig. Furthermore, results released from the porcine genome sequencing project have identified genes underlying the entire QTL regions and can further contribute to mining the region for likely causative genes. Ten protein coding genes or novel transcripts located within the QTL regions were screened for single nucleotide polymorphisms (SNPs). Linkage mapping and association studies were carried out in the ISU Berkshire x Yorkshire (B x Y) pig resource family. The total length of the new SSC17 linkage map was 126.6 cM and additional markers including endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits QTL exceeded the 5% chromosome-wise significance threshold. The association analyses in the B x Y family showed that the EDN3 BslI and PHACTR3 PstI polymorphisms were strongly associated with the subjective colour score and objective colour reflectance measures in the loin, as well as average drip loss percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were associated with some meat colour traits. No significant association between CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected. The association analyses conducted in one commercial pig line found that both EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour reflectance traits such as centre loin hue angle and Minolta Lightness score. The present findings suggested that the EDN3 and PHACTR3 genes might have potential effects on meat colour in pigs, and molecular mechanisms of their functions are worth exploring.

Global analysis of saliva as a source of bacterial genes for insights into human population structure and migration studies.

PubMed

Henne, Karsten; Li, Jing; Stoneking, Mark; Kessler, Olga; Schilling, Hildegard; Sonanini, Anne; Conrads, Georg; Horz, Hans-Peter

2014-08-22

The genetic diversity of the human microbiome holds great potential for shedding light on the history of our ancestors. Helicobacter pylori is the most prominent example as its analysis allowed a fine-scale resolution of past migration patterns including some that could not be distinguished using human genetic markers. However studies of H. pylori require stomach biopsies, which severely limits the number of samples that can be analysed. By focussing on the house-keeping gene gdh (coding for the glucose-6-phosphate dehydrogenase), on the virulence gene gtf (coding for the glucosyltransferase) of mitis-streptococci and on the 16S-23S rRNA internal transcribed spacer (ITS) region of the Fusobacterium nucleatum/periodonticum-group we here tested the hypothesis that bacterial genes from human saliva have the potential for distinguishing human populations. Analysis of 10 individuals from each of seven geographic regions, encompassing Africa, Asia and Europe, revealed that the genes gdh and ITS exhibited the highest number of polymorphic sites (59% and 79%, respectively) and most OTUs (defined at 99% identity) were unique to a given country. In contrast, the gene gtf had the lowest number of polymorphic sites (21%), and most OTUs were shared among countries. Most of the variation in the gdh and ITS genes was explained by the high clonal diversity within individuals (around 80%) followed by inter-individual variation of around 20%, leaving the geographic region as providing virtually no source of sequence variation. Conversely, for gtf the variation within individuals accounted for 32%, between individuals for 57% and among geographic regions for 11%. This geographic signature persisted upon extension of the analysis to four additional locations from the American continent. Pearson correlation analysis, pairwise Fst-cluster analysis as well as UniFrac analyses consistently supported a tree structure in which the European countries clustered tightly together and branched with American countries and South Africa, to the exclusion of Asian countries and the Congo. This study shows that saliva harbours protein-coding bacterial genes that are geographically structured, and which could potentially be used for addressing previously unresolved human migration events.

Paraoxonase 1 (PON1) gene-108C>T and p.Q192R polymorphisms and arylesterase activity of the enzyme in patients with dementia.

PubMed

Bednarska-Makaruk, Małgorzata Ewa; Krzywkowski, Tomasz; Graban, Alla; Lipczyńska-Łojkowska, Wanda; Bochyńska, Anna; Rodo, Maria; Wehr, Hanna; Ryglewicz, Danuta Krystyna

2013-01-01

Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia--136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T polymorphism in the PON1 gene promoter and p.Q192R polymorphism in the coding region were identified. PON1 activity was significantly lower in demented patients as compared with controls particularly in dementia of a neurodegenerative character (AD and MD). The prevalence of PON1-108T allele carriers was significantly higher in the AD group than in controls. The frequencies of the p.Q192R genotypes did not differ significantly between the investigated groups. An association of the rare T-R haplotype with dementia, particularly with dementia of the neurodegenerative type, was found. Multivariate regression analysis showed a significant association of PON1 activity with PON1 -108C>T and p.Q192R polymorphisms. The influence not only of promoter -108C>T, but also of p.Q192R polymorphism on PON1 arylesterase activity was observed. One has to admit that this kind of polymorphism does not preclude interference with the enzyme activity. It could be concluded that the PON1 gene promoter polymorphism plays an additional role in Alzheimer's disease development. It seems however that PON1 activity has a dominating influence on the dementia risk.

TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs.

PubMed

Xu, Zhi; Reynolds, Gavin P; Yuan, Yonggui; Shi, Yanyan; Pu, Mengjia; Zhang, Zhijun

2016-11-01

Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012). A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks' antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form. Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response. These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment. © The Author 2016. Published by Oxford University Press on behalf of CINP.

TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs

PubMed Central

Reynolds, Gavin P.; Yuan, Yonggui; Shi, Yanyan; Pu, Mengjia; Zhang, Zhijun

2016-01-01

Background: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012). Methods: A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks’ antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form. Results: Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response. Conclusions: These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment. PMID:27521242

No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene and polycystic ovary syndrome.

PubMed

Wang, Kehua; Wang, Leiguang; Zhao, Yueran; Shi, Yuhua; Wang, Laicheng; Chen, Zi-Jiang

2009-02-01

Ghrelin plays a role in regulating glucose metabolism and energy balance. Polymorphisms in preproghrelin and ghrelin gene could be responsible for obesity, insulin resistance and low ghrelin levels observed in some individuals. The objective of this study was to evaluate the influence of two single-nucleotide polymorphisms (SNPs) of ghrelin gene on the clinical, the hormonal and metabolic features in women with polycystic ovary syndrome (PCOS) in a Chinese population. A large sample of Chinese PCOS (n = 271) women and a control group (n = 296) of healthy women matched for age were studied. Hormone and metabolic profiles were measured and blood samples were collected for genotype and allelic frequency analysis. Non-synonymous SNPs in the coding region (exon 2) of the preproghrelin gene (Arg51Gln (346 G>A) and Leu72Met (408 C>A) were studied using PCR and restriction fragment length polymorphism analysis. The polymorphism Arg51Gln was not found in the cohorts studied. The distribution of Leu72Met was similar in PCOS group and in healthy controls. There was no significant difference in age, BMI, waist-hip-ratio and levels of FSH, LH, estradiol, testosterone and prolactin between PCOS patients with different genotypes, and the level of plasma glucose and insulin was also similar. No association was found between Leu72Met and Arg51Gln polymorphisms in the ghrelin gene and PCOS in Chinese population.

The genetic architecture of 3'untranslated region of the MICA gene: polymorphisms and haplotypes.

PubMed

Luo, Jia; Tian, Wei; Liu, Xue Xiang; Yu, JunLong; Li, LiXin; Pan, FengHua

2013-10-01

In this study, the 3'untranslated region (3'UTR) of MHC class I chain-related gene A (MICA) were investigated in 104 healthy, unrelated Han individuals recruited from northern China, using PCR-sequencing method. Nine polymorphic sites were detected, which were in very strong linkage disequilibrium with each other .Seven different MICA 3'UTR alleles were identified, among which UTR1 predominated (0.6971),followed by UTR2 (0.2356). Twenty-one extended haplotypes incorporating the 3'UTR and MICA exons 2-5 were observed in this population. Phylogenetic analysis revealed the existence of two MICA lineages, each with multiple subsets. The 2 lineages were primarily linked to UTR1 and UTR2 in the 3'UTR, respectively. Ewens-Watterson homozygosity statistics at MICA coding and 3'UTR regions were consistent with neutral expectations. Our data provided for the first time the data of genetic variation in the 3'UTR of MICA gene in human populations. The findings are valuable for future studies of the mechanisms underlying MICA post-transcriptional regulation, and will inform studies of evolution of the MHC gene complex. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Molecular Population Genetics of Sex Determination Genes: The Transformer Gene of Drosophila Melanogaster

PubMed Central

Walthour, C. S.; Schaeffer, S. W.

1994-01-01

The transformer locus (tra) produces an RNA processing protein that alternatively splices the doublesex pre-mRNA in the sex determination hierarchy of Drosophila melanogaster. Comparisons of the tra coding region among Drosophila species have revealed an unusually high degree of divergence in synonymous and nonsynonymous sites. In this study, we tested the hypothesis that the tra gene will be polymorphic in synonymous and nonsynonymous sites within species by investigating nucleotide sequence variation in eleven tra alleles within D. melanogaster. Of the 1063 nucleotides examined, two synonymous sites were polymorphic and no amino acid variation was detected. Three statistical tests were used to detect departures from an equilibrium neutral model. Two tests failed to reject a neutral model of molecular evolution because of low statisitical power associated with low levels of genetic variation (Tajima/Fu and Li). The Hudson, Kreitman, and Aguade test rejected a neutral model when the tra region was compared to the 5'-flanking region of alcohol dehydrogenase (Adh). The lack of variability in the tra gene is consistent with a recent selective sweep of a beneficial allele in or near the tra locus. PMID:8013913

Genome-wide detection and characterization of positive selection in human populations.

PubMed

Sabeti, Pardis C; Varilly, Patrick; Fry, Ben; Lohmueller, Jason; Hostetter, Elizabeth; Cotsapas, Chris; Xie, Xiaohui; Byrne, Elizabeth H; McCarroll, Steven A; Gaudet, Rachelle; Schaffner, Stephen F; Lander, Eric S; Frazer, Kelly A; Ballinger, Dennis G; Cox, David R; Hinds, David A; Stuve, Laura L; Gibbs, Richard A; Belmont, John W; Boudreau, Andrew; Hardenbol, Paul; Leal, Suzanne M; Pasternak, Shiran; Wheeler, David A; Willis, Thomas D; Yu, Fuli; Yang, Huanming; Zeng, Changqing; Gao, Yang; Hu, Haoran; Hu, Weitao; Li, Chaohua; Lin, Wei; Liu, Siqi; Pan, Hao; Tang, Xiaoli; Wang, Jian; Wang, Wei; Yu, Jun; Zhang, Bo; Zhang, Qingrun; Zhao, Hongbin; Zhao, Hui; Zhou, Jun; Gabriel, Stacey B; Barry, Rachel; Blumenstiel, Brendan; Camargo, Amy; Defelice, Matthew; Faggart, Maura; Goyette, Mary; Gupta, Supriya; Moore, Jamie; Nguyen, Huy; Onofrio, Robert C; Parkin, Melissa; Roy, Jessica; Stahl, Erich; Winchester, Ellen; Ziaugra, Liuda; Altshuler, David; Shen, Yan; Yao, Zhijian; Huang, Wei; Chu, Xun; He, Yungang; Jin, Li; Liu, Yangfan; Shen, Yayun; Sun, Weiwei; Wang, Haifeng; Wang, Yi; Wang, Ying; Xiong, Xiaoyan; Xu, Liang; Waye, Mary M Y; Tsui, Stephen K W; Xue, Hong; Wong, J Tze-Fei; Galver, Luana M; Fan, Jian-Bing; Gunderson, Kevin; Murray, Sarah S; Oliphant, Arnold R; Chee, Mark S; Montpetit, Alexandre; Chagnon, Fanny; Ferretti, Vincent; Leboeuf, Martin; Olivier, Jean-François; Phillips, Michael S; Roumy, Stéphanie; Sallée, Clémentine; Verner, Andrei; Hudson, Thomas J; Kwok, Pui-Yan; Cai, Dongmei; Koboldt, Daniel C; Miller, Raymond D; Pawlikowska, Ludmila; Taillon-Miller, Patricia; Xiao, Ming; Tsui, Lap-Chee; Mak, William; Song, You Qiang; Tam, Paul K H; Nakamura, Yusuke; Kawaguchi, Takahisa; Kitamoto, Takuya; Morizono, Takashi; Nagashima, Atsushi; Ohnishi, Yozo; Sekine, Akihiro; Tanaka, Toshihiro; Tsunoda, Tatsuhiko; Deloukas, Panos; Bird, Christine P; Delgado, Marcos; Dermitzakis, Emmanouil T; Gwilliam, Rhian; Hunt, Sarah; Morrison, Jonathan; Powell, Don; Stranger, Barbara E; Whittaker, Pamela; Bentley, David R; Daly, Mark J; de Bakker, Paul I W; Barrett, Jeff; Chretien, Yves R; Maller, Julian; McCarroll, Steve; Patterson, Nick; Pe'er, Itsik; Price, Alkes; Purcell, Shaun; Richter, Daniel J; Sabeti, Pardis; Saxena, Richa; Schaffner, Stephen F; Sham, Pak C; Varilly, Patrick; Altshuler, David; Stein, Lincoln D; Krishnan, Lalitha; Smith, Albert Vernon; Tello-Ruiz, Marcela K; Thorisson, Gudmundur A; Chakravarti, Aravinda; Chen, Peter E; Cutler, David J; Kashuk, Carl S; Lin, Shin; Abecasis, Gonçalo R; Guan, Weihua; Li, Yun; Munro, Heather M; Qin, Zhaohui Steve; Thomas, Daryl J; McVean, Gilean; Auton, Adam; Bottolo, Leonardo; Cardin, Niall; Eyheramendy, Susana; Freeman, Colin; Marchini, Jonathan; Myers, Simon; Spencer, Chris; Stephens, Matthew; Donnelly, Peter; Cardon, Lon R; Clarke, Geraldine; Evans, David M; Morris, Andrew P; Weir, Bruce S; Tsunoda, Tatsuhiko; Johnson, Todd A; Mullikin, James C; Sherry, Stephen T; Feolo, Michael; Skol, Andrew; Zhang, Houcan; Zeng, Changqing; Zhao, Hui; Matsuda, Ichiro; Fukushima, Yoshimitsu; Macer, Darryl R; Suda, Eiko; Rotimi, Charles N; Adebamowo, Clement A; Ajayi, Ike; Aniagwu, Toyin; Marshall, Patricia A; Nkwodimmah, Chibuzor; Royal, Charmaine D M; Leppert, Mark F; Dixon, Missy; Peiffer, Andy; Qiu, Renzong; Kent, Alastair; Kato, Kazuto; Niikawa, Norio; Adewole, Isaac F; Knoppers, Bartha M; Foster, Morris W; Clayton, Ellen Wright; Watkin, Jessica; Gibbs, Richard A; Belmont, John W; Muzny, Donna; Nazareth, Lynne; Sodergren, Erica; Weinstock, George M; Wheeler, David A; Yakub, Imtaz; Gabriel, Stacey B; Onofrio, Robert C; Richter, Daniel J; Ziaugra, Liuda; Birren, Bruce W; Daly, Mark J; Altshuler, David; Wilson, Richard K; Fulton, Lucinda L; Rogers, Jane; Burton, John; Carter, Nigel P; Clee, Christopher M; Griffiths, Mark; Jones, Matthew C; McLay, Kirsten; Plumb, Robert W; Ross, Mark T; Sims, Sarah K; Willey, David L; Chen, Zhu; Han, Hua; Kang, Le; Godbout, Martin; Wallenburg, John C; L'Archevêque, Paul; Bellemare, Guy; Saeki, Koji; Wang, Hongguang; An, Daochang; Fu, Hongbo; Li, Qing; Wang, Zhen; Wang, Renwu; Holden, Arthur L; Brooks, Lisa D; McEwen, Jean E; Guyer, Mark S; Wang, Vivian Ota; Peterson, Jane L; Shi, Michael; Spiegel, Jack; Sung, Lawrence M; Zacharia, Lynn F; Collins, Francis S; Kennedy, Karen; Jamieson, Ruth; Stewart, John

2007-10-18

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

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.

Immunogenetics as a tool in anthropological studies

PubMed Central

Sanchez-Mazas, Alicia; Fernandez-Viña, Marcelo; Middleton, Derek; Hollenbach, Jill A; Buhler, Stéphane; Di, Da; Rajalingam, Raja; Dugoujon, Jean-Michel; Mack, Steven J; Thorsby, Erik

2011-01-01

The genes coding for the main molecules involved in the human immune system – immunoglobulins, human leucocyte antigen (HLA) molecules and killer-cell immunoglobulin-like receptors (KIR) – exhibit a very high level of polymorphism that reveals remarkable frequency variation in human populations. ‘Genetic marker’ (GM) allotypes located in the constant domains of IgG antibodies have been studied for over 40 years through serological typing, leading to the identification of a variety of GM haplotypes whose frequencies vary sharply from one geographic region to another. An impressive diversity of HLA alleles, which results in amino acid substitutions located in the antigen-binding region of HLA molecules, also varies greatly among populations. The KIR differ between individuals according to both gene content and allelic variation, and also display considerable population diversity. Whereas the molecular evolution of these polymorphisms has most likely been subject to natural selection, principally driven by host–pathogen interactions, their patterns of genetic variation worldwide show significant signals of human geographic expansion, demographic history and cultural diversification. As current developments in population genetic analysis and computer simulation improve our ability to discriminate among different – either stochastic or deterministic – forces acting on the genetic evolution of human populations, the study of these systems shows great promise for investigating both the peopling history of modern humans in the time since their common origin and human adaptation to past environmental (e.g. pathogenic) changes. Therefore, in addition to mitochondrial DNA, Y-chromosome, microsatellites, single nucleotide polymorphisms and other markers, immunogenetic polymorphisms represent essential and complementary tools for anthropological studies. PMID:21480890

A Family-Based Association Study of CYP11A1 and CYP11B1 Gene Polymorphisms With Autism in Chinese Trios.

PubMed

Deng, Hong-Zhu; You, Cong; Xing, Yu; Chen, Kai-Yun; Zou, Xiao-Bing

2016-05-01

Autism spectrum disorder is a group of neurodevelopmental disorders with the higher prevalence in males. Our previous studies have indicated lower progesterone levels in the children with autism spectrum disorder, suggesting involvement of the cytochrome P-450scc gene (CYP11A1) and cytochrome P-45011beta gene (CYP11B1) as candidate genes in autism spectrum disorder. The aim of this study was to investigate the family-based genetic association between single-nucleotide polymorphisms, rs2279357 in the CYP11A1 gene and rs4534 and rs4541 in the CYP11B1 gene and autism spectrum disorder in Chinese children, which were selected according to the location in the coding region and 5' and 3' regions and minor allele frequencies of greater than 0.05 in the Chinese populations. The transmission disequilibrium test and case-control association analyses were performed in 100 Chinese Han autism spectrum disorder family trios. The genotype and allele frequency of the 3 single-nucleotide polymorphisms had no statistical difference between the children with autism spectrum disorder and their parents (P> .05). Transmission disequilibrium test analysis showed transmission disequilibrium of CYP11A1 gene rs2279357 single-nucleotide polymorphisms (χ(2)= 5.038,P< .001). Our findings provide further support for the hypothesis that a susceptibility gene for autism spectrum disorder exists within or near the CYP11A1 gene in the Han Chinese population. © The Author(s) 2015.

No evidence for the effect of MHC on male mating success in the brown bear.

PubMed

Kuduk, Katarzyna; Babik, Wieslaw; Bellemain, Eva; Valentini, Alice; Zedrosser, Andreas; Taberlet, Pierre; Kindberg, Jonas; Swenson, Jon E; Radwan, Jacek

2014-01-01

Mate choice is thought to contribute to the maintenance of the spectacularly high polymorphism of the Major Histocompatibility Complex (MHC) genes, along with balancing selection from parasites, but the relative contribution of the former mechanism is debated. Here, we investigated the association between male MHC genotype and mating success in the brown bear. We analysed fragments of sequences coding for the peptide-binding region of the highly polymorphic MHC class I and class II DRB genes, while controlling for genome-wide effects using a panel of 18 microsatellite markers. Male mating success did not depend on the number of alleles shared with the female or amino-acid distance between potential mates at either locus. Furthermore, we found no indication of female mating preferences for MHC similarity being contingent on the number of alleles the females carried. Finally, we found no significant association between the number of MHC alleles a male carried and his mating success. Thus, our results provided no support for the role of mate choice in shaping MHC polymorphism in the brown bear.

Lack of association between sigma receptor gene variants and schizophrenia.

PubMed

Satoh, Fumiaki; Miyatake, Ryosuke; Furukawa, Aizo; Suwaki, Hiroshi

2004-08-01

Several pharmacological studies suggest the possible involvement of sigma(1) receptors in the pathogenesis of schizophrenia. An association has been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function. To investigate the role of SIGMAR1 in conveying susceptibility to schizophrenia, we performed a case-control study. We initially screened for polymorphisms in the SIGMAR1 coding region using PCR-single strand conformation polymorphism analysis. The distribution of SIGMAR1 polymorphisms was analyzed in 100 schizophrenic and 104 control subjects. A novel G620A variant was detected in exon4. G620A was predicted to alter the amino acid represented by codon 211 from arginine to glutamine. Our case-control study showed no significant association between the T-485 A, GC-241-240TT, Gln2Pro, and G620A (Arg211Gln) variants and schizophrenia and clinical characteristics. These findings suggest that these SIGMAR1 variants may not affect susceptibility to schizophrenia.

Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

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

Villard, E.; Soubrier, F.; Tiret, L.

1996-06-01

Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms couldmore » be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.« less

Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.

PubMed

Tang, Z; Diamond, M A; Chen, J-M; Holly, T A; Bonow, R O; Dasgupta, A; Hyslop, T; Purzycki, A; Wagner, J; McNamara, D M; Kukulski, T; Wos, S; Velazquez, E J; Ardlie, K; Feldman, A M

2007-10-01

The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

PubMed Central

Permuth-Wey, Jennifer; Lawrenson, Kate; Shen, Howard C.; Velkova, Aneliya; Tyrer, Jonathan P.; Chen, Zhihua; Lin, Hui-Yi; Chen, Y. Ann; Tsai, Ya-Yu; Qu, Xiaotao; Ramus, Susan J.; Karevan, Rod; Lee, Janet; Lee, Nathan; Larson, Melissa C.; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis; Armasu, Sebastian M.; Bacot, François; Baglietto, Laura; Bandera, Elisa V.; Barnholtz-Sloan, Jill; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Cai, Qiuyin; Campbell, Ian; Chang-Claude, Jenny; Chanock, Stephen; Chenevix-Trench, Georgia; Cheng, Jin Q.; Cicek, Mine S.; Coetzee, Gerhard A.; Cook, Linda S.; Couch, Fergus J.; Cramer, Daniel W.; Cunningham, Julie M.; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Easton, Douglas F; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David A.; Flanagan, James M.; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind M.; Gonzalez-Bosquet, Jesus; Goodman, Marc T.; Gore, Martin; Górski, Bohdan; Gronwald, Jacek; Hall, Per; Halle, Mari K.; Harter, Philipp; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Claus K.; Høgdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Jim, Heather; Kalli, Kimberly R.; Karlan, Beth Y.; Kaye, Stanley B.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kikkawa, Fumitaka; Konecny, Gottfried E.; Krakstad, Camilla; Kjaer, Susanne Krüger; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Lancaster, Johnathan M.; Le, Nhu D.; Leminen, Arto; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lin, Jie; Lissowska, Jolanta; Lu, Karen H.; Lubiński, Jan; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Raska, Paola; Renner, Stefan P.; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Shvetsov, Yurii B.; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Stram, Daniel; Sutphen, Rebecca; Teo, Soo-Hwang; Terry, Kathryn L.; Tessier, Daniel C.; Thompson, Pamela J.; Tworoger, Shelley S.; van Altena, Anne M.; Vergote, Ignace; Vierkant, Robert A.; Vincent, Daniel; Vitonis, Allison F.; Wang-Gohrke, Shan; Weber, Rachel Palmieri; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Wilkens, Lynne R.; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H.; Xiang, Yong-Bing; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Phelan, Catherine M.; Iversen, Edwin; Schildkraut, Joellen M.; Berchuck, Andrew; Fridley, Brooke L.; Goode, Ellen L.; Pharoah, Paul D. P.; Monteiro, Alvaro N.A.; Sellers, Thomas A.; Gayther, Simon A.

2013-01-01

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P=10−8) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10−10). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes. PMID:23535648

Transcriptome-Derived Tetranucleotide Microsatellites and Their Associated Genes from the Giant Panda (Ailuropoda melanoleuca).

PubMed

Song, Xuhao; Shen, Fujun; Huang, Jie; Huang, Yan; Du, Lianming; Wang, Chengdong; Fan, Zhenxin; Hou, Rong; Yue, Bisong; Zhang, Xiuyue

2016-09-01

Recently, an increasing number of microsatellites or simple sequence repeats (SSRs) have been found and characterized from transcriptomes. Such SSRs can be employed as putative functional markers to easily tag corresponding genes, which play an important role in biomedical studies and genetic analysis. However, the transcriptome-derived SSRs for giant panda (Ailuropoda melanoleuca) are not yet available. In this work, we identified and characterized 20 tetranucleotide microsatellite loci from a transcript database generated from the blood of giant panda. Furthermore, we assigned their predicted transcriptome locations: 16 loci were assigned to untranslated regions (UTRs) and 4 loci were assigned to coding regions (CDSs). Gene identities of 14 transcripts contained corresponding microsatellites were determined, which provide useful information to study the potential contribution of SSRs to gene regulation in giant panda. The polymorphic information content (PIC) values ranged from 0.293 to 0.789 with an average of 0.603 for the 16 UTRs-derived SSRs. Interestingly, 4 CDS-derived microsatellites developed in our study were also polymorphic, and the instability of these 4 CDS-derived SSRs was further validated by re-genotyping and sequencing. The genes containing these 4 CDS-derived SSRs were embedded with various types of repeat motifs. The interaction of all the length-changing SSRs might provide a way against coding region frameshift caused by microsatellite instability. We hope these newly gene-associated biomarkers will pave the way for genetic and biomedical studies for giant panda in the future. In sum, this set of transcriptome-derived markers complements the genetic resources available for giant panda. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Polymorphism of antimalaria drug metabolizing, nuclear receptor, and drug transport genes among malaria patients in Zanzibar, East Africa.

PubMed

Ferreira, Pedro Eduardo; Veiga, Maria Isabel; Cavaco, Isa; Martins, J Paulo; Andersson, Björn; Mushin, Shaliya; Ali, Abullah S; Bhattarai, Achuyt; Ribeiro, Vera; Björkman, Anders; Gil, José Pedro

2008-02-01

Artemisinin-based combination therapy is a main strategy for malaria control in Africa. Zanzibar introduced this new treatment policy in 2003. The authors have studied the prevalence of a number of functional single nucleotide polymorphisms (SNPs) in genes associated with the elimination of the artemisinin-based combination therapy compounds in use in Zanzibar to investigate the frequencies of subgroups potentially at higher drug exposure and therefore possible higher risk of toxicity. One hundred three unrelated children with uncomplicated malaria from the Unguja and Pemba islands of Zanzibar were enrolled. With use of polymerase chain reaction (PCR)-restriction fragment length polymorphism and real-time PCR-based allele discrimination methods, the CYP2B6 (G15631T), CYP3A4 (A-392G), CYP3A5 (A6986G, G14690A, 27131-132 insT, C3699T) SNPs and MDR1 SNPs C3435T, G2677T/A, and T-129C were analyzed. PCR product sequencing was applied to regulatory regions of MDR1, the CYP3A4 proximal promoter, and to exons 2 and 5 of PXR, a gene coding for a nuclear factor activated by artemisinin antimalarials and associated with the transcription induction of most of the studied genes. Homozygous subjects for alleles coding for low activity proteins were found at the following frequencies: 1) MDR1: 2.9%; 2) CYP2B6: 9.7%; 3) CYP3A5: 14.1%; and 4) CYP3A4: 49.5%. No functionally relevant allele was found in the analyzed regions of PXR. A new MDR1 SNP was found (T-158C), located in a putative antigen recognition element. Ten (10.1%) subjects were predicted to be low metabolizers simultaneously for CYP3A4 and CYP3A5. This fraction of the population is suggested to be under higher exposure to certain antimalarials, including lumefantrine and quinine.

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.

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

Regions of extreme synonymous codon selection in mammalian genes

PubMed Central

Schattner, Peter; Diekhans, Mark

2006-01-01

Recently there has been increasing evidence that purifying selection occurs among synonymous codons in mammalian genes. This selection appears to be a consequence of either cis-regulatory motifs, such as exonic splicing enhancers (ESEs), or mRNA secondary structures, being superimposed on the coding sequence of the gene. We have developed a program to identify regions likely to be enriched for such motifs by searching for extended regions of extreme codon conservation between homologous genes of related species. Here we present the results of applying this approach to five mammalian species (human, chimpanzee, mouse, rat and dog). Even with very conservative selection criteria, we find over 200 regions of extreme codon conservation, ranging in length from 60 to 178 codons. The regions are often found within genes involved in DNA-binding, RNA-binding or zinc-ion-binding. They are highly depleted for synonymous single nucleotide polymorphisms (SNPs) but not for non-synonymous SNPs, further indicating that the observed codon conservation is being driven by negative selection. Forty-three percent of the regions overlap conserved alternative transcript isoforms and are enriched for known ESEs. Other regions are enriched for TpA dinucleotides and may contain conserved motifs/structures relating to mRNA stability and/or degradation. We anticipate that this tool will be useful for detecting regions enriched in other classes of coding-sequence motifs and structures as well. PMID:16556911

Divergent evolution of part of the involucrin gene in the hominoids: Unique intragenic duplications in the gorilla and human

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

Teumer, J.; Green, H.

1989-02-01

The gene for involucrin, an epidermal protein, has been remodeled in the higher primates. Most of the coding region of the human gene consists of a modern segment of repeats derived from a 10-codon sequence present in the ancestral segment of the gene. The modern segment can be divided into early, middle, and late regions. The authors report here the nucleotide sequence of three alleles of the gorilla involucrin gene. Each possesses a modern segment homologous to that of the human and consisting of 10-codon repeats. The early and middle regions are similar to the corresponding regions of the humanmore » allele and are nearly identical among the different gorilla alleles. The late region consists of recent duplications whose pattern is unique in each of the gorilla alleles and in the human allele. The early region is located in what is now the 3{prime} third of the modern segment, and the late, polymorphic region is located in what is now the 5{prime} third. Therefore, as the modern segment expanded during evolution, its 3{prime} end became stabilized, and continuing duplications became confined to its 5{prime} end. The expansion of the involucrin coding region, which began long before the separation of the gorilla and human, has continued in both species after their separation.« less

The Number, Organization, and Size of Polymorphic Membrane Protein Coding Sequences as well as the Most Conserved Pmp Protein Differ within and across Chlamydia Species.

PubMed

Van Lent, Sarah; Creasy, Heather Huot; Myers, Garry S A; Vanrompay, Daisy

2016-01-01

Variation is a central trait of the polymorphic membrane protein (Pmp) family. The number of pmp coding sequences differs between Chlamydia species, but it is unknown whether the number of pmp coding sequences is constant within a Chlamydia species. The level of conservation of the Pmp proteins has previously only been determined for Chlamydia trachomatis. As different Pmp proteins might be indispensible for the pathogenesis of different Chlamydia species, this study investigated the conservation of Pmp proteins both within and across C. trachomatis,C. pneumoniae,C. abortus, and C. psittaci. The pmp coding sequences were annotated in 16 C. trachomatis, 6 C. pneumoniae, 2 C. abortus, and 16 C. psittaci genomes. The number and organization of polymorphic membrane coding sequences differed within and across the analyzed Chlamydia species. The length of coding sequences of pmpA,pmpB, and pmpH was conserved among all analyzed genomes, while the length of pmpE/F and pmpG, and remarkably also of the subtype pmpD, differed among the analyzed genomes. PmpD, PmpA, PmpH, and PmpA were the most conserved Pmp in C. trachomatis,C. pneumoniae,C. abortus, and C. psittaci, respectively. PmpB was the most conserved Pmp across the 4 analyzed Chlamydia species. © 2016 S. Karger AG, Basel.

The structure of the human interferon alpha/beta receptor gene.

PubMed

Lutfalla, G; Gardiner, K; Proudhon, D; Vielh, E; Uzé, G

1992-02-05

Using the cDNA coding for the human interferon alpha/beta receptor (IFNAR), the IFNAR gene has been physically mapped relative to the other loci of the chromosome 21q22.1 region. 32,906 base pairs covering the IFNAR gene have been cloned and sequenced. Primer extension and solution hybridization-ribonuclease protection have been used to determine that the transcription of the gene is initiated in a broad region of 20 base pairs. Some aspects of the polymorphism of the gene, including noncoding sequences, have been analyzed; some are allelic differences in the coding sequence that induce amino acid variations in the resulting protein. The exon structure of the IFNAR gene and of that of the available genes for the receptors of the cytokine/growth hormone/prolactin/interferon receptor family have been compared with the predictions for the secondary structure of those receptors. From this analysis, we postulate a common origin and propose an hypothesis for the divergence from the immunoglobulin superfamily.

The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy

PubMed Central

Wang, Danxin; Sadee, Wolfgang

2012-01-01

CYP3A ranks among the most abundant cytochrome P450 enzymes in the liver, playing a dominant role in metabolic elimination of clinically used drugs. A main member in CYP3A family, CYP3A4 expression and activity vary considerably among individuals, attributable to genetic and non-genetic factors, affecting drug dosage and efficacy. However, the extent of genetic influence has remained unclear. This review assesses current knowledge on the genetic factors influencing CYP3A4 activity. Coding region CYP3A4 polymorphisms are rare and account for only a small portion of inter-person variability in CYP3A metabolism. Except for the promoter allele CYP3A4*1B with ambiguous effect on expression, common CYP3A4 regulatory polymorphisms were thought to be lacking. Recent studies have identified a relatively common regulatory polymorphism, designated CYP3A4*22 with robust effects on hepatic CYP3A4 expression. Combining CYP3A4*22 with CYP3A5 alleles *1, *3 and *7 has promise as a biomarker predicting overall CYP3A activity. Also contributing to variable expression, the role of polymorphisms in transcription factors and microRNAs is discussed. PMID:24466438

Variation in the Oxytocin Receptor Gene Predicts Brain Region Specific Expression and Social Attachment

PubMed Central

King, Lanikea B.; Walum, Hasse; Inoue, Kiyoshi; Eyrich, Nicholas W.; Young, Larry J.

2015-01-01

Background Oxytocin (OXT) modulates several aspects of social behavior. Intranasal OXT is a leading candidate for treating social deficits in autism spectrum disorder (ASD) and common genetic variants in the human oxytocin receptor (OXTR) are associated with emotion recognition, relationship quality and ASD. Animal models have revealed that individual differences in Oxtr expression in the brain drive social behavior variation. Our understanding of how genetic variation contributes to brain OXTR expression is very limited. Methods We investigated Oxtr expression in monogamous prairie voles, which have a well characterized OXT system. We quantified brain region-specific levels of Oxtr mRNA and OXTR protein with established neuroanatomical methods. We used pyrosequencing to investigate allelic imbalance of Oxtr mRNA, a molecular signature of polymorphic genetic regulatory elements. We performed next-generation sequencing to discover variants in and near the Oxtr gene. We investigated social attachment using the partner preference test. Results Our allelic imbalance data demonstrates that genetic variants contribute to individual differences in Oxtr expression, but only in particular brain regions, including the nucleus accumbens (NAcc), where OXTR signaling facilitates social attachment. Next-generation sequencing identified one polymorphism in the Oxtr intron, near a putative cis-regulatory element, explaining 74% of the variance in striatal Oxtr expression specifically. Males homozygous for the high expressing allele display enhanced social attachment. Discussion Taken together, these findings provide convincing evidence for robust genetic influence on Oxtr expression and provide novel insights into how non-coding polymorphisms in the OXTR might influence individual differences in human social cognition and behavior PMID:26893121

Genetic Variation Linked to Lung Cancer Survival in White Smokers | Center for Cancer Research

Cancer.gov

CCR investigators have discovered evidence that links lung cancer survival with genetic variations (called single nucleotide polymorphisms) in the MBL2 gene, a key player in innate immunity. The variations in the gene, which codes for a protein called the mannose-binding lectin, occur in its promoter region, where the RNA polymerase molecule binds to start transcription, and in the first exon that is responsible for the correct structure of MBL. The findings appear in the September 19, 2007, issue of the Journal of the National Cancer Institute.

Complete mitochondrial genome of the versicoloured emerald hummingbird Amazilia versicolor, a polymorphic species.

PubMed

Prosdocimi, Francisco; Souto, Helena Magarinos; Ruschi, Piero Angeli; Furtado, Carolina; Jennings, W Bryan

2016-09-01

The genome of the versicoloured emerald hummingbird (Amazilia versicolor) was partially sequenced in one-sixth of an Illumina HiSeq lane. The mitochondrial genome was assembled using MIRA and MITObim software, yielding a circular molecule of 16,861 bp in length and deposited in GenBank under the accession number KF624601. The mitogenome contained 13 protein-coding genes, 22 transfer tRNAs, 2 ribosomal RNAs and 1 non-coding control region. The molecule was assembled using 21,927 sequencing reads of 100 bp each, resulting in ∼130 × coverage of uniformly distributed reads along the genome. This is the forth mitochondrial genome described for this highly diverse family of birds and may benefit further phylogenetic, phylogeographic, population genetic and species delimitation studies of hummingbirds.

Prevalence of factor V leiden, MTHFR C677T and MTHFR A1298C polymorphisms in patients with deep vein thrombosis in Central Iran.

PubMed

Ehsani, Majid; Imani, Aida; Moravveji, Alireza

2018-05-31

Deep vein thrombosis (DVT) is a common disease, especially among elderly patients, which is associated with high costs of treatment and high rates of recurrence. The risk factors for venous thrombosis are primarily related to hypercoagulability, which can be genetic or acquired, or because of immobilization and venous stasis. Among relevant genetic markers are a number of common polymorphisms and mutations in the genes coding for Factor V leiden and methylenetetrahydrofolate reductase. Differential associations of these polymorphisms have been reported in different populations with DVT due to ethnic variations. However, no study has been reported with respect to these polymorphisms in DVT in Iran. Thus, the aim of the present study is to determine the prevalence of FVL, MTHFR C677T and MTHFR A1298C gene polymorphisms in patients with DVT in central Iran. In the present cross-sectional study, a total of 100 patients with first and recurrent episodes of DVT and age less than 70 years were recruited during 2016-2017. Blood sample was collected from the recruited patients and FVL mutation was screened using ARMS-PCR method, MTHFR C677T and MTHFR A1298C mutations were screened using PCR-RFLP method. The results revealed that MTHFR A1298C gene polymorphism in both homozygote and heterozygote form was found to be most frequent i.e. 77% among cases, followed by MTHFR C677T (67%) and FVL (17%). The study highlights the importance of screening of these genetic markers among patients with DVT in this region.

Pathogen-group specific association between CXCR1 polymorphisms and subclinical mastitis in dairy heifers.

PubMed

Verbeke, Joren; Piepers, Sofie; Peelman, Luc; Van Poucke, Mario; De Vliegher, Sarne

2012-08-01

The chemokine (C-X-C motif) receptor 1 (CXCR1) gene encodes the homonymous receptor for interleukin 8 (IL8) on polymorphonuclear neutrophilic leucocytes (PMNL). Binding causes migration from blood to milk, activation and prolonged survival of PMNL, a crucial process in the innate immune defence of the bovine mammary gland against invading mastitis-causing pathogens. The main objective of this study was to screen the entire coding region of the CXCR1 gene for polymorphisms and to analyse their association with udder health of dairy heifers. One-hundred-and-forty Belgian Holstein heifers originating from 20 commercial dairy farms were genotyped by DNA sequencing. Detailed phenotypic data on udder health was available including quarter bacteriological culture results and somatic cell count (SCC) in early lactation and composite milk SCC during first lactation. In total, 16 polymorphisms (including 8 missense mutations) were detected. Polymorphism c.980A>G was associated with pathogen-group specific IMI: heifers with genotype AG were less likely to have an IMI due to major mastitis pathogens compared with heifers with genotype GG but did not have less IMI by coagulase-negative staphylococci, so-called minor pathogens. CXCR1 genotype was neither associated with quarter SCC in early lactation nor with composite SCC during lactation. Although mastitis susceptibility is influenced by many factors, some genetic polymorphisms potentially have major effects on udder health of heifers, as was shown here. These results trigger us to further study the relationship between CXCR1 polymorphisms and mastitis susceptibility in both observational and experimental trials.

Structure and variation of three canine genes involved in serotonin binding and transport: the serotonin receptor 1A gene (htr1A), serotonin receptor 2A gene (htr2A), and serotonin transporter gene (slc6A4).

PubMed

van den Berg, L; Kwant, L; Hestand, M S; van Oost, B A; Leegwater, P A J

2005-01-01

Aggressive behavior is the most frequently encountered behavioral problem in dogs. Abnormalities in brain serotonin metabolism have been described in aggressive dogs. We studied canine serotonergic genes to investigate genetic factors underlying canine aggression. Here, we describe the characterization of three genes of the canine serotonergic system: the serotonin receptor 1A and 2A gene (htr1A and htr2A) and the serotonin transporter gene (slc6A4). We isolated canine bacterial artificial chromosome clones containing these genes and designed oligonucleotides for genomic sequencing of coding regions and intron-exon boundaries. Golden retrievers were analyzed for DNA sequence variations. We found two nonsynonymous single nucleotide polymorphisms (SNPs) in the coding sequence of htr1A; one SNP close to a splice site in htr2A; and two SNPs in slc6A4, one in the coding sequence and one close to a splice site. In addition, we identified a polymorphic microsatellite marker for each gene. Htr1A is a strong candidate for involvement in the domestication of the dog. We genotyped the htr1A SNPs in 41 dogs of seven breeds with diverse behavioral characteristics. At least three SNP haplotypes were found. Our results do not support involvement of the gene in domestication.

Autism-like behavioral phenotypes in BTBR T+tf/J mice.

PubMed

McFarlane, H G; Kusek, G K; Yang, M; Phoenix, J L; Bolivar, V J; Crawley, J N

2008-03-01

Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety-like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo. The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme-regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo, supporting further investigation into the contribution of this polymorphism to autism-like behavioral phenotypes. Robust and selective social deficits, repetitive self-grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms.

A candidate gene for choanal atresia in alpaca.

PubMed

Reed, Kent M; Bauer, Miranda M; Mendoza, Kristelle M; Armién, Aníbal G

2010-03-01

Choanal atresia (CA) is a common nasal craniofacial malformation in New World domestic camelids (alpaca and llama). CA results from abnormal development of the nasal passages and is especially debilitating to newborn crias. CA in camelids shares many of the clinical manifestations of a similar condition in humans (CHARGE syndrome). Herein we report on the regulatory gene CHD7 of alpaca, whose homologue in humans is most frequently associated with CHARGE. Sequence of the CHD7 coding region was obtained from a non-affected cria. The complete coding region was 9003 bp, corresponding to a translated amino acid sequence of 3000 aa. Additional genomic sequences corresponding to a significant portion of the CHD7 gene were identified and assembled from the 2x alpaca whole genome sequence, providing confirmatory sequence for much of the CHD7 coding region. The alpaca CHD7 mRNA sequence was 97.9% similar to the human sequence, with the greatest sequence difference being an insertion in exon 38 that results in a polyalanine repeat (A12). Polymorphism in this repeat was tested for association with CA in alpaca by cloning and sequencing the repeat from both affected and non-affected individuals. Variation in length of the poly-A repeat was not associated with CA. Complete sequencing of the CHD7 gene will be necessary to determine whether other mutations in CHD7 are the cause of CA in camelids.

Analysis of the QTL for sleep homeostasis in mice: Homer1a is a likely candidate.

PubMed

Mackiewicz, M; Paigen, B; Naidoo, N; Pack, A I

2008-03-14

Electroencephalographic oscillations in the frequency range of 0.5-4 Hz, characteristic of slow-wave sleep (SWS), are often referred to as the delta oscillation or delta power. Delta power reflects sleep intensity and correlates with the homeostatic response to sleep loss. A published survey of inbred strains of mice demonstrated that the time course of accumulation of delta power varied among inbred strains, and the segregation of the rebound of delta power in BxD recombinant inbred strains identified a genomic region on chromosome 13 referred to as the delta power in SWS (or Dps1). The quantitative trait locus (QTL) contains genes that modify the accumulation of delta power after sleep deprivation. Here, we narrow the QTL using interval-specific haplotype analysis and present a comprehensive annotation of the remaining genes in the Dps1 region with sequence comparisons to identify polymorphisms within the coding and regulatory regions. We established the expression pattern of selected genes located in the Dps1 interval in sleep and wakefulness in B6 and D2 parental strains. Taken together, these steps reduced the number of potential candidate genes that may underlie the accumulation of delta power after sleep deprivation and explain the Dps1 QTL. The strongest candidate gene is Homer1a, which is supported by expression differences between sleep and wakefulness and the SNP polymorphism in the upstream regulatory regions.

Comparative genomics of the mimicry switch in Papilio dardanus.

PubMed

Timmermans, Martijn J T N; Baxter, Simon W; Clark, Rebecca; Heckel, David G; Vogel, Heiko; Collins, Steve; Papanicolaou, Alexie; Fukova, Iva; Joron, Mathieu; Thompson, Martin J; Jiggins, Chris D; ffrench-Constant, Richard H; Vogler, Alfried P

2014-07-22

The African Mocker Swallowtail, Papilio dardanus, is a textbook example in evolutionary genetics. Classical breeding experiments have shown that wing pattern variation in this polymorphic Batesian mimic is determined by the polyallelic H locus that controls a set of distinct mimetic phenotypes. Using bacterial artificial chromosome (BAC) sequencing, recombination analyses and comparative genomics, we show that H co-segregates with an interval of less than 500 kb that is collinear with two other Lepidoptera genomes and contains 24 genes, including the transcription factor genes engrailed (en) and invected (inv). H is located in a region of conserved gene order, which argues against any role for genomic translocations in the evolution of a hypothesized multi-gene mimicry locus. Natural populations of P. dardanus show significant associations of specific morphs with single nucleotide polymorphisms (SNPs), centred on en. In addition, SNP variation in the H region reveals evidence of non-neutral molecular evolution in the en gene alone. We find evidence for a duplication potentially driving physical constraints on recombination in the lamborni morph. Absence of perfect linkage disequilibrium between different genes in the other morphs suggests that H is limited to nucleotide positions in the regulatory and coding regions of en. Our results therefore support the hypothesis that a single gene underlies wing pattern variation in P. dardanus.

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children

PubMed Central

Jasińska, Kaja K.; Molfese, Peter J.; Kornilov, Sergey A.; Mencl, W. Einar; Frost, Stephen J.; Lee, Maria; Pugh, Kenneth R.; Grigorenko, Elena L.; Landi, Nicole

2016-01-01

Understanding how genes impact the brain’s functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children’s (age 6–10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading–related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes. PMID:27551971

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

PubMed

Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

2016-01-01

Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

Genetic, comparative genomic, and expression analyses of the Mc1r locus in the polychromatic Midas cichlid fish (Teleostei, Cichlidae Amphilophus sp.) species group.

PubMed

Henning, Frederico; Renz, Adina Josepha; Fukamachi, Shoji; Meyer, Axel

2010-05-01

Natural populations of the Midas cichlid species in several different crater lakes in Nicaragua exhibit a conspicuous color polymorphism. Most individuals are dark and the remaining have a gold coloration. The color morphs mate assortatively and sympatric population differentiation has been shown based on neutral molecular data. We investigated the color polymorphism using segregation analysis and a candidate gene approach. The segregation patterns observed in a mapping cross between a gold and a dark individual were consistent with a single dominant gene as a cause of the gold phenotype. This suggests that a simple genetic architecture underlies some of the speciation events in the Midas cichlids. We compared the expression levels of several candidate color genes Mc1r, Ednrb1, Slc45a2, and Tfap1a between the color morphs. Mc1r was found to be up regulated in the gold morph. Given its widespread association in color evolution and role on melanin synthesis, the Mc1r locus was further investigated using sequences derived from a genomic library. Comparative analysis revealed conserved synteny in relation to the majority of teleosts and highlighted several previously unidentified conserved non-coding elements (CNEs) in the upstream and downstream regions in the vicinity of Mc1r. The identification of the CNEs regions allowed the comparison of sequences from gold and dark specimens of natural populations. No polymorphisms were found between in the population sample and Mc1r showed no linkage to the gold phenotype in the mapping cross, demonstrating that it is not causally related to the color polymorphism in the Midas cichlid.

The SLCO1A2 -189_-188InsA polymorphism reduces clearance of rocuronium in patients submitted to elective surgeries.

PubMed

Costa, A C C; Coelho, E B; Lanchote, V L; Correia, B V; Abumansur, J T; Lauretti, G R; de Moraes, N V

2017-08-01

Rocuronium (ROC) is a neuromuscular blocker mainly eliminated by biliary excretion dependent on organic anion transporting polypeptide 1A2 (OATP1A2) hepatocellular uptake. However, the influence of SLCO1A2 (gene encoding OATP1A2) genetic polymorphism on ROC pharmacokinetics was never described before. The objective of this work was to evaluate the influence of genetic polymorphisms of SLCO1A2 on the pharmacokinetics of rocuronium (ROC). Patients undergoing elective surgeries under general anesthesia using rocuronium as a neuromuscular blocker were genotyped for SLCO1A2 polymorphisms in the coding region (41A>G, 382A>T, 404A>T, 502C>T, 516A>C, 559G>A, 830C>A, and 833delA) and in the promoter region (-1105G>A, -1032G>A, -715T>C, -361G>A, and -189_-188insA). Rocuronium pharmacokinetic parameters were estimated by non-compartmental analysis. None of the patients had heterozygous or homozygous variant of 404A>T, 382A>T, 502C>T, 833delA, 830C>A, 41A>G, and -715T>C. A linkage disequilibrium was found between -1105G>A and -1032G>A genotypes. Patients genotyped as -A or AA (n = 17) for SLCO1A2 -189_-188InsA showed reduced total clearance of ROC compared to patients genotyped as -/- (n = 13) (151.6 vs 207.1 mL/min, p ≤ 0.05). The pharmacokinetics parameters of ROC were not significantly different between other SLCO1A2 genotypes. SLCO1A2 -189_-188InsA polymorphism is related to the reduced clearance of rocuronium in patients submitted to elective surgeries under general anesthesia. NCT 02399397 ( ClinicalTrials.gov ).

Identifying disease polymorphisms from case-control genetic association data.

PubMed

Park, L

2010-12-01

In case-control association studies, it is typical to observe several associated polymorphisms in a gene region. Often the most significantly associated polymorphism is considered to be the disease polymorphism; however, it is not clear whether it is the disease polymorphism or there is more than one disease polymorphism in the gene region. Currently, there is no method that can handle these problems based on the linkage disequilibrium (LD) relationship between polymorphisms. To distinguish real disease polymorphisms from markers in LD, a method that can detect disease polymorphisms in a gene region has been developed. Relying on the LD between polymorphisms in controls, the proposed method utilizes model-based likelihood ratio tests to find disease polymorphisms. This method shows reliable Type I and Type II error rates when sample sizes are large enough, and works better with re-sequenced data. Applying this method to fine mapping using re-sequencing or dense genotyping data would provide important information regarding the genetic architecture of complex traits.

Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase.

PubMed Central

McGuire, M C; Nogueira, C P; Bartels, C F; Lightstone, H; Hajra, A; Van der Spek, A F; Lockridge, O; La Du, B N

1989-01-01

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. A polymorphic site near the C terminus of the coded region was detected, but neither allele at this locus segregated consistently with the atypical trait. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of 32P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. We conclude that the Asp-70----Gly mutation (acidic to neutral amino acid substitution) accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool. Images PMID:2915989

Implication of common and disease specific variants in CLU, CR1, and PICALM.

PubMed

Ferrari, Raffaele; Moreno, Jorge H; Minhajuddin, Abu T; O'Bryant, Sid E; Reisch, Joan S; Barber, Robert C; Momeni, Parastoo

2012-08-01

Two recent genome-wide association studies (GWAS) for late onset Alzheimer's disease (LOAD) revealed 3 new genes: clusterin (CLU), phosphatidylinositol binding clathrin assembly protein (PICALM), and complement receptor 1 (CR1). In order to evaluate association with these genome-wide association study-identified genes and to isolate the variants contributing to the pathogenesis of LOAD, we genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions of these genes in our cohort of 342 LOAD patients and 277 control subjects. We confirmed the association of rs3851179 (PICALM) (p = 7.4 × 10(-3)) with the disease status. Through sequencing we identified 18 variants in CLU, 3 of which were found exclusively in patients; 8 variants (out of 65) in CR1 gene were only found in patients and the 16 variants identified in PICALM gene were present in both patients and controls. In silico analysis of the variants in PICALM did not predict any damaging effect on the protein. The haplotype analysis of the variants in each gene predicted a common haplotype when the 3 single nucleotide polymorphisms rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), respectively, were included. For each gene the haplotype structure and size differed between patients and controls. In conclusion, we confirmed association of CLU, CR1, and PICALM genes with the disease status in our cohort through identification of a number of disease-specific variants among patients through the sequencing of the coding region of these genes. Published by Elsevier Inc.

Phylogeographic Differentiation of Mitochondrial DNA in Han Chinese

PubMed Central

Yao, Yong-Gang; Kong, Qing-Peng; Bandelt, Hans-Jürgen; Kivisild, Toomas; Zhang, Ya-Ping

2002-01-01

To characterize the mitochondrial DNA (mtDNA) variation in Han Chinese from several provinces of China, we have sequenced the two hypervariable segments of the control region and the segment spanning nucleotide positions 10171–10659 of the coding region, and we have identified a number of specific coding-region mutations by direct sequencing or restriction-fragment–length–polymorphism tests. This allows us to define new haplogroups (clades of the mtDNA phylogeny) and to dissect the Han mtDNA pool on a phylogenetic basis, which is a prerequisite for any fine-grained phylogeographic analysis, the interpretation of ancient mtDNA, or future complete mtDNA sequencing efforts. Some of the haplogroups under study differ considerably in frequencies across different provinces. The southernmost provinces show more pronounced contrasts in their regional Han mtDNA pools than the central and northern provinces. These and other features of the geographical distribution of the mtDNA haplogroups observed in the Han Chinese make an initial Paleolithic colonization from south to north plausible but would suggest subsequent migration events in China that mainly proceeded from north to south and east to west. Lumping together all regional Han mtDNA pools into one fictive general mtDNA pool or choosing one or two regional Han populations to represent all Han Chinese is inappropriate for prehistoric considerations as well as for forensic purposes or medical disease studies. PMID:11836649

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

Clinical and neuropathological picture of ethylmalonic aciduria - diagnostic dilemma.

PubMed

Jamroz, Ewa; Paprocka, Justyna; Adamek, Dariusz; Pytel, Justyna; Szczechowska, Katarzyna; Grabska, Natalia; Malec, Michalina; Głuszkiewicz, Ewa; Daab, Michał; Wodołażski, Anatolij

2011-01-01

Increased ethylmalonic acid (EMA) in urine is a non-specific finding, and is observed in a number of inborn errors of metabolism, as well as in individuals who carry one of two common polymorphisms identified in the SCAD coding region. The authors present an 8-month-old girl with a suspicion of neuroinfection, although the clinical presentation led to diagnosis of ethylmalonic aciduria. From the neuropathological point of view the most remarkable changes were observed in the brain cortex, which was diffusely damaged practically in all regions of the brain. Of note, the most severe destruction was observed in the deepest regions of the sulci. The cortex of the affected regions showed no normal stratification and its structure was almost totally replaced by a form of "granulation tissue" with a markedly increased number of capillaries. To the authors' knowledge this is the first clinical report of ethylmalonic aciduria with brain autopsy findings.

Partial Shotgun Sequencing of the Boechera stricta Genome Reveals Extensive Microsynteny and Promoter Conservation with Arabidopsis1[W

PubMed Central

Windsor, Aaron J.; Schranz, M. Eric; Formanová, Nataša; Gebauer-Jung, Steffi; Bishop, John G.; Schnabelrauch, Domenica; Kroymann, Juergen; Mitchell-Olds, Thomas

2006-01-01

Comparative genomics provides insight into the evolutionary dynamics that shape discrete sequences as well as whole genomes. To advance comparative genomics within the Brassicaceae, we have end sequenced 23,136 medium-sized insert clones from Boechera stricta, a wild relative of Arabidopsis (Arabidopsis thaliana). A significant proportion of these sequences, 18,797, are nonredundant and display highly significant similarity (BLASTn e-value ≤ 10−30) to low copy number Arabidopsis genomic regions, including more than 9,000 annotated coding sequences. We have used this dataset to identify orthologous gene pairs in the two species and to perform a global comparison of DNA regions 5′ to annotated coding regions. On average, the 500 nucleotides upstream to coding sequences display 71.4% identity between the two species. In a similar analysis, 61.4% identity was observed between 5′ noncoding sequences of Brassica oleracea and Arabidopsis, indicating that regulatory regions are not as diverged among these lineages as previously anticipated. By mapping the B. stricta end sequences onto the Arabidopsis genome, we have identified nearly 2,000 conserved blocks of microsynteny (bracketing 26% of the Arabidopsis genome). A comparison of fully sequenced B. stricta inserts to their homologous Arabidopsis genomic regions indicates that indel polymorphisms >5 kb contribute substantially to the genome size difference observed between the two species. Further, we demonstrate that microsynteny inferred from end-sequence data can be applied to the rapid identification and cloning of genomic regions of interest from nonmodel species. These results suggest that among diploid relatives of Arabidopsis, small- to medium-scale shotgun sequencing approaches can provide rapid and cost-effective benefits to evolutionary and/or functional comparative genomic frameworks. PMID:16607030

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.

DNA octaplex formation with an I-motif of water-mediated A-quartets: reinterpretation of the crystal structure of d(GCGAAAGC).

PubMed

Sato, Yoshiteru; Mitomi, Kenta; Sunami, Tomoko; Kondo, Jiro; Takénaka, Akio

2006-12-01

The crystal structure of the tetragonal form of d(gcGAAAgc) has been revised and reasonably refined including the disordered residues. The two DNA strands form a base-intercalated duplex, and the four duplexes are assembled according to the crystallographic 222 symmetry to form an octaplex. In the central region, the eight strands are associated by I-motif of double A-quartets. Furthermore, eight hydrated-magnesium cations link the four duplexes to support the octaplex formation. Based on these structural features, a proposal that folding of d(GAAA)n, found in the non-coding region of genomes, into an octaplex can induce slippage during replication to facilitate length polymorphism is presented.

Intergenic disease-associated regions are abundant in novel transcripts.

PubMed

Bartonicek, N; Clark, M B; Quek, X C; Torpy, J R; Pritchard, A L; Maag, J L V; Gloss, B S; Crawford, J; Taft, R J; Hayward, N K; Montgomery, G W; Mattick, J S; Mercer, T R; Dinger, M E

2017-12-28

Genotyping of large populations through genome-wide association studies (GWAS) has successfully identified many genomic variants associated with traits or disease risk. Unexpectedly, a large proportion of GWAS single nucleotide polymorphisms (SNPs) and associated haplotype blocks are in intronic and intergenic regions, hindering their functional evaluation. While some of these risk-susceptibility regions encompass cis-regulatory sites, their transcriptional potential has never been systematically explored. To detect rare tissue-specific expression, we employed the transcript-enrichment method CaptureSeq on 21 human tissues to identify 1775 multi-exonic transcripts from 561 intronic and intergenic haploblocks associated with 392 traits and diseases, covering 73.9 Mb (2.2%) of the human genome. We show that a large proportion (85%) of disease-associated haploblocks express novel multi-exonic non-coding transcripts that are tissue-specific and enriched for GWAS SNPs as well as epigenetic markers of active transcription and enhancer activity. Similarly, we captured transcriptomes from 13 melanomas, targeting nine melanoma-associated haploblocks, and characterized 31 novel melanoma-specific transcripts that include fusion proteins, novel exons and non-coding RNAs, one-third of which showed allelically imbalanced expression. This resource of previously unreported transcripts in disease-associated regions ( http://gwas-captureseq.dingerlab.org ) should provide an important starting point for the translational community in search of novel biomarkers, disease mechanisms, and drug targets.

Sequence polymorphism in candidate genes for differences in winter plumage between Scottish and Scandinavian Willow Grouse (Lagopus lagopus).

PubMed

Skoglund, Pontus; Höglund, Jacob

2010-04-23

Population variation in the degree of seasonal polymorphism is rare in birds, and the genetic basis of this phenomenon remains largely undescribed. Both sexes of Scandinavian and Scottish Willow grouse (Lagopus lagopus) display marked differences in their winter phenotypes, with Scottish grouse retaining a pigmented plumage year-round and Scandinavian Willow grouse molting to a white morph during winter. A widely studied pathway implicated in vertebrate pigmentation is the melanin system, for which functional variation has been characterised in many taxa. We sequenced coding regions from four genes involved in melanin pigmentation (DCT, MC1R, TYR and TYRP1), and an additional control involved in the melanocortin pathway (AGRP), to investigate the genetic basis of winter plumage in Lagopus. Despite the well documented role of the melanin system in animal coloration, we found no plumage-associated polymorphism or evidence for selection in a total of approximately 2.6 kb analysed sequence. Our results indicate that the genetic basis of alternating between pigmented and unpigmented seasonal phenotypes is more likely explained by regulatory changes controlling the expression of these or other loci in the physiological pathway leading to pigmentation.

Variable continental distribution of polymorphisms in the coding regions of DNA-repair genes.

PubMed

Mathonnet, Géraldine; Labuda, Damian; Meloche, Caroline; Wambach, Tina; Krajinovic, Maja; Sinnett, Daniel

2003-01-01

DNA-repair pathways are critical for maintaining the integrity of the genetic material by protecting against mutations due to exposure-induced damages or replication errors. Polymorphisms in the corresponding genes may be relevant in genetic epidemiology by modifying individual cancer susceptibility or therapeutic response. We report data on the population distribution of potentially functional variants in XRCC1, APEX1, ERCC2, ERCC4, hMLH1, and hMSH3 genes among groups representing individuals of European, Middle Eastern, African, Southeast Asian and North American descent. The data indicate little interpopulation differentiation in some of these polymorphisms and typical FST values ranging from 10 to 17% at others. Low FST was observed in APEX1 and hMSH3 exon 23 in spite of their relatively high minor allele frequencies, which could suggest the effect of balancing selection. In XRCC1, hMSH3 exon 21 and hMLH1 Africa clusters either with Middle East and Europe or with Southeast Asia, which could be related to the demographic history of human populations, whereby human migrations and genetic drift rather than selection would account for the observed differences.

Molecular cloning, polymorphisms, and expression analysis of the RERG gene in indigenous Chinese goats.

PubMed

Sui, M X; Wang, H H; Wang, Z W

2015-11-24

The current study aimed to investigate the coding sequence, polymorphisms, and expression of the RERG gene in indigenous Chinese goats. cDNA of RERG, obtained through reverse transcription PCR was analyzed using bioinformatic techniques. Polymorphisms in the exon regions of the RERG gene were identified and their associations with growth traits in three varieties of indigenous Chinese goats were investigated. Expression of the RERG gene in three goat breeds of the same age was detected using real-time quantitative PCR. The results revealed that the cDNA of RERG, which contained a complete open reading frame of 20-620 bp, was 629 bp in length. The associated accession numbers in GenBank are JN672576, JQ917222, and JN580309 for the QianBei Ma goat, the GuiZhou white goat, and the GuiZhou black goat, respectively. Four consistent SNP sites were found in the exon regions of the RERG gene for the three goat breeds. mRNA expression of the RERG gene differed between different tissues in adult goats of same age. The highest expression was observed in lung and spleen tissues, while the lowest expression was recorded in thymus gland tissue. In addition, the expression of the RERG gene in the muscle of Guizhou white goat, GuiZhou black goat, and QianBei Ma goat decreased sequentially. Our results lay the foundations for further investigation into the role of the RERG gene in goat growth traits.

Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology(1.).

PubMed

Robarts, Daniel W H; Wolfe, Andrea D

2014-07-01

In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance.

Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

PubMed Central

Robarts, Daniel W. H.; Wolfe, Andrea D.

2014-01-01

In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

Age-related change in the association between a polymorphism in the PER3 gene and preferred timing of sleep and waking activities.

PubMed

Jones, Kay H S; Ellis, Jason; von Schantz, Malcolm; Skene, Debra J; Dijk, Derk-Jan; Archer, Simon N

2007-03-01

The objective of this study was to investigate the effect of age on the association between preferred timing of sleep and waking activities and a coding-region variable number tandem repeat (VNTR) polymorphism in the clock gene PER3. We have previously reported this polymorphism to associate with diurnal preference and delayed sleep phase syndrome (DSPS). Participants (n = 1590; 707 males and 883 females) completed the Horne-Ostberg (HO) questionnaire for diurnal preference and provided a DNA sample. Overall HO scores were plotted against age. The 5% extremes and intermediates were selected for genotyping. Frequencies of the PER3 4- and 5-repeat alleles were examined in separate age groups (18-29, 30-39, 40-49 and 50+ years of age). The 4-repeat allele was significantly more frequent in evening types, and the 5-repeat allele more frequent in morning types (Fisher's exact test, P = 0.016). Analysis in the four age groupings revealed that the strength of this association attenuated with age and was significant only in the youngest group (18-29 years). These results extend our previous finding of an association between the PER3 VNTR and diurnal preference. They also demonstrate that diurnal preference in young people is more closely associated with this polymorphism than it is in other age groups.

A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs.

PubMed

Drögemüller, Cord; Philipp, Ute; Haase, Bianca; Günzel-Apel, Anne-Rose; Leeb, Tosso

2007-01-01

Coat color dilution in several breeds of dog is characterized by a specific pigmentation phenotype and sometimes accompanied by hair loss and recurrent skin inflammation, the so-called color dilution alopecia or black hair follicular dysplasia. Coat color dilution (d) is inherited as a Mendelian autosomal recessive trait. In a previous study, MLPH polymorphisms showed perfect cosegregation with the dilute phenotype within breeds. However, different dilute haplotypes were found in different breeds, and no single polymorphism was identified in the coding sequence that was likely to be causative for the dilute phenotype. We resequenced the 5'-region of the canine MLPH gene and identified a strong candidate single nucleotide polymorphism within the nontranslated exon 1, which showed perfect association to the dilute phenotype in 65 dilute dogs from 7 different breeds. The A/G polymorphism is located at the last nucleotide of exon 1 and the mutant A-allele is predicted to reduce splicing efficiency 8-fold. An MLPH mRNA expression study using quantitative reverse transcriptase-polymerase chain reaction confirmed that dd animals had only about approximately 25% of the MLPH transcript compared with DD animals. These results provide preliminary evidence that the reported regulatory MLPH mutation might represent a causal mutation for coat color dilution in dogs.

Computational Analysis of Single Nucleotide Polymorphisms Associated with Altered Drug Responsiveness in Type 2 Diabetes

PubMed Central

Costa, Valerio; Federico, Antonio; Pollastro, Carla; Ziviello, Carmela; Cataldi, Simona; Formisano, Pietro; Ciccodicola, Alfredo

2016-01-01

Type 2 diabetes (T2D) is one of the most frequent mortality causes in western countries, with rapidly increasing prevalence. Anti-diabetic drugs are the first therapeutic approach, although many patients develop drug resistance. Most drug responsiveness variability can be explained by genetic causes. Inter-individual variability is principally due to single nucleotide polymorphisms, and differential drug responsiveness has been correlated to alteration in genes involved in drug metabolism (CYP2C9) or insulin signaling (IRS1, ABCC8, KCNJ11 and PPARG). However, most genome-wide association studies did not provide clues about the contribution of DNA variations to impaired drug responsiveness. Thus, characterizing T2D drug responsiveness variants is needed to guide clinicians toward tailored therapeutic approaches. Here, we extensively investigated polymorphisms associated with altered drug response in T2D, predicting their effects in silico. Combining different computational approaches, we focused on the expression pattern of genes correlated to drug resistance and inferred evolutionary conservation of polymorphic residues, computationally predicting the biochemical properties of polymorphic proteins. Using RNA-Sequencing followed by targeted validation, we identified and experimentally confirmed that two nucleotide variations in the CAPN10 gene—currently annotated as intronic—fall within two new transcripts in this locus. Additionally, we found that a Single Nucleotide Polymorphism (SNP), currently reported as intergenic, maps to the intron of a new transcript, harboring CAPN10 and GPR35 genes, which undergoes non-sense mediated decay. Finally, we analyzed variants that fall into non-coding regulatory regions of yet underestimated functional significance, predicting that some of them can potentially affect gene expression and/or post-transcriptional regulation of mRNAs affecting the splicing. PMID:27347941

Phylogenetic distribution and expression of a penicillin-binding protein homologue, Ear and its significance in virulence of Staphylococcus aureus.

PubMed

Singh, Vineet K; Ring, Robert P; Aswani, Vijay; Stemper, Mary E; Kislow, Jennifer; Ye, Zhan; Shukla, Sanjay K

2017-12-01

Staphylococcus aureus is an opportunistic human pathogen that can cause serious infections in humans. A plethora of known and putative virulence factors are produced by staphylococci that collectively orchestrate pathogenesis. Ear protein (Escherichia coli ampicillin resistance) in S. aureus is an exoprotein in COL strain, predicted to be a superantigen, and speculated to play roles in antibiotic resistance and virulence. The goal of this study was to determine if expression of ear is modulated by single nucleotide polymorphisms in its promoter and coding sequences and whether this gene plays roles in antibiotic resistance and virulence. Promoter, coding sequences and expression of the ear gene in clinical and carriage S. aureus strains with distinct genetic backgrounds were analysed. The JE2 strain and its isogenic ear mutant were used in a systemic infection mouse model to determine the competiveness of the ear mutant.Results/Key findings. The ear gene showed a variable expression, with USA300FPR3757 showing a high-level expression compared to many of the other strains tested including some showing negligible expression. Higher expression was associated with agr type 1 but not correlated with phylogenetic relatedness of the ear gene based upon single nucleotide polymorphisms in the promoter or coding regions suggesting a complex regulation. An isogenic JE2 (USA300 background) ear mutant showed no significant difference in its growth, antibiotic susceptibility or virulence in a mouse model. Our data suggests that despite being highly expressed in a USA300 genetic background, Ear is not a significant contributor to virulence in that strain.

Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine oxidase A gene (MAOA): a revisit.

PubMed

Groß, Maximilian; Bajanowski, Thomas; Vennemann, Mechtild; Poetsch, Micaela

2014-01-01

Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

Nucleation control and separation of paracetamol polymorphs through swift cooling crystallization process

NASA Astrophysics Data System (ADS)

Sudha, C.; Srinivasan, K.

2014-09-01

Polymorphic nucleation behavior of pharmaceutical solid paracetamol has been investigated by performing swift cooling crystallization process. Saturated aqueous solution prepared at 318 K was swiftly cooled to 274 K in steps of every 1 K in the temperature range from 274 K to 313 K with uniform stirring of 100 rpm. The resultant supersaturation generated in the mother solution favours the nucleation of three different polymorphs of paracetamol. Lower supersaturation region σ=0.10-0.83 favours stable mono form I; the intermediate supersaturation region σ=0.92-1.28 favours metastable ortho form II and the higher supersaturation region σ=1.33-1.58 favours unstable form III polymorphic nucleation. Depending upon the level of supersaturation generated during swift cooling process and the corresponding solubility limit and metastable zone width (MSZW) of each polymorph, the nucleation of a particular polymorph occurs in the system. The type of polymorphs was identified by in-situ optical microscopy and the internal structure was confirmed by Powder X-ray diffraction (PXRD) study. By this novel approach, the preferred nucleation regions of all the three polymorphs of paracetamol are optimized in terms of different cooling ranges employed during the swift cooling process. Also solution mediated polymorphic transformations from unstable to mono and ortho to mono polymorphs have been studied by in-situ.

Polymorphisms of clip domain serine proteinase and serine proteinase homolog in the swimming crab Portunus trituberculatus and their association with Vibrio alginolyticus

NASA Astrophysics Data System (ADS)

Liu, Meng; Liu, Yuan; Hui, Min; Song, Chengwen; Cui, Zhaoxia

2017-03-01

Clip domain serine proteases (cSPs) and their homologs (SPHs) play an important role in various biological processes that are essential components of extracellular signaling cascades, especially in the innate immune responses of invertebrates. Here, polymorphisms of PtcSP and PtSPH from the swimming crab Portunus trituberculatus were investigated to explore their association with resistance/susceptibility to Vibrio alginolyticus. Polymorphic loci were identified using Clustal X, and characterized with SPSS 16.0 software, and then the significance of genotype and allele frequencies between resistant and susceptible stocks was determined by a χ 2 test. A total of 109 and 77 single nucleotide polymorphisms (SNPs) were identified in the genomic fragments of PtcSP and PtSPH, respectively. Notably, nearly half of PtSPH polymorphisms were found in the non-coding exon 1. Fourteen SNPs investigated were significantly associated with susceptibility/resistance to V. alginolyticus ( P <0.05). Among them, eight SNPs were observed in introns, and one synonymous, four non-synonymous SNPs and one ins-del were found in coding exons. In addition, five simple sequence repeats (SSRs) were detected in intron 3 of PtcSP. Although there was no statistically significant difference of allele frequencies, the SSRs showed different polymorphic alleles on the basis of the repeat number between resistant and susceptible stocks. After further validation, polymorphisms investigated here might be applied to select potential molecular markers of P. trituberculatus with resistance to V. alginolyticus.

Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs.

PubMed

Dierks, C; Mömke, S; Philipp, U; Distl, O

2013-08-01

Hitherto, the only known mutant gene leading to the long-hair phenotype in mammals is the fibroblast growth factor 5 (FGF5). In many dog breeds, the previously discovered FGF5:p.Cys95Phe mutation appeared completely concordant with the long-hair phenotype, but for some breeds, the long-hair phenotype could not be resolved. First, we studied the role of the FGF5:p.Cys95Phe and FGF5:g.145_150dupACCAGC mutations in 268 dogs descending from 27 breeds and seven wolves. As these mutations did not explain all the long-hair phenotypes, all exons and their neighbouring regions of FGF5 were re-sequenced. We detected three novel mutations in the coding sequence and one novel non-coding splice-site mutation in FGF5 associated with the long-hair phenotype. The FGF5:p.Ala193Val polymorphism was perfectly consistent with long hair in Akitas and probably in Siberian huskies, too. Dogs of the long-hair breed Samoyed were either homozygous or compound heterozygous for the FGF5:p.Ala193Val or the FGF5:p.Cys95Phe polymorphisms respectively. The two newly detected polymorphisms FGF5:c.559_560dupGG and FGF5:g.8193T>A and the known mutation FGF5:p.Cys95Phe explained the long-hair phenotype of all Afghan hounds analysed. An FGF5:c.556_571del16 mutation was found in one longhaired Eurasier. All long-hair-associated mutations follow a recessive mode of inheritance, and allelic heterogeneity was a common finding in breeds other than Akita. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

An Intronic Polymorphism in couch potato Is Not Distributed Clinally in European Drosophila melanogaster Populations nor Does It Affect Diapause Inducibility.

PubMed

Zonato, Valeria; Fedele, Giorgio; Kyriacou, Charalambos P

2016-01-01

couch potato (cpo) encodes an RNA binding protein that has been reported to be expressed in the peripheral and central nervous system of embryos, larvae and adults, including the major endocrine organ, the ring gland. A polymorphism in the D. melanogaster cpo gene coding region displays a latitudinal cline in frequency in North American populations, but as cpo lies within the inversion In(3R)Payne, which is at high frequencies and itself shows a strong cline on this continent, interpretation of the cpo cline is not straightforward. A second downstream SNP in strong linkage disequilibrium with the first has been claimed to be primarily responsible for the latitudinal cline in diapause incidence in USA populations.Here, we investigate the frequencies of these two cpo SNPs in populations of Drosophila throughout continental Europe. The advantage of studying cpo variation in Europe is the very low frequency of In(3R)Payne, which we reveal here, does not appear to be clinally distributed. We observe a very different geographical scenario for cpo variation from the one in North America, suggesting that the downstream SNP does not play a role in diapause. In an attempt to verify whether the SNPs influence diapause we subsequently generated lines with different combinations of the two cpo SNPs on known timeless (tim) genetic backgrounds, because polymorphism in the clock gene tim plays a significant role in diapause inducibility. Our results reveal that the downstream cpo SNP does not seem to play any role in diapause induction in European populations in contrast to the upstream coding cpo SNP. Consequently, all future diapause studies on strains of D. melanogaster should initially determine their tim and cpo status.

Two new mutations in the 3' coding region of the glycogen debranching enzyme in a glycogen storage disease type IIIa Ashkenazi Jewish patient.

PubMed

Parvari, R; Shen, J; Hershkovitz, E; Chen, Y T; Moses, S W

1998-04-01

Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen debranching enzyme (AGL). We report the finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both mutations are insertion of an adenine into a stretch of 8 adenines towards the 3' end of the coding region, one at position 3904 (3904insA) in exon 30, the second at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and premature terminations of the glycogen debranching enzyme, the first causing a frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408 of the total of 1532. These mutations demonstrate the importance of the 125 amino acids at the carboxy-terminus of the debrancher enzyme for its activity and support the suggestion that the putative glycogen binding domain is located in the carboxy-terminus of the AGL. The mutations cause distinctive single-strand conformation polymorphism (SSCP) patterns enabling easy detection.

Functional characterization of naturally occurring melittin peptide isoforms in two honey bee species, Apis mellifera and Apis cerana.

PubMed

Park, Doori; Jung, Je Won; Lee, Mi Ok; Lee, Si Young; Kim, Boyun; Jin, Hye Jun; Kim, Jiyoung; Ahn, Young-Joon; Lee, Ki Won; Song, Yong Sang; Hong, Seunghun; Womack, James E; Kwon, Hyung Wook

2014-03-01

Insect-derived antimicrobial peptides (AMPs) have diverse effects on antimicrobial properties and pharmacological activities such as anti-inflammation and anticancer properties. Naturally occurring genetic polymorphism have a direct and/or indirect influence on pharmacological effect of AMPs, therefore information on single nucleotide polymorphism (SNP) occurring in natural AMPs provides an important clue to therapeutic applications. Here we identified nucleotide polymorphisms in melittin gene of honey bee populations, which is one of the potent AMP in bee venoms. We found that the novel SNP of melittin gene exists in these two honey bee species, Apis mellifera and Apis cerana. Nine polymorphisms were identified within the coding region of the melittin gene, of which one polymorphism that resulted in serine (Ser) to asparagine (Asp) substitution that can potentially effect on biological activities of melittin peptide. Serine-substituted melittin (Mel-S) showed more cytotoxic effect than asparagine-substituted melittin (Mel-N) against E. coli. Also, Mel-N and Mel-S had different inhibitory effects on the production of inflammatory factors such as IL-6 and TNF-α in BV-2 cells. Moreover, Mel-S showed stronger cytotoxic activities than Mel-N peptide against two human ovarian cancer cell lines. Using carbon nanotube-based transistor, we here characterized that Mel-S interacted with small unilamellar liposomes more strongly than Mel-N. Taken together, our present study demonstrates that there exist different characteristics of the gene frequency and the biological activities of the melittin peptide in two honey bee species, Apis mellifera and A. cerana. Copyright © 2014 Elsevier Inc. All rights reserved.

UBXN1 polymorphism and its expression in porcine M. longissimus dorsi are associated with water holding capacity.

PubMed

Loan, Huynh Thi Phuong; Muráni, Eduard; Maak, Steffen; Ponsuksili, Siriluck; Wimmers, Klaus

2014-03-01

The UBX domain containing protein 1-like gene (UBXN1) promotes the protein degradation that affects meat quality, in particular traits related to water holding capacity. The aim of our study was to identify UBXN1 polymorphisms and to analyse their association with meat quality traits. Moreover, the relationship of UBXN1 polymorphisms and its transcript abundance as well as the link between UBXN1 expression and water holding capacity were addressed. Pigs of the breed German landrace (GL) and the commercial crossbreed of Pietrain × [German large white × GL] (PiF1) were used for this study. In GL, the novel SNP c.355 C > T showed significant association with conductivity and drip loss (P ≤ 0.05). Another SNP at nt 674 of the coding sequence [SNP c.674C>T (p.Thr225Ile)] was associated with drip loss (P ≤ 0.05) and pH1 (P ≤ 0.1). In PiF1, the SNP UBXN1 c.674C>T was associated with conductivity (P ≤ 0.01). Moreover, the haplotype combinations showed effects on conductivity within both commercial populations at P ≤ 0.1. In both populations, high expression of UBXN1 tended to decrease water holding capacity in the early post mortem period. The analysis of triangular relationship of UBXN1 polymorphism, transcript abundance, and water holding capacity evidences the existence of a causal polymorphism in cis-regulatory regions of UBXN1 that influences its expression.

Ty1-copia elements reveal diverse insertion sites linked to polymorphisms among flax (Linum usitatissimum L.) accessions.

PubMed

Galindo-González, Leonardo; Mhiri, Corinne; Grandbastien, Marie-Angèle; Deyholos, Michael K

2016-12-07

Initial characterization of the flax genome showed that Ty1-copia retrotransposons are abundant, with several members being recently inserted, and in close association with genes. Recent insertions indicate a potential for ongoing transpositional activity that can create genomic diversity among accessions, cultivars or varieties. The polymorphisms generated constitute a good source of molecular markers that may be associated with phenotype if the insertions alter gene activity. Flax, where accessions are bred mainly for seed nutritional properties or for fibers, constitutes a good model for studying the relationship of transpositional activity with diversification and breeding. In this study, we estimated copy number and used a type of transposon display known as Sequence-Specific Amplification Polymorphisms (SSAPs), to characterize six families of Ty1-copia elements across 14 flax accessions. Polymorphic insertion sites were sequenced to find insertions that could potentially alter gene expression, and a preliminary test was performed with selected genes bearing transposable element (TE) insertions. Quantification of six families of Ty1-copia elements indicated different abundances among TE families and between flax accessions, which suggested diverse transpositional histories. SSAPs showed a high level of polymorphism in most of the evaluated retrotransposon families, with a trend towards higher levels of polymorphism in low-copy number families. Ty1-copia insertion polymorphisms among cultivars allowed a general distinction between oil and fiber types, and between spring and winter types, demonstrating their utility in diversity studies. Characterization of polymorphic insertions revealed an overwhelming association with genes, with insertions disrupting exons, introns or within 1 kb of coding regions. A preliminary test on the potential transcriptional disruption by TEs of four selected genes evaluated in three different tissues, showed one case of significant impact of the insertion on gene expression. We demonstrated that specific Ty1-copia families have been active since breeding commenced in flax. The retrotransposon-derived polymorphism can be used to separate flax types, and the close association of many insertions with genes defines a good source of potential mutations that could be associated with phenotypic changes, resulting in diversification processes.

Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation.

PubMed

Revathidevi, Sundaramoorthy; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Rajkumar, Kottayasamy Seenivasagam; Ramani, Rajendran; Rajaraman, Ramamurthy; Ajay, Chandrasekar; Munirajan, Arasambattu Kannan

2016-09-01

Breast cancer and cervical cancer are the leading causes of death in women worldwide as well as in India, whilst oral cancer is the top most common cancer among Asian especially in Indian men in terms of both incidence and mortality rate. Genetic factors determining the predisposition to cancer are being explored to identify the signature genetic variations associated with these cancers. Recently, a germline deletion polymorphism in APOBEC3 gene cluster which completely deletes APOBEC3B coding region has been studied for its association with cancer risk. We screened the germline deletion polymorphism in 409 cancer patients (224 breast cancer, 88 cervical cancer and 97 oral cancer samples), 478 controls and 239 cervical cancer tissue DNAs of South Indian origin. The results suggest that the APOBEC3A/3B deletion polymorphism is not significantly associated with cancer risk in our study population (OR 0.739, 95 % CI, p value 0.91457). Considering the viral restriction property of APOBEC3s, we also screened cervical cancer tissue DNAs for the human papilloma virus infection. We observed a gradual increase in the frequency of HPV16 infection from AA/BB cases (66.86 %) to AA/-- cases (71.43) which signifies the impact of this deletion polymorphism in HPV infection. In addition, we performed in silico analysis to understand the effect of this polymorphism on miRNA regulation of the APOBEC3A/3B fusion transcript. Only 8 APOBEC3B targeting miRNAs were observed to regulate the fusion transcript of which miR-34b-3p and miR-138-5p were found to be frequently downregulated in cancers suggesting miRNA-mediated deregulation of APOBEC3A expression in cancer patients harbouring this particular deletion polymorphism.

An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster

PubMed Central

Glaser-Schmitt, Amanda; Duchen, Pablo; Parsch, John

2016-01-01

Insertions and deletions (indels) are a major source of genetic variation within species and may result in functional changes to coding or regulatory sequences. In this study we report that an indel polymorphism in the 3’ untranslated region (UTR) of the metallothionein gene MtnA is associated with gene expression variation in natural populations of Drosophila melanogaster. A derived allele of MtnA with a 49-bp deletion in the 3' UTR segregates at high frequency in populations outside of sub-Saharan Africa. The frequency of the deletion increases with latitude across multiple continents and approaches 100% in northern Europe. Flies with the deletion have more than 4-fold higher MtnA expression than flies with the ancestral sequence. Using reporter gene constructs in transgenic flies, we show that the 3' UTR deletion significantly contributes to the observed expression difference. Population genetic analyses uncovered signatures of a selective sweep in the MtnA region within populations from northern Europe. We also find that the 3’ UTR deletion is associated with increased oxidative stress tolerance. These results suggest that the 3' UTR deletion has been a target of selection for its ability to confer increased levels of MtnA expression in northern European populations, likely due to a local adaptive advantage of increased oxidative stress tolerance. PMID:27120580

A comprehensive study of small non-frameshift insertions/deletions in proteins and prediction of their phenotypic effects by a machine learning method (KD4i)

PubMed Central

2014-01-01

Background Small insertion and deletion polymorphisms (Indels) are the second most common mutations in the human genome, after Single Nucleotide Polymorphisms (SNPs). Recent studies have shown that they have significant influence on genetic variation by altering human traits and can cause multiple human diseases. In particular, many Indels that occur in protein coding regions are known to impact the structure or function of the protein. A major challenge is to predict the effects of these Indels and to distinguish between deleterious and neutral variants. When an Indel occurs within a coding region, it can be either frameshifting (FS) or non-frameshifting (NFS). FS-Indels either modify the complete C-terminal region of the protein or result in premature termination of translation. NFS-Indels insert/delete multiples of three nucleotides leading to the insertion/deletion of one or more amino acids. Results In order to study the relationships between NFS-Indels and Mendelian diseases, we characterized NFS-Indels according to numerous structural, functional and evolutionary parameters. We then used these parameters to identify specific characteristics of disease-causing and neutral NFS-Indels. Finally, we developed a new machine learning approach, KD4i, that can be used to predict the phenotypic effects of NFS-Indels. Conclusions We demonstrate in a large-scale evaluation that the accuracy of KD4i is comparable to existing state-of-the-art methods. However, a major advantage of our approach is that we also provide the reasons for the predictions, in the form of a set of rules. The rules are interpretable by non-expert humans and they thus represent new knowledge about the relationships between the genotype and phenotypes of NFS-Indels and the causative molecular perturbations that result in the disease. PMID:24742296

Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in affected women of European ancestry.

PubMed

Mutharasan, Priscilla; Galdones, Eugene; Peñalver Bernabé, Beatriz; Garcia, Obed A; Jafari, Nadereh; Shea, Lonnie D; Woodruff, Teresa K; Legro, Richard S; Dunaif, Andrea; Urbanek, Margrit

2013-01-01

A previous genome-wide association study in Chinese women with polycystic ovary syndrome (PCOS) identified a region on chromosome 2p16.3 encoding the LH/choriogonadotropin receptor (LHCGR) and FSH receptor (FSHR) genes as a reproducible PCOS susceptibility locus. The objective of the study was to determine the role of the LHCGR and/or FSHR gene in the etiology of PCOS in women of European ancestry. This was a genetic association study in a European ancestry cohort of women with PCOS. The study was conducted at an academic medical center. Participants in the study included 905 women with PCOS diagnosed by National Institutes of Health criteria and 956 control women. We genotyped 94 haplotype-tagging single-nucleotide polymorphisms and two coding single-nucleotide polymorphisms mapping to the coding region of LHCGR and FSHR plus 20 kb upstream and downstream of the genes and test for association in the case control cohort and for association with nine quantitative traits in the women with PCOS. We found strong evidence for an association of PCOS with rs7562215 (P = 0.0037) and rs10495960 (P = 0.0046). Although the marker with the strongest association in the Chinese PCOS genome-wide association study (rs13405728) was not informative in the European populations, we identified and genotyped three markers (rs35960650, rs2956355, and rs7562879) within 5 kb of rs13405728. Of these, rs7562879 was nominally associated with PCOS (P = 0.020). The strongest evidence for association mapping to FSHR was observed with rs1922476 (P = 0.0053). Furthermore, markers with the FSHR gene region were associated with FSH levels in women with PCOS. Fine mapping of the chromosome 2p16.3 Chinese PCOS susceptibility locus in a European ancestry cohort provides evidence for association with two independent loci and PCOS. The gene products LHCGR and FSHR therefore are likely to be important in the etiology of PCOS, regardless of ethnicity.

SNPs of bovine HGF gene and their association with growth traits in Nanyang cattle.

PubMed

Cai, Hanfang; Lan, Xianyong; Li, Aimin; Zhou, Yang; Sun, Jiajie; Lei, Chuzhao; Zhang, Chunlei; Chen, Hong

2013-10-01

Hepatocyte growth factor (HGF) is one of the multifunctional cell factors that regulates cellular proliferation, motility and morphogenesis in mammalians. And its medical research has deep significance. In this paper, polymorphisms of HGF gene were investigated in 1433 health and irrelated Chinese cattle by PCR-RFLP and DNA sequencing approach. Ten novel Single nucleotide polymorphisms (SNPs) were identified, which included one missense mutation, g.72801G>A in the coding region, and the others in the intron. Association analysis between four of them, g.288T>C, g.72801G>A, g.77172G>T, and g.77408T>G, and growth traits in Nanyang, were performed. The results indicated that SNPs within bovine HGF gene were significantly associated with growth traits. Phylogenetic analysis showed that the genetic background of Caoyuan Red cattle was different from the others in the tested breeds. The findings will provide a background for application of bovine HGF gene in the selection program in Chinese cattle. Copyright © 2013 Elsevier Ltd. All rights reserved.

G20210A prothrombin gene mutation identified in patients with venous leg ulcers.

PubMed

Jebeleanu, G; Procopciuc, L

2001-01-01

The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients with deep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.

5HT-2C receptor polymorphism in suicide victims. Association studies in German and Slavic populations.

PubMed

Stefulj, Jasminka; Büttner, Andreas; Kubat, Milovan; Zill, Peter; Balija, Melita; Eisenmenger, Wolfgang; Bondy, Brigitta; Jernej, Branimir

2004-08-01

Sustainable observations suggest that suicidal behaviour by itself may have biological correlates, among which those related to the serotonergic synapse hold the key position. Based on the association of suicide and serotonergic dysfunction, it was proposed that genetic mechanisms affecting suicidal behaviour could be related to the alterations of the genes encoding the elements of 5HT synapse. The present study tested the association of the polymorphism in the serotonin 2C (5HT-2C) receptor coding region (Cys23Ser) with suicide commitment. Study was based on two independent samples, one of German (284 suicide victims versus 297 controls) and other of Slavic/Croatian (118 suicide victims versus 275 controls) ethnicity. No significant differences in allele or genotype frequencies between victims and controls were demonstrated. Results did not provide supporting evidence for the potential involvement of the investigated variants of 5HT-2C receptor in the susceptibility to suicide.

Desmoglein 4 diversity and correlation analysis with coat color in goat.

PubMed

E, G X; Zhao, Y J; Ma, Y H; Cao, G L; He, J N; Na, R S; Zhao, Z Q; Jiang, C D; Zhang, J H; Arlvd, S; Chen, L P; Qiu, X Y; Hu, W; Huang, Y F

2016-03-04

Desmoglein 4 (DSG4) has an important role in the development of wool traits in domestic animals. The full-length DSG4 gene, which contains 3918 bp, a complete open-reading-frame, and encodes a 1040-amino acid protein, was amplified from Liaoning cashmere goat. The sequence was compared with that of DSG4 from other animals and the results show that the DSG4 coding region is consistent with interspecies conservation. Thirteen single-nucleotide polymorphisms (SNPs) were identified in a highly variable region of DSG4, and one SNP (M-1, G>T) was significantly correlated with white and black coat color in goat. Haplotype distribution of the highly variable region of DSG4 was assessed in 179 individuals from seven goat breeds to investigate its association with coat color and its differentiation among populations. However, the lack of a signature result indicates DGS4 haplotypes related with the color of goat coat.

Porcine MYF6 gene: sequence, homology analysis, and variation in the promoter region.

PubMed

Wyszyńska-Koko, J; Kurył, J

2004-01-01

MYF6 gene codes for the bHLH transcription factor belonging to MyoD family. Its expression accompanies the processes of differentiation and maturation of myotubes during embriogenesis and continues on a relatively high level after birth, affecting the muscle phenotype. The porcine MYF6 gene was amplified and sequenced and compared with MYF6 gene sequences of other species. The amino acid sequence was deduced and an interspecies homology analysis was performed. Myf-6 protein shows a high conservation among species of 99 and 97% identity when comparing pig with cow and human, respectively, and of 93% when comparing pig with mouse and rat. The single nucleotide polymorphism (SNP) was revealed within the promoter region, which appeared to be T --> C transition recognized by a MspI restriction enzyme.

Polymorphisms of 20 regulatory proteins between Mycobacterium tuberculosis and Mycobacterium bovis.

PubMed

Bigi, María M; Blanco, Federico Carlos; Araújo, Flabio R; Thacker, Tyler C; Zumárraga, Martín J; Cataldi, Angel A; Soria, Marcelo A; Bigi, Fabiana

2016-08-01

Mycobacterium tuberculosis and Mycobacterium bovis are responsible for tuberculosis in humans and animals, respectively. Both species are closely related and belong to the Mycobacterium tuberculosis complex (MTC). M. tuberculosis is the most ancient species from which M. bovis and other members of the MTC evolved. The genome of M. bovis is over >99.95% identical to that of M. tuberculosis but with seven deletions ranging in size from 1 to 12.7 kb. In addition, 1200 single nucleotide mutations in coding regions distinguish M. bovis from M. tuberculosis. In the present study, we assessed 75 M. tuberculosis genomes and 23 M. bovis genomes to identify non-synonymous mutations in 202 coding sequences of regulatory genes between both species. We identified species-specific variants in 20 regulatory proteins and confirmed differential expression of hypoxia-related genes between M. bovis and M. tuberculosis. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Transcriptome-wide single nucleotide polymorphisms (SNPs) for abalone (Haliotis midae): validation and application using GoldenGate medium-throughput genotyping assays.

PubMed

Bester-Van Der Merwe, Aletta; Blaauw, Sonja; Du Plessis, Jana; Roodt-Wilding, Rouvay

2013-09-23

Haliotis midae is one of the most valuable commercial abalone species in the world, but is highly vulnerable, due to exploitation, habitat destruction and predation. In order to preserve wild and cultured stocks, genetic management and improvement of the species has become crucial. Fundamental to this is the availability and employment of molecular markers, such as microsatellites and single nucleotide (SNPs). Transcriptome sequences generated through sequencing-by-synthesis technology were utilized for the in vitro and in silico identification of 505 putative SNPs from a total of 316 selected contigs. A subset of 234 SNPs were further validated and characterized in wild and cultured abalone using two Illumina GoldenGate genotyping assays. Combined with VeraCode technology, this genotyping platform yielded a 65%-69% conversion rate (percentage polymorphic markers) with a global genotyping success rate of 76%-85% and provided a viable means for validating SNP markers in a non-model species. The utility of 31 of the validated SNPs in population structure analysis was confirmed, while a large number of SNPs (174) were shown to be informative and are, thus, good candidates for linkage map construction. The non-synonymous SNPs (50) located in coding regions of genes that showed similarities with known proteins will also be useful for genetic applications, such as the marker-assisted selection of genes of relevance to abalone aquaculture.

Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson's disease.

PubMed

Zhao, Na; Xiao, Jianqiu; Zheng, Zhiyong; Fei, Guoqiang; Zhang, Feng; Jin, Lirong; Zhong, Chunjiu

2015-04-01

Our previous studies have demonstrated that ceruloplasmin (CP) dysmetabolism is correlated with Parkinson's disease (PD). However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene (both promoter and coding regions) were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms (SNPs). High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/iron metabolism. The frequencies of eight SNPs (one intronic SNP and seven promoter SNPs of the CP gene) and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

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.

Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae).

PubMed

Weitemier, Kevin; Straub, Shannon C K; Fishbein, Mark; Liston, Aaron

2015-01-01

Despite knowledge that concerted evolution of high-copy loci is often imperfect, studies that investigate the extent of intragenomic polymorphisms and comparisons across a large number of species are rarely made. We present a bioinformatic pipeline for characterizing polymorphisms within an individual among copies of a high-copy locus. Results are presented for nuclear ribosomal DNA (nrDNA) across the milkweed genus, Asclepias. The 18S-26S portion of the nrDNA cistron of Asclepias syriaca served as a reference for assembly of the region from 124 samples representing 90 species of Asclepias. Reads were mapped back to each individual's consensus and at each position reads differing from the consensus were tallied using a custom perl script. Low frequency polymorphisms existed in all individuals (mean = 5.8%). Most nrDNA positions (91%) were polymorphic in at least one individual, with polymorphic sites being less frequent in subunit regions and loops. Highly polymorphic sites existed in each individual, with highest abundance in the "noncoding" ITS regions. Phylogenetic signal was present in the distribution of intragenomic polymorphisms across the genus. Intragenomic polymorphisms in nrDNA are common in Asclepias, being found at higher frequency than any other study to date. The high and variable frequency of polymorphisms across species highlights concerns that phylogenetic applications of nrDNA may be error-prone. The new analytical approach provided here is applicable to other taxa and other high-copy regions characterized by low coverage genome sequencing (genome skimming).

Distribution and linkage disequilibrium analysis of polymorphisms of GH1 gene in different populations of pigs associated with body size.

PubMed

Cheng, Yunyun; Liu, Songcai; Su, Dan; Lu, Chao; Zhang, Xin; Wu, Qingyan; Li, Siming; Fu, Haoyu; Yu, Hao; Hao, Linlin

2016-03-01

Growth hormone (GH) has been considered as a candidate gene for growth and body size in pigs. In this study, polymorphisms of the GH1 gene were evaluated for associations with body size traits in 190 pig individuals. Seventeen single-nucleotide polymorphisms (SNPs) were identified in GH1 gene of the large pig breeds and miniature pig breeds using direct sequencing and genotyped by allele-specific PCR approach. Notably, six (g.237A>G, g.283T>C, g.309A>G, g.318A>G, g.540A>G and g.544A>G) of them were significantly associated with body size, of which three loci (g.283T>C, g.309A>G, g.318A>G) located in the signal-peptide coding region of GH1 gene compose a CGG haplotype for large pigs and TAA haplotype for miniature pigs (P <0.001), two loci (g.540A>G and g.544A>G) located in the second intron of GH1 gene compose a GG haplotype for large pigs and AA haplotype for miniature pigs (P < 0.001). Our results demonstrate that these SNPs in GH1 gene are associated with the body size of pigs providing genetic basis for pig breeding with the improved economic benefits.

Complete chloroplast genome sequence of a major allogamous forage species, perennial ryegrass (Lolium perenne L.).

PubMed

Diekmann, Kerstin; Hodkinson, Trevor R; Wolfe, Kenneth H; van den Bekerom, Rob; Dix, Philip J; Barth, Susanne

2009-06-01

Lolium perenne L. (perennial ryegrass) is globally one of the most important forage and grassland crops. We sequenced the chloroplast (cp) genome of Lolium perenne cultivar Cashel. The L. perenne cp genome is 135 282 bp with a typical quadripartite structure. It contains genes for 76 unique proteins, 30 tRNAs and four rRNAs. As in other grasses, the genes accD, ycf1 and ycf2 are absent. The genome is of average size within its subfamily Pooideae and of medium size within the Poaceae. Genome size differences are mainly due to length variations in non-coding regions. However, considerable length differences of 1-27 codons in comparison of L. perenne to other Poaceae and 1-68 codons among all Poaceae were also detected. Within the cp genome of this outcrossing cultivar, 10 insertion/deletion polymorphisms and 40 single nucleotide polymorphisms were detected. Two of the polymorphisms involve tiny inversions within hairpin structures. By comparing the genome sequence with RT-PCR products of transcripts for 33 genes, 31 mRNA editing sites were identified, five of them unique to Lolium. The cp genome sequence of L. perenne is available under Accession number AM777385 at the European Molecular Biology Laboratory, National Center for Biotechnology Information and DNA DataBank of Japan.

Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.

PubMed

Jacobo, Sarah Melissa P; Deangelis, Margaret M; Kim, Ivana K; Kazlauskas, Andrius

2013-05-01

Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD.

Transposon Variants and Their Effects on Gene Expression in Arabidopsis

PubMed Central

Wang, Xi; Weigel, Detlef; Smith, Lisa M.

2013-01-01

Transposable elements (TEs) make up the majority of many plant genomes. Their transcription and transposition is controlled through siRNAs and epigenetic marks including DNA methylation. To dissect the interplay of siRNA–mediated regulation and TE evolution, and to examine how TE differences affect nearby gene expression, we investigated genome-wide differences in TEs, siRNAs, and gene expression among three Arabidopsis thaliana accessions. Both TE sequence polymorphisms and presence of linked TEs are positively correlated with intraspecific variation in gene expression. The expression of genes within 2 kb of conserved TEs is more stable than that of genes next to variant TEs harboring sequence polymorphisms. Polymorphism levels of TEs and closely linked adjacent genes are positively correlated as well. We also investigated the distribution of 24-nt-long siRNAs, which mediate TE repression. TEs targeted by uniquely mapping siRNAs are on average farther from coding genes, apparently because they more strongly suppress expression of adjacent genes. Furthermore, siRNAs, and especially uniquely mapping siRNAs, are enriched in TE regions missing in other accessions. Thus, targeting by uniquely mapping siRNAs appears to promote sequence deletions in TEs. Overall, our work indicates that siRNA–targeting of TEs may influence removal of sequences from the genome and hence evolution of gene expression in plants. PMID:23408902

Direct Detection of Insertion/Deletion Polymorphisms in an Autosomal Region by Analyzing High-Density Markers in Individual Spermatozoa

PubMed Central

Pramanik, Sreemanta; Li, Honghua

2002-01-01

Direct polymerase chain reaction (PCR) detection of insertion/deletion (indel) polymorphisms requires sample homozygosity. For the indel polymorphisms that have the deletion allele with a relatively low frequency in the autosomal regions, direct PCR detection becomes difficult or impossible. The present study is, to our knowledge, the first designed to directly detect indel polymorphisms in a human autosomal region (i.e., the immunoglobulin VH region), through use of single haploid sperm cells as subjects. Unique marker sequences (n=32), spaced at ∼5-kb intervals, were selected near the 3′ end of the VH region. A two-round multiplex PCR protocol was used to amplify these sequences from single sperm samples from nine unrelated healthy donors. The parental haplotypes of the donors were determined by examining the presence or absence of these markers. Seven clustered markers in 6 of the 18 haplotypes were missing and likely represented a 35–40-kb indel polymorphism. The genotypes of the donors, with respect to this polymorphism, perfectly matched the expectation under Hardy-Weinberg equilibrium. Three VH gene segments, of which two are functional, are affected by this polymorphism. According to these results, >10% of individuals in the human population may not have these gene segments in their genome, and ∼44% may have only one copy of these gene segments. The biological impact of this polymorphism would be very interesting to study. The approach used in the present study could be applied to understand the physical structure and diversity of all other autosomal regions. PMID:12442231

Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: no impact of chitotriosidase and mannose-binding lectin polymorphisms.

PubMed

Klostergaard, Anja; Steffensen, Rudi; Møller, Jens K; Peterslund, Niels; Juhl-Christensen, Caroline; Mølle, Ingolf

2010-07-01

Infections after chemotherapy often cause significant morbidity in patients with acute myeloid leukaemia (AML). Chitotriosidase (CHIT) and mannose-binding lectin (MBL) are part of the innate immune system. Polymorphism in the CHIT-coding gene (CHIT1) may be associated with Gram-negative sepsis in children with AML, and polymorphism in the MBL-coding gene (MBL2) seems to modify the risk of infections in several patient groups. The purpose of this study was to investigate the possible associations between polymorphisms in CHIT1, MBL2 and sepsis in adult patients treated with high-dose chemotherapy for AML. We included 190 patients treated with 526 cycles of chemotherapy. The follow-up period was 6 months from the diagnosis of AML. Prophylactic antibiotics were not used. We identified 604 febrile episodes with 246 episodes of sepsis. Thirty-two patients (17%) either died from infection or infection was a major concomitant factor for death. No significant associations between CHIT1 polymorphism and sepsis (P = 0.85) or death caused by sepsis (P = 0.14) were found. Furthermore, no significant associations between MBL2 polymorphism and sepsis (P = 0.76) or death caused by sepsis (P = 0.24) were observed. The severe and long-lasting neutropenia and mucositis after chemotherapy may explain why the MBL system does not protect against sepsis in patients with AML. Replacement therapy with recombinant MBL is not likely to decrease the risk of sepsis in patients with AML.

Screening for rare variants in the PNPLA3 gene in obese liver biopsy patients.

PubMed

Zegers, Doreen; Verrijken, An; Francque, Sven; de Freitas, Fenna; Beckers, Sigri; Aerts, Evi; Ruppert, Martin; Hubens, Guy; Michielsen, Peter; Van Hul, Wim; Van Gaal, Luc F

2016-12-01

Previous research has clearly implicated the PNPLA3 gene in the etiology of nonalcoholic fatty liver disease as a polymorphism in the gene was found to be robustly associated to the disease. However, data on the involvement of rare PNPLA3 variants in the development of nonalcoholic fatty liver disease (NAFLD) is currently limited. Therefore, we performed an extensive mutation analysis study on a cohort of obese liver biopsy patients to determine PNPLA3 variation and its correlation with fatty liver disease. We screened the entire coding region of the PNPLA3 gene in DNA samples of 393 obese liver biopsy patients with varying degrees of fatty liver disease. Mutation analysis was performed by high-resolution melting curve analysis in combination with direct sequencing. We identified several common polymorphisms as well as one rare synonymous variant (c.867G>A rs139896256), one rare intronic variant (c.979+13C>T) and 3 nonsynonymous coding variants (p.A76T, p.A104V and p.T200M) in the PNPLA3 gene. In silico analysis indicated that the p.A104V variant will probably have no functional effect, whereas for the p.A76T and p.T200M variant a possible pathogenic effect is suggested. Overall, we showed that novel variants in PNPLA3 are very rare in our liver biopsy cohort, thereby indicating that their impact on the etiology of NAFLD is probably limited. Nevertheless, for the three rare coding variants that were identified in patients with advanced liver disease, further functional characterization will be essential to verify their potential disease causality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The importance of immune gene variability (MHC) in evolutionary ecology and conservation

PubMed Central

Sommer, Simone

2005-01-01

Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of adaptive genetic variability with respect to human impact and conservation, and implications for future studies. PMID:16242022

Genetic Predictors of Interindividual Variability in Hepatic CYP3A4 ExpressionS⃞

PubMed Central

Lamba, Vishal; Panetta, John C.; Strom, Stephen

2010-01-01

Variability in hepatic CYP3A4 cannot be explained by common CYP3A4 coding variants. We previously identified polymorphisms in pregnane X receptor (PXR) and ATP-binding cassette subfamily B member 1 (ABCB1) associated with CYP3A4 mRNA levels in small cohorts of human livers. However, the relative contributions of these genetic variations or of polymorphisms in other CYP3A4 regulators to variable CYP3A4 expression were not known. We phenotyped livers from white donors (n = 128) by quantitative real-time polymerase chain reaction for expression of CYP3A4, CYP3A5, and CYP3A7 and nine transcriptional regulators, coactivators, and corepressors. We resequenced hepatic nuclear factor-3-β (HNF3β, FoxA2), HNF4α, HNF3γ (FoxA3), nuclear receptor corepressor 2 (NCoR2), and regions of the CYP3A4 promoter and genotyped informative single-nucleotide polymorphisms in PXR and ABCB1 in the same livers. CYP3A4 mRNA was positively correlated with PXR and FoxA2 and negatively correlated with NCoR2 mRNA. A common silent polymorphism and a polymorphic trinucleotide (CCT) repeat in FoxA2 were associated with CYP3A4 expression. The transcriptional activity of the FoxA2 polymorphic CCT repeat alleles (wild-type, n = 14 and variant, n = 13, 15, and 19) when assayed by luciferase reporter transactivation assays was greatest for the wild-type repeat, with deviations from this number having decreased transcriptional activity. This corresponded with higher expression of FoxA2 mRNA and its targets PXR and CYP3A4 in human livers with (CCT) n = 14 genotypes. Multiple linear regression analysis was used to quantify the contributions of selected genetic polymorphisms to variable CYP3A4 expression. This approach identified sex and polymorphisms in FoxA2, HNF4α, FoxA3, PXR, ABCB1, and the CYP3A4 promoter that together explained as much as 24.6% of the variation in hepatic CYP3A4 expression. PMID:19934400

Effect of paraoxonase 1 gene polymorphisms on clinical course of Henoch-Schönlein purpura.

PubMed

Yilmaz, Alev; Emre, Sevinc; Agachan, Bedia; Bilge, Ilmay; Yilmaz, Hulya; Ergen, Arzu; Isbir, Turgay; Sirin, Aydan

2009-01-01

Henoch-Schönlein purpura (HSP) is a systemic vasculitis; its pathogenesis is still unknown. Oxidative stress may play a role in the pathogenesis of HSP. Paraoxonase1 (PON1) is an antioxidant enzyme. Two polymorphisms have been defined in the coding region of the PON1 gene, Q/R192 and L/M55. In the present study, we aimed to investigate the effect of PON1 gene polymorphisms on the course and renal involvement of HSP in Turkish children. Forty-six patients with HSP were compared with 34 healthy children regarding the distribution of PON1 polymorphisms. PON1 Q/R192 genotype distribution was 58.6% QQ, 32.6% QR and 8.8% RR in the HSP group and 14.3% QQ, 50% QR and 35.7% RR in the control group. The frequency of QQ genotype was higher in the HSP group, and the presence of QQ genotype increased the risk by 3.42-fold for developing HSP (p=0.000, Fisher exact test; odds ratio [OR] = 2.048; 95% confidence interval [95% CI], 1.396-3.00). PON1 L/M55 genotype distribution was 50% LL, 43.5% LM and 6.5% MM in the HSP group and 48% LL, 26% LM and 26% MM in the control group. The frequency of MM genotype was lower in the HSP group, and the presence of MM genotype decreased the risk by 7.38-fold for developing HSP (p=0.009, Fisher exact test; OR=7.380, 95% CI, 1.474-36.953). PON1 polymorphisms may contribute to the pathogenesis and course of HSP, but we suggest that further investigations with larger patient groups are required to confirm our results.

Allelic association of a dopamine transporter gene polymorphism with antisocial behaviour in heroin-dependent patients.

PubMed

Gerra, Gilberto; Garofano, Luciano; Pellegrini, Caterina; Bosari, Silvano; Zaimovic, Amir; Moi, Gabriele; Avanzini, Paola; Talarico, Enrica; Gardini, Federica; Donnini, Claudia

2005-09-01

Polymorphism of a variable number of tandem repeats (VNTR) in the 3' untranslated region of exon 15 of the SLC6A3 gene, coding for the dopamine transporter (DAT), was analysed to test whether length variation contributes to differences in the individual susceptibility to aggressive - criminal behaviour and liability to heroin dependence. The repeat number of the DAT polymorphism was assessed in 125 healthy subjects and 104 heroin-dependent subjects (including 52 addicted individuals with violent behaviour and criminal records). There was no significant difference in the frequencies of genotypes and alleles between heroin-dependent subjects and control subjects. On the contrary, there was a significant difference between offenders and non-offenders, p = 0.004 and p = 0.002, respectively, among heroin-dependent subjects. No association was found between DAT polymorphism and history of suicide. Buss - Durkee Hostility Inventory (BDHI) mean total scores were significantly higher in heroin addicts than in controls (p < 0.001) and in antisocial - violent heroin addicts in comparison with addicted individuals without antisocial behaviour (p < 0.005). The regression analysis of BDHI subscales, performed to provide an estimate of the magnitude of any potential effect on the risk of aggressiveness associated with the variants in DAT VNTR, showed that the presence of the 9 - 9 genotype significantly increases the risk of irritability and direct aggressiveness more than six and 10 times with respect to the 9 - 10 genotype. Our findings suggest that the 9-repeat allele of the DAT polymorphism confers increased susceptibility to antisocial - violent behaviour and aggressiveness, rather than drug dependence per se in heroin-dependent males.

MBL-2 polymorphisms (codon 54 and Y-221X) and low MBL levels are associated with susceptibility to multi organ dysfunction in P. falciparum malaria in Odisha, India.

PubMed

Das, Bidyut K; Panda, Aditya K

2015-01-01

Mannose binding lectin, a plasma protein protects host from virus, bacteria, and parasites. Deficiency in MBL levels has been associated with susceptibility to various infectious diseases including P. falciparum malaria. Common MBL polymorphisms in promoter and coding regions are associated with decrease in plasma MBL levels or production of deformed MBL, respectively. In the present study, we hypothesized that MBL2 variants and plasma MBL levels could be associated with different clinical phenotypes of severe P. falciparum malaria. A hospital based study was conducted in eastern Odisha, India which is endemic to P. falciparum malaria. Common MBL-2 polymorphisms (codon 54, H-550L, and Y-221X) were typed in 336 cases of severe malaria (SM) [94 cerebral malaria (CM), 120 multi-organ dysfunction (MOD), 122 non-cerebral severe malaria (NCSM)] and 131 un-complicated malaria patients (UM). Plasma MBL levels were quantified by ELISA. Severe malaria patients displayed lower plasma levels of MBL compared to uncomplicated falciparum malaria. Furthermore, on categorization of severe malaria patients into various subtypes, plasma MBL levels were very low in MOD patients compared to other categories. Higher frequency of AB genotype and allele B was observed in MOD compared to UM (AB genotype: P = 0.006; B allele: P = 0.008). In addition, prevalence of YX genotype of MBL Y-221X polymorphism was also statistically more frequent in MOD case than UM (P = 0.009). The observations of the present study reveal that MBL-2 polymorphisms (codon 54 and Y-221X) and lower plasma MBL levels are associated with increased susceptibility to multi organ dysfunctions in P. falciparum malaria.

Semiconductor Whole Exome Sequencing for the Identification of Genetic Variants in Colombian Patients Clinically Diagnosed with Long QT Syndrome.

PubMed

Burgos, Mariana; Arenas, Alvaro; Cabrera, Rodrigo

2016-08-01

Inherited long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of QT interval and the risk of syncope, cardiac arrest, and sudden cardiac death. Genetic diagnosis of LQTS is critical in medical practice as results can guide adequate management of patients and distinguish phenocopies such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, extensive screening of large genomic regions is required in order to reliably identify genetic causes. Semiconductor whole exome sequencing (WES) is a promising approach for the identification of variants in the coding regions of most human genes. DNA samples from 21 Colombian patients clinically diagnosed with LQTS were enriched for coding regions using multiplex polymerase chain reaction (PCR) and subjected to WES using a semiconductor sequencer. Semiconductor WES showed mean coverage of 93.6 % for all coding regions relevant to LQTS at >10× depth with high intra- and inter-assay depth heterogeneity. Fifteen variants were detected in 12 patients in genes associated with LQTS. Three variants were identified in three patients in genes associated with CPVT. Co-segregation analysis was performed when possible. All variants were analyzed with two pathogenicity prediction algorithms. The overall prevalence of LQTS and CPVT variants in our cohort was 71.4 %. All LQTS variants previously identified through commercial genetic testing were identified. Standardized WES assays can be easily implemented, often at a lower cost than sequencing panels. Our results show that WES can identify LQTS-causing mutations and permits differential diagnosis of related conditions in a real-world clinical setting. However, high heterogeneity in sequencing depth and low coverage in the most relevant genes is expected to be associated with reduced analytical sensitivity.

Population-wide sampling of retrotransposon insertion polymorphisms using deep sequencing and efficient detection.

PubMed

Yu, Qichao; Zhang, Wei; Zhang, Xiaolong; Zeng, Yongli; Wang, Yeming; Wang, Yanhui; Xu, Liqin; Huang, Xiaoyun; Li, Nannan; Zhou, Xinlan; Lu, Jie; Guo, Xiaosen; Li, Guibo; Hou, Yong; Liu, Shiping; Li, Bo

2017-09-01

Active retrotransposons play important roles during evolution and continue to shape our genomes today, especially in genetic polymorphisms underlying a diverse set of diseases. However, studies of human retrotransposon insertion polymorphisms (RIPs) based on whole-genome deep sequencing at the population level have not been sufficiently undertaken, despite the obvious need for a thorough characterization of RIPs in the general population. Herein, we present a novel and efficient computational tool called Specific Insertions Detector (SID) for the detection of non-reference RIPs. We demonstrate that SID is suitable for high-depth whole-genome sequencing data using paired-end reads obtained from simulated and real datasets. We construct a comprehensive RIP database using a large population of 90 Han Chinese individuals with a mean ×68 depth per individual. In total, we identify 9342 recent RIPs, and 8433 of these RIPs are novel compared with dbRIP, including 5826 Alu, 2169 long interspersed nuclear element 1 (L1), 383 SVA, and 55 long terminal repeats. Among the 9342 RIPs, 4828 were located in gene regions and 5 were located in protein-coding regions. We demonstrate that RIPs can, in principle, be an informative resource to perform population evolution and phylogenetic analyses. Taking the demographic effects into account, we identify a weak negative selection on SVA and L1 but an approximately neutral selection for Alu elements based on the frequency spectrum of RIPs. SID is a powerful open-source program for the detection of non-reference RIPs. We built a non-reference RIP dataset that greatly enhanced the diversity of RIPs detected in the general population, and it should be invaluable to researchers interested in many aspects of human evolution, genetics, and disease. As a proof of concept, we demonstrate that the RIPs can be used as biomarkers in a similar way as single nucleotide polymorphisms. © The Authors 2017. Published by Oxford University Press.

Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae)

PubMed Central

Straub, Shannon C.K.; Fishbein, Mark; Liston, Aaron

2015-01-01

Despite knowledge that concerted evolution of high-copy loci is often imperfect, studies that investigate the extent of intragenomic polymorphisms and comparisons across a large number of species are rarely made. We present a bioinformatic pipeline for characterizing polymorphisms within an individual among copies of a high-copy locus. Results are presented for nuclear ribosomal DNA (nrDNA) across the milkweed genus, Asclepias. The 18S-26S portion of the nrDNA cistron of Asclepias syriaca served as a reference for assembly of the region from 124 samples representing 90 species of Asclepias. Reads were mapped back to each individual’s consensus and at each position reads differing from the consensus were tallied using a custom perl script. Low frequency polymorphisms existed in all individuals (mean = 5.8%). Most nrDNA positions (91%) were polymorphic in at least one individual, with polymorphic sites being less frequent in subunit regions and loops. Highly polymorphic sites existed in each individual, with highest abundance in the “noncoding” ITS regions. Phylogenetic signal was present in the distribution of intragenomic polymorphisms across the genus. Intragenomic polymorphisms in nrDNA are common in Asclepias, being found at higher frequency than any other study to date. The high and variable frequency of polymorphisms across species highlights concerns that phylogenetic applications of nrDNA may be error-prone. The new analytical approach provided here is applicable to other taxa and other high-copy regions characterized by low coverage genome sequencing (genome skimming). PMID:25653903

Presence of tannins in sorghum grains is conditioned by different natural alleles of Tannin1

PubMed Central

Wu, Yuye; Li, Xianran; Xiang, Wenwen; Zhu, Chengsong; Lin, Zhongwei; Wu, Yun; Li, Jiarui; Pandravada, Satchidanand; Ridder, Dustan D.; Bai, Guihua; Wang, Ming L.; Trick, Harold N.; Bean, Scott R.; Tuinstra, Mitchell R.; Tesso, Tesfaye T.; Yu, Jianming

2012-01-01

Sorghum, an ancient old-world cereal grass, is the dietary staple of over 500 million people in more than 30 countries in the tropics and semitropics. Its C4 photosynthesis, drought resistance, wide adaptation, and high nutritional value hold the promise to alleviate hunger in Africa. Not present in other major cereals, such as rice, wheat, and maize, condensed tannins (proanthocyanidins) in the pigmented testa of some sorghum cultivars have been implicated in reducing protein digestibility but recently have been shown to promote human health because of their high antioxidant capacity and ability to fight obesity through reduced digestion. Combining quantitative trait locus mapping, meta-quantitative trait locus fine-mapping, and association mapping, we showed that the nucleotide polymorphisms in the Tan1 gene, coding a WD40 protein, control the tannin biosynthesis in sorghum. A 1-bp G deletion in the coding region, causing a frame shift and a premature stop codon, led to a nonfunctional allele, tan1-a. Likewise, a different 10-bp insertion resulted in a second nonfunctional allele, tan1-b. Transforming the sorghum Tan1 ORF into a nontannin Arabidopsis mutant restored the tannin phenotype. In addition, reduction in nucleotide diversity from wild sorghum accessions to landraces and cultivars was found at the region that codes the highly conserved WD40 repeat domains and the C-terminal region of the protein. Genetic research in crops, coupled with nutritional and medical research, could open the possibility of producing different levels and combinations of phenolic compounds to promote human health. PMID:22699509

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

PubMed

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

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

Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.

The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies havemore » found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.« less

LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women.

PubMed

Giroux, Sylvie; Elfassihi, Latifa; Cardinal, Guy; Laflamme, Nathalie; Rousseau, François

2007-05-01

Bone mineral density has a strong genetic component but it is also influenced by environmental factors making it a complex trait to study. LRP5 gene was previously shown to be involved in rare diseases affecting bone mass. Mutations associated with gain-of-function were described as well as loss-of-function mutations. Following this discovery, many frequent LRP5 polymorphisms were tested against the variation of BMD in the normal population. Heel bone parameters (SOS, BUA) were measured by right calcaneal QUS in 5021 healthy French-Canadian women and for 2104 women, BMD evaluated by DXA at two sites was available (femoral neck (FN) and lumbar spine (LS)). Among women with QUS measures and those with DXA measures, 26.5% and 32.8% respectively were premenopausal, 9.2% and 10.7% were perimenopausal and 64.2% and 56.5% were postmenopausal. About a third of the peri- and postmenopausal women never received hormone therapy. Two single nucleotide coding polymorphisms (Val667Met and Ala1330Val) in LRP5 gene were genotyped by allele-specific PCR. All bone measures were tested individually for associations with each polymorphism by analysis of covariance with adjustment for non genetic risk factors. Furthermore, haplotype analysis was performed to take into account the strong linkage disequilibrium between the two polymorphisms. The two LRP5 polymorphisms were found to be associated with all five bone measures (L2L4 and femoral neck DXA as well as heel SOS, BUA and stiffness index) in the whole sample. Premenopausal women drove the association as expected from the proposed role of LRP5 in peak bone mass. Our results suggest that the Val667Met polymorphism is the causative variant but this remains to be functionally proven.

Association between Mitofusin 2 Gene Polymorphisms and Late-Onset Alzheimer's Disease in the Korean Population

PubMed Central

Kim, Young Jong; Park, Jin Kyung; Kang, Won Sub; Kim, Su Kang; Han, Changsu; Na, Hae Ri; Park, Hae Jeong; Kim, Jong Woo; Kim, Young Youl; Park, Moon Ho

2017-01-01

Objective Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. Methods One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). Results Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. Conclusion These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD. PMID:28096879

Transforming growth factor beta-1 (TGF-β1) gene single nucleotide polymorphisms (SNPs) and susceptibility to pre-eclampsia in Iranian women: A case-control study.

PubMed

Khani, Masood; Amani, Davar; Taheripanah, Robabeh; Sanadgol, Nima; Feizollahzadeh, Sadegh; Rahmani, Zahra

2015-10-01

Pre-eclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and proteinuria. Transforming growth factor beta-1 (TGF-β1) is an important replicated PE candidate gene, and few studies have evaluated the direct association of TGF-β polymorphisms and risk to PE. The aim of this study was to investigate the association between three SNPs of TGF-β1 and serum level of this cytokine in PE patients and controls. In this study the polymorphisms of the TGF-β1 gene at the coding region, and positions 29T→C (Leu 10 Pro), 74G→C (Arg 25 Pro) and 788C→T (Thr 263 Ile) were studied in 123 PE and 120 normal subjects using PCR-restriction fragment length polymorphism PCR-(RFLP) and amplification refractory mutation system (ARMS)-PCR methods. Moreover, serum TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) technique. At positions 74G→C and 29T→C the genotypes and allele frequencies showed no significant differences between PE patients and normal controls (P=0.3 and P=0.5 respectively). While in the case of position 788C→T both genotypes and allele frequencies were significantly different between PE patients and controls (P=0.02). Haplotype analysis on three polymorphic sites showed no significant differences between PE and control individuals (P=0.8). TGC and CGC haplotypes were the most frequent in both studied groups. The mean serum TGF-β1 level was significantly higher (62.73ng/ml) in PE patients compared with pregnant (47.01ng/ml) and non-pregnant (40.68ng/ml) control groups (P=0.0001). The results of this study suggest that TGF-β1 gene 788C→T polymorphism is an important factor mediating the casual pathway of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

A survey of genome-wide single nucleotide polymorphisms through genome resequencing in the Périgord black truffle (Tuber melanosporum Vittad.).

PubMed

Payen, Thibaut; Murat, Claude; Gigant, Anaïs; Morin, Emmanuelle; De Mita, Stéphane; Martin, Francis

2015-09-01

The Périgord black truffle (Tuber melanosporum Vittad.), considered a gastronomic delicacy worldwide, is an ectomycorrhizal filamentous fungus that is ecologically important in Mediterranean French, Italian and Spanish woodlands. In this study, we developed a novel resource of single nucleotide polymorphisms (SNPs) for T. melanosporum using Illumina high-throughput resequencing. The genome from six T. melanosporum geographical accessions was sequenced to a depth of approximately 20×. These geographical accessions were selected from different populations within the northern and southern regions of the geographical species distribution. Approximately 80% of the reads for each of the six resequenced geographical accessions mapped against the reference T. melanosporum genome assembly, estimating the core genome size of this organism to be approximately 110 Mbp. A total of 442 326 SNPs corresponding to 3540 SNPs/Mbps were identified as being included in all seven genomes. The SNPs occurred more frequently in repeated sequences (85%), although 4501 SNPs were also identified in the coding regions of 2587 genes. Using the ratio of nonsynonymous mutations per nonsynonymous site (pN) to synonymous mutations per synonymous site (pS) and Tajima's D index scanning the whole genome, we were able to identify genomic regions and genes potentially subjected to positive or purifying selection. The SNPs identified represent a valuable resource for future population genetics and genomics studies. © 2015 John Wiley & Sons Ltd.

Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study

PubMed Central

2010-01-01

Background Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development. Methods We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic. Results We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany. Conclusion A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (Ptrend = 0.004). PMID:20920174

Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study.

PubMed

Campa, Daniele; Pardini, Barbara; Naccarati, Alessio; Vodickova, Ludmila; Novotny, Jan; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Kötting, Judith; Betz, Beate; Kloor, Matthias; Engel, Christoph; Büttner, Reinhard; Propping, Peter; Försti, Asta; Hemminki, Kari; Barale, Roberto; Vodicka, Pavel; Canzian, Federico

2010-09-28

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development. We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic. We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany. A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (Ptrend = 0.004).

Opioid system genes in alcoholism: a case-control study in Croatian population.

PubMed

Cupic, B; Stefulj, J; Zapletal, E; Matosic, A; Bordukalo-Niksic, T; Cicin-Sain, L; Gabrilovac, J

2013-10-01

Due to their involvement in dependence pathways, opioid system genes represent strong candidates for association studies investigating alcoholism. In this study, single nucleotide polymorphisms within the genes for mu (OPRM1) and kappa (OPRK1) opioid receptors and precursors of their ligands - proopiomelanocortin (POMC), coding for beta-endorphin and prodynorphin (PDYN) coding for dynorphins, were analyzed in a case-control study that included 354 male alcohol-dependent and 357 male control subjects from Croatian population. Analysis of allele and genotype frequencies of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN revealed no differences between the tested groups. The same was true when alcohol-dependent persons were subdivided according to the Cloninger's criteria into type-1 and type-2 groups, known to differ in the extent of genetic control. Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.

PubMed

Zhou, Wei; Yuan, Weiming; Huang, Longguang; Wang, Ping; Rong, Xiao; Tang, Juan

2015-07-01

The aim of the present study was to investigate the association of neonatal necrotizing enterocolitis (NEC) with myeloid differentiation-(MD-2) and GM2 activator protein (GM2A) genetic polymorphisms. Gene resequencing of the MD-2 and GM2A gene exons was performed on 42 neonates, diagnosed with NEC (NEC group), as well as in the rs11465996 locus, located in the MD-2 gene promoter region. The aim was to detect the genetic polymorphisms present in the neonates with NEC and compare the functional polymorphic loci with 83 neonates without NEC (control group), who had been born during the same period. A polymorphic locus with abnormal frequency was detected in the exon region of the MD-2 gene. In the NEC group, the frequency of genotypes carrying the low frequency allele (G) in the rs11465996 locus (MD-2 promoter region) was significantly higher compared with the control group (χ(2)=4.388, P=0.036). Furthermore, the frequencies of genotypes carrying the low frequency A and C alleles in the rs1048719 (GM2A gene exon 1) and rs2075783 loci (GM2A intron), respectively, were significantly higher in the NEC group compared with the control group (χ(2)=4.316, P=0.038; and χ(2)=13.717, P=0.000, respectively). In addition, the rs11465996 polymorphism in the MD-2 gene promoter region was found to be associated with the severity of NEC. Furthermore, the rs2075783 polymorphism in the GM2A gene exon 1 and the rs1048719 polymorphism in the intron region of this gene, were associated with the occurrence of NEC. The present study demonstrated that gene polymorphisms of MD-2 and GM2A were associated with the occurrence or severity of NEC; however, further in-depth exploration is required to clarify the associations between genetic predispositions to polymorphisms, and NEC.

A new variation in the promoter region, the -604 C>T, and the Leu72Met polymorphism of the ghrelin gene are associated with protection to insulin resistance.

PubMed

Zavarella, S; Petrone, A; Zampetti, S; Gueorguiev, M; Spoletini, M; Mein, C A; Leto, G; Korbonits, M; Buzzetti, R

2008-04-01

Previous studies suggested that polymorphisms in the coding region of the preproghrelin were involved in the etiology of obesity and might modulate glucose-induced insulin secretion. We evaluated the association of a new variation, -604C>T, in the promoter region of the ghrelin gene, of Leu72Met (247C>A) and of Gln90Leu (265A>T), all haplotype-tagging single nucleotide polymorphisms (SNPs), with measures of insulin sensitivity in 1420 adult individuals. The three SNPs were genotyped using ABI PRISM 7900 HT Sequence Detection System. We used multiple linear regression analysis for quantitative traits and THESIAS software for haplotype analysis. We observed a protective effect exerted by Met72 variant of Leu72Met SNP on insulin resistance parameters; a significant decreasing trend from Leu/Leu to Leu/Met and to Met/Met homozygous subjects in triglycerides, fasting insulin levels and HOMA-IR index (P=0.02, 0.01 and 0.003, respectively), and, consistently, an increase in ghrelin levels (P=0.003) was found. A significant decrease from CC to TC and to TT genotypes in insulin levels and HOMA-IR index was also detected (P=0.00l for both), but only in subjects homozygous for Leu72, where the protective effect of Met72 was not present. The haplotype analysis results supported the data obtained by the evaluation of each single SNP, showing the highest value of insulin levels and HOMA-IR index in the -604(c)247(c) haplotype intermediate value in -604(T)247(C) and lowest value in -604(C)247(A). Our observations suggest a protective role of the Met72 variant and of -604 T allele in modulating insulin resistance. These SNPs or an unknown functional variant in linkage disequilibrium could increase ghrelin levels and probably insulin sensitivity.

Association between long non-coding RNA polymorphisms and cancer risk: a meta-analysis.

PubMed

Huang, Xin; Zhang, Weiyue; Shao, Zengwu

2018-05-25

Several studies have suggested that long non-coding RNA (lncRNA) gene polymorphisms are associated with cancer risk. In the present study, we conducted a meta-analysis related to studies on the association between lncRNA single-nucleotide polymorphisms (SNPs) and the overall risk of cancer. A total 12 SNPs in five common lncRNA genes were finally included in the meta-analysis. In the lncRNA antisense noncoding RNA in the INK4 locus (ANRIL), the rs1333048 A/C, rs4977574 A/G, and rs10757278 A/G polymorphisms, but not rs1333045 C/T, were correlated with overall cancer risk. Our study also demonstrated that other SNPs were correlated with overall cancer risk, namely, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1, rs619586 A/G), HOXA distal transcript antisense RNA (HOTTIP, rs1859168 A/C) and highly up-regulated in liver cancer (HULC, rs7763881 A/C). Moreover, four prostate cancer‑associated non‑coding RNA 1 (PRNCR1, rs16901946 G/A, rs13252298 G/A, rs1016343 T/C, and rs1456315 G/A) SNPs were in association with cancer risk. No association was found between the PRNCR1 (rs7007694 C/T) SNP and the risk of cancer. In conclusion, our results suggest that several studied lncRNA SNPs are associated with overall cancer risk. Therefore, they might be potential predictive biomarkers for the risk of cancer. More studies based on larger sample sizes and more lncRNA SNPs are warranted to confirm these findings. ©2018 The Author(s).

Molecular genetics of cystinuria: Identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity

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

Gasparini, P.; Bisceglia, L.; Notarangelo, A.

A cystinuria disease gene (rBAT) has been recently identified, and some mutations causing the disease have been described. The frequency of these mutations has been investigated in a large sample of 51 Italian and Spanish cystinuric patients. In addition, to identify new mutated alleles, genomic DNA has been analyzed by an accurate and sensitive method able to detect nucleotide changes. Because of the lack of information available on the genomic structure of rBAT gene, the study was carried out using the sequence data so far obtained by us. More than 70% of the entire coding sequence and 8 intron-exon boundariesmore » have been analyzed. Four new mutations and seven intragenic polymorphisms have been detected. All mutations so far identified in rBAT belong only to cystinuria type I alleles, accounting for {approximately} 44% of all type I cystinuric chromosomes. Mutation M467T is the most common mutated allele in the Italian and Spanish populations. After analysis of 70% of the rBAT coding region, we have detected normal sequences in cystinuria type II and type III chromosomes. The presence of rBAT mutated alleles only in type I chromosomes of homozygous (type I/I) and heterozygous (type I/III) patients provides evidence for genetic heterogeneity where rBAT would be responsible only for type I cystinuria and suggests a complementation mechanism to explain the intermediate type I/type III phenotype. 25 refs., 1 fig., 3 tabs.« less

Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.

PubMed Central

Morgan, L; Crawshaw, S; Baker, P N; Brookfield, J F; Broughton Pipkin, F; Kalsheker, N

1998-01-01

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion. PMID:9719367

Gender Difference in Interactions between MAOA Promoter uVNTR Polymorphism and Negative Familial Stressors on Body Mass Index among Chinese Adolescents

PubMed Central

Xie, Bin; Li, Dalin; London, Stephanie J.; Palmer, Paula H.; Johnshon, C. Anderson; Li, Yan; Shih, Jean; Bergen, Andrew W.; Nishita, Denise; Swan, Gary E.; Ahn, Rosa; Conti, David V.

2014-01-01

Summary Objectives Monoamine oxidase A (MAOA) modulates metabolism of serotonin and dopamine metabolism, neurotransmitters involved in regulation of appetite and food intake. The gene coding for MAOA contains a 30-bp tandem repeat (uVNTR) polymorphism in its promoter region that has been previously identified to be associated with obesity with mixed findings in the literature. Our goals were to replicate the population effects of this functional polymorphism on obesity risk, and to further explore gender differences and interaction effects with negative stressors. Methods Analyses were conducted with data on genotypes, measured weight and height, and self-reported behavioral characteristics among 1,101 Chinese adolescents 11-15 years old living in Wuhan, China. Results Girls with the high activity allele had significantly lower BMI (β=-0.25±0.98, p=0.011) compared to those with the low activity allele. Experience of negative familial stressors(e.g., death or illness of family members, hit or scolded by parents and increased quarreling with parents, parents argued frequently) significantly weakened this protective genetic effect on BMI (p for interaction=0.043). Stratified analyses showed a significant protective genetic effect on BMI only within the stratum of low stress level (β=-0.44±0.14, p=0.002). No similar effect was observed among boys. Conclusions Our findings confirm the genetic effects of MAOA uVNTR polymorphism on BMI in a Chinese adolescent population and suggest potential genetic interactions with negative familial stressors. PMID:23761378

A functionally significant SNP in TP53 and breast cancer risk in African-American women.

PubMed

Murphy, Maureen E; Liu, Song; Yao, Song; Huo, Dezheng; Liu, Qin; Dolfi, Sonia C; Hirshfield, Kim M; Hong, Chi-Chen; Hu, Qiang; Olshan, Andrew F; Ogundiran, Temidayo O; Adebamowo, Clement; Domchek, Susan M; Nathanson, Katherine L; Nemesure, Barbara; Ambs, Stefan; Blot, William J; Feng, Ye; John, Esther M; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Haiman, Christopher A; Olopade, Olufunmilayo I; Lunetta, Kathryn L; Palmer, Julie R; Ambrosone, Christine B

2017-01-01

A coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in TP53 tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women from the AMBER and ROOT consortia, there was a per allele odds ratio of 1.72 (95% confidence interval 1.08-2.76; p -value = 0.023). Although the Pro47Ser variant was not associated with overall breast cancer risk, it may increase risk among pre-menopausal women of African ancestry. Following up on more studies in human populations may better elucidate the role of this variant in breast cancer etiology. However, because of the low frequency of the polymorphism in women of African ancestry, its impact at a population level may be minimal.

Association of genetic variants and expression levels of porcine FABP4 and FABP5 genes.

PubMed

Ballester, M; Puig-Oliveras, A; Castelló, A; Revilla, M; Fernández, A I; Folch, J M

2017-12-01

The FABP4 and FABP5 genes, coding for fatty acid transport proteins, have long been studied as positional candidate genes for SSC4 QTL affecting fat deposition and composition traits in pigs. Polymorphisms in these genes, FABP4:g.2634_2635insC and FABP5:g.3000T>G, have previously been associated with fatness traits in an Iberian by Landrace cross (IBMAP). The aim of the present work was to evaluate the functional implication of these genetic variants. For this purpose, FABP4 and FABP5 mRNA expression levels in 114 BC1_LD animals (25% Iberian × 75% Landrace) were analyzed using real-time quantitative PCR in backfat and muscle. FABP4 gene expression in backfat, but not in muscle, was associated with FABP4:g.2634_2635insC. In contrast, FABP5:g.3000T>G was not associated with gene expression levels. An expression-based genome-wide association study highlighted the FABP4:g.2634_2635insC polymorphism as the polymorphism most associated with FABP4 gene expression in backfat. Furthermore, other genomic regions associated in trans with the mRNA expression of FABP4 in backfat and FABP5 in muscle were also identified. Finally, two putative transcription binding sites for PPARG and NR4A2 may be affected by the FABP4:g.2634_2635insC polymorphism, modifying FABP4 gene expression. Our results reinforce FABP4 as a candidate gene for fatness traits on SSC4. © 2017 Stichting International Foundation for Animal Genetics.

The role of polymorphisms in the spliced leader addition domain in determining promoter activity in Brugia malayi.

PubMed

Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R

2011-03-01

Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.

AlleleCoder: a PERL script for coding codominant polymorphism data for PCA analysis

USDA-ARS?s Scientific Manuscript database

A useful biological interpretation of diploid heterozygotes is in terms of the dose of the common allele (0, 1 or 2 copies). We have developed a PERL script that converts FASTA files into coded spreadsheets suitable for Principal Component Analysis (PCA). In combination with R and R Commander, two- ...

Polymorphism and methylation of the MC4R gene in obese and non-obese dogs.

PubMed

Mankowska, Monika; Nowacka-Woszuk, Joanna; Graczyk, Aneta; Ciazynska, Paulina; Stachowiak, Monika; Switonski, Marek

2017-08-01

The dog is considered to be a useful biomedical model for human diseases and disorders, including obesity. One of the numerous genes associated with human polygenic obesity is MC4R, encoding the melanocortin 4 receptor. The aim of our study was to analyze polymorphisms and methylation of the canine MC4R in relation to adiposity. Altogether 270 dogs representing four breeds predisposed to obesity: Labrador Retriever (n = 187), Golden Retriever (n = 38), Beagle (n = 28) and Cocker Spaniel (n = 17), were studied. The dogs were classified into three groups: lean, overweight and obese, according to the 5-point Body Condition Score (BCS) scale. In the cohort of Labradors a complete phenotypic data (age, sex, neutering status, body weight and BCS) were collected for 127 dogs. The entire coding sequence as well as 5' and 3'-flanking regions of the studied gene were sequenced and six polymorphic sites were reported. Genotype frequencies differed considerably between breeds and Labrador Retrievers appeared to be the less polymorphic. Moreover, distribution of some polymorphic variants differed significantly (P < 0.05) between small cohorts with diverse BCS in Golden Retrievers (c.777T>C, c.868C>T and c.*33C>G) and Beagles (c.-435T>C and c.637G>T). On the contrary, in Labradors no association between the studied polymorphisms and BCS or body weight was observed. Methylation analysis, using bisulfite DNA conversion followed by Sanger sequencing, was carried out for 12 dogs with BCS = 3 and 12 dogs with BCS = 5. Two intragenic CpG islands, containing 19 cytosines, were analyzed and the methylation profile did not differ significantly between lean and obese animals. We conclude that an association of the MC4R gene polymorphism with dog obesity or body weight is unlikely, in spite of the fact that some associations were found in small cohorts of Beagles and Golden Retrievers. Also methylation level of this gene is not related with dog adiposity.

Utilizing Gene Tree Variation to Identify Candidate Effector Genes in Zymoseptoria tritici

PubMed Central

McDonald, Megan C.; McGinness, Lachlan; Hane, James K.; Williams, Angela H.; Milgate, Andrew; Solomon, Peter S.

2016-01-01

Zymoseptoria tritici is a host-specific, necrotrophic pathogen of wheat. Infection by Z. tritici is characterized by its extended latent period, which typically lasts 2 wks, and is followed by extensive host cell death, and rapid proliferation of fungal biomass. This work characterizes the level of genomic variation in 13 isolates, for which we have measured virulence on 11 wheat cultivars with differential resistance genes. Between the reference isolate, IPO323, and the 13 Australian isolates we identified over 800,000 single nucleotide polymorphisms, of which ∼10% had an effect on the coding regions of the genome. Furthermore, we identified over 1700 probable presence/absence polymorphisms in genes across the Australian isolates using de novo assembly. Finally, we developed a gene tree sorting method that quickly identifies groups of isolates within a single gene alignment whose sequence haplotypes correspond with virulence scores on a single wheat cultivar. Using this method, we have identified < 100 candidate effector genes whose gene sequence correlates with virulence toward a wheat cultivar carrying a major resistance gene. PMID:26837952

Human immunodeficiency virus type 1 seroprevalence and antiretroviral drug resistance-associated mutations in miners in Gabon, central Africa.

PubMed

Caron, Mélanie; Makuwa, Maria; Souquière, Sandrine; Descamps, Diane; Brun-Vézinet, Françoise; Kazanji, Mirdad

2008-09-01

Miners in sub-Saharan African are known to have an extremely high prevalence of HIV-1 infection. We therefore evaluated the prevalence of HIV-1 infection among manganese miners in Gabon, central Africa and examined the diversity of HIV-1 strains by characterizing the polymorphism of the pol gene in order to observe drug resistance-associated mutations. In 857 samples tested, the HIV-1 prevalence was 2.9%. By pol sequence analysis, we showed that all the HIV-1 strains belonged to group M, with a majority of CRF02_AG (57%) followed by subtype A (9%) and CRF01_AE or subtype B (4%). The remaining HIV-1 strains demonstrated discordant genomic results and exhibited a mosaic pol genome (30%). Most of the mutations detected in pol coding regions corresponded to the subtype polymorphism, with no specific antiretroviral drug resistance. To avoid the rapid emergence of resistant viruses in this part of central Africa, continuous surveillance of the circulation of drug-resistant viruses must be maintained to guide treatment strategies.

Maternal and neonatal interleukin-1 receptor antagonist genotype and pregnancy outcome in a population with a high rate of pre-term birth.

PubMed

Chaves, José Humberto Belmino; Babayan, Arthur; Bezerra, Cledna de Melo; Linhares, Iara M; Witkin, Steven S

2008-10-01

We evaluated associations between a length polymorphism in intron 2 of the gene coding for IL-1ra (gene symbol IL1RN) and pregnancy outcome in a population with a high rate of preterm birth. Subjects were pregnant women in Maceio, Brazil and their newborns. DNA was tested for IL1RN genotypes and alleles by gene amplification using primer pairs that spanned the polymorphic region. Every subject completed a detailed questionnaire. The frequency of allele 2 (IL1RN*2) carriage was elevated in mothers with a spontaneous preterm birth (SPTB) in the current pregnancy (P = 0.02) and also with a prior preterm delivery (P = .01). Both SPTB with intact membranes (P = 0.01) and SPTB preceded by pre-term premature rupture of membranes (P = .03) were associated with ILlRN*2 carriage. A previous fetal demise was more than twice as prevalent in mothers positive for two copies of IL1RN*2. Maternal carriage of ILlRN*2 increases susceptibility to inflammation-triggered spontaneous pre-term birth.

Polymorphism of the Tryptophan Hydroxylase 2 (TPH2) Gene Is Associated with Chimpanzee Neuroticism

PubMed Central

Morimura, Naruki; Udono, Toshifumi; Hayasaka, Ikuo; Humle, Tatyana; Murayama, Yuichi; Ito, Shin'ichi; Inoue-Murayama, Miho

2011-01-01

In the brain, serotonin production is controlled by tryptophan hydroxylase 2 (TPH2), a genotype. Previous studies found that mutations on the TPH2 locus in humans were associated with depression and studies of mice and studies of rhesus macaques have shown that the TPH2 locus was involved with aggressive behavior. We previously reported a functional single nucleotide polymorphism (SNP) in the form of an amino acid substitution, Q468R, in the chimpanzee TPH2 gene coding region. In the present study we tested whether this SNP was associated with neuroticism in captive and wild-born chimpanzees living in Japan and Guinea, respectively. Even after correcting for multiple tests (Bonferroni p = 0.05/6 = 0.008), Q468R was significantly related to higher neuroticism (β = 0.372, p = 0.005). This study is the first to identify a genotype linked to a personality trait in chimpanzees. In light of the prior studies on humans, mice, and rhesus macaques, these findings suggest that the relationship between neuroticism and TPH2 has deep phylogenetic roots. PMID:21765945

[Comparison of the sensibility and specificity between single-stranded conformation polymorphism and denaturing high-performance liquid chromatography in screening hMSH2 and hMLH1 gene mutations in hereditary non-polyposis colorectal cancer].

PubMed

Wei, Guang-hui; Zhao, Bo; Wang, Zhen-jun

2008-09-01

To compare the sensibility and specificity between single-stranded conformation polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) in screening hMSH2 and hMLH1 gene mutations for the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC). Seven Chinese HNPCC kindreds were collected. PCR-SSCP and DHPLC were used to screen the coding regions of hMSH2 and hMLH1 genes and the abnormal profiles were sequenced by a 377 DNA sequencer. Seven gene sequence variations of hMSH2 or hMLH1 were found. Among them, 4 variations were not found by SSCP, but by DHPLC. The sensibility of SSCP and DHPLC were 51.6% and 100% respectively, and the specificity were 66.6% and 93.3% respectively. DHPLC has better sensibility and specificity in screening hMSH2 and hMLH1 gene mutation as compared to SSCP. DHPLC is an ideal method in the diagnosis of HNPCC.

Mutation screening of HOXA7 and HOXA9 genes in Chinese women with Müllerian duct abnormalities.

PubMed

Chen, Xinxia; Mu, Yulan; Li, Chunyan; Li, Guangyu; Zhao, Hui; Qin, Yingying; Chen, Zi-Jiang

2014-11-01

HOXA genes in groups 7-13 have been proven to play a role in determining positional identity along the genitalia axis. The aim of the present study was to explore the relationship between HOXA7 and HOXA9 mutations and Müllerian duct abnormalities (MDA). One hundred and ninety-two Chinese patients with MDA abnormalities and 192 healthy controls were recruited. All coding regions of HOXA7 and HOXA9 were amplified and sequenced directly. Rs2301721 and rs2301720 in HOXA7, rs35355140 and rs7810502 in HOXA9 were identified in patients with MDA and controls. One rare single nucleotide polymorphism rs189587233 in 3' UTR of HOXA9 gene was detected in one patient with didelphic uterus and absent in the 192 controls. This polymorphism, however, is known to exist in the normal Chinese population. Our results indicated that variants in the HOXA7 and HOXA9 genes were not common in Chinese women with Müllerian duct abnormalities. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

MERE1, a low-copy-number copia-type retroelement in Medicago truncatula active during tissue culture.

PubMed

Rakocevic, Alexandra; Mondy, Samuel; Tirichine, Leïla; Cosson, Viviane; Brocard, Lysiane; Iantcheva, Anelia; Cayrel, Anne; Devier, Benjamin; Abu El-Heba, Ghada Ahmed; Ratet, Pascal

2009-11-01

We have identified an active Medicago truncatula copia-like retroelement called Medicago RetroElement1-1 (MERE1-1) as an insertion in the symbiotic NSP2 gene. MERE1-1 belongs to a low-copy-number family in the sequenced Medicago genome. These copies are highly related, but only three of them have a complete coding region and polymorphism exists between the long terminal repeats of these different copies. This retroelement family is present in all M. truncatula ecotypes tested but also in other legume species like Lotus japonicus. It is active only during tissue culture in both R108 and Jemalong Medicago accessions and inserts preferentially in genes.

Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes.

PubMed

Sarahan, Kari A; Fisler, Janis S; Warden, Craig H

2011-09-22

We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

Identification of the razor clam species Ensis arcuatus, E. siliqua, E. directus, E. macha, and Solen marginatus using PCR-RFLP analysis of the 5S rDNA region.

PubMed

Fernandez-Tajes, Juan; Méndez, Josefina

2007-09-05

Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis of the 5S ribosomal DNA region has been applied to the establishment of DNA-based molecular markers for the identification of five razor clam species: Ensis arcuatus, E. siliqua, E. directus, E. macha, and Solen marginatus. PCR amplifications were carried out using a pair of universal primers from the coding region of 5S rDNA. S. marginatus was simply distinguished by the different size of the amplicons obtained. Species-specific restriction endonuclease patterns were found with the enzymes Hae III for E. arcuatus, E. siliqua, and E. directus, and Acs I for E. macha, and when two enzymes were combined, the four species were also identified. Thus, this work provides a simple, reliable, and rapid protocol for the accurate identification of Ensis and Solen species in fresh and canned products, which is very useful for traceability and to enforce labeling regulations.

Genome-Wide Association Study on the Development of Cross-Reactive Neutralizing Antibodies in HIV-1 Infected Individuals

PubMed Central

Euler, Zelda; van Gils, Marit J.; Boeser-Nunnink, Brigitte D.; Schuitemaker, Hanneke; van Manen, Daniëlle

2013-01-01

Broadly neutralizing antibodies may protect against HIV-1 acquisition. In natural infection, only 10–30% of patients have cross-reactive neutralizing humoral immunity which may relate to viral and or host factors. To explore the role of host genetic markers in the formation of cross-reactive neutralizing activity (CrNA) in HIV-1 infected individuals, we performed a genome-wide association study (GWAS), in participants of the Amsterdam Cohort Studies with known CrNA in their sera. Single-nucleotide polymorphisms (SNPs) with the strongest P-values are located in the major histocompatibility complex (MHC) region, close to MICA (P = 7.68×10−7), HLA-B (P = 6.96×10−6) and in the coding region of HCP5 (P = 1.34×10−5). However, none of the signals reached genome-wide significance. Our findings underline the potential involvement of genes close or within the MHC region with the development of CrNA. PMID:23372753

Screening of Israeli Holstein-Friesian cattle for restriction fragment length polymorphisms using homologous and heterologous deoxyribonucleic acid probes.

PubMed

Hallerman, E M; Nave, A; Soller, M; Beckmann, J S

1988-12-01

Genomic DNA of Israeli Holstein-Friesian dairy cattle were screened with a battery of 17 cloned or subcloned DNA probes in an attempt to document restriction fragment length polymorphisms at a number of genetic loci. Restriction fragment length polymorphisms were observed at the chymosin, oxytocin-neurophysin I, lutropin beta, keratin III, keratin VI, keratin VII, prolactin, and dihydrofolate reductase loci. Use of certain genomic DNA fragments as probes produced hybridization patterns indicative of satellite DNA at the respective loci. Means for distinguishing hybridizations to coding sequences for unique genes from those to satellite DNA were developed. Results of this study are discussed in terms of strategy for the systematic development of large numbers of bovine genomic polymorphisms.

Essentials of Conservation Biotechnology: A mini review

NASA Astrophysics Data System (ADS)

Merlyn Keziah, S.; Subathra Devi, C.

2017-11-01

Equilibrium of biodiversity is essential for the maintenance of the ecosystem as they are interdependent on each other. The decline in biodiversity is a global problem and an inevitable threat to the mankind. Major threats include unsustainable exploitation, habitat destruction, fragmentation, transformation, genetic pollution, invasive exotic species and degradation. This review covers the management strategies of biotechnology which include sin situ, ex situ conservation, computerized taxonomic analysis through construction of phylogenetic trees, calculating genetic distance, prioritizing the group for conservation, digital preservation of biodiversities within the coding and decoding keys, molecular approaches to asses biodiversity like polymerase chain reaction, real time, randomly amplified polymorphic DNA, restriction fragment length polymorphism, amplified fragment length polymorphism, single sequence repeats, DNA finger printing, single nucleotide polymorphism, cryopreservation and vitrification.

Allelic variation of the Waxy gene in foxtail millet [Setaria italica (L.) P. Beauv.] by single nucleotide polymorphisms.

PubMed

Van, K; Onoda, S; Kim, M Y; Kim, K D; Lee, S-H

2008-03-01

The Waxy (Wx) gene product controls the formation of a straight chain polymer of amylose in the starch pathway. Dominance/recessiveness of the Wx allele is associated with amylose content, leading to non-waxy/waxy phenotypes. For a total of 113 foxtail millet accessions, agronomic traits and the molecular differences of the Wx gene were surveyed to evaluate genetic diversities. Molecular types were associated with phenotypes determined by four specific primer sets (non-waxy, Type I; low amylose, Type VI; waxy, Type IV or V). Additionally, the insertion of transposable element in waxy was confirmed by ex1/TSI2R, TSI2F/ex2, ex2int2/TSI7R and TSI7F/ex4r. Seventeen single nucleotide polymorphims (SNPs) were observed from non-coding regions, while three SNPs from coding regions were non-synonymous. Interestingly, the phenotype of No. 88 was still non-waxy, although seven nucleotides (AATTGGT) insertion at 2,993 bp led to 78 amino acids shorter. The rapid decline of r (2) in the sequenced region (exon 1-intron 1-exon 2) suggested a low level of linkage disequilibrium and limited haplotype structure. K (s) values and estimation of evolutionary events indicate early divergence of S. italica among cereal crops. This study suggested the Wx gene was one of the targets in the selection process during domestication.

Detection of genetic diversity and selection at the coding region of the melanocortin receptor 1 (MC1R) gene in Tibetan pigs and Landrace pigs.

PubMed

Liu, Rui; Jin, Long; Long, Keren; Chai, Jie; Ma, Jideng; Tang, Qianzi; Tian, Shilin; Hu, Yaodong; Lin, Ling; Wang, Xun; Jiang, Anan; Li, Xuewei; Li, Mingzhou

2016-01-10

Domestication and subsequent selective pressures have produced a large variety of pig coat colors in different regions and breeds. The melanocortin 1 receptor (MC1R) gene plays a crucial role in determining coat color of mammals. Here, we investigated genetic diversity and selection at the coding region of the porcine melanocortin receptor 1 (MC1R) in Tibetan pigs and Landrace pigs. By contrast, genetic variability was much lower in Landrace pigs than in Tibetan pigs. Meanwhile, haplotype analysis showed that Tibetan pigs possessed shared haplotypes, suggesting a possibility of recent introgression event by way of crossbreeding with neighboring domestic pigs or shared ancestral polymorphism. Additionally, we detected positive selection at the MC1R in both Tibetan pigs and Landrace pigs through the dN/dS analysis. These findings suggested that novel phenotypic change (dark coat color) caused by novel mutations may help Tibetan pigs against intensive solar ultraviolet (UV) radiation and camouflage in wild environment, whereas white coat color in Landrace were intentionally selected by human after domestication. Furthermore, both the phylogenetic analysis and the network analysis provided clues that MC1R in Asian and European wild boars may have initially experienced different selective pressures, and MC1R alleles diversified in modern domesticated pigs. Copyright © 2015 Elsevier B.V. All rights reserved.

The alpaca melanocortin 1 receptor: gene mutations, transcripts, and relative levels of expression in ventral skin biopsies.

PubMed

Chandramohan, Bathrachalam; Renieri, Carlo; La Manna, Vincenzo; La Terza, Antonietta

2015-01-01

The objectives of the present study were to characterize the MC1R gene, its transcripts and the single nucleotide polymorphisms (SNPs) associated with coat color in alpaca. Full length cDNA amplification revealed the presence of two transcripts, named as F1 and F2, differing only in the length of their 5'-terminal untranslated region (UTR) sequences and presenting a color specific expression. Whereas the F1 transcript was common to white and colored (black and brown) alpaca phenotypes, the shorter F2 transcript was specific to white alpaca. Further sequencing of the MC1R gene in white and colored alpaca identified a total of twelve SNPs; among those nine (four silent mutations (c.126C>A, c.354T>C, c.618G>A, and c.933G>A); five missense mutations (c.82A>G, c.92C>T, c.259A>G, c.376A>G, and c.901C>T)) were observed in coding region and three in the 3'UTR. A 4 bp deletion (c.224 227del) was also identified in the coding region. Molecular segregation analysis uncovered that the combinatory mutations in the MC1R locus could cause eumelanin and pheomelanin synthesis in alpaca. Overall, our data refine what is known about the MC1R gene and provides additional information on its role in alpaca pigmentation.

TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region.

PubMed

Wise, C A; Chiang, L C; Paznekas, W A; Sharma, M; Musy, M M; Ashley, J A; Lovett, M; Jabs, E W

1997-04-01

Treacher Collins Syndrome (TCS) is the most common of the human mandibulofacial dysostosis disorders. Recently, a partial TCOF1 cDNA was identified and shown to contain mutations in TCS families. Here we present the entire exon/intron genomic structure and the complete coding sequence of TCOF1. TCOF1 encodes a low complexity protein of 1,411 amino acids, whose predicted protein structure reveals repeated motifs that mirror the organization of its exons. These motifs are shared with nucleolar trafficking proteins in other species and are predicted to be highly phosphorylated by casein kinase. Consistent with this, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localization signals. Throughout the open reading frame, we detected an additional eight mutations in TCS families and several polymorphisms. We postulate that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.

New Population and Phylogenetic Features of the Internal Variation within Mitochondrial DNA Macro-Haplogroup R0

PubMed Central

Cerezo, Maria; Quintáns, Beatriz; Zarrabeitia, Maria Teresa; Cuscó, Ivon; Lareu, Maria Victoria; García, Óscar; Pérez-Jurado, Luis; Carracedo, Ángel; Salas, Antonio

2009-01-01

Background R0 embraces the most common mitochondrial DNA (mtDNA) lineage in West Eurasia, namely, haplogroup H (∼40%). R0 sub-lineages are badly defined in the control region and therefore, the analysis of diagnostic coding region polymorphisms is needed in order to gain resolution in population and medical studies. Methodology/Principal Findings We sequenced the first hypervariable segment (HVS-I) of 518 individuals from different North Iberian regions. The mtDNAs belonging to R0 (∼57%) were further genotyped for a set of 71 coding region SNPs characterizing major and minor branches of R0. We found that the North Iberian Peninsula shows moderate levels of population stratification; for instance, haplogroup V reaches the highest frequency in Cantabria (north-central Iberia), but lower in Galicia (northwest Iberia) and Catalonia (northeast Iberia). When compared to other European and Middle East populations, haplogroups H1, H3 and H5a show frequency peaks in the Franco-Cantabrian region, declining from West towards the East and South Europe. In addition, we have characterized, by way of complete genome sequencing, a new autochthonous clade of haplogroup H in the Basque country, named H2a5. Its coalescence age, 15.6±8 thousand years ago (kya), dates to the period immediately after the Last Glacial Maximum (LGM). Conclusions/Significance In contrast to other H lineages that experienced re-expansion outside the Franco-Cantabrian refuge after the LGM (e.g. H1 and H3), H2a5 most likely remained confined to this area till present days. PMID:19340307

Molecular genotyping of Echinococcus granulosus from dromedaries (Camelus dromedarius) in eastern Iran.

PubMed

Moghaddas, E; Borji, H; Naghibi, A; Shayan, P; Razmi, G R

2015-01-01

With the aim of genotyping Echinococcus granulosus cysts found in Iranian dromedaries (Camelus dromedarius), 50 cysts of E. granulosus were collected from five geographical regions in Iran. Cysts were characterized using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the internal transcribed spacer 1 (ITS1) gene and sequencing fragments of the genes coding for mitochondrial cytochrome c oxidase subunit 1 (cox1). Morphological criteria using rostellar hook dimensions were also undertaken. The present results have shown that 27 out of 50 E. granulosus cysts (54%) were determined as the G1 strain, and the other (46%) were determined as the G6 strain. The molecular analysis of the ITS1 region of ribosomal DNA corresponded with the morphological findings. Because of its recognized infectivity in humans, the G1 genotype is a direct threat to human health and its presence in Iranian dromedaries is of urgent public health importance.

SEQassembly: A Practical Tools Program for Coding Sequences Splicing

NASA Astrophysics Data System (ADS)

Lee, Hongbin; Yang, Hang; Fu, Lei; Qin, Long; Li, Huili; He, Feng; Wang, Bo; Wu, Xiaoming

CDS (Coding Sequences) is a portion of mRNA sequences, which are composed by a number of exon sequence segments. The construction of CDS sequence is important for profound genetic analysis such as genotyping. A program in MATLAB environment is presented, which can process batch of samples sequences into code segments under the guide of reference exon models, and splice these code segments of same sample source into CDS according to the exon order in queue file. This program is useful in transcriptional polymorphism detection and gene function study.

Partitioning of genetic variation between regulatory and coding gene segments: the predominance of software variation in genes encoding introvert proteins.

PubMed

Mitchison, A

1997-01-01

In considering genetic variation in eukaryotes, a fundamental distinction can be made between variation in regulatory (software) and coding (hardware) gene segments. For quantitative traits the bulk of variation, particularly that near the population mean, appears to reside in regulatory segments. The main exceptions to this rule concern proteins which handle extrinsic substances, here termed extrovert proteins. The immune system includes an unusually large proportion of this exceptional category, but even so its chief source of variation may well be polymorphism in regulatory gene segments. The main evidence for this view emerges from genome scanning for quantitative trait loci (QTL), which in the case of the immune system points to a major contribution of pro-inflammatory cytokine genes. Further support comes from sequencing of major histocompatibility complex (Mhc) class II promoters, where a high level of polymorphism has been detected. These Mhc promoters appear to act, in part at least, by gating the back-signal from T cells into antigen-presenting cells. Both these forms of polymorphism are likely to be sustained by the need for flexibility in the immune response. Future work on promoter polymorphism is likely to benefit from the input from genome informatics.

Comparative analysis of the 5{prime} genomic and promoter regions between the mouse (Hdh) and human Huntington disease (HD) gene

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

Kalchman, M.; Lin, B.; Nasir, J.

1994-09-01

The mouse homologue of the Huntington disease gene (Hdh) has recently been cloned and mapped to a region of synteny with the human, on mouse chromosome 5. The two genes share a high degree of both coding (90% amino acid) and nucleotide (86.2%) identity. We have subsequently performed a detailed comparison of the genomic organization of the 5{prime} region of the two genes encompassing the promoter region and first five exons of both the human and mouse genes. The comparative sequence analysis of the promoter region between HD and Hdh reveals two highly conserved regions. One region (-56 to -118)more » (+1 is the ATG start codon), shared 84% nucleotide identity and another region (-130 to -206) had 81% nucleotide identity. Nine putative Sp1 sites appear in the human promoter region contrasted with only 3 in a similar region in the mouse. Furthermore, 17 and 20 base pair direct repeats present in the HD 5{prime} region are absent in the similar Hdh region. Although both the mouse and human intron/exon boundaries conform to the GT/AG rule, the intron sizes between HD and Hdh are markedly different. The first four introns in Hdh are 15, 7, 5 and 0.5 kb compared to sizes of 10, 15, 7 and 0.5 kb, respectively. Comparison between the mouse and human intronic sequences immediately adjacent to the first five exons (excluding exon 1) reveals only about 46 to 50% identity within the first 60 bp of intronic sequence. Furthermore, we have identified novel polymorphic di-, tri- and tetra-nucleotide repeats in Hdh introns of various mouse strains that are not present in the human. For example, polymorphic CT repeats are present in introns 2 and 4 of Hdh and a novel mouse 56 AAG trinucleotide repeat (interrupted by an AAGG) is also located within intron 2. This information concerning the promoter and genomic organization of both HD and Hdh is critical for designing appropriate gene targetting vectors for studying the normal function of the HD and Hdh genes in model systems.« less

Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides

PubMed Central

Granados, Diana Paola; Sriranganadane, Dev; Daouda, Tariq; Zieger, Antoine; Laumont, Céline M.; Caron-Lizotte, Olivier; Boucher, Geneviève; Hardy, Marie-Pierre; Gendron, Patrick; Côté, Caroline; Lemieux, Sébastien; Thibault, Pierre; Perreault, Claude

2014-01-01

For decades, the global impact of genomic polymorphisms on the repertoire of peptides presented by major histocompatibility complex (MHC) has remained a matter of speculation. Here we present a novel approach that enables high-throughput discovery of polymorphic MHC class I-associated peptides (MIPs), which play a major role in allorecognition. On the basis of comprehensive analyses of the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings, we show that 0.5% of non-synonymous single nucleotide variations are represented in the MIP repertoire. The 34 polymorphic MIPs found in our subjects are encoded by bi-allelic loci with dominant and recessive alleles. Our analyses show that, at the population level, 12% of the MIP-coding exome is polymorphic. Our method provides fundamental insights into the relationship between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens). PMID:24714562

Contrasting Histories of Three Gene Regions Associated with In(3l)payne of Drosophila Melanogaster

PubMed Central

Hasson, E.; Eanes, W. F.

1996-01-01

In the present report, we studied nucleotide variation in three gene regions of Drosophila melanogaster, spanning >5 kb and showing different degrees of association with the cosmopolitan inversion In(3-L)Payne. The analysis of sequence variation in the regions surrounding the breakpoints and the heat shock 83 (Hsp83) gene locus, located close to the distal breakpoint, revealed the absence of shared polymorphisms and the presence of a number of fixed differences between arrangements, indicating absence of genetic exchange. In contrast, for the esterase-6 gene region, located in the center of the inversion, we observed the presence of shared polymorphisms between arrangements suggesting genetic exchange. In the regions close to the breakpoints, the common St arrangement is 10 times more polymorphic than inverted chromosomes. We propose that the lack of recombination between arrangements in these regions coupled with genetic hitchhiking is the best explanation for the low heterozygosity observed in inverted lines. Using the data for the breakpoints, we estimate that this inversion polymorphism is around 0.36 million yr old. Although it is widely accepted that inversions are examples of balanced polymorphisms, none of the current neutrality tests including our Monte Carlo simulations showed significant departure from neutral expectations. PMID:8978045

β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study.

PubMed

Wu, Pingsheng; Larkin, Emma K; Reiss, Sara S; Carroll, Kecia N; Summar, Marshall L; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Islam, Jessica Y; Hartert, Tina V; Moore, Paul E

2015-09-14

Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95% confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy.

Diachronic investigations of mitochondrial and Y-chromosomal genetic markers in pre-Columbian Andean highlanders from South Peru.

PubMed

Fehren-Schmitz, Lars; Warnberg, Ole; Reindel, Markus; Seidenberg, Verena; Tomasto-Cagigao, Elsa; Isla-Cuadrado, Johny; Hummel, Susanne; Herrmann, Bernd

2011-03-01

This study examines the reciprocal effects of cultural evolution, and population dynamics in pre-Columbian southern Peru by the analysis of DNA from pre-Columbian populations that lived in the fringe area between the Andean highlands and the Pacific coast. The main objective is to reveal whether the transition from the Middle Horizon (MH: 650-1000 AD) to the Late Intermediate Period (LIP: 1000-1400 AD) was accompanied or influenced by population dynamic processes. Tooth samples from 90 individuals from several archaeological sites, dating to the MH and LIP, in the research area were collected to analyse mitochodrial, and Y-chromosomal genetic markers. Coding region polymorphisms were successfully analysed and replicated for 72 individuals, as were control region sequences for 65 individuals and Y-chromosomal single nucleotide polymorphisms (SNPs) for 19 individuals, and these were compared to a large set of ancient and modern indigenous South American populations. The diachronic comparison of the upper valley samples from both time periods reveals no genetic discontinuities accompanying the cultural dynamic processes. A high genetic affinity for other ancient and modern highland populations can be observed, suggesting genetic continuity in the Andean highlands at the latest from the MH. A significant matrilineal differentiation to ancient Peruvian coastal populations can be observed suggesting a differential population history. © 2010 The Authors Annals of Human Genetics © 2010 Blackwell Publishing Ltd/University College London.

Genome-wide association study on growth traits in Colombian creole breeds and crossbreeds with Zebu cattle.

PubMed

Martínez, R; Gómez, Y; Rocha, J F M

2014-08-25

Whole genome selection represents an important tool for improving parameters related to the production of livestock. In order to build genomic selection indexes within a particular breed, it is important to identify polymorphisms that have the most significant association with a desired trait. A genome-wide marker association approach based on the Illumina BovineSNP50 BeadChip(TM) was used to identify genomic regions affecting birth weight (BW), weaning weight (WW), and daily weight gain (DWG) in purebred and crossbred creole cattle populations. We genotyped 654 individuals of Blanco Orejinegro (BON), Romosinuano (ROMO) and Cebú breeds and the crossbreeds BON x Cebú and ROMO x Cebú, and tested 5 genetic control models. In total, 85 single nucleotide polymorphisms (SNPs) were related (P < 0.05) to the 3 evaluated traits; BW was associated with the highest number of SNPs. For statistical false-positive correction, Bonferroni correction was used. From the results, we identified 7, 6, and 4 SNPs with strong associations with BW, WW, and DWG, respectively. Many of these SNPs were located on important coding regions of the bovine genome; their ontology and interactions are discussed herein. The results could contribute to the identification of genes involved in the physiology of beef cattle growth and the development of new strategies for breeding management via genomic selection to improve the productivity of creole cattle herds.

Genetic association of sequence variation in exon 3 of the swine leukocyte antigen-DQA gene with piglet diarrhea in Large White, Landrace, and Duroc piglets.

PubMed

Yang, Q L; Huang, X Y; Kong, J J; Zhao, S G; Liu, L X; Gun, S B

2016-08-19

Piglet diarrhea is one of the primary factors that affects the benefits of the swine industry. Recent studies have shown that exon 2 of the swine leukocyte antigen-DQA gene is associated with piglet resistance to diarrhea; however, the contributions of additional exon coding regions of this gene remain unclear. Here, we detected and sequenced variants in the exon 3 region and examined their associations with diarrhea infection in 425 suckling piglets using the polymerase chain reaction-single-strand conformational polymorphism and sequencing analysis. The results revealed that exon 3 of the swine leukocyte antigen-DQA gene is highly polymorphic and pivotal to both diarrhea susceptibility and resistance in piglets. We identified 14 genotypes (AA, AB, BB, BC, CC, EE, EF, BE, BF, CF, DD, DH, GG, and GF) and eight alleles (A-H) that were generated by 14 nucleotide variants, eight of which were novel, and three nucleotide deletions. Statistical analyses revealed that the genotypes AB and EF were associated with resistance to diarrheal disease (P < 0.05), and the genotype DD may contribute to diarrhea susceptibility but was unique to Large White pigs (P > 0.05). These results elucidate the genetic and immunological background to piglet diarrhea, and provide useful information for resistance breeding programs.

Whole-genome sequencing of the efficient industrial fuel-ethanol fermentative Saccharomyces cerevisiae strain CAT-1.

PubMed

Babrzadeh, Farbod; Jalili, Roxana; Wang, Chunlin; Shokralla, Shadi; Pierce, Sarah; Robinson-Mosher, Avi; Nyren, Pål; Shafer, Robert W; Basso, Luiz C; de Amorim, Henrique V; de Oliveira, Antonio J; Davis, Ronald W; Ronaghi, Mostafa; Gharizadeh, Baback; Stambuk, Boris U

2012-06-01

The Saccharomyces cerevisiae strains widely used for industrial fuel-ethanol production have been developed by selection, but their underlying beneficial genetic polymorphisms remain unknown. Here, we report the draft whole-genome sequence of the S. cerevisiae strain CAT-1, which is a dominant fuel-ethanol fermentative strain from the sugarcane industry in Brazil. Our results indicate that strain CAT-1 is a highly heterozygous diploid yeast strain, and the ~12-Mb genome of CAT-1, when compared with the reference S228c genome, contains ~36,000 homozygous and ~30,000 heterozygous single nucleotide polymorphisms, exhibiting an uneven distribution among chromosomes due to large genomic regions of loss of heterozygosity (LOH). In total, 58 % of the 6,652 predicted protein-coding genes of the CAT-1 genome constitute different alleles when compared with the genes present in the reference S288c genome. The CAT-1 genome contains a reduced number of transposable elements, as well as several gene deletions and duplications, especially at telomeric regions, some correlated with several of the physiological characteristics of this industrial fuel-ethanol strain. Phylogenetic analyses revealed that some genes were likely associated with traits important for bioethanol production. Identifying and characterizing the allelic variations controlling traits relevant to industrial fermentation should provide the basis for a forward genetics approach for developing better fermenting yeast strains.

[Association of the cocaine and amphetamine-regulated transcript gene with type 2 diabetes mellitus].

PubMed

Fu, Mao; Cheng, Hua; Chen, Lihong; Wu, Bin; Cai, Mengyin; Xie, Ding; Fu, Zuzhi

2002-12-01

To investigate whether genetic variation in cocaine and amphetamine-regulated transcript (CART) gene might contribute to the genesis of type 2 diabetes. Screening for mutations in the entire coding region for the CART gene were performed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in 180 normoglycemic control subjects and 221 patients with type 2 diabetes. (1) Adenine deletion was identified at position 1,457 nucleotide located at untranslation area of exon 3. In normal weight control, the frequencies of CART-A + and CART-A-alleles were 83.6% and 16.4% respectively. The frequencies of CART-A + A +, A + A-, A-A- genotype were 68.9%, 29.4% and 1.7% respectively. (2) In diabetic patients, the frequencies of CART-A + and A-alleles were 84.6% and 15.4% respectively; the frequencies of CART-A + A +, A + A-, A-A- genotype were 71.9%, 25.3% and 2.7% respectively. The frequency of A deletion of the CART gene in diabetic patients did not differ significantly from normoglycemic control subjects. (3) Diabetic patients with the A deletion had increased total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Polymorphism was found in the 3'-untranslated region (Delta A1457) of CART in Chinese. A deletion in CART is not associated with type 2 diabetes, but may contribute to dyslipidemia.

Polymorphisms upstream of the melanocortin-1 receptor coding region are associated with human pigmentation variation in a Brazilian population.

PubMed

Neitzke-Montinelli, Vanessa; Urmenyi, Turan P; Rondinelli, Edson; Cabello, Pedro Hernan; Silva, Rosane; Moura-Neto, Rodrigo S

2012-01-01

We describe an association of two SNPs, rs3212345:C>T and rs3212346:G>A, located approximately 2.5 kb upstream of the melanocortin-1 receptor (MC1R) translation initiation codon, with pigmentation phenotype variation in a Southeast Brazilian miscegenated population. One hundred thirty-eight genetically unrelated subjects, with multicolor phenotype, were selected from the southeast region of Brazil. Skin, hair and eye color, and tanning ability were rated. Genotypes for each SNP (rs3212345:C>T and rs3212346:G>A) were determined. A logistic regression analysis was performed with the additive model to determine which of the polymorphisms contributed to a specific phenotype. We found that the rs3212345:C>T is associated with light skin, red hair, and poor tanning ability, while the rs3212346:G>A is associated with dark skin, black hair, and strong tanning ability. The presence of rs3212345-C and rs3212346-A alleles in human, chimpanzee, gorilla, orangutan, and marmoset genomes suggests that they are the ancestral alleles. These data suggest that the rs3212345-T and rs3212346-G alleles may have contributed to lighter pigmentation phenotypes in modern humans. Genotyping for these SNPs may prove useful to the fields of molecular anthropology and forensic genetics. Copyright © 2012 Wiley Periodicals, Inc.

Regulatory versus coding signatures of natural selection in a candidate gene involved in the adaptive divergence of whitefish species pairs (Coregonus spp.)

PubMed Central

Jeukens, Julie; Bernatchez, Louis

2012-01-01

While gene expression divergence is known to be involved in adaptive phenotypic divergence and speciation, the relative importance of regulatory and structural evolution of genes is poorly understood. A recent next-generation sequencing experiment allowed identifying candidate genes potentially involved in the ongoing speciation of sympatric dwarf and normal lake whitefish (Coregonus clupeaformis), such as cytosolic malate dehydrogenase (MDH1), which showed both significant expression and sequence divergence. The main goal of this study was to investigate into more details the signatures of natural selection in the regulatory and coding sequences of MDH1 in lake whitefish and test for parallelism of these signatures with other coregonine species. Sequencing of the two regions in 118 fish from four sympatric pairs of whitefish and two cisco species revealed a total of 35 single nucleotide polymorphisms (SNPs), with more genetic diversity in European compared to North American coregonine species. While the coding region was found to be under purifying selection, an SNP in the proximal promoter exhibited significant allele frequency divergence in a parallel manner among independent sympatric pairs of North American lake whitefish and European whitefish (C. lavaretus). According to transcription factor binding simulation for 22 regulatory haplotypes of MDH1, putative binding profiles were fairly conserved among species, except for the region around this SNP. Moreover, we found evidence for the role of this SNP in the regulation of MDH1 expression level. Overall, these results provide further evidence for the role of natural selection in gene regulation evolution among whitefish species pairs and suggest its possible link with patterns of phenotypic diversity observed in coregonine species. PMID:22408741

Regulatory versus coding signatures of natural selection in a candidate gene involved in the adaptive divergence of whitefish species pairs (Coregonus spp.).

PubMed

Jeukens, Julie; Bernatchez, Louis

2012-01-01

While gene expression divergence is known to be involved in adaptive phenotypic divergence and speciation, the relative importance of regulatory and structural evolution of genes is poorly understood. A recent next-generation sequencing experiment allowed identifying candidate genes potentially involved in the ongoing speciation of sympatric dwarf and normal lake whitefish (Coregonus clupeaformis), such as cytosolic malate dehydrogenase (MDH1), which showed both significant expression and sequence divergence. The main goal of this study was to investigate into more details the signatures of natural selection in the regulatory and coding sequences of MDH1 in lake whitefish and test for parallelism of these signatures with other coregonine species. Sequencing of the two regions in 118 fish from four sympatric pairs of whitefish and two cisco species revealed a total of 35 single nucleotide polymorphisms (SNPs), with more genetic diversity in European compared to North American coregonine species. While the coding region was found to be under purifying selection, an SNP in the proximal promoter exhibited significant allele frequency divergence in a parallel manner among independent sympatric pairs of North American lake whitefish and European whitefish (C. lavaretus). According to transcription factor binding simulation for 22 regulatory haplotypes of MDH1, putative binding profiles were fairly conserved among species, except for the region around this SNP. Moreover, we found evidence for the role of this SNP in the regulation of MDH1 expression level. Overall, these results provide further evidence for the role of natural selection in gene regulation evolution among whitefish species pairs and suggest its possible link with patterns of phenotypic diversity observed in coregonine species.

Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene.

PubMed

Tu, N; Chen, H; Winnikes, U; Reinert, I; Marmann, G; Pirke, K M; Lentes, K U

1999-01-01

Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75-150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The hUCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon /intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7 - 13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3'-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.

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.

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

PubMed Central

Hu, Hae-Jin; Jin, Eun-Heui; Yim, Seon-Hee; Yang, So-Young; Jung, Seung-Hyun; Shin, Seung-Hun; Kim, Wan-Uk; Shim, Seung-Cheol; Kim, Tai-Gyu

2011-01-01

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 ± 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA. PMID:21844665

Identification of single nucleotide polymorphisms in the agouti signaling protein (ASIP) gene in some goat breeds in tropical and temperate climates.

PubMed

Adefenwa, Mufliat A; Peters, Sunday O; Agaviezor, Brilliant O; Wheto, Matthew; Adekoya, Khalid O; Okpeku, Moses; Oboh, Bola; Williams, Gabriel O; Adebambo, Olufunmilayo A; Singh, Mahipal; Thomas, Bolaji; De Donato, Marcos; Imumorin, Ikhide G

2013-07-01

The agouti-signaling protein (ASIP) plays a major role in mammalian pigmentation as an antagonist to melanocortin-1 receptor gene to stimulate pheomelanin synthesis, a major pigment conferring mammalian coat color. We sequenced a 352 bp fragment of ASIP gene spanning part of exon 2 and part of intron 2 in 215 animals representing six goat breeds from Nigeria and the United States: West African Dwarf, predominantly black; Red Sokoto, mostly red; and Sahel, mostly white from Nigeria; black and white Alpine, brown and white Spanish and white Saanen from the US. Twenty haplotypes from nine mutations representing three intronic, one silent and five missense (p.S19R, p.N35K, p.L36V, p.M42L and p.L45W) mutations were identified in Nigerian goats. Approximately 89 % of Nigerian goats carry haplotype 1 (TGCCATCCG) which seems to be the wild type configuration of mutations in this region of the gene. Although we found no association between these polymorphisms in the ASIP gene and coat color in Nigerian goats, in-silico functional analysis predicts putative deleterious functional impact of the p.L45W mutation on the basic amino-terminal domain of ASIP. In the American goats, two intronic mutations, g.293G>A and g.327C>A, were identified in the Alpine breed, although the g.293G>A mutation is common to American and Nigerian goat populations. All Sannen and Sahel goats in this study belong to haplotypes 1 of both populations which seem to be the wild-type composite ASIP haplotype. Overall, there was no clear association of this portion of the ASIP gene interrogated in this study with coat color variation. Therefore, additional genomic analyses of promoter sequence, the entire coding and non-coding regions of the ASIP gene will be required to obtain a definite conclusion.

Analysis of the Functional Polymorphism in the Cytochrome P450 CYP2C8 Gene rs11572080 with Regard to Colorectal Cancer Risk

PubMed Central

Ladero, José M.; Agúndez, José A. G.; Martínez, Carmen; Amo, Gemma; Ayuso, Pedro; García-Martín, Elena

2012-01-01

In addition to the known effects on drug metabolism and response, functional polymorphisms of genes coding for xenobiotic-metabolizing enzymes (XME) play a role in cancer. Genes coding for XME act as low-penetrance genes and confer modest but consistent and significant risks for a variety of cancers related to the interaction of environmental and genetic factors. Consistent evidence supports a role for polymorphisms of the cytochrome P450 CYP2C9 gene as a protecting factor for colorectal cancer susceptibility. It has been shown that CYP2C8 and CYP2C9 overlap in substrate specificity. Because CYP2C8 has the common functional polymorphisms rs11572080 and rs10509681 (CYP2C8*3), it could be speculated that part of the findings attributed to CYP2C9 polymorphisms may actually be related to the presence of polymorphisms in the CYP2C8 gene. Nevertheless, little attention has been paid to the role of the CYP2C8 polymorphism in colorectal cancer. We analyzed the influence of the CYP2C8*3 allele in the risk of developing colorectal cancer in genomic DNA from 153 individuals suffering colorectal cancer and from 298 age- and gender-matched control subjects. Our findings do not support any effect of the CYP2C8*3 allele (OR for carriers of functional CYP2C8 alleles = 0.50 (95% CI = 0.16–1.59; p = 0.233). The absence of a relative risk related to CYP2C8*3 did not vary depending on the tumor site. We conclude that the risk of developing colorectal cancer does not seem to be related to the commonest functional genetic variation in the CYP2C8 gene. PMID:23420707

The relationship in Japanese infants between a genetic polymorphism in the promoter region of the insulin-like growth factor I gene and the plasma level.

PubMed

Kinoshita, Yumiko; Kizaki, Zenro; Ishihara, Yasunori; Nakajima, Hisakazu; Adachi, Shinsuke; Kosaka, Kitaro; Kinugasa, Akihiko; Sugimoto, Tohru

2007-01-01

Evidence is accumulating that the promoter region of the insulin-like growth factor I (IGF-I) gene polymorphism and low levels of IGF-I are associated with type 2 diabetes, cardiovascular disease and birth weight; however, the number of wild-type alleles is different in each country. This study aimed to examine the 737/738 marker, a cytosine-adenine repeat in the promoter region of the IGF-I gene polymorphism, and plasma IGF-I levels in Japanese infants and analyze the genetic background. Data were collected for 15 months in Kyoto Prefectural University of Medicine. The body composition parameters of all infants were determined at birth. At 5 days after birth, we took blood samples to measure the product size of the promoter region of the IGF-I gene polymorphism and plasma IGF-I. In a population-based sample of 160 subjects, 6 different alleles and 16 genotypes were identified in the promoter region of the IGF-I gene polymorphism. The existence of a 196-bp allele has proved to result in a low plasma IGF-I level, a small head and chest circumference (p < 0.05) and no significant for premature birth, short-birth height and low-birth weight. This is the first study showing the role of the promoter region of the IGF-I gene polymorphism and the level of plasma IGF-I and body composition parameters in Japanese infants. Our results suggest genetical influence on prenatal growth and serum IGF-I levels.

[Analysis of mitochondrial SNPs in addition to conventional STR-typing in a case of aggravated theft].

PubMed

Röper, Andrea; Reichert, Walter; Mattern, Rainer

2007-01-01

In the field of forensic DNA typing, the analysis of Short Tandem Repeats (STRs) can fail in cases of degraded DNA. The typing of coding region Single Nucleotide Polymorphisms (SNPs) of the mitochondrial genome provides an approach to acquire additional information. In the examined case of aggravated theft, both suspects could be excluded of having left the analyzed hair on the crime scene by SNP typing. This conclusion was not possible subsequent to STR typing. SNP typing of the trace on the torch light left on the crime scene increased the likelihood for suspect no. 2 to be the origin of this trace. This finding was already indicated by STR analysis. Suspect no. 1 was excluded for being the origin of this trace by SNP typing which was also indicated by STR analysis. A limiting factor for the analysis of SNPs is the maternal inheritance of mitochondrial DNA. Individualisation is not possible. In conclusion, it can be said that in the case of traces which cause problems with conventional STR typing the supplementary analysis of coding region SNPs from the mitochondrial genome is very reasonable and greatly contributes to the refinement of analysis methods in the field of forensic genetics.

Functional non-coding polymorphism in an EPHA2 promoter PAX2 binding site modifies expression and alters the MAPK and AKT pathways.

PubMed

Ma, Xiaoyin; Ma, Zhiwei; Jiao, Xiaodong; Hejtmancik, J Fielding

2017-08-30

To identify possible genetic variants influencing expression of EPHA2 (Ephrin-receptor Type-A2), a tyrosine kinase receptor that has been shown to be important for lens development and to contribute to both congenital and age related cataract when mutated, the extended promoter region of EPHA2 was screened for variants. SNP rs6603883 lies in a PAX2 binding site in the EPHA2 promoter region. The C (minor) allele decreased EPHA2 transcriptional activity relative to the T allele by reducing the binding affinity of PAX2. Knockdown of PAX2 in human lens epithelial (HLE) cells decreased endogenous expression of EPHA2. Whole RNA sequencing showed that extracellular matrix (ECM), MAPK-AKT signaling pathways and cytoskeleton related genes were dysregulated in EPHA2 knockdown HLE cells. Taken together, these results indicate a functional non-coding SNP in EPHA2 promoter affects PAX2 binding and reduces EPHA2 expression. They further suggest that decreasing EPHA2 levels alters MAPK, AKT signaling pathways and ECM and cytoskeletal genes in lens cells that could contribute to cataract. These results demonstrate a direct role for PAX2 in EPHA2 expression and help delineate the role of EPHA2 in development and homeostasis required for lens transparency.

Genomic anatomy of the Tyrp1 (brown) deletion complex

PubMed Central

Smyth, Ian M.; Wilming, Laurens; Lee, Angela W.; Taylor, Martin S.; Gautier, Phillipe; Barlow, Karen; Wallis, Justine; Martin, Sancha; Glithero, Rebecca; Phillimore, Ben; Pelan, Sarah; Andrew, Rob; Holt, Karen; Taylor, Ruth; McLaren, Stuart; Burton, John; Bailey, Jonathon; Sims, Sarah; Squares, Jan; Plumb, Bob; Joy, Ann; Gibson, Richard; Gilbert, James; Hart, Elizabeth; Laird, Gavin; Loveland, Jane; Mudge, Jonathan; Steward, Charlie; Swarbreck, David; Harrow, Jennifer; North, Philip; Leaves, Nicholas; Greystrong, John; Coppola, Maria; Manjunath, Shilpa; Campbell, Mark; Smith, Mark; Strachan, Gregory; Tofts, Calli; Boal, Esther; Cobley, Victoria; Hunter, Giselle; Kimberley, Christopher; Thomas, Daniel; Cave-Berry, Lee; Weston, Paul; Botcherby, Marc R. M.; White, Sharon; Edgar, Ruth; Cross, Sally H.; Irvani, Marjan; Hummerich, Holger; Simpson, Eleanor H.; Johnson, Dabney; Hunsicker, Patricia R.; Little, Peter F. R.; Hubbard, Tim; Campbell, R. Duncan; Rogers, Jane; Jackson, Ian J.

2006-01-01

Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (l4Rn1, l4Rn2, and l4Rn3) and the fitness mutant brown-associated fitness (baf). We have also characterized misexpression of the basonuclin homologue, Bnc2, associated with the inversion-mediated coat color mutant white-based brown (Bw). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis. PMID:16505357

Polymorphisms in the interferon-induced helicase (IFIH1) locus and susceptibility to Addison's disease.

PubMed

Zurawek, Magdalena; Fichna, Marta; Januszkiewicz, Danuta; Fichna, Piotr; Nowak, Jerzy

2013-02-01

The interferon-induced helicase C domain-containing protein 1 (IFIH1) gene encodes a sensor for double-stranded RNA that initiates antiviral activity against enteroviruses. Previous investigations have indicated a role for IFIH1 in autoimmunity, as common and rare polymorphisms in this gene have been associated with type 1 diabetes. We hypothesized that polymorphisms in the IFIH1 locus may play a role in the pathogenesis of autoimmune Addison's disease (AAD). We analysed the association of rs3747517, rs1990760, rs2111485 and rs13422767 single-nucleotide polymorphisms (SNPs) in the IFIH1 gene and intergenic region with AAD in a Polish cohort. The study comprised 120 patients with AAD and 689 healthy control individuals. Genotyping was performed using TaqMan genotyping assays. The major AA genotype of the coding SNP rs1990760 appeared significantly more frequently in AAD compared with healthy individuals (AG vs AA OR 0·62, 95%CI 0·40-0·95, P = 0·03). We also observed a significant difference in the distribution of the rs13422767 SNP alleles. The major G allele was more frequent in the AAD group (A vs G OR 0·65, 95%CI 0·43-0·98, P = 0·04). Both statistically significant differences, for rs1990760 and rs13422767 SNPs, did not survive the Bonferroni correction (P = 0·11 and P = 0·15, for AA genotype and G allele, respectively). Subsequently, a meta-analysis of 519 patients with AAD and 1362 controls from three different European populations was performed. Under a fixed-effect model, a pooled OR for A allele and AA genotype of rs1990760 did not display any significant increase among AAD (OR = 1·05, P = 0·56 and OR = 1·08, P = 0·50, respectively). The IFIH1 locus polymorphisms are unlikely to be associated with Addison's disease. © 2012 Blackwell Publishing Ltd.

Lack of genetic diversity across diverse immune genes in an endangered mammal, the Tasmanian devil (Sarcophilus harrisii).

PubMed

Morris, Katrina M; Wright, Belinda; Grueber, Catherine E; Hogg, Carolyn; Belov, Katherine

2015-08-01

The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction due to the spread of devil facial tumour disease. Polymorphisms in immune genes can provide adaptive potential to resist diseases. Previous studies in diversity at immune loci in wild species have almost exclusively focused on genes of the major histocompatibility complex (MHC); however, these genes only account for a fraction of immune gene diversity. Devils lack diversity at functionally important immunity loci, including MHC and Toll-like receptor genes. Whether there are polymorphisms at devil immune genes outside these two families is unknown. Here, we identify polymorphisms in a wide range of key immune genes, and develop assays to type single nucleotide polymorphisms (SNPs) within a subset of these genes. A total of 167 immune genes were examined, including cytokines, chemokines and natural killer cell receptors. Using genome-level data from ten devils, SNPs within coding regions, introns and 10 kb flanking genes of interest were identified. We found low polymorphism across 167 immune genes examined bioinformatically using whole-genome data. From this data, we developed long amplicon assays to target nine genes. These amplicons were sequenced in 29-220 devils and found to contain 78 SNPs, including eight SNPS within exons. Despite the extreme paucity of genetic diversity within these genes, signatures of balancing selection were exhibited by one chemokine gene, suggesting that remaining diversity may hold adaptive potential. The low functional diversity may leave devils highly vulnerable to infectious disease, and therefore, monitoring and preserving remaining diversity will be critical for the long-term management of this species. Examining genetic variation in diverse immune genes should be a priority for threatened wildlife species. This study can act as a model for broad-scale immunogenetic diversity analysis in threatened species. © 2015 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Interaction between beta2 adrenergic receptor polymorphisms determines the extent of isoproterenol-induced vasodilatation ex vivo.

PubMed

Khalaila, Jawad M; Elami, Amir; Caraco, Yoseph

2007-10-01

Single nucleotide polymorphisms at nucleotides 46, 79 and 491 of the beta2 adrenergic receptor (beta2AR) gene modify its pharmacological properties and may alter the response to agonists. The purpose of this study was to evaluate the role played by beta2AR polymorphisms on isoproterenol-induced relaxation of internal mammary arteries ex vivo. Internal mammary leftover segments were collected from 96 patients undergoing coronary artery bypass operation. Vascular rings were allowed to reach equilibrium with physiological Krebs solution before precontraction with U46619. Using the organ bath technique, cumulative dose-response curve of isoproterenol was constructed and average EC50 calculated. beta2AR genotyping was performed using a PCR-RFLP analysis. Arterial segments obtained from Gly16 homozygotes displayed reduced sensitivity to isoproterenol compared with carriers of Arg16 allele(s) [Mean (-log) EC50+/-SD, 6.42+/-0.24, 95% confidence interval (CI) 6.32-6.53 vs. 6.67+/-0.25, 95% CI 6.62-6.73, P<0.001]. Among Gly16 homozygotes, the presence of two Glu27 alleles restored vascular response to the level noted among Arg16 carriers (6.58+/-0.17, 95% CI 6.41-6.76). The least response to isoproterenol was noted in a single patient carrying the Gly16Gly-Gln27Glu-Thr164Ile combined genotype requiring almost six-fold higher isoproterenol concentration than carriers of the wild-type genotype to achieve half the maximal arterial dilatation (17.78 x 10(-7) vs. 3.01 x 10(-7) +/- 2.62 x 10(-7) mol/l). Vascular dilatation by isoproterenol is determined by a complex interaction between polymorphisms at nucleotides 46, 79 and 491 of the beta2AR gene. Further studies are warranted to evaluate the effect of additional polymorphisms in the coding and noncoding regions on vascular reactivity.

Vitamin D receptor polymorphisms in patients with cutaneous melanoma.

PubMed

Orlow, Irene; Roy, Pampa; Reiner, Anne S; Yoo, Sarah; Patel, Himali; Paine, Susan; Armstrong, Bruce K; Kricker, Anne; Marrett, Loraine D; Millikan, Robert C; Thomas, Nancy E; Gruber, Stephen B; Anton-Culver, Hoda; Rosso, Stefano; Gallagher, Richard P; Dwyer, Terence; Kanetsky, Peter A; Busam, Klaus; From, Lynn; Begg, Colin B; Berwick, Marianne

2012-01-15

The vitamin D receptor (VDR) gene has been associated with cancer risk, but only a few polymorphisms have been studied in relation to melanoma risk and the results have been inconsistent. We examined 38 VDR gene single nucleotide polymorphisms (SNPs) in a large international multicenter population-based case-control study of melanoma. Buccal DNAs were obtained from 1,207 people with incident multiple primary melanoma and 2,469 with incident single primary melanoma. SNPs with known or suspected impact on VDR activity, haplotype tagging SNPs with ≥ 10% minor allele frequency in Caucasians, and SNPs reported as significant in other association studies were examined. Logistic regression was used to calculate the relative risks conferred by the individual SNP. Eight of 38 SNPs in the promoter, coding, and 3' gene regions were individually significantly associated with multiple primary melanoma after adjusting for covariates. The estimated increase in risk for individuals who were homozygous for the minor allele ranged from 25 to 33% for six polymorphisms: rs10875712 (odds ratios [OR] 1.28; 95% confidence interval (CI), 1.01-1.62), rs4760674 (OR 1.33; 95% CI, 1.06-1.67), rs7139166 (OR 1.26; 95%CI, 1.02-1.56), rs4516035 (OR 1.25; 95%CI, 1.01-1.55), rs11168287 (OR 1.27; 95%CI, 1.03-1.57) and rs1544410 (OR 1.30; 95%CI, 1.04-1.63); for two polymorphisms, homozygous carriers had a decreased risk: rs7305032 (OR 0.81; 95%CI 0.65-1.02) and rs7965281 (OR, 0.78; 95%CI, 0.62-0.99). We recognize the potential false positive findings because of multiple comparisons; however, the eight significant SNPs in our study outnumbered the two significant tests expected to occur by chance. The VDR may play a role in melanomagenesis. Copyright © 2011 UICC.

Non-synonymous single nucleotide polymorphisms in genes for immunoregulatory galectins: association of galectin-8 (F19Y) occurrence with autoimmune diseases in a Caucasian population.

PubMed

Pál, Zsuzsanna; Antal, Péter; Srivastava, Sanjeev Kumar; Hullám, Gábor; Semsei, Agnes F; Gál, János; Svébis, Mihály; Soós, Györgyi; Szalai, Csaba; André, Sabine; Gordeeva, Elena; Nagy, György; Kaltner, Herbert; Bovin, Nicolai V; Molnár, Mária Judit; Falus, András; Gabius, Hans-Joachim; Buzás, Edit Irén

2012-10-01

Galectins are potent immune regulators, with galectin-8 acting as a pro-apoptotic effector on synovial fluid cells and thymocytes and stimulator on T-cells. To set a proof-of-principle example for risk assessment in autoimmunity, and for a mutation affecting physiological galectin sensor functions, a polymorphism in the coding region of the galectin-8 gene (rs2737713; F19Y) was studied for its association with two autoimmune disorders, i.e. rheumatoid arthritis and myasthenia gravis. A case-control analysis and a related quantitative trait-association study were performed to investigate the association of this polymorphism in patients (myasthenia gravis 149, rheumatoid arthritis 214 and 134 as primary and repetitive cohorts, respectively) and 365 ethnically matched (Caucasian) healthy controls. Distribution was also investigated in patients grouped according to their antibody status and age at disease onset. Comparative testing for lectin activity was carried out in ELISA/ELLA-based binding tests with both wild-type and F19Y mutant galectin-8 from peripheral blood mononuclear cell lysates of healthy individuals with different genotypes as well as with recombinant wild-type and F19Y mutant galectin-8 proteins. A strong association was found for rheumatoid arthritis, and a mild one with myasthenia gravis. Furthermore, the presence of the sequence deviation also correlated with age at disease onset in the case of rheumatoid arthritis. The F19Y substitution did not appear to affect carbohydrate binding in solid-phase assays markedly. This is the first report of an association between a galectin-based polymorphism leading to a mutant protein and autoimmune diseases, with evidence for antagonistic pleiotropy. Copyright © 2012 Elsevier B.V. All rights reserved.

A novel single nucleotide polymorphism in exon 7 of LPL gene and its association with carcass traits and visceral fat deposition in yak (Bos grunniens) steers.

PubMed

Ding, X Z; Liang, C N; Guo, X; Xing, C F; Bao, P J; Chu, M; Pei, J; Zhu, X S; Yan, P

2012-01-01

Lipoprotein lipase (LPL) is considered as a key enzyme in the lipid deposition and metabolism in tissues. It is assumed to be a major candidate gene for genetic markers in lipid deposition. Therefore, the polymorphisms of the LPL gene and associations with carcass traits and viscera fat content were examined in 398 individuals from five yak (Bos grunniens) breeds using PCR-SSCP analysis and DNA sequencing. A novel nucleotide polymorphism (SNP)-C→T (nt19913) was identified located in exon 7 in the coding region of the LPL gene, which replacement was responsible for a Phe-to-Ser substitution at amino acid. Two alleles (A and B) and three genotypes designed as AA, AB and BB were detected in the PCR products. The frequencies of allele A were 0.7928, 0.7421, 0.7357, 0.6900 and 0.7083 for Tianzhu white yak (WY), Gannan yak (GY), Qinghai-Plateau yak (PY), Xinjiang yak (XY) and Datong yak (DY), respectively. The SNP loci was in Hardy-Weinberg equilibrium in five yak populations (P>0.05). Polymorphism of LPL gene was shown to be associated with carcass traits and lipid deposition. Least squares analysis revealed that there was a significant effect on live-weight (LW) (P<0.01), average daily weight gain (ADG) and carcass weight (P<0.05). Individuals with genotype BB had lower mean values than those with genotype AA and AB for loin eye area and viscera fat weight (% of LW) in 25-36 months (P<0.05). The results indicated that LPL gene is a strong candidate gene that affects carcass traits and fat deposition in yak.

Ménière's Disease: Molecular Analysis of Aquaporins 2, 3 and Potassium Channel KCNE1 Genes in Brazilian Patients.

PubMed

Lopes, Karen de Carvalho; Sartorato, Edi Lúcia; da Silva-Costa, Sueli M; de Macedo Adamov, Nadya Soares; Ganança, Fernando Freitas

2016-09-01

Ménière's disease (MD) is a complex disease of unknown etiology characterized by a symptomatic tetrad of vertigo, hearing loss, tinnitus, and aural fullness. In addition to factors related to homeostasis of the inner ear, genetic factors have been implicated in its pathophysiology, including genes related to the transport of water and ionic composition maintenance of the endolymph, such as the aquaporin genes AQP2 and AQP3, and the potassium channel gene KCNE1. The aim of this study was to identify polymorphisms of these genes and determine their association with clinical characteristics of patients with MD. A case-control genetic association study was carried out, including 30 patients with definite Ménière's disease and 30 healthy controls. The coding regions of the target genes were amplified from blood samples by polymerase chain reaction (PCR), followed by direct sequencing. The associations of polymorphisms with clinical characteristics were analyzed with logistic regression. Five polymorphisms were identified: rs426496 in AQP2; rs591810 in AQP3; and rs1805127, rs1805128, and rs17173510 in KCNE1. After adjustment, rs426496 was significantly associated with tinnitus during the initial crisis and with altered electronystagmography, and rs1805127 was significantly associated with nephropathy. The genetic variant rs426496 in AQP2; rs591810 in AQP3 and rs1805127, rs1805128, and rs17173510, in KCNE1 were found in patients with Ménière's disease. The polymorphism rs426496, in AQP2, is associated with tinnitus at the onset of Ménière's disease and altered electronystagmography. In addition, rs1805127, in KCNE1, is associated with the presence of nephropathy.

Gender difference in interactions between MAOA promoter uVNTR polymorphism and negative familial stressors on body mass index among Chinese adolescents.

PubMed

Xie, B; Li, D; London, S J; Palmer, P H; Johnshon, C A; Li, Y; Shih, J; Bergen, A W; Nishita, D; Swan, G E; Ahn, R; Conti, D V

2014-10-01

Monoamine oxidase A (MAOA) modulates metabolism of serotonin and dopamine metabolism, neurotransmitters involved in regulation of appetite and food intake. The gene coding for MAOA contains a 30-bp tandem repeat (uVNTR) polymorphism in its promoter region that has been previously identified to be associated with obesity with mixed findings in the literature. Our goals were to replicate the population effects of this functional polymorphism on obesity risk, and to further explore gender differences and interaction effects with negative stressors. Analyses were conducted with data on genotypes, measured weight and height, and self-reported behavioural characteristics among 1101 Chinese adolescents 11-15 years old living in Wuhan, China. Girls with the high-activity allele had significantly lower body mass index (BMI; β = -0.25 ± 0.98, P = 0.011) compared to those with the low activity allele. Experience of negative familial stressors (e.g., death or illness of family members, hit or scolded by parents and increased quarrelling with parents, parents argued frequently) significantly weakened this protective genetic effect on BMI (P for interaction = 0.043). Stratified analyses showed a significant protective genetic effect on BMI only within the stratum of low stress level (β = -0.44 ± 0.14, P = 0.002). No similar effect was observed among boys. Our findings confirm the genetic effects of MAOA uVNTR polymorphism on BMI in a Chinese adolescent population and suggest potential genetic interactions with negative familial stressors. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

Association of CD147 genetic polymorphisms with carotid atherosclerotic plaques in a Han Chinese population with cerebral infarction.

PubMed

Ni, Tongtian; Chen, Min; Yang, Kang; Shao, Jianwei; Fu, Yi; Zhou, Weijun

2017-08-01

Given the important role of CD147 in the development of atherosclerosis, we speculated that CD147 genetic polymorphisms might influence the formation of carotid atherosclerotic plaques. The study was to investigate the association between CD147 gene polymorphisms and susceptibility to carotid atherosclerotic plaques in individuals with cerebral infarction (CI). Eight SNPs in the regulatory and coding regions of the CD147 gene were examined using polymerase chain reaction-ligase detection reaction (PCR-LDR) in DNA samples from 732 Chinese patients with CI, divided into a carotid plaque group (n=475) and a non-carotid plaque group (n=257). Significant differences were found in the genotypes and allele frequencies of the rs4919862 SNP between the carotid plaque and non-carotid plaque groups of CI patients (P<0.05), while the frequencies of the C allele and the CC genotype in the non-carotid plaque group were significantly lower than those in the carotid plaque group, and the frequencies of the T allele in the non-carotid plaque group were significantly higher than those in the carotid plaque group (P<0.05). In addition, there was strong linkage disequilibrium among the rs4919862, rs8637 and rs8259 sites. In a haplotype analysis, the occurrence rate of the haplotype GATGCAGC was 2.095 times higher in the carotid plaque group than in the non-carotid plaque group (P<0.05). These results showed that the rs4919862 SNP of CD147 was closely associated with carotid atherosclerotic plaques formation. Thus, polymorphisms of the CD147 gene may be related to the tendency for carotid atherosclerotic plaques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate.

PubMed

Ntege, Edward H; Arisue, Nobuko; Ito, Daisuke; Hasegawa, Tomoyuki; Palacpac, Nirianne M Q; Egwang, Thomas G; Horii, Toshihiro; Takashima, Eizo; Tsuboi, Takafumi

2016-11-04

Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is comparatively more diverse, with varied number of regions having insertions and deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and pfmspdbl1 are polymorphic and genetically diverse among the isolates with antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood-stage vaccine candidate for next-generation vaccines against P. falciparum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children.

PubMed

Cicchetti, Dante; Rogosch, Fred A

2014-11-01

Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report on the Children's Depression Inventory and adult counselor report on the Teacher Report Form. DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter, and corticotropin releasing hormone receptor 1. Analyses of covariance with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their Gene × Environment (G × E) interactions. Maltreatment consistently was associated with higher Children's Depression Inventory and Teacher Report Form symptoms. The results for child self-report symptoms indicated a G × E interaction for BDNF and maltreatment. In addition, BDNF and triallelic 5-HTTLPR interacted with child maltreatment in a G × G × E interaction. Analyses for counselor report of child anxiety/depression symptoms on the Teacher Report Form indicated moderation of child maltreatment effects by triallelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. Norepinephrine transporter was found to further moderate the G × E interaction of 5-HTTLPR and maltreatment status, revealing a G × G × E interaction. This G × G × E was extended by consideration of variation in maltreatment subtype experiences. Finally, G × G × E effects were observed for the co-action of BDNF and the corticotropin releasing hormone receptor 1 haplotype. The findings illustrate the variable influence of specific genotypes in G × E interactions based on variation in maltreatment experiences and the importance of a multigenic approach for understanding influences on depression and internalizing symptoms among African American children.

The correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase (hTERT) gene with postoperative recurrence in patients with thyroid carcinoma (TC).

PubMed

Li, Jian-Jun; Zheng, Ping Chen Jue-Ru; Wang, Yao-Zong

2017-06-06

This study aims at exploring the correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase (hTERT) gene and postoperative recurrence in patients with thyroid carcinoma (TC). A total of 312 patients diagnosed with TC were chosen for the study and categorized into recurrence (n = 75) and non-recurrence (n = 237) groups. The hTERT rs2736100 and rs2736098 polymorphisms were detected by performing polymerase chain reaction-restriction fragment length polymorphism. DNA methylation in the promoter region of hTERT gene was evaluated by pyrosequencing. A telephonic and/or outpatient follow-up was conducted for all patients. The correlations of DNA methylation and polymorphisms in the promoter region of hTERT with postoperative recurrence of TC patients underwent analysis. The patient in the recurrence group showed evidently different pathological types and tumor stages in comparison to the non-recurrence group. The GG genotype of hTERT rs2736100 might increase the recurrence risk of TC patients. No correlations between hTERT rs2736098 polymorphisms and recurrence risk were observed. Compared to the TT + TG genotype frequency, the rs2736100 GG genotype frequency increased in patients without multicentricity, patients with extrathyroidal invasion, patients with lymph node metastasis, patients with undifferentiated carcinoma, and patients in the III + IV stage. The recurrence group showed significantly higher DNA methylation level compared to the non-recurrence group. The DNA methylation level was closely associated to tumor stage and lymph node metastasis of TC patients in the recurrence group. The DNA methylation and rs2736100 polymorphisms in the promoter region of hTERT gene might be in correlation to postoperative recurrence of TC patients.

Gelatinous drop-like corneal dystrophy in a child with developmental delay: clinicopathological features and exclusion of the M1S1 gene.

PubMed

Akhtar, S; Bron, A J; Qin, X; Creer, R C; Guggenheim, J A; Meek, K M

2005-02-01

Gelatinous drop-like corneal dystrophy (GDLD) is an early-onset, autosomal recessive condition characterised by amyloid deposits within the cornea. We report the histopathological and molecular genetic findings in a Caucasian child with GDLD who also exhibited global developmental delay. Bilateral lamellar keratoplasty was carried out at age 6 and 7 years. Tissue was fixed for light and electron microscopy, including immunoelectronmicroscopy. The coding region of the M1S1 gene was screened for mutations in the affected proband and available relatives, using DNA extracted from mouthwashes. Nodular deposits, which were present subepithelially and in the central superficial stroma, stained typically for amyloid with PAS and Congo red. A nodular deposit of amyloid, together with large amounts of lactoferrin and sparse amounts of keratoepithelin (betaig-h3), was present in the central superficial stroma, causing destruction of Bowman's layer and elevation of the thinned, degenerate epithelium. Around the deposit zone, the stroma exhibited large numbers of thick filamentous proteoglycan deposits. While the affected child was homozygous for a novel A1133 C single-nucleotide polymorphism (SNP) that resulted in an aspartic acid to alanine substitution at position 173 of the M1S1 coding sequence, this polymorphism was also found at relatively high frequency in a sample of normal controls, enabling exclusion of the M1S1 gene as the disease locus. Increased epithelial permeability in GDLD may be explained in part by an altered membrane permeability of the superficial epithelial cells. An association with developmental delay has not been reported previously.

Vitamin K epoxide reductase complex subunit 1 (Vkorc1) haplotype diversity in mouse priority strains

PubMed Central

Song, Ying; Vera, Nicole; Kohn, Michael H

2008-01-01

Background Polymorphisms in the vitamin K-epoxide reductase complex subunit 1 gene, Vkorc1, could affect blood coagulation and other vitamin K-dependent proteins, such as osteocalcin (bone Gla protein, BGP). Here we sequenced the Vkorc1 gene in 40 mouse priority strains. We analyzed Vkorc1 haplotypes with respect to prothrombin time (PT) and bone mineral density and composition (BMD and BMC); phenotypes expected to be vitamin K-dependent and represented by data in the Mouse Phenome Database (MPD). Findings In the commonly used laboratory strains of Mus musculus domesticus we identified only four haplotypes differing in the intron or 5' region sequence of the Vkorc1. Six haplotypes differing by coding and non-coding polymorphisms were identified in the other subspecies of Mus. We detected no significant association of Vkorc1 haplotypes with PT, BMD and BMC within each subspecies of Mus. Vkorc1 haplotype sequences divergence between subspecies was associated with PT, BMD and BMC. Conclusion Phenotypic variation in PT, BMD and BMC within subspecies of Mus, while substantial, appears to be dominated by genetic variation in genes other than the Vkorc1. This was particularly evident for M. m. domesticus, where a single haplotype was observed in conjunction with virtually the entire range of PT, BMD and BMC values of all 5 subspecies of Mus included in this study. Differences in these phenotypes between subspecies also should not be attributed to Vkorc1 variants, but should be viewed as a result of genome wide genetic divergence. PMID:19046458

HLA-E coding and 3' untranslated region variability determined by next-generation sequencing in two West-African population samples.

PubMed

Castelli, Erick C; Mendes-Junior, Celso T; Sabbagh, Audrey; Porto, Iane O P; Garcia, André; Ramalho, Jaqueline; Lima, Thálitta H A; Massaro, Juliana D; Dias, Fabrício C; Collares, Cristhianna V A; Jamonneau, Vincent; Bucheton, Bruno; Camara, Mamadou; Donadi, Eduardo A

2015-12-01

HLA-E is a non-classical Human Leucocyte Antigen class I gene with immunomodulatory properties. Whereas HLA-E expression usually occurs at low levels, it is widely distributed amongst human tissues, has the ability to bind self and non-self antigens and to interact with NK cells and T lymphocytes, being important for immunosurveillance and also for fighting against infections. HLA-E is usually the most conserved locus among all class I genes. However, most of the previous studies evaluating HLA-E variability sequenced only a few exons or genotyped known polymorphisms. Here we report a strategy to evaluate HLA-E variability by next-generation sequencing (NGS) that might be used to other HLA loci and present the HLA-E haplotype diversity considering the segment encoding the entire HLA-E mRNA (including 5'UTR, introns and the 3'UTR) in two African population samples, Susu from Guinea-Conakry and Lobi from Burkina Faso. Our results indicate that (a) the HLA-E gene is indeed conserved, encoding mainly two different protein molecules; (b) Africans do present several unknown HLA-E alleles presenting synonymous mutations; (c) the HLA-E 3'UTR is quite polymorphic and (d) haplotypes in the HLA-E 3'UTR are in close association with HLA-E coding alleles. NGS has proved to be an important tool on data generation for future studies evaluating variability in non-classical MHC genes. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

The evaluation of the photocatalytic activity of magnetic and non-magnetic polymorphs of Fe2O3 in natural sunlight exposure: A comparison of photocatalytic activity

NASA Astrophysics Data System (ADS)

Aslam, M.; Qamar, M. Tariq; Rehman, Ateeq Ur; Soomro, M. Tahir; Ali, Shahid; Ismail, I. M. I.; Hameed, A.

2018-09-01

The non-magnetic and magnetic polymorphs of iron oxide (Fe2O3) namely: α-Fe2O3 (hematite) and γ-Fe2O3 (maghemite) respectively, were synthesized by a facile surfactant aided hydrogel route. The synthesized polymorphs were characterized by diffuse reflectance, photoluminescence and raman spectroscopy for optical properties whereas the morphological, structural, chemical and electronic state evaluation were performed by FESEM, HRTEM, XRD, and XPS. The charge transport and the stability of the materials were examined electrochemically. The photocatalytic activity of the synthesized polymorphs was evaluated for the degradation of 2-chlorophenol and 2-nitrophenol in the exposure of the visible region and complete spectrum natural sunlight. Both the polymorphs exhibited a significantly high activity for the degradation of the phenolic substrate in the exposure of the complete spectrum of sunlight, however, the activity in the visible region of the sunlight was relatively lower. A substantial increase in the activity in the visible region was noticed when the polymorphs were exposed to complete spectrum sunlight prior to the photocatalytic experiments. The comparison of the exposed and unexposed samples revealed the induction of defects that served as traps for the excited electrons and increased activity of the polymorphs.

Merging molecular mechanism and evolution: theory and computation at the interface of biophysics and evolutionary population genetics

PubMed Central

Serohijos, Adrian W.R.; Shakhnovich, Eugene I.

2014-01-01

The variation among sequences and structures in nature is both determined by physical laws and by evolutionary history. However, these two factors are traditionally investigated by disciplines with different emphasis and philosophy—molecular biophysics on one hand and evolutionary population genetics in another. Here, we review recent theoretical and computational approaches that address the critical need to integrate these two disciplines. We first articulate the elements of these integrated approaches. Then, we survey their contribution to our mechanistic understanding of molecular evolution, the polymorphisms in coding region, the distribution of fitness effects (DFE) of mutations, the observed folding stability of proteins in nature, and the distribution of protein folds in genomes. PMID:24952216

Merging molecular mechanism and evolution: theory and computation at the interface of biophysics and evolutionary population genetics.

PubMed

Serohijos, Adrian W R; Shakhnovich, Eugene I

2014-06-01

The variation among sequences and structures in nature is both determined by physical laws and by evolutionary history. However, these two factors are traditionally investigated by disciplines with different emphasis and philosophy-molecular biophysics on one hand and evolutionary population genetics in another. Here, we review recent theoretical and computational approaches that address the crucial need to integrate these two disciplines. We first articulate the elements of these approaches. Then, we survey their contribution to our mechanistic understanding of molecular evolution, the polymorphisms in coding region, the distribution of fitness effects (DFE) of mutations, the observed folding stability of proteins in nature, and the distribution of protein folds in genomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Disease-modifying polymorphisms and C609Y mutation of RET associated with high penetrance of phaeochromocytoma and low rate of MTC in MEN2A.

PubMed

Speak, Rowena; Cook, Jackie; Harrison, Barney; Newell-Price, John

2016-01-01

Mutations of the rearranged during transfection ( RET ) proto-oncogene, located on chromosome 10q11.2, cause multiple endocrine neoplasia type 2A (MEN2A). Patients with mutations at the codon 609 usually exhibit a high penetrance of medullary thyroid cancer (MTC), but a sufficiently low penetrance of phaeochromocytoma that screening for this latter complication has been called to question. Patients with other RET mutations are at higher risk of younger age onset phaeochromocytoma if they also possess other RET polymorphisms (L769L, S836S, G691S and S904S), but there are no similar data for patients with 609 mutations. We investigated the unusual phenotypic presentation in a family with MEN2A due to a C609Y mutation in RET . Sanger sequencing of the entire RET -coding region and exon-intron boundaries was performed. Five family members were C609Y mutation positive: 3/5 initially presented with phaeochromocytoma, but only 1/5 had MTC. The index case aged 73 years had no evidence of MTC, but presented with phaeochromocytoma. Family members also possessed the G691S and S904S RET polymorphisms. We illustrate a high penetrance of phaeochromocytoma and low penetrance of MTC in patients with a RET C609Y mutation and polymorphisms G691S and S904S. These data highlight the need for life-long screening for the complications of MEN2A in these patients and support the role for the screening of RET polymorphisms for the purposes of risk stratification. C609Y RET mutations may be associated with a life-long risk of phaeochromocytoma indicating the importance of life-long screening for this condition in patients with MEN2A.C609Y RET mutations may be associated with a lower risk of MTC than often quoted, questioning the need for early prophylactic thyroid surgery discussion at the age of 5 years.There may be a role for the routine screening of RET polymorphisms, and this is greatly facilitated by the increasing ease of access to next-generation sequencing.

Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study

PubMed Central

Taylor, Steve M.; Parobek, Christian M.; DeConti, Derrick K.; Kayentao, Kassoum; Coulibaly, Sheick Oumar; Greenwood, Brian M.; Tagbor, Harry; Williams, John; Bojang, Kalifa; Njie, Fanta; Desai, Meghna; Kariuki, Simon; Gutman, Julie; Mathanga, Don P.; Mårtensson, Andreas; Ngasala, Billy; Conrad, Melissa D.; Rosenthal, Philip J.; Tshefu, Antoinette K.; Moormann, Ann M.; Vulule, John M.; Doumbo, Ogobara K.; ter Kuile, Feiko O.; Meshnick, Steven R.; Bailey, Jeffrey A.; Juliano, Jonathan J.

2015-01-01

Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance. PMID:25180240

Haplotypes and Sequence Variation in the Ovine Adiponectin Gene (ADIPOQ)

PubMed Central

An, Qing-Ming; Zhou, Hui-Tong; Hu, Jiang; Luo, Yu-Zhu; Hickford, Jon G. H.

2015-01-01

The adiponectin gene (ADIPOQ) plays an important role in energy homeostasis. In this study five separate regions (regions 1 to 5) of ovine ADIPOQ were analysed using PCR-SSCP. Four different PCR-SSCP patterns (A1-D1, A2-D2) were detected in region-1 and region-2, respectively, with seven and six SNPs being revealed. In region-3, three different patterns (A3-C3) and three SNPs were observed. Two patterns (A4-B4, A5-B5) and two and one SNPs were observed in region-4 and region-5, respectively. In total, nineteen SNPs were detected, with five of them in the coding region and two (c.46T/C and c.515G/A) putatively resulting in amino acid changes (p.Tyr16His and p.Lys172Arg). In region-1, -2 and -3 of 316 sheep from eight New Zealand breeds, variants A1, A2 and A3 were the most common, although variant frequencies differed in the eight breeds. Across region-1 and region-3, nine haplotypes were identified and haplotypes A1-A3, A1-C3, B1-A3 and B1-C3 were most common. These results indicate that the ADIPOQ gene is polymorphic and suggest that further analysis is required to see if the variation in the gene is associated with animal production traits. PMID:26610572

MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy.

PubMed

Mykkänen, A K; Koho, N M; Reeben, M; McGowan, C M; Pösö, A R

2011-12-01

Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val(432)Ile and Lys(457)Gln) and one in CD147 (Met(125)Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Polymorphism in the Serotonin Transporter Gene (SLC6A4) and Emotional Bipolar Disorder in Two Regional Mental Health Centers from the Eje Cafetero (Colombia)].

PubMed

Ramos, Lucero Rengifo; Arias, Duverney Gaviria; Salazar, Liliana Salazar; Vélez, Juan Pablo; Pardo, Stella Lozano

2012-03-01

The indel polymorphisms in the promoting region and the 2(nd) intron polymorphisms in the serotonin transporter gene (SLC6A4) have been associated to bipolar disorder 1 (BD1) in several population studies. The objective was to analyze the genotypic and allelic frequencies in both gene regions in a study of cases and controls with individuals from Risaralda and Quindío (Colombia) so as to establish possible associations to BD1, and compare results with previous and similar studies. 133 patients and 120 controls were studied. L and S indel polymorphisms in the promoting region were analyzed by PCR, together with VNTR STin2.10 and STin 2.12 VNTRs polymorphisms in the 2(nd) intron of the SL-C6A4 gene Genotypic and allelic frequencies for the S and L polymorphisms were similar both in cases and controls. However, the LL genotype was significantly increased both in BD1 population (OR=1.89; CI95%=1.1-3.68), and when discriminated by gender. This particular genotype in general population is OR=2.22; IC95%=1.04-5.66 for women, and OR=1.62; IC 95%=0.71-4.39 for men. No significant genotypic and allelic differences were found for VNTR STin2.10 and STin 2.12. polymorphisms. No association was found between polymorphisms of 5-HTTLPR polymorphisms and the 2(nd) intron of the serotonin transporting gene in general patients with BD1, nor when compared by gender. Our results are similar to those reported for Caucasian populations and differ from those of Asian and Brazilian populations. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Prolonged neutropenia after irinotecan-based chemotherapy in a child with polymorphisms of UGT1A1 and SLCO1B1.

PubMed

Sakaguchi, S; Garcia-Bournissen, F; Kim, R; Schwarz, U I; Nathan, P C; Ito, S

2009-12-01

Genetic polymorphisms of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and SLCO1B1 coding organic anion-transporter polypeptide 1B1, are independent risk factors known to increase irinotecan toxicity in adults. Although combined occurrence of polymorphisms in these 2 genes is likely to influence susceptibility to irinotecan toxicity, data are scarce, especially in children. We report an 11-year-old female with severe and prolonged neutropenia after irinotecan-based chemotherapy. The patient's genotyping revealed polymorphisms in both UGT1A1 and SLCO1B1. To our knowledge, this is the first case report of combined genotyping of both UGT1A1 and SLCO1B1 in a child with severe irinotecan toxicity.

Rapid Mitochondrial Genome Evolution through Invasion of Mobile Elements in Two Closely Related Species of Arbuscular Mycorrhizal Fungi

PubMed Central

Beaudet, Denis; Nadimi, Maryam; Iffis, Bachir; Hijri, Mohamed

2013-01-01

Arbuscular mycorrhizal fungi (AMF) are common and important plant symbionts. They have coenocytic hyphae and form multinucleated spores. The nuclear genome of AMF is polymorphic and its organization is not well understood, which makes the development of reliable molecular markers challenging. In stark contrast, their mitochondrial genome (mtDNA) is homogeneous. To assess the intra- and inter-specific mitochondrial variability in closely related Glomus species, we performed 454 sequencing on total genomic DNA of Glomus sp. isolate DAOM-229456 and we compared its mtDNA with two G. irregulare isolates. We found that the mtDNA of Glomus sp. is homogeneous, identical in gene order and, with respect to the sequences of coding regions, almost identical to G. irregulare. However, certain genomic regions vary substantially, due to insertions/deletions of elements such as introns, mitochondrial plasmid-like DNA polymerase genes and mobile open reading frames. We found no evidence of mitochondrial or cytoplasmic plasmids in Glomus species, and mobile ORFs in Glomus are responsible for the formation of four gene hybrids in atp6, atp9, cox2, and nad3, which are most probably the result of horizontal gene transfer and are expressed at the mRNA level. We found evidence for substantial sequence variation in defined regions of mtDNA, even among closely related isolates with otherwise identical coding gene sequences. This variation makes it possible to design reliable intra- and inter-specific markers. PMID:23637766

Rapid mitochondrial genome evolution through invasion of mobile elements in two closely related species of arbuscular mycorrhizal fungi.

PubMed

Beaudet, Denis; Nadimi, Maryam; Iffis, Bachir; Hijri, Mohamed

2013-01-01

Arbuscular mycorrhizal fungi (AMF) are common and important plant symbionts. They have coenocytic hyphae and form multinucleated spores. The nuclear genome of AMF is polymorphic and its organization is not well understood, which makes the development of reliable molecular markers challenging. In stark contrast, their mitochondrial genome (mtDNA) is homogeneous. To assess the intra- and inter-specific mitochondrial variability in closely related Glomus species, we performed 454 sequencing on total genomic DNA of Glomus sp. isolate DAOM-229456 and we compared its mtDNA with two G. irregulare isolates. We found that the mtDNA of Glomus sp. is homogeneous, identical in gene order and, with respect to the sequences of coding regions, almost identical to G. irregulare. However, certain genomic regions vary substantially, due to insertions/deletions of elements such as introns, mitochondrial plasmid-like DNA polymerase genes and mobile open reading frames. We found no evidence of mitochondrial or cytoplasmic plasmids in Glomus species, and mobile ORFs in Glomus are responsible for the formation of four gene hybrids in atp6, atp9, cox2, and nad3, which are most probably the result of horizontal gene transfer and are expressed at the mRNA level. We found evidence for substantial sequence variation in defined regions of mtDNA, even among closely related isolates with otherwise identical coding gene sequences. This variation makes it possible to design reliable intra- and inter-specific markers.

PTEN/MMAC1 Mutations in Hepatocellular Carcinomas: Somatic Inactivation of Both Alleles in Tumors

PubMed Central

Kawamura, Naoki; Nagai, Hisaki; Bando, Koichi; Koyama, Masaaki; Matsumoto, Satoshi; Tajiri, Takashi; Onda, Masahiko; Fujimoto, Jiro; Ueki, Takahiro; Konishi, Noboru; Shiba, Tadayoshi

1999-01-01

Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1‐bp insertion at codon 83–84 in exon 4 and two 4‐bp deletions, both at codon 318–319 in exon 8; two C‐to‐G transversion mutation, both at ‐9 bp from the initiation codon in the 5’non‐coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors. PMID:10363579

The Alpaca Melanocortin 1 Receptor: Gene Mutations, Transcripts, and Relative Levels of Expression in Ventral Skin Biopsies

PubMed Central

Renieri, Carlo; La Terza, Antonietta

2015-01-01

The objectives of the present study were to characterize the MC1R gene, its transcripts and the single nucleotide polymorphisms (SNPs) associated with coat color in alpaca. Full length cDNA amplification revealed the presence of two transcripts, named as F1 and F2, differing only in the length of their 5′-terminal untranslated region (UTR) sequences and presenting a color specific expression. Whereas the F1 transcript was common to white and colored (black and brown) alpaca phenotypes, the shorter F2 transcript was specific to white alpaca. Further sequencing of the MC1R gene in white and colored alpaca identified a total of twelve SNPs; among those nine (four silent mutations (c.126C>A, c.354T>C, c.618G>A, and c.933G>A); five missense mutations (c.82A>G, c.92C>T, c.259A>G, c.376A>G, and c.901C>T)) were observed in coding region and three in the 3′UTR. A 4 bp deletion (c.224 227del) was also identified in the coding region. Molecular segregation analysis uncovered that the combinatory mutations in the MC1R locus could cause eumelanin and pheomelanin synthesis in alpaca. Overall, our data refine what is known about the MC1R gene and provides additional information on its role in alpaca pigmentation. PMID:25685836

New Findings in eNOS gene and Thalidomide Embryopathy Suggest pre-transcriptional effect variants as susceptibility factors

PubMed Central

Kowalski, Thayne Woycinck; Fraga, Lucas Rosa; Tovo-Rodrigues, Luciana; Sanseverino, Maria Teresa Vieira; Hutz, Mara Helena; Schuler-Faccini, Lavínia; Vianna, Fernanda Sales Luiz

2016-01-01

Antiangiogenic properties of thalidomide have created an interest in the use of the drug in treatment of cancer. However, thalidomide is responsible for thalidomide embryopathy (TE). A lack of knowledge regarding the mechanisms of thalidomide teratogenesis acts as a barrier in the aim to synthesize a safer analogue of thalidomide. Recently, our group detected a higher frequency of alleles that impair the pro-angiogenic mechanisms of endothelial nitric oxide synthase (eNOS), coded by the NOS3 gene. In this study we evaluated variable number tandem repeats (VNTR) functional polymorphism in intron 4 of NOS3 in individuals with TE (38) and Brazilians without congenital anomalies (136). Haplotypes were estimated for this VNTR with previously analyzed polymorphisms, rs2070744 (−786C > T) and rs1799983 (894T > G), in promoter region and exon 7, respectively. Haplotypic distribution was different between the groups (p = 0.007). Alleles −786C (rs2070744) and 4b (VNTR), associated with decreased NOS3 expression, presented in higher frequency in TE individuals (p = 0.018; OR = 2.57; IC = 1.2–5.8). This association was not identified with polymorphism 894T > G (p = 0.079), which influences eNOS enzymatic activity. These results suggest variants in NOS3, with pre-transcriptional effects as susceptibility factors, influencing the risk TE development. This finding generates insight for a new approach to research that pursues a safer analogue. PMID:27004986

Genetic screening of the lipoprotein lipase gene for mutations in Chinese subjects with or without hypertriglyceridemia.

PubMed

Yang, Yuhong; Mu, Yunxiang; Zhao, Yu; Liu, Xinyu; Zhao, Lili; Wang, Junmei; Xie, Yonghong

2007-05-01

To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG). The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese subjects with (108 cases in the HTG group) or without HTG (278 cases in the control group), by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. One novel silent mutation L103L, one missense mutation P207L, three splicing mutations Int3/3'-ass/C(-6) --> T, and the common S447X polymorphism has been identified in the whole coding region and exon-intron junctions of the LPL gene were examined. Heterozygous P207L found in the HTG group was the first case reported in Asia and subsequently another P207L heterozygote was found in the proband's family, all of which suggested that P207L was one of the causes of familial combined hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3'-ass/C(-6) --> T was found in both groups in the present study although it was regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial polymorphism S447X, there was also some supportive evidence that the levels of triglycerides (TG) in S447X carriers were significantly lower than noncarriers in the subjects without HTG. The association between the LPL variants and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale screening should be necessary and justifiable.

High-resolution melting analysis of sequence variations in the cytidine deaminase gene (CDA) in patients with cancer treated with gemcitabine.

PubMed

Raynal, Caroline; Ciccolini, Joseph; Mercier, Cédric; Boyer, Jean-Christophe; Polge, Anne; Lallemant, Benjamin; Mouzat, Kévin; Lumbroso, Serge; Brouillet, Jean-Paul; Evrard, Alexandre

2010-02-01

Gemcitabine (2',2'-difluorodeoxycytidine) is a major antimetabolite cytotoxic drug with a wide spectrum of activity against solid tumors. Hepatic elimination of gemcitabine depends on a catabolic pathway through a deamination step driven by the enzyme cytidine deaminase (CDA). Severe hematologic toxicity to gemcitabine was reported in patients harboring genetic polymorphisms in CDA gene. High-resolution melting (HRM) analysis of polymerase chain reaction amplicon emerges today as a powerful technique for both genotyping and gene scanning strategies. In this study, 46 DNA samples from gemcitabine-treated patients were subjected to HRM analysis on a LightCycler 480 platform. Residual serum CDA activity was assayed as a surrogate marker for the overall functionality of this enzyme. Genotyping of three well-described single nucleotide polymorphisms in coding region (c.79A>C, c.208G>A and c.435C>T) was successfully achieved by HRM analysis of small polymerase chain reaction fragments, whereas unknown single nucleotide polymorphisms were searched by a gene scanning strategy with longer amplicons (up to 622 bp). The gene scanning strategy allowed us to find a new intronic mutation c.246+37G>A in a female patient displaying marked CDA deficiency and who had an extreme toxic reaction with a fatal outcome to gemcitabine treatment. Our work demonstrates that HRM-based methods, owing to their simplicity, reliability, and speed, are useful tools for diagnosis of CDA deficiency and could be of interest for personalized medicine.

Differential contribution of genomic regions to marked genetic variation and prediction of quantitative traits in broiler chickens.

PubMed

Abdollahi-Arpanahi, Rostam; Morota, Gota; Valente, Bruno D; Kranis, Andreas; Rosa, Guilherme J M; Gianola, Daniel

2016-02-03

Genome-wide association studies in humans have found enrichment of trait-associated single nucleotide polymorphisms (SNPs) in coding regions of the genome and depletion of these in intergenic regions. However, a recent release of the ENCyclopedia of DNA elements showed that ~80 % of the human genome has a biochemical function. Similar studies on the chicken genome are lacking, thus assessing the relative contribution of its genic and non-genic regions to variation is relevant for biological studies and genetic improvement of chicken populations. A dataset including 1351 birds that were genotyped with the 600K Affymetrix platform was used. We partitioned SNPs according to genome annotation data into six classes to characterize the relative contribution of genic and non-genic regions to genetic variation as well as their predictive power using all available quality-filtered SNPs. Target traits were body weight, ultrasound measurement of breast muscle and hen house egg production in broiler chickens. Six genomic regions were considered: intergenic regions, introns, missense, synonymous, 5' and 3' untranslated regions, and regions that are located 5 kb upstream and downstream of coding genes. Genomic relationship matrices were constructed for each genomic region and fitted in the models, separately or simultaneously. Kernel-based ridge regression was used to estimate variance components and assess predictive ability. Contribution of each class of genomic regions to dominance variance was also considered. Variance component estimates indicated that all genomic regions contributed to marked additive genetic variation and that the class of synonymous regions tended to have the greatest contribution. The marked dominance genetic variation explained by each class of genomic regions was similar and negligible (~0.05). In terms of prediction mean-square error, the whole-genome approach showed the best predictive ability. All genic and non-genic regions contributed to phenotypic variation for the three traits studied. Overall, the contribution of additive genetic variance to the total genetic variance was much greater than that of dominance variance. Our results show that all genomic regions are important for the prediction of the targeted traits, and the whole-genome approach was reaffirmed as the best tool for genome-enabled prediction of quantitative traits.

Associations between period 3 gene polymorphisms and sleep- /chronotype-related variables in patients with late-life insomnia.

PubMed

Mansour, Hader A; Wood, Joel; Chowdari, Kodavali V; Tumuluru, Divya; Bamne, Mikhil; Monk, Timothy H; Hall, Martica H; Buysse, Daniel J; Nimgaonkar, Vishwajit L

2017-01-01

A variable number tandem repeat polymorphism (VNTR) in the period 3 (PER3) gene has been associated with heritable sleep and circadian variables, including self-rated chronotypes, polysomnographic (PSG) variables, insomnia and circadian sleep-wake disorders. This report describes novel molecular and clinical analyses of PER3 VNTR polymorphisms to better define their functional consequences. As the PER3 VNTR is located in the exonic (protein coding) region of PER3, we initially investigated whether both alleles (variants) are transcribed into messenger RNA in human fibroblasts. The VNTR showed bi-allelic gene expression. We next investigated genetic associations in relation to clinical variables in 274 older adult Caucasian individuals. Independent variables included genotypes for the PER3 VNTR as well as a representative set of single nucleotide polymorphisms (SNPs) that tag common variants at the PER3 locus (linkage disequilibrium (LD) between genetic variants < 0.5). In order to comprehensively evaluate variables analyzed individually in prior analyses, dependent measures included PSG total sleep time and sleep latency, self-rated chronotype, estimated with the Composite Scale (CS), and lifestyle regularity, estimated using the social rhythm metric (SRM). Initially, genetic polymorphisms were individually analyzed in relation to each outcome variable using analysis of variance (ANOVA). Nominally significant associations were further tested using regression analyses that incorporated individual ANOVA-associated DNA variants as potential predictors and each of the selected sleep/circadian variables as outcomes. The covariates included age, gender, body mass index and an index of medical co-morbidity. Significant genetic associations with the VNTR were not detected with the sleep or circadian variables. Nominally significant associations were detected between SNP rs1012477 and CS scores (p = 0.003) and between rs10462021 and SRM (p = 0.047); rs11579477 and average delta power (p = 0.043) (analyses uncorrected for multiple comparisons). In conclusion, alleles of the VNTR are expressed at the transcript level and may have a functional effect in cells expressing the PER3 gene. PER3 polymorphisms had a modest impact on selected sleep/circadian variables in our sample, suggesting that PER3 is associated with sleep and circadian function beyond VNTR polymorphisms. Further replicate analyses in larger, independent samples are recommended.

A possible association between panic disorder and a polymorphism in the preproghrelingene.

PubMed

Hansson, Caroline; Annerbrink, Kristina; Nilsson, Staffan; Bah, Jessica; Olsson, Marie; Allgulander, Christer; Andersch, Sven; Sjödin, Ingemar; Eriksson, Elias; Dickson, Suzanne L

2013-03-30

The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

MC1R Genotype and Plumage Colouration in the Zebra Finch (Taeniopygia guttata): Population Structure Generates Artefactual Associations

PubMed Central

Hoffman, Joseph I.; Krause, E. Tobias; Lehmann, Katrin; Krüger, Oliver

2014-01-01

Polymorphisms at the melanocortin-1 receptor (MC1R) gene have been linked to coloration in many vertebrate species. However, the potentially confounding influence of population structure has rarely been controlled for. We explored the role of the MC1R in a model avian system by sequencing the coding region in 162 zebra finches comprising 79 wild type and 83 white individuals from five stocks. Allelic counts differed significantly between the two plumage morphs at multiple segregating sites, but these were mostly synonymous. To provide a control, the birds were genotyped at eight microsatellites and subjected to Bayesian cluster analysis, revealing two distinct groups. We therefore crossed wild type with white individuals and backcrossed the F1s with white birds. No significant associations were detected in the resulting offspring, suggesting that our original findings were a byproduct of genome-wide divergence. Our results are consistent with a previous study that found no association between MC1R polymorphism and plumage coloration in leaf warblers. They also contribute towards a growing body of evidence suggesting that care should be taken to quantify, and where necessary control for, population structure in association studies. PMID:24489736

Missense polymorphisms in the MC1R gene of the dog, red fox, arctic fox and Chinese raccoon dog.

PubMed

Nowacka-Woszuk, J; Salamon, S; Gorna, A; Switonski, M

2013-04-01

Coat colour variation is determined by many genes, one of which is the melanocortin receptor type 1 (MC1R) gene. In this study, we examined the whole coding sequence of this gene in four species belonging to the Canidae family (dog, red fox, arctic fox and Chinese raccoon dog). Although the comparative analysis of the obtained nucleotide sequences revealed a high conservation, which varied between 97.9 and 99.1%, we altogether identified 22 SNPs (10 in dogs, six in farmed red foxes, two in wild red foxes, three in arctic foxes and one in Chinese raccoon dog). Among them, seven appeared to be novel: one silent in the dog, three missense and one silent in the red fox, one in the 3'-flanking region in the arctic fox and one silent in the Chinese raccoon dog. In dogs and red foxes, the SNPs segregated as 10 and four haplotypes, respectively. Taking into consideration the published reports and results of this study, the highest number of missense polymorphisms was until now found in the dog (9) and red fox (7). © 2012 Blackwell Verlag GmbH.

Cloning, tissue expression and polymorphisms of chicken Krüppel-like factor 7 gene.

PubMed

Zhang, Zhi-Wei; Wang, Zhi-Peng; Zhang, Kun; Wang, Ning; Li, Hui

2013-07-01

Krüppel-like factor 7 (KLF7) has been extensively studied in mammalian species, but its role in birds is still unclear. In the current study, cloning and sequencing showed that the full-length coding region of chicken KLF7 (Gallus gallus KLF7, gKLF7) was 891 bp long, encoding 296 amino acids. In addition, real-time RT-PCR analysis showed that gKLF7 was broadly expressed in all 15 chicken tissues selected, and its expression was significantly different in spleen, proventriculus, abdominal fat, brain, leg muscle, gizzard and heart between fat and lean broilers at 7 weeks of age. Additionally, one novel single nucleotide polymorphism (SNP), XM_426569.3: c. A141G, was identified in the second exon of gKLF7. Association analysis showed that this locus was significantly associated with fatness traits in Arbor Acres broiler random population and the eighth generation of Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) population (P < 0.05). These results suggest that gKLF7 might be a candidate gene for chicken fatness traits. © 2013 Japanese Society of Animal Science.

Cracking the genomic piggy bank: identifying secrets of the pig genome.

PubMed

Mote, B E; Rothschild, M F

2006-01-01

Though researchers are uncovering valuable information about the pig genome at unprecedented speed, the porcine genome community is barely scratching the surface as to understanding interactions of the biological code. The pig genetic linkage map has nearly 5,000 loci comprised of genes, microsatellites, and amplified fragment length polymorphism markers. Likewise, the physical map is becoming denser with nearly 6,000 markers. The long awaited sequencing efforts are providing multidimensional benefits with sequence available for comparative genomics and identifying single nucleotide polymorphisms for use in linkage and trait association studies. Scientists are using exotic and commercial breeds for quantitative trait loci scans. Additionally, candidate gene studies continue to identify chromosomal regions or genes associated with economically important traits such as growth rate, leanness, feed intake, meat quality, litter size, and disease resistance. The commercial pig industry is actively incorporating these markers in marker-assisted selection along with traditional performance information to improve said traits. Researchers are utilizing novel tools including pig microarrays along with advanced bioinformatics to identify new candidate genes, understand gene function, and piece together gene networks involved in important biological processes. Advances in pig genomics and implications to the pork industry as well as human health are reviewed.

Null mutation of the MdACS3 gene, coding for a ripening-specific 1-aminocyclopropane-1-carboxylate synthase, leads to long shelf life in apple fruit.

PubMed

Wang, Aide; Yamakake, Junko; Kudo, Hisayuki; Wakasa, Yuhya; Hatsuyama, Yoshimichi; Igarashi, Megumi; Kasai, Atsushi; Li, Tianzhong; Harada, Takeo

2009-09-01

Expression of MdACS1, coding for 1-aminocyclopropane-1-carboxylate synthase (ACS), parallels the level of ethylene production in ripening apple (Malus domestica) fruit. Here we show that expression of another ripening-specific ACS gene (MdACS3) precedes the initiation of MdACS1 expression by approximately 3 weeks; MdACS3 expression then gradually decreases as MdACS1 expression increases. Because MdACS3 expression continues in ripening fruit treated with 1-methylcyclopropene, its transcription appears to be regulated by a negative feedback mechanism. Three genes in the MdACS3 family (a, b, and c) were isolated from a genomic library, but two of them (MdACS3b and MdACS3c) possess a 333-bp transposon-like insertion in their 5' flanking region that may prevent transcription of these genes during ripening. A single nucleotide polymorphism in the coding region of MdACS3a results in an amino acid substitution (glycine-289 --> valine) in the active site that inactivates the enzyme. Furthermore, another null allele of MdACS3a, Mdacs3a, showing no ability to be transcribed, was found by DNA sequencing. Apple cultivars homozygous or heterozygous for both null allelotypes showed no or very low expression of ripening-related genes and maintained fruit firmness. These results suggest that MdACS3a plays a crucial role in regulation of fruit ripening in apple, and is a possible determinant of ethylene production and shelf life in apple fruit.

Short poly-glutamine repeat in the androgen receptor in New World monkeys.

PubMed

Hiramatsu, Chihiro; Paukner, Annika; Kuroshima, Hika; Fujita, Kazuo; Suomi, Stephen J; Inoue-Murayama, Miho

2017-12-01

The androgen receptor mediates various physiological and developmental functions and is highly conserved in mammals. Although great intraspecific length polymorphisms in poly glutamine (poly-Q) and poly glycine (poly-G) regions of the androgen receptor in humans, apes and several Old World monkeys have been reported, little is known about the characteristics of these regions in New World monkeys. In this study, we surveyed 17 species of New World monkeys and found length polymorphisms in these regions in three species (common squirrel monkeys, tufted capuchin monkeys and owl monkeys). We found that the poly-Q region in New World monkeys is relatively shorter than that in catarrhines (humans, apes and Old World monkeys). In addition, we observed that codon usage for poly-G region in New World monkeys is unique among primates. These results suggest that the length of polymorphic regions in androgen receptor genes have evolved uniquely in New World monkeys.

BIALLELIC POLYMORPHISM IN THE INTRON REGION OF B-TUBULIN GENE OF CRYPTOSPORIDIUM PARASITES

EPA Science Inventory

Nucleotide sequencing of polymerase chain reaction-amplified intron region of the Cryptosporidium parvum B-tubulin gene in 26 human and 15 animal isolates revealed distinct genetic polymorphism between the human and bovine genotypes. The separation of 2 genotypes of C. parvum is...

Variations in endothelin receptor B subtype 2 (EDNRB2) coding sequences and mRNA expression levels in 4 Muscovy duck plumage colour phenotypes.

PubMed

Wu, N; Qin, H; Wang, M; Bian, Y; Dong, B; Sun, G; Zhao, W; Chang, G; Xu, Q; Chen, G

2017-04-01

1. Endothelin receptor B subtype 2 (EDNRB2) is a paralog of EDNRB, which encodes a 7-transmembrane G-protein coupled receptor. Previous studies reported that EDNRB was essential for melanoblast migration in mammals and ducks. 2. Muscovy ducks have different plumage colour phenotypes. Variations in EDNRB2 coding sequences (CDSs) and mRNA expression levels were investigated in 4 different Muscovy duck plumage colour phenotypes, including black, black mutant, silver and white head. 3. The EDNRB2 gene from Muscovy duck was cloned; it had a length of 6435 bp and encoded 437 amino acids. The coding region was screened and potential single nucleotide polymorphisms were identified. Eight mutations were obtained, including one missense variant (c.64C > T) and 7 synonymous substitutions. The substitutions were associated with plumage colour phenotypes. 4. The EDNRB2 mRNA expression levels were compared between feather pulp from black birds and black mutant birds. The results indicated that EDNRB2 transcripts in feather pulp were significantly higher in black feathers than in white feathers. 5. The results determined the variation of EDNRB2 CDS and mRNA expression in Muscovy ducks of various plumage colours.

New insights into mitogenomic phylogeny and copy number in eight indigenous sheep populations based on the ATP synthase and cytochrome c oxidase genes.

PubMed

Xiao, P; Niu, L L; Zhao, Q J; Chen, X Y; Wang, L J; Li, L; Zhang, H P; Guo, J Z; Xu, H Y; Zhong, T

2017-11-16

The origins and phylogeny of different sheep breeds has been widely studied using polymorphisms within the mitochondrial hypervariable region. However, little is known about the mitochondrial DNA (mtDNA) content and phylogeny based on mtDNA protein-coding genes. In this study, we assessed the phylogeny and copy number of the mtDNA in eight indigenous (population size, n=184) and three introduced (n=66) sheep breeds in China based on five mitochondrial coding genes (COX1, COX2, ATP8, ATP6 and COX3). The mean haplotype and nucleotide diversities were 0.944 and 0.00322, respectively. We identified a correlation between the lineages distribution and the genetic distance, whereby Valley-type Tibetan sheep had a closer genetic relationship with introduced breeds (Dorper, Poll Dorset and Suffolk) than with other indigenous breeds. Similarly, the Median-joining profile of haplotypes revealed the distribution of clusters according to genetic differences. Moreover, copy number analysis based on the five mitochondrial coding genes was affected by the genetic distance combining with genetic phylogeny; we also identified obvious non-synonymous mutations in ATP6 between the different levels of copy number expressions. These results imply that differences in mitogenomic compositions resulting from geographical separation lead to differences in mitochondrial function.

Molecular characterization of the canine mitochondrial DNA control region for forensic applications.

PubMed

Eichmann, Cordula; Parson, Walther

2007-09-01

The canine mitochondrial DNA (mtDNA) control region of 133 dogs living in the area around Innsbruck, Austria was sequenced. A total of 40 polymorphic sites were observed in the first hypervariable segment and 15 in the second, which resulted in the differentiation of 40 distinct haplotypes. We observed five nucleotide positions that were highly polymorphic within different haplogroups, and they represent good candidates for mtDNA screening. We found five point heteroplasmic positions; all located in HVS-I and a polythymine region in HVS-II, the latter often being associated with length heteroplasmy. In contrast to human mtDNA, the canine control region contains a hypervariable 10 nucleotide repeat region, which is located between the two hypervariable regions. In our population sample, we observed eight different repeat types, which we characterized by direct sequencing and fragment length analysis. The discrimination power of the canine mtDNA control region was 0.93, not taking the polymorphic repeat region into consideration.

Single Nucleotide Polymorphisms Can Create Alternative Polyadenylation Signals and Affect Gene Expression through Loss of MicroRNA-Regulation

PubMed Central

Thomas, Laurent F.; Sætrom, Pål

2012-01-01

Alternative polyadenylation (APA) can for example occur when a protein-coding gene has several polyadenylation (polyA) signals in its last exon, resulting in messenger RNAs (mRNAs) with different 3′ untranslated region (UTR) lengths. Different 3′UTR lengths can give different microRNA (miRNA) regulation such that shortened transcripts have increased expression. The APA process is part of human cells' natural regulatory processes, but APA also seems to play an important role in many human diseases. Although altered APA in disease can have many causes, we reasoned that mutations in DNA elements that are important for the polyA process, such as the polyA signal and the downstream GU-rich region, can be one important mechanism. To test this hypothesis, we identified single nucleotide polymorphisms (SNPs) that can create or disrupt APA signals (APA-SNPs). By using a data-integrative approach, we show that APA-SNPs can affect 3′UTR length, miRNA regulation, and mRNA expression—both between homozygote individuals and within heterozygote individuals. Furthermore, we show that a significant fraction of the alleles that cause APA are strongly and positively linked with alleles found by genome-wide studies to be associated with disease. Our results confirm that APA-SNPs can give altered gene regulation and that APA alleles that give shortened transcripts and increased gene expression can be important hereditary causes for disease. PMID:22915998

Analysis of nucleotide diversity among alleles of the major bacterial blight resistance gene Xa27 in cultivars of rice (Oryza sativa) and its wild relatives.

PubMed

Bimolata, Waikhom; Kumar, Anirudh; Sundaram, Raman Meenakshi; Laha, Gouri Shankar; Qureshi, Insaf Ahmed; Reddy, Gajjala Ashok; Ghazi, Irfan Ahmad

2013-08-01

Xa27 is one of the important R-genes, effective against bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo). Using natural population of Oryza, we analyzed the sequence variation in the functionally important domains of Xa27 across the Oryza species. DNA sequences of Xa27 alleles from 27 rice accessions revealed higher nucleotide diversity among the reported R-genes of rice. Sequence polymorphism analysis revealed synonymous and non-synonymous mutations in addition to a number of InDels in non-coding regions of the gene. High sequence variation was observed in the promoter region including the 5'UTR with 'π' value 0.00916 and 'θ w ' = 0.01785. Comparative analysis of the identified Xa27 alleles with that of IRBB27 and IR24 indicated the operation of both positive selection (Ka/Ks > 1) and neutral selection (Ka/Ks ≈ 0). The genetic distances of alleles of the gene from Oryza nivara were nearer to IRBB27 as compared to IR24. We also found the presence of conserved and null UPT (upregulated by transcriptional activator) box in the isolated alleles. Considerable amino acid polymorphism was localized in the trans-membrane domain for which the functional significance is yet to be elucidated. However, the absence of functional UPT box in all the alleles except IRBB27 suggests the maintenance of single resistant allele throughout the natural population.

Positive selection in the SLC11A1 gene in the family Equidae.

PubMed

Bayerova, Zuzana; Janova, Eva; Matiasovic, Jan; Orlando, Ludovic; Horin, Petr

2016-05-01

Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence identity across the family. Single nucleotide polymorphisms (SNPs) were found in the coding and noncoding regions of the gene. Seven codon sites were identified to be under strong purifying selection. Codons located in three regions, including the glycosylated extracellular loop, were shown to be under diversifying selection. A 3-bp indel resulting in a deletion of the amino acid 321 in the predicted protein was observed in all horses, while it has been maintained in all other equid species. This codon comprised in an N-glycosylation site was found to be under positive selection. Interspecific variation in the presence of predicted N-glycosylation sites was observed.

Genetic polymorphisms of the IGF-II gene intron 8 coding region and its association with growth and carcass traits in yak.

PubMed

Zeng, Y F; Ding, X Z; Cheng, S R; Yu, S J

2013-12-11

Insulin-like growth factor II (IGF-II) plays a key role in mammalian growth and is involved in stimulating fetal cell division, differentiation, and metabolic regulation. IGF-II is considered a candidate gene for genetic markers of growth and carcass traits. Therefore, in this study, the associations of single nucleotide polymorphisms (SNPs) in the IGF-II gene region with growth and carcass characteristics in five yak breeds were investigated. Two SNPs, G(330)C and A(358)G, were identified by sequencing intron 8 of the IGF-II gene in homozygotes. Two alleles, A and B, and three genotypes, AA, AB, and BB, were identified by polymerase chain reaction. Genotypic frequencies of IGF-II allele B were 0.8623, 0.8936, 0.8535, 0.8676, and 0.8300 for Datong yak, Gannan yak, Tianzhu white yak, Qinghai Plateau yak, and Xinjiang yak, respectively. Allele and the genotype of IGF-II were strongly associated with growth and carcass traits. Least square analysis revealed a significant effect (P < 0.01) of genotypes AA and AB compared with genotype BB on live-weight (at 12, 13-24, and 25-36 months of age), average daily weight gain (P < 0.01) and carcass weight (P < 0.05). Animals with genotype AB had a higher mean rib eye area, and a lower mean yield grade. The results indicated that the IGF-II gene acts by a primarily additive biological mechanism by adding weight independently of skeletal growth.

Mutational screening of FGFR1, CER1, and CDON in a large cohort of trigonocephalic patients.

PubMed

Jehee, Fernanda Sarquis; Alonso, Luis G; Cavalcanti, Denise P; Kim, Chong; Wall, Steven A; Mulliken, John B; Sun, Miao; Jabs, Ethylin Wang; Boyadjiev, Simeon A; Wilkie, Andrew O M; Passos-Bueno, Maria Rita

2006-03-01

Screen the known craniosynostotic related gene, FGFR1 (exon 7), and two new identified potential candidates, CER1 and CDON, in patients with syndromic and nonsyndromic metopic craniosynostosis to determine if they might be causative genes. Using single-strand conformational polymorphisms (SSCPs), denaturing high-performance liquid chromatography, and/or direct sequencing, we analyzed a total of 81 patients for FGFR1 (exon 7), 70 for CER1, and 44 for CDON. Patients were ascertained in the Centro de Estudos do Genoma Humano in São Paulo, Brazil (n = 39), the Craniofacial Unit, Oxford, U.K. (n = 23), and the Johns Hopkins University, Baltimore, Maryland (n = 31). Clinical inclusion criteria included a triangular head and/or forehead, with or without a metopic ridge, and a radiographic documentation of metopic synostosis. Both syndromic and nonsyndromic patients were studied. No sequence alterations were found for FGFR1 (exon 7). Different patterns of SSCP migration for CER1 compatible with the segregation of single nucleotide polymorphisms reported in the region were identified. Seventeen sequence alterations were detected in the coding region of CDON, seven of which are new, but segregation analysis in parents and homology studies did not indicate a pathological role. FGFR1 (exon 7), CER1, and CDON are not related to trigonocephaly in our sample and should not be considered as causative genes for metopic synostosis. Screening of FGFR1 (exon 7) for diagnostic purposes should not be performed in trigonocephalic patients.

How the Leopard Hides Its Spots: ASIP Mutations and Melanism in Wild Cats

PubMed Central

Schneider, Alexsandra; David, Victor A.; Johnson, Warren E.; O'Brien, Stephen J.; Barsh, Gregory S.; Menotti-Raymond, Marilyn; Eizirik, Eduardo

2012-01-01

The occurrence of melanism (darkening of the background coloration) is documented in 13 felid species, in some cases reaching high frequencies at the population level. Recent analyses have indicated that it arose multiple times in the Felidae, with three different species exhibiting unique mutations associated with this trait. The causative mutations in the remaining species have so far not been identified, precluding a broader assessment of the evolutionary dynamics of melanism in the Felidae. Among these, the leopard (Panthera pardus) is a particularly important target for research, given the iconic status of the ‘black panther’ and the extremely high frequency of melanism observed in some Asian populations. Another felid species from the same region, the Asian golden cat (Pardofelis temminckii), also exhibits frequent records of melanism in some areas. We have sequenced the coding region of the Agouti Signaling Protein (ASIP) gene in multiple leopard and Asian golden cat individuals, and identified distinct mutations strongly associated with melanism in each of them. The single nucleotide polymorphism (SNP) detected among the P. pardus individuals was caused by a nonsense mutation predicted to completely ablate ASIP function. A different SNP was identified in P. temminckii, causing a predicted amino acid change that should also induce loss of function. Our results reveal two additional cases of species-specific mutations implicated in melanism in the Felidae, and indicate that ASIP mutations may play an important role in naturally-occurring coloration polymorphism. PMID:23251368

How the leopard hides its spots: ASIP mutations and melanism in wild cats.

PubMed

Schneider, Alexsandra; David, Victor A; Johnson, Warren E; O'Brien, Stephen J; Barsh, Gregory S; Menotti-Raymond, Marilyn; Eizirik, Eduardo

2012-01-01

The occurrence of melanism (darkening of the background coloration) is documented in 13 felid species, in some cases reaching high frequencies at the population level. Recent analyses have indicated that it arose multiple times in the Felidae, with three different species exhibiting unique mutations associated with this trait. The causative mutations in the remaining species have so far not been identified, precluding a broader assessment of the evolutionary dynamics of melanism in the Felidae. Among these, the leopard (Panthera pardus) is a particularly important target for research, given the iconic status of the 'black panther' and the extremely high frequency of melanism observed in some Asian populations. Another felid species from the same region, the Asian golden cat (Pardofelis temminckii), also exhibits frequent records of melanism in some areas. We have sequenced the coding region of the Agouti Signaling Protein (ASIP) gene in multiple leopard and Asian golden cat individuals, and identified distinct mutations strongly associated with melanism in each of them. The single nucleotide polymorphism (SNP) detected among the P. pardus individuals was caused by a nonsense mutation predicted to completely ablate ASIP function. A different SNP was identified in P. temminckii, causing a predicted amino acid change that should also induce loss of function. Our results reveal two additional cases of species-specific mutations implicated in melanism in the Felidae, and indicate that ASIP mutations may play an important role in naturally-occurring coloration polymorphism.

Natural variations in OsγTMT contribute to diversity of the α-tocopherol content in rice.

PubMed

Wang, Xiao-Qiang; Yoon, Min-Young; He, Qiang; Kim, Tae-Sung; Tong, Wei; Choi, Bu-Woong; Lee, Young-Sang; Park, Yong-Jin

2015-12-01

Tocopherols and tocotrienols, collectively known as tocochromanols, are lipid-soluble molecules that belong to the group of vitamin E compounds. Among them, α-tocopherol (αΤ) is one of the antioxidants with diverse functions and benefits for humans and animals. Thus, understanding the genetic basis of these traits would be valuable to improve nutritional quality by breeding in rice. Genome-wide association study (GWAS) has emerged as a powerful strategy for identifying genes or quantitative trait loci (QTL) underlying complex traits in plants. To discover the genes or QTLs underlying the naturally occurring variations of αΤ content in rice, we performed GWAS using 1.44 million high-quality single-nucleotide polymorphisms acquired from re-sequencing of 137 accessions from a diverse rice core collection. Thirteen candidate genes were found across 2-year phenotypic data, among which gamma-tocopherol methyltransferase (OsγTMT) was identified as the major factor responsible for the αΤ content among rice accessions. Nucleotide variations in the coding region of OsγTMT were significantly associated with the αΤ content variations, while nucleotide polymorphisms in the promoter region of OsγTMT also could partly demonstrate the correlation with αΤ content variations, according to our RNA expression analyses. This study provides useful information for genetic factors underlying αΤ content variations in rice, which will significantly contribute the research on αΤ biosynthesis mechanisms and αΤ improvement of rice.

Genetic variations in the hotspot region of RS1 gene in Indian patients with juvenile X-linked retinoschisis.

PubMed

Suganthalakshmi, Balasubbu; Shukla, Dhananjay; Rajendran, Anand; Kim, Ramasamy; Nallathambi, Jeyabalan; Sundaresan, Periasamy

2007-04-19

X-linked juvenile retinoschisis (XLRS) is the leading cause of macular degeneration in males. This condition is caused by mutations in the RS1 gene and is, characterized by schisis within the retina. The purpose of this study was to identify the mutations in the RS1 gene associated with XLRS in an Indian cohort. The coding region of RS1 was analyzed for mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and restriction fragment length polymorphism (RFLP) analysis in six unrelated subjects clinically diagnosed as having XLRS and in their available family members. Direct sequencing was performed for all samples that displayed an electrophoretic mobility shift in SSCP gel. Mutation analysis of RS1 gene revealed five mutations in exon 6 like c.574C>T, c.583A>G, c.608C>T, c.617G>A, and c.637C>T, respectively, among them four missense mutations, one nonsense mutation, and two novel sequence variations. These mutations were found in individuals who exhibited clinical features of bilateral foveal and peripheral retinoschisis consistent with XLRS. The mutations were absent in the 100 age matched control samples analyzed. This is the first report of mutations in RS1 to be associated with XLRS in the Indian population. The identified genetic variations, phenotype and genotype correlations were consistent with other studies. Identification of the causative mutation in patients with XLRS is helpful in confirming the diagnosis and in counseling of family members.

Chromosomal localization and partial genomic structure of the human peroxisome proliferator activated receptor-gamma (hPPAR gamma) gene.

PubMed

Beamer, B A; Negri, C; Yen, C J; Gavrilova, O; Rumberger, J M; Durcan, M J; Yarnall, D P; Hawkins, A L; Griffin, C A; Burns, D K; Roth, J; Reitman, M; Shuldiner, A R

1997-04-28

We determined the chromosomal localization and partial genomic structure of the coding region of the human PPAR gamma gene (hPPAR gamma), a nuclear receptor important for adipocyte differentiation and function. Sequence analysis and long PCR of human genomic DNA with primers that span putative introns revealed that intron positions and sizes of hPPAR gamma are similar to those previously determined for the mouse PPAR gamma gene[13]. Fluorescent in situ hybridization localized hPPAR gamma to chromosome 3, band 3p25. Radiation hybrid mapping with two independent primer pairs was consistent with hPPAR gamma being within 1.5 Mb of marker D3S1263 on 3p25-p24.2. These sequences of the intron/exon junctions of the 6 coding exons shared by hPPAR gamma 1 and hPPAR gamma 2 will facilitate screening for possible mutations. Furthermore, D3S1263 is a suitable polymorphic marker for linkage analysis to evaluate PPAR gamma's potential contribution to genetic susceptibility to obesity, lipoatrophy, insulin resistance, and diabetes.

Microsatellite primers for vulnerable seagrass Halophila beccarii (Hydrocharitaceae).

PubMed

Jiang, Kai; Shi, Yi-Su; Zhang, Jian; Xu, Na-Na

2011-06-01

Polymorphic microsatellite primers were developed in the vulnerable seagrass Halophila beccarii to investigate genetic variation and provide necessary markers for studying its population genetic structure. Six polymorphic and six monomorphic microsatellite loci were developed in H. beccarii. Most loci were successfully amplified across 40 H. beccarii individuals collected from three populations from coastal regions of southern China. Two to four alleles per locus were observed at the six polymorphic loci. The highest expected heterozygosity was 0.5737. The results demonstrate low levels of polymorphism in H. beccarii from coastal regions of southern China. They also illustrate that these primers may be useful for studying the mating system and population genetics of H. beccarii on a global scale.

Dynamically Alterable Arrays of Polymorphic Data Types

NASA Technical Reports Server (NTRS)

James, Mark

2006-01-01

An application library package was developed that represents data packets for Deep Space Network (DSN) message packets as dynamically alterable arrays composed of arbitrary polymorphic data types. The software was to address a limitation of the present state of the practice for having an array directly composed of a single monomorphic data type. This is a severe limitation when one is dealing with science data in that the types of objects one is dealing with are typically not known in advance and, therefore, are dynamic in nature. The unique feature of this approach is that it enables one to define at run-time the dynamic shape of the matrix with the ability to store polymorphic data types in each of its indices. Existing languages such as C and C++ have the restriction that the shape of the array must be known in advance and each of its elements be a monomorphic data type that is strictly defined at compile-time. This program can be executed on a variety of platforms. It can be distributed in either source code or binary code form. It must be run in conjunction with any one of a number of Lisp compilers that are available commercially or as shareware.

Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.

PubMed

Hewett, Duncan; Samuelsson, Lena; Polding, Joanne; Enlund, Fredrik; Smart, Devi; Cantone, Kathryn; See, Chee Gee; Chadha, Sapna; Inerot, Annica; Enerback, Charlotta; Montgomery, Doug; Christodolou, Chris; Robinson, Phil; Matthews, Paul; Plumpton, Mary; Wahlstrom, Jan; Swanbeck, Gunnar; Martinsson, Tommy; Roses, Allen; Riley, John; Purvis, Ian

2002-03-01

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

A modified Stillinger-Weber potential for TlBr and its polymorphic extension

DOE PAGES

Zhou, Xiaowang; Foster, Michael E.; Jones, Reese E.; ...

2015-04-30

TlBr is promising for g- and x- radiation detection, but suffers from rapid performance degradation under the operating external electric fields. To enable molecular dynamics (MD) studies of this degradation, we have developed a Stillinger-Weber type of TlBr interatomic potential. During this process, we have also addressed two problems of wider interests. First, the conventional Stillinger-Weber potential format is only applicable for tetrahedral structures (e.g., diamond-cubic, zinc-blende, or wurtzite). Here we have modified the analytical functions of the Stillinger-Weber potential so that it can now be used for other crystal structures. Second, past modifications of interatomic potentials cannot always bemore » applied by a broad community because any new analytical functions of the potential would require corresponding changes in the molecular dynamics codes. Here we have developed a polymorphic potential model that simultaneously incorporates Stillinger-Weber, Tersoff, embedded-atom method, and any variations (i.e., modified functions) of these potentials. As a result, we have implemented this polymorphic model in MD code LAMMPS, and demonstrated that our TlBr potential enables stable MD simulations under external electric fields.« less

Informativeness of single nucleotide polymorphisms and relationships among onion populations from important world production regions

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) were genotyped using a high-density array and DNAs from individual plants from important onion populations from major production regions world-wide and the likely progenitor of onion, Allium vavilovii. Genotypes at 1226 SNPs were used to estimate genetic relati...

Relationships among calpastatin single nucleotide polymorphisms, calpastatin expression and tenderness in pork longissimus

USDA-ARS?s Scientific Manuscript database

Genome scans in the pig have identified a region on chromosome 2 (SSC2) associated with tenderness. Calpastatin is a likely positional candidate gene in this region because of its inhibitory role in the calpain system that is involved in postmortem tenderization. Novel single nucleotide polymorphism...

Variability of CAG tandem repeats in exon 1 of the androgen receptor gene is not related with dog intersexuality.

PubMed

Nowacka-Woszuk, J; Switonski, M

2010-02-01

Numerous mutations of the human androgen receptor (AR) gene cause an intersexual phenotype, called the androgen insensitivity syndrome. The intersexual phenotype is also quite often diagnosed in dogs. The aim of this study was to conduct a comparative analysis of the entire coding sequence (eight exons) of the AR gene in healthy and four intersex dogs, as well as in three other canids (the red fox, arctic fox and Chinese raccoon dog). The coding sequence of the studied species appeared to be conserved (similarity above 97%) and polymorphism was found in exon 1 only. Altogether, 2 SNPs were identified in healthy dogs, 14 in red foxes, 16 in arctic foxes and 6 were found in Chinese raccoon dogs, respectively. Moreover, a variable number of tandem repeats (CAG and CAA), encoding an array of glutamines, was also observed in this exon. The CAA codon numbers were invariable within species, but the CAG repeats were polymorphic. The highest number of the CAG and CAA repeats was found in dogs (from 40 to 42) and the observed variability was similar in intersex and healthy dogs. In the other canids the variability fell within the following ranges: 29-37 (red fox), 37-39 (arctic fox) and 29-32 (Chinese raccoon dog). In addition, a polymorphic microsatellite marker in intron 2 was found in the dog, red fox and Chinese raccoon dog. It was concluded that the polymorphism level of the AR gene in the dog was lower than in the other canids and none of the detected polymorphisms, including variability of the CAG tandem repeats, could be related with the intersexual phenotype of the studied dogs.

Pharmacogenetics of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1): gene resequencing, sequence variation, and functional genomics.

PubMed

Xu, Zhen-Hua; Thomae, Bianca A; Eckloff, Bruce W; Wieben, Eric D; Weinshilboum, Richard M

2003-06-01

3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is the high-energy "sulfate donor" for reactions catalyzed by sulfotransferase (SULT) enzymes. The strict requirement of SULTs for PAPS suggests that PAPS synthesis might influence the rate of sulfate conjugation. In humans, PAPS is synthesized from ATP and SO(4)(2-) by two isoforms of PAPS synthetase (PAPSS): PAPSS1 and PAPSS2. As a step toward pharmacogenetic studies, we have resequenced the entire coding sequence of the human PAPSS1 gene, including exon-intron splice junctions, using DNA samples from 60 Caucasian-American and 58 African-American subjects. Twenty-one genetic polymorphisms were observed-1 insertion-deletion event and 20 single nucleotide polymorphisms (SNPs)-including two non-synonymous coding SNPs (cSNPs) that altered the following amino acids: Arg333Cys and Glu531Gln. Twelve pairs of these polymorphisms were tightly linked, and a total of twelve unequivocal haplotypes could be identified-two that were common to both ethnic groups and ten that were ethnic-specific. The Arg333Cys polymorphism, with an allele frequency of 2.5%, was observed only in DNA samples from Caucasian subjects. The Glu531Gln polymorphism was rare, with only a single copy of that allele in a DNA sample from an African-American subject. Transient expression in mammalian cells showed that neither of the non-synonymous cSNPs resulted in a change in the basal level of enzyme activity measured under optimal assay conditions. However, the Glu531Gln polymorphism altered the substrate kinetic properties of the enzyme. The Gln531 variant allozyme had a 5-fold higher K(m) value for SO(4)(2-) than did the wild-type allozyme and displayed monophasic kinetics for Na(2)SO(4). The wild-type allozyme (Glu531) showed biphasic kinetics for that substrate. These observations represent a step toward testing the hypothesis that genetic variation in PAPS synthesis catalyzed by PAPSS1 might alter in vivo sulfate conjugation.

Variation in conserved non-coding sequences on chromosome 5q andsusceptibility to asthma and atopy

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

Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng

2005-09-10

Background: Evolutionarily conserved sequences likely havebiological function. Methods: To determine whether variation in conservedsequences in non-coding DNA contributes to risk for human disease, westudied six conserved non-coding elements in the Th2 cytokine cluster onhuman chromosome 5q31 in a large Hutterite pedigree and in samples ofoutbred European American and African American asthma cases and controls.Results: Among six conserved non-coding elements (>100 bp,>70percent identity; human-mouse comparison), we identified one singlenucleotide polymorphism (SNP) in each of two conserved elements and sixSNPs in the flanking regions of three conserved elements. We genotypedour samples for four of these SNPs and an additional three SNPs eachmore » inthe IL13 and IL4 genes. While there was only modest evidence forassociation with single SNPs in the Hutterite and European Americansamples (P<0.05), there were highly significant associations inEuropean Americans between asthma and haplotypes comprised of SNPs in theIL4 gene (P<0.001), including a SNP in a conserved non-codingelement. Furthermore, variation in the IL13 gene was strongly associatedwith total IgE (P = 0.00022) and allergic sensitization to mold allergens(P = 0.00076) in the Hutterites, and more modestly associated withsensitization to molds in the European Americans and African Americans (P<0.01). Conclusion: These results indicate that there is overalllittle variation in the conserved non-coding elements on 5q31, butvariation in IL4 and IL13, including possibly one SNP in a conservedelement, influence asthma and atopic phenotypes in diversepopulations.« less

Characterization of a new high copy Stowaway family MITE, BRAMI-1 in Brassica genome

PubMed Central

2013-01-01

Background Miniature inverted-repeat transposable elements (MITEs) are expected to play important roles in evolution of genes and genome in plants, especially in the highly duplicated plant genomes. Various MITE families and their roles in plants have been characterized. However, there have been fewer studies of MITE families and their potential roles in evolution of the recently triplicated Brassica genome. Results We identified a new MITE family, BRAMI-1, belonging to the Stowaway super-family in the Brassica genome. In silico mapping revealed that 697 members are dispersed throughout the euchromatic regions of the B. rapa pseudo-chromosomes. Among them, 548 members (78.6%) are located in gene-rich regions, less than 3 kb from genes. In addition, we identified 516 and 15 members in the 470 Mb and 15 Mb genomic shotgun sequences currently available for B. oleracea and B. napus, respectively. The resulting estimated copy numbers for the entire genomes were 1440, 1464 and 2490 in B. rapa, B. oleracea and B. napus, respectively. Concurrently, only 70 members of the related Arabidopsis ATTIRTA-1 MITE family were identified in the Arabidopsis genome. Phylogenetic analysis revealed that BRAMI-1 elements proliferated in the Brassica genus after divergence from the Arabidopsis lineage. MITE insertion polymorphism (MIP) was inspected for 50 BRAMI-1 members, revealing high levels of insertion polymorphism between and within species of Brassica that clarify BRAMI-1 activation periods up to the present. Comparative analysis of the 71 genes harbouring the BRAMI-1 elements with their non-insertion paralogs (NIPs) showed that the BRAMI-1 insertions mainly reside in non-coding sequences and that the expression levels of genes with the elements differ from those of their NIPs. Conclusion A Stowaway family MITE, named as BRAMI-1, was gradually amplified and remained present in over than 1400 copies in each of three Brassica species. Overall, 78% of the members were identified in gene-rich regions, and it is assumed that they may contribute to the evolution of duplicated genes in the highly duplicated Brassica genome. The resulting MIPs can serve as a good source of DNA markers for Brassica crops because the insertions are highly dispersed in the gene-rich euchromatin region and are polymorphic between or within species. PMID:23547712

Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.

PubMed

Janova, Eva; Matiasovic, Jan; Vahala, Jiri; Vodicka, Roman; Van Dyk, Enette; Horin, Petr

2009-07-01

The major histocompatibility complex genes coding for antigen binding and presenting molecules are the most polymorphic genes in the vertebrate genome. We studied the DRA and DQA gene polymorphism of the family Equidae. In addition to 11 previously reported DRA and 24 DQA alleles, six new DRA sequences and 13 new DQA alleles were identified in the genus Equus. Phylogenetic analysis of both DRA and DQA sequences provided evidence for trans-species polymorphism in the family Equidae. The phylogenetic trees differed from species relationships defined by standard taxonomy of Equidae and from trees based on mitochondrial or neutral gene sequence data. Analysis of selection showed differences between the less variable DRA and more variable DQA genes. DRA alleles were more often shared by more species. The DQA sequences analysed showed strong amongst-species positive selection; the selected amino acid positions mostly corresponded to selected positions in rodent and human DQA genes.

Fine-scale genetic mapping of a hybrid sterility factor between Drosophila simulans and D. mauritiana: the varied and elusive functions of "speciation genes".

PubMed

Araripe, Luciana O; Montenegro, Horácio; Lemos, Bernardo; Hartl, Daniel L

2010-12-14

Hybrid male sterility (HMS) is a usual outcome of hybridization between closely related animal species. It arises because interactions between alleles that are functional within one species may be disrupted in hybrids. The identification of genes leading to hybrid sterility is of great interest for understanding the evolutionary process of speciation. In the current work we used marked P-element insertions as dominant markers to efficiently locate one genetic factor causing a severe reduction in fertility in hybrid males of Drosophila simulans and D. mauritiana. Our mapping effort identified a region of 9 kb on chromosome 3, containing three complete and one partial coding sequences. Within this region, two annotated genes are suggested as candidates for the HMS factor, based on the comparative molecular characterization and public-source information. Gene Taf1 is partially contained in the region, but yet shows high polymorphism with four fixed non-synonymous substitutions between the two species. Its molecular functions involve sequence-specific DNA binding and transcription factor activity. Gene agt is a small, intronless gene, whose molecular function is annotated as methylated-DNA-protein-cysteine S-methyltransferase activity. High polymorphism and one fixed non-synonymous substitution suggest this is a fast evolving gene. The gene trees of both genes perfectly separate D. simulans and D. mauritiana into monophyletic groups. Analysis of gene expression using microarray revealed trends that were similar to those previously found in comparisons between whole-genome hybrids and parental species. The identification following confirmation of the HMS candidate gene will add another case study leading to understanding the evolutionary process of hybrid incompatibility.

Analysis of the mitochondrial genome of cheetahs (Acinonyx jubatus) with neurodegenerative disease.

PubMed

Burger, Pamela A; Steinborn, Ralf; Walzer, Christian; Petit, Thierry; Mueller, Mathias; Schwarzenberger, Franz

2004-08-18

The complete mitochondrial genome of Acinonyx jubatus was sequenced and mitochondrial DNA (mtDNA) regions were screened for polymorphisms as candidates for the cause of a neurodegenerative demyelinating disease affecting captive cheetahs. The mtDNA reference sequences were established on the basis of the complete sequences of two diseased and two nondiseased animals as well as partial sequences of 26 further individuals. The A. jubatus mitochondrial genome is 17,047-bp long and shows a high sequence similarity (91%) to the domestic cat. Based on single nucleotide polymorphisms (SNPs) in the control region (CR) and pedigree information, the 18 myelopathic and 12 non-myelopathic cheetahs included in this study were classified into haplotypes I, II and III. In view of the phenotypic comparability of the neurodegenerative disease observed in cheetahs and human mtDNA-associated diseases, specific coding regions including the tRNAs leucine UUR, lysine, serine UCN, and partial complex I and V sequences were screened. We identified a heteroplasmic and a homoplasmic SNP at codon 507 in the subunit 5 (MTND5) of complex I. The heteroplasmic haplotype I-specific valine to methionine substitution represents a nonconservative amino acid change and was found in 11 myelopathic and eight non-myelopathic cheetahs with levels ranging from 29% to 79%. The homoplasmic conservative amino acid substitution valine to alanine was identified in two myelopathic animals of haplotype II. In addition, a synonymous SNP in the codon 76 of the MTND4L gene was found in the single haplotype III animal. The amino acid exchanges in the MTND5 gene were not associated with the occurrence of neurodegenerative disease in captive cheetahs.

Candidate gene association mapping of Sclerotinia stalk rot resistance in sunflower (Helianthus annuus L.) uncovers the importance of COI1 homologs.

PubMed

Talukder, Zahirul I; Hulke, Brent S; Qi, Lili; Scheffler, Brian E; Pegadaraju, Venkatramana; McPhee, Kevin; Gulya, Thomas J

2014-01-01

Functional markers for Sclerotinia basal stalk rot resistance in sunflower were obtained using gene-level information from the model species Arabidopsis thaliana. Sclerotinia stalk rot, caused by Sclerotinia sclerotiorum, is one of the most destructive diseases of sunflower (Helianthus annuus L.) worldwide. Markers for genes controlling resistance to S. sclerotiorum will enable efficient marker-assisted selection (MAS). We sequenced eight candidate genes homologous to Arabidopsis thaliana defense genes known to be associated with Sclerotinia disease resistance in a sunflower association mapping population evaluated for Sclerotinia stalk rot resistance. The total candidate gene sequence regions covered a concatenated length of 3,791 bp per individual. A total of 187 polymorphic sites were detected for all candidate gene sequences, 149 of which were single nucleotide polymorphisms (SNPs) and 38 were insertions/deletions. Eight SNPs in the coding regions led to changes in amino acid codons. Linkage disequilibrium decay throughout the candidate gene regions declined on average to an r (2) = 0.2 for genetic intervals of 120 bp, but extended up to 350 bp with r (2) = 0.1. A general linear model with modification to account for population structure was found the best fitting model for this population and was used for association mapping. Both HaCOI1-1 and HaCOI1-2 were found to be strongly associated with Sclerotinia stalk rot resistance and explained 7.4 % of phenotypic variation in this population. These SNP markers associated with Sclerotinia stalk rot resistance can potentially be applied to the selection of favorable genotypes, which will significantly improve the efficiency of MAS during the development of stalk rot resistant cultivars.

Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

PubMed Central

Juneja, Punita; Ariani, Cristina V.; Ho, Yung Shwen; Akorli, Jewelna; Palmer, William J.; Pain, Arnab; Jiggins, Francis M.

2015-01-01

Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait. PMID:25815506

Survey and analysis of simple sequence repeats in the Laccaria bicolor genome, with development of microsatellite markers

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

Labbe, Jessy L; Murat, Claude; Morin, Emmanuelle

It is becoming clear that simple sequence repeats (SSRs) play a significant role in fungal genome organization, and they are a large source of genetic markers for population genetics and meiotic maps. We identified SSRs in the Laccaria bicolor genome by in silico survey and analyzed their distribution in the different genomic regions. We also compared the abundance and distribution of SSRs in L. bicolor with those of the following fungal genomes: Phanerochaete chrysosporium, Coprinopsis cinerea, Ustilago maydis, Cryptococcus neoformans, Aspergillus nidulans, Magnaporthe grisea, Neurospora crassa and Saccharomyces cerevisiae. Using the MISA computer program, we detected 277,062 SSRs in themore » L. bicolor genome representing 8% of the assembled genomic sequence. Among the analyzed basidiomycetes, L. bicolor exhibited the highest SSR density although no correlation between relative abundance and the genome sizes was observed. In most genomes the short motifs (mono- to trinucleotides) were more abundant than the longer repeated SSRs. Generally, in each organism, the occurrence, relative abundance, and relative density of SSRs decreased as the repeat unit increased. Furthermore, each organism had its own common and longest SSRs. In the L. bicolor genome, most of the SSRs were located in intergenic regions (73.3%) and the highest SSR density was observed in transposable elements (TEs; 6,706 SSRs/Mb). However, 81% of the protein-coding genes contained SSRs in their exons, suggesting that SSR polymorphism may alter gene phenotypes. Within a L. bicolor offspring, sequence polymorphism of 78 SSRs was mainly detected in non-TE intergenic regions. Unlike previously developed microsatellite markers, these new ones are spread throughout the genome; these markers could have immediate applications in population genetics.« less

Polymorphisms in the selectin gene cluster are associated with fertility and survival time in a population of Holstein Friesian cows

PubMed Central

Chen, Xing; Zhang, Shujun; Cheng, Zhangrui; Cooke, Jessica S.; Werling, Dirk

2017-01-01

Selectins are adhesion molecules, which mediate attachment between leucocytes and endothelium. They aid extravasation of leucocytes from blood into inflamed tissue during the mammary gland’s response to infection. Selectins are also involved in attachment of the conceptus to the endometrium and subsequent placental development. Poor fertility and udder health are major causes for culling dairy cows. The three identified bovine selectin genes SELP, SELL and SELE are located in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in SELP and SELE are associated with human vascular disease, while SELP SNP rs6127 has been associated with recurrent pregnancy loss in women. This study describes the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and SELE (n = 1) with fertility, milk production and longevity traits in a population of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at 6 months of age and animals were monitored until either culling or 2,340 days from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala substitution at rs42312260. This region was associated with poor fertility and reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus in the linking region between consensus repeats 4 and 5, which may influence glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA homozygotes present in the population and AG heterozygotes had significantly worse fertility than GG homozygotes. Small changes in milk production associated with some SNP could not account for the reduced fertility and only SELPEx6 showed any association with somatic cell count. These results suggest that polymorphisms in SELP and SELE are associated with the likelihood of successful pregnancy, potentially through compromised implantation and placental development. PMID:28419109

A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness

PubMed Central

Russell, Theron A.; Blizinsky, Katherine D.; Cobia, Derin J.; Cahill, Michael; Xie, Zhong; Sweet, Robert A.; Duan, Jubao; Gejman, Pablo V.; Wang, Lei; Csernansky, John G.; Penzes, Peter

2014-01-01

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability catalyze the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homolog of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex. PMID:25224588

A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness.

PubMed

Russell, Theron A; Blizinsky, Katherine D; Cobia, Derin J; Cahill, Michael E; Xie, Zhong; Sweet, Robert A; Duan, Jubao; Gejman, Pablo V; Wang, Lei; Csernansky, John G; Penzes, Peter

2014-09-16

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability to catalyse the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homologue of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex.

Development and Characterization of Microsatellite Markers for the Cape Gooseberry Physalis peruviana

PubMed Central

Simbaqueba, Jaime; Sánchez, Pilar; Sanchez, Erika; Núñez Zarantes, Victor Manuel; Chacon, Maria Isabel; Barrero, Luz Stella; Mariño-Ramírez, Leonardo

2011-01-01

Physalis peruviana, commonly known as Cape gooseberry, is an Andean Solanaceae fruit with high nutritional value and interesting medicinal properties. In the present study we report the development and characterization of microsatellite loci from a P. peruviana commercial Colombian genotype. We identified 932 imperfect and 201 perfect Simple Sequence Repeats (SSR) loci in untranslated regions (UTRs) and 304 imperfect and 83 perfect SSR loci in coding regions from the assembled Physalis peruviana leaf transcriptome. The UTR SSR loci were used for the development of 162 primers for amplification. The efficiency of these primers was tested via PCR in a panel of seven P. peruviana accessions including Colombia, Kenya and Ecuador ecotypes and one closely related species Physalis floridana. We obtained an amplification rate of 83% and a polymorphic rate of 22%. Here we report the first P. peruviana specific microsatellite set, a valuable tool for a wide variety of applications, including functional diversity, conservation and improvement of the species. PMID:22039540

Characterization of mutations in the FOXE1 gene in a cohort of unrelated Malaysian patients with congenital hypothyroidism and thyroid dysgenesis.

PubMed

Kang, In-Nee; Musa, Maslinda; Harun, Fatimah; Junit, Sarni Mat

2010-02-01

The FOXE1 gene was screened for mutations in a cohort of 34 unrelated patients with congenital hypothyroidism, 14 of whom had thyroid dysgenesis and 18 were normal (the thyroid status for 2 patients was unknown). The entire coding region of the FOXE1 gene was PCR-amplified, then analyzed using single-stranded conformational polymorphism, followed by confirmation by direct DNA sequencing. DNA sequencing analysis revealed a heterozygous A>G transition at nucleotide position 394 in one of the patients. The nucleotide transition changed asparagine to aspartate at codon 132 in the highly conserved region of the forkhead DNA binding domain of the FOXE1 gene. This mutation was not detected in a total of 104 normal healthy individuals screened. The binding ability of the mutant FOXE1 protein to the human thyroperoxidase (TPO) promoter was slightly reduced compared with the wild-type FOXE1. The mutation also caused a 5% loss of TPO transcriptional activity.

α satellite DNA variation and function of the human centromere

PubMed Central

Sullivan, Lori L.; Chew, Kimberline

2017-01-01

ABSTRACT Genomic variation is a source of functional diversity that is typically studied in genic and non-coding regulatory regions. However, the extent of variation within noncoding portions of the human genome, particularly highly repetitive regions, and the functional consequences are not well understood. Satellite DNA, including α satellite DNA found at human centromeres, comprises up to 10% of the genome, but is difficult to study because its repetitive nature hinders contiguous sequence assemblies. We recently described variation within α satellite DNA that affects centromere function. On human chromosome 17 (HSA17), we showed that size and sequence polymorphisms within primary array D17Z1 are associated with chromosome aneuploidy and defective centromere architecture. However, HSA17 can counteract this instability by assembling the centromere at a second, “backup” array lacking variation. Here, we discuss our findings in a broader context of human centromere assembly, and highlight areas of future study to uncover links between genomic and epigenetic features of human centromeres. PMID:28406740

Development and characterization of microsatellite markers for the Cape gooseberry Physalis peruviana.

PubMed

Simbaqueba, Jaime; Sánchez, Pilar; Sanchez, Erika; Núñez Zarantes, Victor Manuel; Chacon, Maria Isabel; Barrero, Luz Stella; Mariño-Ramírez, Leonardo

2011-01-01

Physalis peruviana, commonly known as Cape gooseberry, is an Andean Solanaceae fruit with high nutritional value and interesting medicinal properties. In the present study we report the development and characterization of microsatellite loci from a P. peruviana commercial Colombian genotype. We identified 932 imperfect and 201 perfect Simple Sequence Repeats (SSR) loci in untranslated regions (UTRs) and 304 imperfect and 83 perfect SSR loci in coding regions from the assembled Physalis peruviana leaf transcriptome. The UTR SSR loci were used for the development of 162 primers for amplification. The efficiency of these primers was tested via PCR in a panel of seven P. peruviana accessions including Colombia, Kenya and Ecuador ecotypes and one closely related species Physalis floridana. We obtained an amplification rate of 83% and a polymorphic rate of 22%. Here we report the first P. peruviana specific microsatellite set, a valuable tool for a wide variety of applications, including functional diversity, conservation and improvement of the species.

Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study.

PubMed

Taylor, Steve M; Parobek, Christian M; DeConti, Derrick K; Kayentao, Kassoum; Coulibaly, Sheick Oumar; Greenwood, Brian M; Tagbor, Harry; Williams, John; Bojang, Kalifa; Njie, Fanta; Desai, Meghna; Kariuki, Simon; Gutman, Julie; Mathanga, Don P; Mårtensson, Andreas; Ngasala, Billy; Conrad, Melissa D; Rosenthal, Philip J; Tshefu, Antoinette K; Moormann, Ann M; Vulule, John M; Doumbo, Ogobara K; Ter Kuile, Feiko O; Meshnick, Steven R; Bailey, Jeffrey A; Juliano, Jonathan J

2015-03-01

Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A comparative analysis of MC4R gene sequence, polymorphism, and chromosomal localization in Chinese raccoon dog and Arctic fox.

PubMed

Skorczyk, Anna; Flisikowski, Krzysztof; Switonski, Marek

2012-05-01

Numerous mutations of the human melanocortin receptor type 4 (MC4R) gene are responsible for monogenic obesity, and some of them appear to be associated with predisposition or resistance to polygenic obesity. Thus, this gene is considered a functional candidate for fat tissue accumulation and body weight in domestic mammals. The aim of the study was comparative analysis of chromosome localization, nucleotide sequence, and polymorphism of the MC4R gene in two farmed species of the Canidae family, namely the Chinese raccoon dog (Nycterutes procyonoides procyonoides) and the arctic fox (Alopex lagopus). The whole coding sequence, including fragments of 3'UTR and 5'UTR, shows 89% similarity between the arctic fox (1276 bp) and Chinese raccoon dog (1213 bp). Altogether, 30 farmed Chinese raccoon dogs and 30 farmed arctic foxes were searched for polymorphisms. In the Chinese raccoon dog, only one silent substitution in the coding sequence was identified; whereas in the arctic fox, four InDels and two single-nucleotide polymorphisms (SNPs) in the 5'UTR and six silent SNPs in the exon were found. The studied gene was mapped by FISH to the Chinese raccoon dog chromosome 9 (NPP9q1.2) and arctic fox chromosome 24 (ALA24q1.2-1.3). The obtained results are discussed in terms of genome evolution of species belonging to the family Canidae and their potential use in animal breeding.

Mutational analysis of the Wolfram syndrome gene in two families with chromosome 4p-linked bipolar affective disorder.

PubMed

Evans, K L; Lawson, D; Meitinger, T; Blackwood, D H; Porteous, D J

2000-04-03

Bipolar affective disorder (BPAD) is a complex disease with a significant genetic component. Heterozygous carriers of Wolfram syndrome (WFS) are at increased risk of psychiatric illness. A gene for WFS (WFS1) has recently been cloned and mapped to chromosome 4p, in the general region we previously reported as showing linkage to BPAD. Here we present sequence analysis of the WFS1 coding sequence in five affected individuals from two chromosome 4p-linked families. This resulted in the identification of six polymorphisms, two of which are predicted to change the amino acid sequence of the WFS1 protein, however none of the changes segregated with disease status. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:158-160, 2000. Copyright 2000 Wiley-Liss, Inc.

Genetic diversity of 38 insertion-deletion polymorphisms in Jewish populations.

PubMed

Ferragut, J F; Pereira, R; Castro, J A; Ramon, C; Nogueiro, I; Amorim, A; Picornell, A

2016-03-01

Population genetic data of 38 non-coding biallelic autosomal indels are reported for 466 individuals, representing six populations with Jewish ancestry (Ashkenazim, Mizrahim, Sephardim, North African, Chuetas and Bragança crypto-Jews). Intra-population diversity and forensic parameters values showed that this set of indels was highly informative for forensic applications in the Jewish populations studied. Genetic distance analysis demonstrated that this set of markers efficiently separates populations from different continents, but does not seem effective for molecular anthropology studies in Mediterranean region. Finally, it is important to highlight that although the genetic distances between Jewish populations were small, significant differences were observed for Chuetas and Bragança Jews, and therefore, specific databases must be used for these populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Xenopus laevis ribosomal protein genes: isolation of recombinant cDNA clones and study of the genomic organization.

PubMed Central

Bozzoni, I; Beccari, E; Luo, Z X; Amaldi, F

1981-01-01

Poly-A+ mRNA from Xenopus laevis oocytes, partially enriched for r-protein coding capacity has been used as starting material for preparing a cDNA bank in plasmid pBR322. The clones containing sequences specific for r-proteins have been selected by translation of the complementary mRNAs. Clones for six different r-proteins have been identified and utilized as probes for studying their genomic organization. Two gene copies per haploid genome were found for r-proteins L1, L14, S19, and four-five for protein S1, S8 and L32. Moreover a population polymorphism has been observed for the genomic regions containing sequences for r-protein S1, S8 and L14. Images PMID:6112733

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

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer.

PubMed

Wojcik, Sylwia E; Rossi, Simona; Shimizu, Masayoshi; Nicoloso, Milena S; Cimmino, Amelia; Alder, Hansjuerg; Herlea, Vlad; Rassenti, Laura Z; Rai, Kanti R; Kipps, Thomas J; Keating, Michael J; Croce, Carlo M; Calin, George A

2010-02-01

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas.

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer

PubMed Central

Wojcik, Sylwia E.; Rossi, Simona; Shimizu, Masayoshi; Nicoloso, Milena S.; Cimmino, Amelia; Alder, Hansjuerg; Herlea, Vlad; Rassenti, Laura Z.; Rai, Kanti R.; Kipps, Thomas J.; Keating, Michael J.

2010-01-01

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas. PMID:19926640

Using information content and base frequencies to distinguish mutations from genetic polymorphisms in splice junction recognition sites.

PubMed

Rogan, P K; Schneider, T D

1995-01-01

Predicting the effects of nucleotide substitutions in human splice sites has been based on analysis of consensus sequences. We used a graphic representation of sequence conservation and base frequency, the sequence logo, to demonstrate that a change in a splice acceptor of hMSH2 (a gene associated with familial nonpolyposis colon cancer) probably does not reduce splicing efficiency. This confirms a population genetic study that suggested that this substitution is a genetic polymorphism. The information theory-based sequence logo is quantitative and more sensitive than the corresponding splice acceptor consensus sequence for detection of true mutations. Information analysis may potentially be used to distinguish polymorphisms from mutations in other types of transcriptional, translational, or protein-coding motifs.

Landscape heterogeneity predicts gene flow in a widespread polymorphic bumble bee, Bombus bifarius (Hymentoptera: Apidae).

USDA-ARS?s Scientific Manuscript database

Bombus bifarius is a widespread bumble bee that occurs in montane regions of western North America. This species has several major color polymorphisms, and shows evidence of genetic structuring among regional populations. We test whether this structure is evidence for discrete gene flow barriers tha...

Identification of susceptible genes for complex chronic diseases based on disease risk functional SNPs and interaction networks.

PubMed

Li, Wan; Zhu, Lina; Huang, Hao; He, Yuehan; Lv, Junjie; Li, Weimin; Chen, Lina; He, Weiming

2017-10-01

Complex chronic diseases are caused by the effects of genetic and environmental factors. Single nucleotide polymorphisms (SNPs), one common type of genetic variations, played vital roles in diseases. We hypothesized that disease risk functional SNPs in coding regions and protein interaction network modules were more likely to contribute to the identification of disease susceptible genes for complex chronic diseases. This could help to further reveal the pathogenesis of complex chronic diseases. Disease risk SNPs were first recognized from public SNP data for coronary heart disease (CHD), hypertension (HT) and type 2 diabetes (T2D). SNPs in coding regions that were classified into nonsense and missense by integrating several SNP functional annotation databases were treated as functional SNPs. Then, regions significantly associated with each disease were screened using random permutations for disease risk functional SNPs. Corresponding to these regions, 155, 169 and 173 potential disease susceptible genes were identified for CHD, HT and T2D, respectively. A disease-related gene product interaction network in environmental context was constructed for interacting gene products of both disease genes and potential disease susceptible genes for these diseases. After functional enrichment analysis for disease associated modules, 5 CHD susceptible genes, 7 HT susceptible genes and 3 T2D susceptible genes were finally identified, some of which had pleiotropic effects. Most of these genes were verified to be related to these diseases in literature. This was similar for disease genes identified from another method proposed by Lee et al. from a different aspect. This research could provide novel perspectives for diagnosis and treatment of complex chronic diseases and susceptible genes identification for other diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

A non-synonymous SNP within the isopentenyl transferase 2 locus is associated with kernel weight in Chinese maize inbreds (Zea mays L.).

PubMed

Weng, Jianfeng; Li, Bo; Liu, Changlin; Yang, Xiaoyan; Wang, Hongwei; Hao, Zhuanfang; Li, Mingshun; Zhang, Degui; Ci, Xiaoke; Li, Xinhai; Zhang, Shihuang

2013-07-05

Kernel weight, controlled by quantitative trait loci (QTL), is an important component of grain yield in maize. Cytokinins (CKs) participate in determining grain morphology and final grain yield in crops. ZmIPT2, which is expressed mainly in the basal transfer cell layer, endosperm, and embryo during maize kernel development, encodes an isopentenyl transferase (IPT) that is involved in CK biosynthesis. The coding region of ZmIPT2 was sequenced across a panel of 175 maize inbred lines that are currently used in Chinese maize breeding programs. Only 16 single nucleotide polymorphisms (SNPs) and seven haplotypes were detected among these inbred lines. Nucleotide diversity (π) within the ZmIPT2 window and coding region were 0.347 and 0.0047, respectively, and they were significantly lower than the mean nucleotide diversity value of 0.372 for maize Chromosome 2 (P < 0.01). Association mapping revealed that a single nucleotide change from cytosine (C) to thymine (T) in the ZmIPT2 coding region, which converted a proline residue into a serine residue, was significantly associated with hundred kernel weight (HKW) in three environments (P <0.05), and explained 4.76% of the total phenotypic variation. In vitro characterization suggests that the dimethylallyl diphospate (DMAPP) IPT activity of ZmIPT2-T is higher than that of ZmIPT2-C, as the amounts of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) consumed by ZmIPT2-T were 5.48-, 2.70-, and 1.87-fold, respectively, greater than those consumed by ZmIPT2-C. The effects of artificial selection on the ZmIPT2 coding region were evaluated using Tajima's D tests across six subgroups of Chinese maize germplasm, with the most frequent favorable allele identified in subgroup PB (Partner B). These results showed that ZmIPT2, which is associated with kernel weight, was subjected to artificial selection during the maize breeding process. ZmIPT2-T had higher IPT activity than ZmIPT2-C, and this favorable allele for kernel weight could be used in molecular marker-assisted selection for improvement of grain yield components in Chinese maize breeding programs.

Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease.

PubMed

Gora, Sarah; Perret, Claire; Jemel, Ikram; Nicaud, Viviane; Lambeau, Gérard; Cambien, François; Ninio, Ewa; Blankenberg, Stefan; Tiret, Laurence; Karabina, Sonia-Athina

2009-07-01

Among secreted phospholipases A2 (sPLA2s), human group X sPLA2 (hGX sPLA2) is emerging as a novel attractive therapeutic target due to its implication in inflammatory diseases. To elucidate whether hGX sPLA2 plays a causative role in coronary artery disease (CAD), we screened the human PLA2G10 gene to identify polymorphisms and possible associations with CAD end-points in a prospective study, AtheroGene. We identified eight polymorphisms, among which, one non-synonymous polymorphism R38C in the propeptide region of the sPLA2. The T-512C polymorphism located in the 5' untranslated region was associated with a decreased risk of recurrent cardiovascular events during follow-up. The functional analysis of the R38C polymorphism showed that it leads to a profound change in expression and activity of hGX sPLA2, although there was no detectable impact on CAD risk. Due to the potential role of hGX sPLA2 in inflammatory processes, these polymorphisms should be investigated in other inflammatory diseases.

Susceptibility to breast cancer and three polymorphisms of GSTZ1.

PubMed

Saadat, Iraj; Khalili, Maryam; Nafissi, Samane; Omidvari, Shahpour; Saadat, Mostafa

2012-03-01

Glutathione S-transferases class zeta (GSTζ) is involved in the detoxification of xenobiotic compounds and catalyzes the biotransformation of a variety of α-haloacids including dichloroacetic acid and chlorofluoroacetic acid. It has been reported that, in mice, deficiency of Gstz1 (a member of GSTζ) resulted in the generation of a constant level of oxidative stress. The present study was carried out to investigate the association between genetic polymorphisms of GSTZ1 (in promoter site G-1002A and in coding sites Glu32Lys and Gly42Arg) and risk of breast cancer. We included 106 females with breast cancer and 106 healthy females frequency matched for age. The study polymorphisms were not associated with risk of breast cancer (p>0.05). The polymorphisms of GSTZ1 showed strong linkage disequilibrium among cancer patients and control subjects (p<0.0001). There was no significant difference between cancer patients and controls for frequencies of the GSTZ1 haplotypes (p>0.05). It seems there is no meaningful relationship between the genetic polymorphisms of GSTZ1 and risk of breast cancer.

Mutations in exons of the CYP17-II gene affect sex steroid concentration in male Japanese flounder ( Paralichthys olivaceus)

NASA Astrophysics Data System (ADS)

Ma, Ruiqin; He, Feng; Wen, Haishen; Li, Jifang; Shi, Bao; Shi, Dan; Liu, Miao; Mu, Weijie; Zhang, Yuanqing; Hu, Jian; Han, Weiguo; Zhang, Jianan; Wang, Qingqing; Yuan, Yuren; Liu, Qun

2012-03-01

As a specific gene of fish, cytochrome P450c17-II ( CYP17-II) gene plays a key role in the growth, development an reproduction level of fish. In this study, the single-stranded conformational polymorphism (SSCP) technique was used to characterize polymorphisms within the coding region of CYP17-II gene in a population of 75 male Japanese flounder ( Paralichthys olivaceus). Three single nucleotide polymorphisms (SNPs) were identified in CYP17-II gene of Japanese flounder. They were c.G594A (p.G188R), c.G939A and c.G1502A (p.G490D). SNP1 (c.G594A), located in exon 4 of CYP17-II gene, was significantly associated with gonadosomatic index (GSI). Individuals with genotype GG of SNP1 had significantly lower GSI ( P < 0.05) than those with genotype AA or AG. SNP2 (c.G939A) located at the CpG island of CYP17-II gene. The mutation changed the methylation of exon 6. Individuals with genotype AA of SNP2 had significantly lower serum testosterone (T) level and hepatosomatic index (HSI) compared to those with genotype GG. The results suggested that SNP2 could influence the reproductive endocrine of male Japanese flounder. However, the SNP3 (c.G1502A) located in exon 9 did not affect the four measured reproductive traits. This study showed that CYP17-II gene could be a potentially useful candidate gene for the research of genetic breeding and physiological aspects of Japanese flounder.

Phylogenetic inference and SSR characterization of tropical woody bamboos tribe Bambuseae (Poaceae: Bambusoideae) based on complete plastid genome sequences.

PubMed

Vieira, Leila do Nascimento; Dos Anjos, Karina Goulart; Faoro, Helisson; Fraga, Hugo Pacheco de Freitas; Greco, Thiago Machado; Pedrosa, Fábio de Oliveira; de Souza, Emanuel Maltempi; Rogalski, Marcelo; de Souza, Robson Francisco; Guerra, Miguel Pedro

2016-05-01

The complete plastome sequencing is an efficient option for increasing phylogenetic resolution and evolutionary studies, as well as may greatly facilitate the use of plastid DNA markers in plant population genetic studies. Merostachys and Guadua stand out as the most common and the highest potential utilization bamboos indigenous of Brazil. Here, we sequenced the complete plastome sequences of the Brazilian Guadua chacoensis and Merostachys sp. to perform full plastome phylogeny and characterize the occurrence, type, and distribution of SRRs using 20 Bambuseae species. The determined plastome sequence of Merostachys sp. and G. chacoensis is 136,334 and 135,403 bp in size, respectively, with an identical gene content and typical quadripartite structure consisting of a pair of IRs separated by the LSC and SSC regions. The Maximum Likelihood and Bayesian Inference analyses produced phylogenomic trees identical in topology. These trees supported monophyly of Paleotropical and Neotropical Bamboos clades. The Neotropical bamboos segregated into three well-supported lineages, Chusqueinae, Guaduinae, and Arthrostylidiinae, with the last two forming a well-supported sister relationship. Paleotropical bamboos segregated into two well-supported lineages, Hickeliinae and Bambusinae + Melocanninae. We identified 141.8 cpSSR in Bambuseae plastomes and an inferior value (38.15) for plastome coding sequences. Among them, we identified 16 polymorphic SSR loci, with number of alleles varying from 3 to 10. These 16 polymorphic cpSSR loci in Bambuseae plastome can be assessed for the intraspecific level of polymorphism, leading to innovative highly sensitive phylogeographic and population genetics studies for this tribe.

Protein functional features are reflected in the patterns of mRNA translation speed.

PubMed

López, Daniel; Pazos, Florencio

2015-07-09

The degeneracy of the genetic code makes it possible for the same amino acid string to be coded by different messenger RNA (mRNA) sequences. These "synonymous mRNAs" may differ largely in a number of aspects related to their overall translational efficiency, such as secondary structure content and availability of the encoded transfer RNAs (tRNAs). Consequently, they may render different yields of the translated polypeptides. These mRNA features related to translation efficiency are also playing a role locally, resulting in a non-uniform translation speed along the mRNA, which has been previously related to some protein structural features and also used to explain some dramatic effects of "silent" single-nucleotide-polymorphisms (SNPs). In this work we perform the first large scale analysis of the relationship between three experimental proxies of mRNA local translation efficiency and the local features of the corresponding encoded proteins. We found that a number of protein functional and structural features are reflected in the patterns of ribosome occupancy, secondary structure and tRNA availability along the mRNA. One or more of these proxies of translation speed have distinctive patterns around the mRNA regions coding for certain protein local features. In some cases the three patterns follow a similar trend. We also show specific examples where these patterns of translation speed point to the protein's important structural and functional features. This support the idea that the genome not only codes the protein functional features as sequences of amino acids, but also as subtle patterns of mRNA properties which, probably through local effects on the translation speed, have some consequence on the final polypeptide. These results open the possibility of predicting a protein's functional regions based on a single genomic sequence, and have implications for heterologous protein expression and fine-tuning protein function.

Complete chloroplast genome sequences of Hordeum vulgare, Sorghum bicolor and Agrostis stolonifera, and comparative analyses with other grass genomes

PubMed Central

Saski, Christopher; Lee, Seung-Bum; Fjellheim, Siri; Guda, Chittibabu; Jansen, Robert K.; Luo, Hong; Tomkins, Jeffrey; Rognli, Odd Arne; Clarke, Jihong Liu

2009-01-01

Comparisons of complete chloroplast genome sequences of Hordeum vulgare, Sorghum bicolor and Agrostis stolonifera to six published grass chloroplast genomes reveal that gene content and order are similar but two microstructural changes have occurred. First, the expansion of the IR at the SSC/IRa boundary that duplicates a portion of the 5′ end of ndhH is restricted to the three genera of the subfamily Pooideae (Agrostis, Hordeum and Triticum). Second, a 6 bp deletion in ndhK is shared by Agrostis, Hordeum, Oryza and Triticum, and this event supports the sister relationship between the subfamilies Erhartoideae and Pooideae. Repeat analysis identified 19–37 direct and inverted repeats 30 bp or longer with a sequence identity of at least 90%. Seventeen of the 26 shared repeats are found in all the grass chloroplast genomes examined and are located in the same genes or intergenic spacer (IGS) regions. Examination of simple sequence repeats (SSRs) identified 16–21 potential polymorphic SSRs. Five IGS regions have 100% sequence identity among Zea mays, Saccharum officinarum and Sorghum bicolor, whereas no spacer regions were identical among Oryza sativa, Triticum aestivum, H. vulgare and A. stolonifera despite their close phylogenetic relationship. Alignment of EST sequences and DNA coding sequences identified six C–U conversions in both Sorghum bicolor and H. vulgare but only one in A. stolonifera. Phylogenetic trees based on DNA sequences of 61 protein-coding genes of 38 taxa using both maximum parsimony and likelihood methods provide moderate support for a sister relationship between the subfamilies Erhartoideae and Pooideae. PMID:17534593

Linkage disequilibria at the D[sub 2] dopamine receptor locus (DRD2) in alcoholics and controls

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

Suarez, B.K.; Parsian, A.; Hampe, C.L.

1994-01-01

Because of its central role in the neuromodulation of appetitive behaviors, the D[sub 2] dopamine receptor gene (DRD2) has received considerable scrutiny as a possible candidate that may affect susceptibility to addictive behaviors--especially alcoholism. Association studies that compare the frequencies of anonymous restriction fragment length polymorphisms (RFLPs) in alcoholics and controls have yielded equivocal results, suggesting that any role played by this receptor will account for only part of the variation. Since these RFLPs are not located in coding regions, the hypothesis has been advanced that the association seen in some studies results from linkage disequilibrium between these markers andmore » one or more functional DRD2 alleles that affect susceptibility. To test this hypothesis, the authors have assayed four DRD2 RFLPs that span coding regions as well as a 3[prime] flanking RFLP in an expanded sample of 88 unrelated Caucasian alcoholics and 89 unrelated race-matched controls. No significant difference for any RFLP frequency between these samples was observed, although for one marker (phD2-244), the alcoholic sample showed a significant departure from the Hardy-Weinberg equilibrium. The pattern of pairwise composite disequilibrium coefficients is broadly similar in the two samples, although when the five-marker haplotype frequencies are compared, a significant difference is revealed. This difference appears to be due to greater linkage disequilibrium of the control sample. These results do not support the involvement of the DRD2 region in the etiology of alcoholism. 64 refs., 2 figs., 6 tabs.« less

Adaptive Evolution Is Substantially Impeded by Hill–Robertson Interference in Drosophila

PubMed Central

Castellano, David; Coronado-Zamora, Marta; Campos, Jose L.; Barbadilla, Antonio; Eyre-Walker, Adam

2016-01-01

Hill–Robertson interference (HRi) is expected to reduce the efficiency of natural selection when two or more linked selected sites do not segregate freely, but no attempt has been done so far to quantify the overall impact of HRi on the rate of adaptive evolution for any given genome. In this work, we estimate how much HRi impedes the rate of adaptive evolution in the coding genome of Drosophila melanogaster. We compiled a data set of 6,141 autosomal protein-coding genes from Drosophila, from which polymorphism levels in D. melanogaster and divergence out to D. yakuba were estimated. The rate of adaptive evolution was calculated using a derivative of the McDonald–Kreitman test that controls for slightly deleterious mutations. We find that the rate of adaptive amino acid substitution at a given position of the genome is positively correlated to both the rate of recombination and the mutation rate, and negatively correlated to the gene density of the region. These correlations are robust to controlling for each other, for synonymous codon bias and for gene functions related to immune response and testes. We show that HRi diminishes the rate of adaptive evolution by approximately 27%. Interestingly, genes with low mutation rates embedded in gene poor regions lose approximately 17% of their adaptive substitutions whereas genes with high mutation rates embedded in gene rich regions lose approximately 60%. We conclude that HRi hampers the rate of adaptive evolution in Drosophila and that the variation in recombination, mutation, and gene density along the genome affects the HRi effect. PMID:26494843

Null Mutation of the MdACS3 Gene, Coding for a Ripening-Specific 1-Aminocyclopropane-1-Carboxylate Synthase, Leads to Long Shelf Life in Apple Fruit1[W][OA

PubMed Central

Wang, Aide; Yamakake, Junko; Kudo, Hisayuki; Wakasa, Yuhya; Hatsuyama, Yoshimichi; Igarashi, Megumi; Kasai, Atsushi; Li, Tianzhong; Harada, Takeo

2009-01-01

Expression of MdACS1, coding for 1-aminocyclopropane-1-carboxylate synthase (ACS), parallels the level of ethylene production in ripening apple (Malus domestica) fruit. Here we show that expression of another ripening-specific ACS gene (MdACS3) precedes the initiation of MdACS1 expression by approximately 3 weeks; MdACS3 expression then gradually decreases as MdACS1 expression increases. Because MdACS3 expression continues in ripening fruit treated with 1-methylcyclopropene, its transcription appears to be regulated by a negative feedback mechanism. Three genes in the MdACS3 family (a, b, and c) were isolated from a genomic library, but two of them (MdACS3b and MdACS3c) possess a 333-bp transposon-like insertion in their 5′ flanking region that may prevent transcription of these genes during ripening. A single nucleotide polymorphism in the coding region of MdACS3a results in an amino acid substitution (glycine-289 → valine) in the active site that inactivates the enzyme. Furthermore, another null allele of MdACS3a, Mdacs3a, showing no ability to be transcribed, was found by DNA sequencing. Apple cultivars homozygous or heterozygous for both null allelotypes showed no or very low expression of ripening-related genes and maintained fruit firmness. These results suggest that MdACS3a plays a crucial role in regulation of fruit ripening in apple, and is a possible determinant of ethylene production and shelf life in apple fruit. PMID:19587104

Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli.

PubMed

Beevers, Christopher G; Wells, Tony T; Ellis, Alissa J; McGeary, John E

2009-08-01

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among nondepressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cuing task using emotional stimuli. Results from Study 1 (N = 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared with long allele homozygotes. Study 2 participants (N = 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low-expressing 5-HTTLPR alleles (i.e., S and LG) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high-expressing 5-HTTLPR homozygotes. Because this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences.

Enhanced Gene Expression Rather than Natural Polymorphism in Coding Sequence of the OsbZIP23 Determines Drought Tolerance and Yield Improvement in Rice Genotypes

PubMed Central

Dey, Avishek; Samanta, Milan Kumar; Gayen, Srimonta; Sen, Soumitra K.; Maiti, Mrinal K.

2016-01-01

Drought is one of the major limiting factors for productivity of crops including rice (Oryza sativa L.). Understanding the role of allelic variations of key regulatory genes involved in stress-tolerance is essential for developing an effective strategy to combat drought. The bZIP transcription factors play a crucial role in abiotic-stress adaptation in plants via abscisic acid (ABA) signaling pathway. The present study aimed to search for allelic polymorphism in the OsbZIP23 gene across selected drought-tolerant and drought-sensitive rice genotypes, and to characterize the new allele through overexpression (OE) and gene-silencing (RNAi). Analyses of the coding DNA sequence (CDS) of the cloned OsbZIP23 gene revealed single nucleotide polymorphism at four places and a 15-nucleotide deletion at one place. The single-copy OsbZIP23 gene is expressed at relatively higher level in leaf tissues of drought-tolerant genotypes, and its abundance is more in reproductive stage. Cloning and sequence analyses of the OsbZIP23-promoter from drought-tolerant O. rufipogon and drought-sensitive IR20 cultivar showed variation in the number of stress-responsive cis-elements and a 35-nucleotide deletion at 5’-UTR in IR20. Analysis of the GFP reporter gene function revealed that the promoter activity of O. rufipogon is comparatively higher than that of IR20. The overexpression of any of the two polymorphic forms (1083 bp and 1068 bp CDS) of OsbZIP23 improved drought tolerance and yield-related traits significantly by retaining higher content of cellular water, soluble sugar and proline; and exhibited decrease in membrane lipid peroxidation in comparison to RNAi lines and non-transgenic plants. The OE lines showed higher expression of target genes-OsRab16B, OsRab21 and OsLEA3-1 and increased ABA sensitivity; indicating that OsbZIP23 is a positive transcriptional-regulator of the ABA-signaling pathway. Taken together, the present study concludes that the enhanced gene expression rather than natural polymorphism in coding sequence of OsbZIP23 is accountable for improved drought tolerance and yield performance in rice genotypes. PMID:26959651

STK15 polymorphisms and association with risk of invasive ovarian cancer.

PubMed

Dicioccio, Richard A; Song, Honglin; Waterfall, Christy; Kimura, Makoto T; Nagase, Hiroki; McGuire, Valerie; Hogdall, Estrid; Shah, Mitul N; Luben, Robert N; Easton, Douglas F; Jacobs, Ian J; Ponder, Bruce A J; Whittemore, Alice S; Gayther, Simon A; Pharoah, Paul D P; Kruger-Kjaer, Susan

2004-10-01

STK15 is a putative oncogene that codes for a centrosome-associated, serine/threonine kinase, the normal function of which is to ensure accurate segregation of chromosomes during mitosis. Amplification of STK15 has been reported in ovarian tumors, suggesting a role in ovarian cancer pathology. STK15 is polymorphic with two single nucleotide substitutions (449t/a and 527g/a) in evolutionarily conserved regions causing amino acid changes (F31I and V57I). Two other nucleotide substitutions (287c/g and 1891g/c) of unknown significance are in 5' and 3' untranslated regions (UTR), respectively. To learn more about the involvement of STK15 in ovarian cancer, we genotyped and haplotyped these polymorphisms in three population-based ovarian cancer case-control studies from the United Kingdom, United States, and Denmark with 1,821 combined cases and 2,467 combined controls and calculated risks for developing ovarian cancer. Genotypes of individual polymorphisms in control groups of the United Kingdom, United States, and Denmark conformed to Hardy-Weinberg equilibrium. In combined cases and combined controls, rare allele frequencies were 0.23 and 0.21 for I31, 0.16 and 0.17 for I57, 0.08 and 0.07 for 5' UTR g, and 0.25 and 0.24 for 3' UTR c, respectively. Using FF common homozygotes of F31I as comparator, there was increased ovarian cancer risk to FI heterozygotes (odds ratio, 1.18; 95% confidence interval, 1.01-1.36), II homozygotes (odds ratio, 1.25; 95% confidence interval, 0.89-1.75), and I31 allele carriers (odds ratio, 1.17; 95% confidence interval, 1.02-1.35) in the combined group data. For either V57I, 5' UTR C/G, or 3' UTR G/C, all genotypic ovarian cancer risks were essentially in unity relative to their respective common homozygotes, VV, cc, or gg. Haplotype analysis of combined group data revealed seven haplotypes with frequencies between 0.02 and 0.5, with c-F-V-g the most common. None of the haplotype-specific risks significantly differed from unity relative to c-F-V-g. These results suggest a model of dominant inheritance of ovarian cancer risk by the I31 allele of F31I and that the I31 allele may be a common ovarian cancer susceptibility allele of low penetrance.

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

PubMed Central

Grimmer, Timo; Goldhardt, Oliver; Guo, Liang-Hao; Yousefi, Behrooz H.; Förster, Stefan; Drzezga, Alexander; Sorg, Christian; Alexopoulos, Panagiotis; Förstl, Hans; Kurz, Alexander; Perneczky, Robert

2014-01-01

Objective Impaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood–brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [11C]PiB. Materials and methods 72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined. Results The regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, β = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism. Discussion In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD. PMID:24596678

[Polymorphism in the regulatory regions -С2578A and +C936T of the vascular endothelial growth factor (VEGF-A) gene in Russian women with rheumatoid arthritis].

PubMed

Shevchenko, A V; Prokofyev, V F; Korolev, M A; Banshchikova, N E; Konenkov, V I

To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA). The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis. There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women. The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

Exome sequencing and arrayCGH detection of gene sequence and copy number variation between ILS and ISS mouse strains.

PubMed

Dumas, Laura; Dickens, C Michael; Anderson, Nathan; Davis, Jonathan; Bennett, Beth; Radcliffe, Richard A; Sikela, James M

2014-06-01

It has been well documented that genetic factors can influence predisposition to develop alcoholism. While the underlying genomic changes may be of several types, two of the most common and disease associated are copy number variations (CNVs) and sequence alterations of protein coding regions. The goal of this study was to identify CNVs and single-nucleotide polymorphisms that occur in gene coding regions that may play a role in influencing the risk of an individual developing alcoholism. Toward this end, two mouse strains were used that have been selectively bred based on their differential sensitivity to alcohol: the Inbred long sleep (ILS) and Inbred short sleep (ISS) mouse strains. Differences in initial response to alcohol have been linked to risk for alcoholism, and the ILS/ISS strains are used to investigate the genetics of initial sensitivity to alcohol. Array comparative genomic hybridization (arrayCGH) and exome sequencing were conducted to identify CNVs and gene coding sequence differences, respectively, between ILS and ISS mice. Mouse arrayCGH was performed using catalog Agilent 1 × 244 k mouse arrays. Subsequently, exome sequencing was carried out using an Illumina HiSeq 2000 instrument. ArrayCGH detected 74 CNVs that were strain-specific (38 ILS/36 ISS), including several ISS-specific deletions that contained genes implicated in brain function and neurotransmitter release. Among several interesting coding variations detected by exome sequencing was the gain of a premature stop codon in the alpha-amylase 2B (AMY2B) gene specifically in the ILS strain. In total, exome sequencing detected 2,597 and 1,768 strain-specific exonic gene variants in the ILS and ISS mice, respectively. This study represents the most comprehensive and detailed genomic comparison of ILS and ISS mouse strains to date. The two complementary genome-wide approaches identified strain-specific CNVs and gene coding sequence variations that should provide strong candidates to contribute to the alcohol-related phenotypic differences associated with these strains.

Cloning of polymorphisms (COP): enrichment of polymorphic sequences from complex genomes

PubMed Central

Li, Jingfeng; Wang, Fuli; Zabarovska, Veronika; Wahlestedt, Claes; Zabarovsky, Eugene R.

2000-01-01

Here we describe a new procedure (cloning of polymorphisms, COP) for enrichment of single nucleotide polymorphisms (SNPs) that represent restriction fragment length polymorphisms (RFLPs). COP would be applicable to the isolation of SNPs from particular regions of the genome, e.g. CpG islands, chromosomal bands, YACs or PAC contigs. A combination of digestion with restriction enzymes, treatment with uracil-DNA glycosylase and mung bean nuclease, PCR amplification and purification with streptavidin magnetic beads was used to isolate polymorphic sequences from the genomes of two human samples. After only two cycles of enrichment, 80% of the isolated clones were found to contain RFLPs. A simple method for the PCR detection of these polymorphisms was also developed. PMID:10606669

The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility.

PubMed

Martínez-Nava, Gabriela Angélica; Fernández-Torres, Javier; Martínez-Flores, Karina; Zamudio-Cuevas, Yessica; Clavijo-Cornejo, Denise; Espinosa-Morales, Rolando; Lozada, Carlos A; Gutierrez, Marwin; Granados, Julio; Pineda, Carlos; Madrid-Marina, Vicente; López-Reyes, Alberto

2018-04-01

Recent studies have identified AKNA as a potential susceptibility gene for several inflammatory diseases. Here, we aimed to assess the potential association of AKNA polymorphisms with knee osteoarthritis (KOA) susceptibility in a Mexican population, following STREGA recommendations. From a DNA bank of 181 KOA patients and 140 healthy controls, two AKNA SNPs were genotyped using TaqMan probes. The association between KOA susceptibility and AKNA polymorphisms genotypes was evaluated by multivariated logistic regression analysis. Information regarding patients' inflammatory biomarkers levels was obtained and their association with AKNA polymorphisms genotypes was assessed by lineal regression. We found a positive association with the recessive inheritance model of both AKNA polymorphisms (A/A genotype for both) and KOA susceptibility adjusting by age, body mass index (BMI), gender and place of birth (OR = 2.48, 95% CI 1.09-5.65 for rs10817595 polymorphism; and OR = 4.96; 95% CI 2.421-10.2 for rs3748176 polymorphism). Additionally these associations were also seen after stratifying patients by KOA severity and age. Furthermore the total leukocyte count was positively associated with rs10817595 AKNA polymorphism (β = 1.39; 95% CI 0.44-2.34) adjusting by age, BMI, gender, place of birth and disease severity. We suggest that regulatory and coding polymorphisms of the inflammatory modulator gene AKNA can influence the development of KOA. Further structural and functional studies might reveal the role of AKNA in OA and other rheumatic diseases.

Vitamin D receptor polymorphisms in patients with cutaneous melanoma

PubMed Central

Orlow, Irene; Roy, Pampa; Reiner, Anne S.; Yoo, Sarah; Patel, Himali; Paine, Susan; Armstrong, Bruce K.; Kricker, Anne; Marrett, Loraine D.; Millikan, Robert C.; Thomas, Nancy E.; Gruber, Stephen B.; Anton-Culver, Hoda; Rosso, Stefano; Gallagher, Richard P.; Dwyer, Terence; Kanetsky, Peter A.; Busam, Klaus; From, Lynn; Begg, Colin B.; Berwick, Marianne

2011-01-01

The vitamin D receptor (VDR) gene has been associated with cancer risk, but only a few polymorphisms have been studied in relation to melanoma risk and the results have been inconsistent. We examined 38 VDR gene SNPs in a large international multi-center population-based case-control study of melanoma. Buccal DNAs were obtained from 1207 people with incident multiple primary melanoma and 2469 with incident single primary melanoma. SNPs with known or suspected impact on VDR activity, htSNPs with ≥10% MAF in Caucasians, and SNPs reported as significant in other association studies were examined. Logistic regression was used to calculate the relative risks conferred by the individual SNP. Eight of 38 SNPs in the promoter, coding, and 3’ gene regions were individually significantly associated with multiple primary melanoma after adjusting for covariates. The estimated increase in risk for individuals who were homozygous for the minor allele ranged from 25% to 33% for 6 polymorphisms: rs10875712 (OR 1.28; 95%CI, 1.01–1.62), rs4760674 (OR 1.33; 95% CI, 1.06–1.67), rs7139166 (OR 1.26; 95%CI, 1.02–1.56), rs4516035 (OR 1.25; 95%CI, 1.01–1.55), rs11168287 (OR 1.27; 95%CI, 1.03–1.57), rs1544410 (OR 1.30; 95%CI, 1.04–1.63); for 2 polymorphisms, homozygous carriers had a decreased risk: rs7305032 (OR 0.81; 95%CI 0.65–1.02), rs7965281 (OR, 0.78; 95%CI, 0.62–0.99). We recognize the potential false positive findings due to multiple comparisons; however the 8 significant SNPs in this study outnumbered the 2 significant tests expected to occur by chance. The vitamin D receptor may play a role in melanomagenesis. PMID:21365644

Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility.

PubMed

Cukier, Holly N; Skaar, David A; Rayner-Evans, Melissa Y; Konidari, Ioanna; Whitehead, Patrice L; Jaworski, James M; Cuccaro, Michael L; Pericak-Vance, Margaret A; Gilbert, John R

2009-10-01

Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint ( approximately 108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation.

A Novel Route Controlling Begomovirus Resistance by the Messenger RNA Surveillance Factor Pelota

PubMed Central

Lapidot, Moshe; Karniel, Uri; Gelbart, Dana; Fogel, Doron; Evenor, Dalia; Kutsher, Yaarit; Makhbash, Zion; Nahon, Sahadia; Shlomo, Haviva; Chen, Lea; Reuveni, Moshe; Levin, Ilan

2015-01-01

Tomato yellow leaf curl virus (TYLCV) is a devastating disease of tomato (Solanum lycopersicum) that can be effectively controlled by the deployment of resistant cultivars. The TYLCV-resistant line TY172 carries a major recessive locus for TYLCV resistance, designated ty-5, on chromosome 4. In this study, the association between 27 polymorphic DNA markers, spanning the ty-5 locus, and the resistance characteristics of individual plants inoculated with TYLCV in 51 segregating recombinant populations were analyzed. These analyses localized ty-5 into a 425 bp region containing two transversions: one in the first exon of a gene encoding the tomato homolog of the messenger RNA surveillance factor Pelota (Pelo), and a second in its proximal promoter. Analyses of susceptible and resistant lines revealed that the relative transcript level of the gene remained unchanged, regardless of whether the plants were infected with TYLCV or not. This suggests that the polymorphism discovered in the coding region of the gene controls the resistance. Silencing of Pelo in a susceptible line rendered the transgenic plants highly resistant, while in the resistant line TY172 had no effect on symptom development. In addition, over-expression of the susceptible allele of the gene in the resistant TY172 line rendered it susceptible, while over-expression of the resistant allele in susceptible plants had no effect. These results confirm that Pelo is the gene controlling resistance at the ty-5 locus. Pelo, implicated in the ribosome recycling-phase of protein synthesis, offers an alternative route to promote resistance to TYLCV and other viruses. PMID:26448569

Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects.

PubMed

Sipiläinen, R; Uusitupa, M; Heikkinen, S; Rissanen, A; Laakso, M

1997-08-01

Fatty acid binding protein 2 gene (FABP2) has been proposed to be an important candidate gene for insulin resistance; therefore, it also could be a promising candidate gene for obesity. We screened the whole coding region of the FABP2 gene in 40 obese nondiabetic Finnish subjects. Furthermore, we investigated the effects of the codon 54 polymorphism of this gene (Ala-->Thr) on insulin levels and basal metabolic rate in 170 obese subjects. The frequencies of the variants found in exon 4 (GTA-->GTG) and 3'-noncoding region (GCGCA-->GCACA), as well as the allele frequencies for the variable lengths of the ATT repeat sequence in intron 2 did not differ between the obese subjects and nonobese controls. The frequency of threonine-encoding allele in codon 54 of the FABP2 gene did not differ between obese and control subjects (28 vs. 29%, respectively). In the obese group there were no differences in gender distribution, age, weight, body mass index, lean body mass, percentage of body fat, waist circumference, and waist-to-hip ratio among the individuals homozygous for Ala54, heterozygous for Thr54, and homozygous for Thr54-encoding alleles. Similarly, fasting serum insulin, glucose, lipids and lipoprotein concentrations, basal metabolic rate (adjusted for lean body mass and age), respiratory quotient, and rates of glucose and lipid oxidation did not differ among the groups. We conclude that obesity is not associated with specific variants in the FABP2 gene. Furthermore, the codon 54 Ala to Thr polymorphism of this gene does not influence insulin levels or basal metabolic rate in obese Finns.

A Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next-Generation Sequencing Assay for Inherited Heart Diseases.

PubMed

Wilson, Kitchener D; Shen, Peidong; Fung, Eula; Karakikes, Ioannis; Zhang, Angela; InanlooRahatloo, Kolsoum; Odegaard, Justin; Sallam, Karim; Davis, Ronald W; Lui, George K; Ashley, Euan A; Scharfe, Curt; Wu, Joseph C

2015-09-11

Thousands of mutations across >50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited because many sequencing services and off-the-shelf kits suffer from slow turnaround, inefficient capture of genomic DNA, and high cost. Furthermore, customization of these assays to cover emerging targets that suit individual needs is often expensive and time consuming. We sought to develop a custom high throughput, clinical-grade next-generation sequencing assay for detecting cardiac disease gene mutations with improved accuracy, flexibility, turnaround, and cost. We used double-stranded probes (complementary long padlock probes), an inexpensive and customizable capture technology, to efficiently capture and amplify the entire coding region and flanking intronic and regulatory sequences of 88 genes and 40 microRNAs associated with inherited cardiomyopathies, congenital heart disease, and cardiac development. Multiplexing 11 samples per sequencing run resulted in a mean base pair coverage of 420, of which 97% had >20× coverage and >99% were concordant with known heterozygous single nucleotide polymorphisms. The assay correctly detected germline variants in 24 individuals and revealed several polymorphic regions in miR-499. Total run time was 3 days at an approximate cost of $100 per sample. Accurate, high-throughput detection of mutations across numerous cardiac genes is achievable with complementary long padlock probe technology. Moreover, this format allows facile insertion of additional probes as more cardiomyopathy and congenital heart disease genes are discovered, giving researchers a powerful new tool for DNA mutation detection and discovery. © 2015 American Heart Association, Inc.

Selection on the human bitter taste gene, TAS2R16, in Eurasian populations.

PubMed

Li, Hui; Pakstis, Andrew J; Kidd, Judith R; Kidd, Kenneth K

2011-06-01

Bitter taste is one of the most important senses alerting humans to noxious foods. In gatherer communities, sensitivity to bitterness is presumably advantageous because of various noxious plants. TAS2R16 is the gene coding the taste receptor molecules for some of the most common toxins in plants. A previous study of this gene indicated selection has increased the frequency of a derived allele in this gene that arose before the human expansion out of Africa. We have applied a different methodology for detecting selection, the Long Range Haplotype (LRH) analysis, to TAS2R16 in a larger sampling of populations from around the world. The haplotype with the derived alleles at both the functional polymorphism and a polymorphism in the regulatory region of TAS2R16 showed evidence for recent positive selection in most of the Eurasian populations, though the highest selection signal occurs in Mbuti Pygmies, an African hunter-gatherer group. In Eurasia, only populations of Mesopotamia and the southeast coast of China have no signals of selection. The evidence of recent selection found in most Eurasian populations differs from the geographic pattern seen in the earlier study of selection. One can speculate that the difference may result from a gathering lifestyle extending into the most recent 10,000 yrs and the need to recognize newly encountered bitter natural toxins as populations expanded into new environments and the biota changes with the ending of the most recent ice age. Alternatively, the promoter region variant may be a marker for altered function beyond what the derived amino acid allele conferred.

Genetic variations in the hotspot region of RS1 gene in Indian patients with juvenile X-linked retinoschisis

PubMed Central

Suganthalakshmi, Balasubbu; Shukla, Dhananjay; Rajendran, Anand; Kim, Ramasamy; Nallathambi, Jeyabalan

2007-01-01

Purpose X-linked juvenile retinoschisis (XLRS) is the leading cause of macular degeneration in males. This condition is caused by mutations in the RS1 gene and is, characterized by schisis within the retina. The purpose of this study was to identify the mutations in the RS1 gene associated with XLRS in an Indian cohort. Methods The coding region of RS1 was analyzed for mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and restriction fragment length polymorphism (RFLP) analysis in six unrelated subjects clinically diagnosed as having XLRS and in their available family members. Direct sequencing was performed for all samples that displayed an electrophoretic mobility shift in SSCP gel. Results Mutation analysis of RS1 gene revealed five mutations in exon 6 like c.574C>T, c.583A>G, c.608C>T, c.617G>A, and c.637C>T, respectively, among them four missense mutations, one nonsense mutation, and two novel sequence variations. These mutations were found in individuals who exhibited clinical features of bilateral foveal and peripheral retinoschisis consistent with XLRS. The mutations were absent in the 100 age matched control samples analyzed. Conclusions This is the first report of mutations in RS1 to be associated with XLRS in the Indian population. The identified genetic variations, phenotype and genotype correlations were consistent with other studies. Identification of the causative mutation in patients with XLRS is helpful in confirming the diagnosis and in counseling of family members. PMID:17515881

The 5-HTTLPR confers susceptibility to anorexia nervosa in Han Chinese: evidence from a case-control and family-based study.

PubMed

Chen, Jue; Kang, Qing; Jiang, Wenhui; Fan, Juan; Zhang, Mingdao; Yu, Shunying; Zhang, Chen

2015-01-01

Accumulating evidence has implied that serotonin system dysfunction may be involved in the etiology of anorexia nervosa (AN). Serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism is the genetic variant coding for the serotonin transporter and has a modulatory effect on its expression. This study aimed to investigate the possible association between the 5-HTTLPR and the susceptibility and severity of AN in Han Chinese using a case-control (255 patients and 351 controls) and family based study (198 trios). Eating disorder examination was used to measure the severity of AN behavioral symptoms. For the case-control study, the 5-HTTLPR showed significant association with AN in our sample (genotypic P = 0.03). The frequency of S allele was significantly higher in patients than that in controls (OR = 1.38, 95%CI: 1.06-1.79, P = 0.017). For the family-based study, the S allele of 5-HTTLPR was preferentially transmitted rather than non-transmitted from the parents to affected offspring (P = 0.013). The results of ANCOVA test revealed no significant association between the 5-HTTLPR polymorphism and severity of AN. Our findings suggested that 5-HTTLPR is able to confer susceptibility to AN in Han Chinese.

Development of genic cleavage markers in association with seed glucosinolate content in canola.

PubMed

Fu, Ying; Lu, Kun; Qian, Lunwen; Mei, Jiaqin; Wei, Dayong; Peng, Xuhui; Xu, Xinfu; Li, Jiana; Frauen, Martin; Dreyer, Felix; Snowdon, Rod J; Qian, Wei

2015-06-01

The orthologues of Arabidopsis involved in seed glucosinolates metabolism within QTL confidence intervals were identified, and functional markers were developed to facilitate breeding for ultra-low glucosinolates in canola. Further reducing the content of seed glucosinolates will have a positive impact on the seed quality of canola (Brassica napus). In this study 43 quantitative trait loci (QTL) for seed glucosinolate (GSL) content in a low-GSL genetic background were mapped over seven environments in Germany and China in a doubled haploid population from a cross between two low-GSL oilseed rape parents with transgressive segregation. By anchoring these QTL to the reference genomes of B. rapa and B. oleracea, we identified 23 orthologues of Arabidopsis involved in GSL metabolism within the QTL confidence intervals. Sequence polymorphisms between the corresponding coding regions of the parental lines were used to develop cleaved amplified polymorphic site markers for two QTL-linked genes, ISOPROPYLMALATE DEHYDROGENASE1 and ADENOSINE 5'-PHOSPHOSULFATE REDUCTASE 3. The genic cleavage markers were mapped in the DH population into the corresponding intervals of QTL explaining 3.36-6.88 and 4.55-8.67 % of the phenotypic variation for seed GSL, respectively. The markers will facilitate breeding for ultra-low seed GSL content in canola.

Mutation and deletion analysis of GFRα-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours

PubMed Central

Gimm, O; Gössling, A; Marsh, D J; Dahia, P L M; Mulligan, L M; Deimling, A von; Eng, C

1999-01-01

Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFRα-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain tumours for the presence of mutations in GDNF and GFRα-1. No mutations were found in the coding region of GDNF. We identified six previously described GFRα-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFRα-1 are not a common aetiologic event in brain tumours. However, either deletion of GFRα-1 and/or nearby genes may contribute to the pathogenesis of these tumours. © 1999 Cancer Research Campaign PMID:10408842

Association of a single-nucleotide polymorphism in the promoter region of the VEGF gene with the risk of renal cell carcinoma.

PubMed

Ajaz, Sadia; Khaliq, Shagufta; Abid, Aiysha; Hassan, Asad Shehzad; Hashmi, Altaf; Sultan, Gauhar; Mohsin, Rehan; Mubarrak, Mohammad; Naqvi, Syed Ali Anwar; Rizvi, Syed Adib-ul-Hasan; Mehdi, Syed Qasim

2011-09-01

Vascular endothelial growth factor (VEGF) protein plays an important role in tumor development and progression. Polymorphisms in the VEGF gene may lead to over- or underexpression of the protein and may be associated with either risk or progression of malignancy. The aim of this case-control study is to identify and quantify the correlation between VEGF polymorphisms and renal cell carcinoma (RCC). Restriction fragment length polymorphism methods were used for the analysis of VEGF polymorphisms at -2578 and +936 positions in the promoter and 3'-untranslated regions, respectively. The VEGF -2578 A-allele was associated with an increased risk of RCC (odds ratio: 1.6; 95% CI: 1.2-2.3) and A-carrier genotypes were strongly correlated (odds ratio: 2.7; 95% CI: 1.5-4.7) with higher risk. Comparison of VEGF +936 C/T polymorphism between patient and control groups revealed no association with renal carcinoma. Both VEGF -2578 C/A and VEGF +936 C/T polymorphisms showed no significant association with the histopathological parameters of RCC. This study shows that VEGF -2578 A-allele and A-carrier genotypes are associated with an increased risk of RCC. In groups with higher incidence of RCC, a screening test for this polymorphism may be recommended in conjunction with other established markers.

Serotonin Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype and Stressful Life Events Interact to Predict Preschool-Onset Depression: A Replication and Developmental Extension

ERIC Educational Resources Information Center

Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Tillman, Rebecca; Luby, Joan L.

2014-01-01

Background: Scientific enthusiasm about gene × environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) × SLEs (stressful life events) interaction predicting depression, have recently been tempered by sober realizations of small effects and meta-analyses reaching opposing conclusions. These mixed findings…

Molecular characterization of the U.S. Phaseolus acutifolius A. Gray collection using Amplified Fragment Length Polymorphism (AFLP) and Targeted Region Amplification Polymorphism (TRAP) markers.

USDA-ARS?s Scientific Manuscript database

Tepary bean (Phaseolus acutifolius A. Gray), a truly Native American crop, is a short life-cycle annual desert legume indigenous to northwestern Mexico and the southwestern USA and is considered drought and heat tolerant. The Western Regional Plant Introduction Station currently maintains 211 acce...

Simple sequence repeats in Escherichia coli: abundance, distribution, composition, and polymorphism.

PubMed

Gur-Arie, R; Cohen, C J; Eitan, Y; Shelef, L; Hallerman, E M; Kashi, Y

2000-01-01

Computer-based genome-wide screening of the DNA sequence of Escherichia coli strain K12 revealed tens of thousands of tandem simple sequence repeat (SSR) tracts, with motifs ranging from 1 to 6 nucleotides. SSRs were well distributed throughout the genome. Mononucleotide SSRs were over-represented in noncoding regions and under-represented in open reading frames (ORFs). Nucleotide composition of mono- and dinucleotide SSRs, both in ORFs and in noncoding regions, differed from that of the genomic region in which they occurred, with 93% of all mononucleotide SSRs proving to be of A or T. Computer-based analysis of the fine position of every SSR locus in the noncoding portion of the genome relative to downstream ORFs showed SSRs located in areas that could affect gene regulation. DNA sequences at 14 arbitrarily chosen SSR tracts were compared among E. coli strains. Polymorphisms of SSR copy number were observed at four of seven mononucleotide SSR tracts screened, with all polymorphisms occurring in noncoding regions. SSR polymorphism could prove important as a genome-wide source of variation, both for practical applications (including rapid detection, strain identification, and detection of loci affecting key phenotypes) and for evolutionary adaptation of microbes.

Neuropsychological correlates of transcription factor AP-2Beta, and its interaction with COMT and MAOA in healthy females.

PubMed

Schabram, Ina; Eggermann, Thomas; Siegel, Steven J; Gründer, Gerhard; Zerres, Klaus; Vernaleken, Ingo

2013-01-01

The transcription factor AP-2β has been shown to impact clinical and neuropsychological properties. Apparently, it regulates the transcription of genes that code for molecules which are part of the catecholaminergic transmission system. This investigation focuses on possible effects of the transcription factor AP-2β intron 2 polymorphism on cognitive performance parameters. This hypothesis-driven investigation examined the effects and interactions of the transcription factor AP-2β intron 2 polymorphism, the Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive performance parameters within a group of 200 healthy women (age: mean ± SD, 23.93 ± 3.33 years). The AP-2β polymorphism significantly influenced cognitive performance (in particular, the Trail Making Test part B), whereas the MAOA and COMT polymorphisms did not. However, there was an interaction effect of the AP-2β × MAOA × COMT genotypes on the decision bias β of the degraded-stimulus version of the continuous performance task. Only the Val158Met COMT polymorphism showed an influence on personality questionnaires (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and Character Inventory). The transcription factor AP-2β intron 2 polymorphism had more influence on cognition than the MAOA and COMT polymorphisms. Possibly, the AP-2β genotype might influence cognition through pathways other than those that regulate MAOA and COMT transcription. Interactions of transcription factor AP-2β, COMT, and MAOA polymorphisms suggest higher leverage effects of transcription factor AP-2β in subjects with high dopamine availability. Copyright © 2013 S. Karger AG, Basel.

A Genome-Wide Scan for Evidence of Selection in a Maize Population Under Long-Term Artificial Selection for Ear Number

PubMed Central

Beissinger, Timothy M.; Hirsch, Candice N.; Vaillancourt, Brieanne; Deshpande, Shweta; Barry, Kerrie; Buell, C. Robin; Kaeppler, Shawn M.; Gianola, Daniel; de Leon, Natalia

2014-01-01

A genome-wide scan to detect evidence of selection was conducted in the Golden Glow maize long-term selection population. The population had been subjected to selection for increased number of ears per plant for 30 generations, with an empirically estimated effective population size ranging from 384 to 667 individuals and an increase of more than threefold in the number of ears per plant. Allele frequencies at >1.2 million single-nucleotide polymorphism loci were estimated from pooled whole-genome resequencing data, and FST values across sliding windows were employed to assess divergence between the population preselection and the population postselection. Twenty-eight highly divergent regions were identified, with half of these regions providing gene-level resolution on potentially selected variants. Approximately 93% of the divergent regions do not demonstrate a significant decrease in heterozygosity, which suggests that they are not approaching fixation. Also, most regions display a pattern consistent with a soft-sweep model as opposed to a hard-sweep model, suggesting that selection mostly operated on standing genetic variation. For at least 25% of the regions, results suggest that selection operated on variants located outside of currently annotated coding regions. These results provide insights into the underlying genetic effects of long-term artificial selection and identification of putative genetic elements underlying number of ears per plant in maize. PMID:24381334

Replicative genetic association study between functional polymorphisms in AVPR1A and social behavior scales of autism spectrum disorder in the Korean population.

PubMed

Yang, So Young; Kim, Soon Ae; Hur, Gang Min; Park, Mira; Park, Jong-Eun; Yoo, Hee Jeong

2017-01-01

Arginine vasopressin has been shown to affect social and emotional behaviors, which is mediated by the arginine vasopressin receptor (AVPR1A). Genetic polymorphisms in the AVPR1A promoter region have been identified to be associated with susceptibility to social deficits in autism spectrum disorder (ASD). We hypothesize that alleles of polymorphisms in the promoter region of AVPR1A may differentially interact with certain transcriptional factors, which in turn affect quantitative traits, such as sociality, in children with autism. We performed an association study between ASD and polymorphisms in the AVPR1A promoter region in the Korean population using a family-based association test (FBAT). We evaluated the correlation between genotypes and the quantitative traits that are related to sociality in children with autism. We also performed a promoter assay in T98G cells and evaluated the binding affinities of transcription factors to alleles of rs7294536. The polymorphisms-RS1, RS3, rs7294536, and rs10877969-were analyzed. Under the dominant model, RS1-310, the shorter allele, was preferentially transmitted. The FBAT showed that the rs7294536 A allele was also preferentially transmitted in an additive and dominant model under the bi-allelic mode. When quantitative traits were used in the FBAT, rs7294536 and rs10877969 were statistically significant in all genotype models and modes. Luciferase and electrophoretic mobility-shift assays suggest that the rs7294536 A/G allele results in a Nf-κB binding site that exhibits differential binding affinities depending on the allele. These results demonstrate that polymorphisms in the AVPR1A promoter region might be involved in pathophysiology of ASD and in functional regulation of the expression of AVPR1A .

Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility.

PubMed

Latini, Andrea; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

2017-08-01

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate the expression of multiple protein-encoding genes at the post-transcriptional level. MicroRNAs are involved in different pathways, such as cellular proliferation and differentiation, signal transduction and inflammation, and play crucial roles in the development of several diseases, such as cancer, diabetes, and cardiovascular diseases. They have recently been recognized to play a role also in the pathogenesis of autoimmune diseases. Although the majority of studies are focused on miRNA expression profiles investigation, a growing number of studies have been investigating the role of polymorphisms in miRNA genes in the autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes can modify the set of targets they regulate or the maturation efficiency. This review is aimed to give an overview about the available studies that have investigated the association of miRNA gene polymorphisms with the susceptibility to various autoimmune diseases and to their clinical phenotypes.

Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

PubMed

Cross, Deanna S; Ivacic, Lynn C; Stefanski, Elisha L; McCarty, Catherine A

2010-06-17

There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and implementation of studies and for determining the relevance of a disease associated polymorphism for a given population.

Diversity of chloroplast genome among local clones of cocoa (Theobroma cacao, L.) from Central Sulawesi

NASA Astrophysics Data System (ADS)

Suwastika, I. Nengah; Pakawaru, Nurul Aisyah; Rifka, Rahmansyah, Muslimin, Ishizaki, Yoko; Cruz, André Freire; Basri, Zainuddin; Shiina, Takashi

2017-02-01

Chloroplast genomes typically range in size from 120 to 170 kilo base pairs (kb), which relatively conserved among plant species. Recent evaluation on several species, certain unique regions showed high variability which can be utilized in the phylogenetic analysis. Many fragments of coding regions, introns, and intergenic spacers, such as atpB-rbcL, ndhF, rbcL, rpl16, trnH-psbA, trnL-F, trnS-G, etc., have been used for phylogenetic reconstructions at various taxonomic levels. Based on that status, we would like to analysis the diversity of chloroplast genome within species of local cacao (Theobroma cacao L.) from Central Sulawesi. Our recent data showed, there were more than 20 clones from local farming in Central Sulawesi, and it can be detected based on phenotypic and nuclear-genome-based characterization (RAPD- Random Amplified Polymorphic DNA and SSR- Simple Sequences Repeat) markers. In developing DNA marker for this local cacao, here we also included analysis based on the variation of chloroplast genome. At least several regions such as rpl32-TurnL, it can be considered as chloroplast markers on our local clone of cocoa. Furthermore, we could develop phylogenetic analysis in between clones of cocoa.

Evolutionary genomics of animal personality.

PubMed

van Oers, Kees; Mueller, Jakob C

2010-12-27

Research on animal personality can be approached from both a phenotypic and a genetic perspective. While using a phenotypic approach one can measure present selection on personality traits and their combinations. However, this approach cannot reconstruct the historical trajectory that was taken by evolution. Therefore, it is essential for our understanding of the causes and consequences of personality diversity to link phenotypic variation in personality traits with polymorphisms in genomic regions that code for this trait variation. Identifying genes or genome regions that underlie personality traits will open exciting possibilities to study natural selection at the molecular level, gene-gene and gene-environment interactions, pleiotropic effects and how gene expression shapes personality phenotypes. In this paper, we will discuss how genome information revealed by already established approaches and some more recent techniques such as high-throughput sequencing of genomic regions in a large number of individuals can be used to infer micro-evolutionary processes, historical selection and finally the maintenance of personality trait variation. We will do this by reviewing recent advances in molecular genetics of animal personality, but will also use advanced human personality studies as case studies of how molecular information may be used in animal personality research in the near future.

Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas

PubMed Central

Freihoff, D; Kempe, A; Beste, B; Wappenschmidt, B; Kreyer, E; Hayashi, Y; Meindl, A; Krebs, D; Wiestler, O D; Deimling, A von; Schmutzler, R K

1999-01-01

PTEN is a novel tumour-suppressor gene located on chromosomal band 10q23.3. This region displays frequent loss of heterozygosity (LOH) in a variety of human neoplasms including breast carcinomas. The detection of PTEN mutations in Cowden disease and in breast carcinoma cell lines suggests that PTEN may be involved in mammary carcinogenesis. We here report a mutational analysis of tumour specimens from 103 primary breast carcinomas and constitutive DNA from 25 breast cancer families. The entire coding region of PTEN was screened by single-strand conformation polymorphism (SSCP) analysis and direct sequencing using intron-based primers. No germline mutations could be identified in the breast cancer families and only one sporadic carcinoma carried a PTEN mutation at one allele. In addition, all sporadic tumours were analysed for homozygous deletions by differential polymerase chain reaction (PCR) and for allelic loss using the microsatellite markers D10S215, D10S564 and D10S573. No homozygous deletions were detected and only 10 out of 94 informative tumours showed allelic loss in the PTEN region. These results suggest that PTEN does not play a major role in breast cancer formation. 1999 Cancer Research Campaign PMID:10070865

Correlation approach to identify coding regions in DNA sequences

NASA Technical Reports Server (NTRS)

Ossadnik, S. M.; Buldyrev, S. V.; Goldberger, A. L.; Havlin, S.; Mantegna, R. N.; Peng, C. K.; Simons, M.; Stanley, H. E.

1994-01-01

Recently, it was observed that noncoding regions of DNA sequences possess long-range power-law correlations, whereas coding regions typically display only short-range correlations. We develop an algorithm based on this finding that enables investigators to perform a statistical analysis on long DNA sequences to locate possible coding regions. The algorithm is particularly successful in predicting the location of lengthy coding regions. For example, for the complete genome of yeast chromosome III (315,344 nucleotides), at least 82% of the predictions correspond to putative coding regions; the algorithm correctly identified all coding regions larger than 3000 nucleotides, 92% of coding regions between 2000 and 3000 nucleotides long, and 79% of coding regions between 1000 and 2000 nucleotides. The predictive ability of this new algorithm supports the claim that there is a fundamental difference in the correlation property between coding and noncoding sequences. This algorithm, which is not species-dependent, can be implemented with other techniques for rapidly and accurately locating relatively long coding regions in genomic sequences.

Common Polymorphisms in the PKP3-SIGIRR-TMEM16J Gene Region Are Associated With Susceptibility to Tuberculosis

PubMed Central

Randhawa, April K.; Chau, Tran T. H.; Bang, Nguyen D.; Yen, Nguyen T. B.; Farrar, Jeremy J.; Dunstan, Sarah J.; Hawn, Thomas R.

2012-01-01

(See the editorial commentary by Wilkinson, on pages 525–7.) Background. Tuberculosis has been associated with genetic variation in host immunity. We hypothesized that single-nucleotide polymorphisms (SNPs) in SIGIRR, a negative regulator of Toll-like receptor/IL-1R signaling, are associated with susceptibility to tuberculosis. Methods. We used a case-population study design in Vietnam with cases that had either tuberculous meningitis or pulmonary tuberculosis. We genotyped 6 SNPs in the SIGIRR gene region (including the adjacent genes PKP3 and TMEM16J) in a discovery cohort of 352 patients with tuberculosis and 382 controls. Significant associations were genotyped in a validation cohort (339 patients with tuberculosis, 376 controls). Results. Three SNPs (rs10902158, rs7105848, rs7111432) were associated with tuberculosis in discovery and validation cohorts. The polymorphisms were associated with both tuberculous meningitis and pulmonary tuberculosis and were strongest with a recessive genetic model (odds ratios, 1.5–1.6; P = .0006–.001). Coinheritance of these polymorphisms with previously identified risk alleles in Toll-like receptor 2 and TIRAP was associated with an additive risk of tuberculosis susceptibility. Conclusions. These results demonstrate a strong association of SNPs in the PKP3-SIGIRR-TMEM16J gene region and tuberculosis in discovery and validation cohorts. To our knowledge, these are the first associations of polymorphisms in this region with any disease. PMID:22223854

Polymorphism in the promoter region of the Toll-like receptor 9 gene and cervical human papillomavirus infection.

PubMed

Oliveira, Lucas Boeno; Louvanto, Karolina; Ramanakumar, Agnihotram V; Franco, Eduardo L; Villa, Luisa L

2013-08-01

Polymorphism in the Toll-like receptor (TLR) 9 gene has been shown to have a significant role in some diseases; however, little is known about its possible role in the natural history of human papillomavirus (HPV) infections. We investigated the association between a single-nucleotide polymorphism (SNP) (rs5743836) in the promoter region of TLR9 (T1237C) and type-specific HPV infections. Specimens were derived from a cohort of 2462 women enrolled in the Ludwig-McGill Cohort Study. We randomly selected 500 women who had a cervical HPV infection detected at least once during the study as cases. We defined two control groups: (i) a random sample of 300 women who always tested HPV negative, and (ii) a sample of 234 women who were always HPV negative but had a minimum of ten visits during the study. TLR9 genotyping was performed using bidirectional PCR amplification of specific alleles. Irrespective of group, the WT homozygous TLR9 genotype (TT) was the most common form, followed by the heterozygous (TC) and the mutant homozygous (CC) forms. There were no consistent associations between polymorphism and infection risk, either overall or by type or species. Likewise, there were no consistently significant associations between polymorphism and HPV clearance or persistence. We concluded that this polymorphism in the promoter region of TLR9 gene does not seem to have a mediating role in the natural history of the HPV infection.

Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus.

PubMed

Pritchard, Victoria L; Viitaniemi, Heidi M; McCairns, R J Scott; Merilä, Juha; Nikinmaa, Mikko; Primmer, Craig R; Leder, Erica H

2017-01-05

Much adaptive evolutionary change is underlain by mutational variation in regions of the genome that regulate gene expression rather than in the coding regions of the genes themselves. An understanding of the role of gene expression variation in facilitating local adaptation will be aided by an understanding of underlying regulatory networks. Here, we characterize the genetic architecture of gene expression variation in the threespine stickleback (Gasterosteus aculeatus), an important model in the study of adaptive evolution. We collected transcriptomic and genomic data from 60 half-sib families using an expression microarray and genotyping-by-sequencing, and located expression quantitative trait loci (eQTL) underlying the variation in gene expression in liver tissue using an interval mapping approach. We identified eQTL for several thousand expression traits. Expression was influenced by polymorphism in both cis- and trans-regulatory regions. Trans-eQTL clustered into hotspots. We did not identify master transcriptional regulators in hotspot locations: rather, the presence of hotspots may be driven by complex interactions between multiple transcription factors. One observed hotspot colocated with a QTL recently found to underlie salinity tolerance in the threespine stickleback. However, most other observed hotspots did not colocate with regions of the genome known to be involved in adaptive divergence between marine and freshwater habitats. Copyright © 2017 Pritchard et al.

A sequence-based genetic map of Medicago truncatula and comparison of marker colinearity with M. sativa.

PubMed Central

Choi, Hong-Kyu; Kim, Dongjin; Uhm, Taesik; Limpens, Eric; Lim, Hyunju; Mun, Jeong-Hwan; Kalo, Peter; Penmetsa, R Varma; Seres, Andrea; Kulikova, Olga; Roe, Bruce A; Bisseling, Ton; Kiss, Gyorgy B; Cook, Douglas R

2004-01-01

A core genetic map of the legume Medicago truncatula has been established by analyzing the segregation of 288 sequence-characterized genetic markers in an F(2) population composed of 93 individuals. These molecular markers correspond to 141 ESTs, 80 BAC end sequence tags, and 67 resistance gene analogs, covering 513 cM. In the case of EST-based markers we used an intron-targeted marker strategy with primers designed to anneal in conserved exon regions and to amplify across intron regions. Polymorphisms were significantly more frequent in intron vs. exon regions, thus providing an efficient mechanism to map transcribed genes. Genetic and cytogenetic analysis produced eight well-resolved linkage groups, which have been previously correlated with eight chromosomes by means of FISH with mapped BAC clones. We anticipated that mapping of conserved coding regions would have utility for comparative mapping among legumes; thus 60 of the EST-based primer pairs were designed to amplify orthologous sequences across a range of legume species. As an initial test of this strategy, we used primers designed against M. truncatula exon sequences to rapidly map genes in M. sativa. The resulting comparative map, which includes 68 bridging markers, indicates that the two Medicago genomes are highly similar and establishes the basis for a Medicago composite map. PMID:15082563

Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus

PubMed Central

Pritchard, Victoria L.; Viitaniemi, Heidi M.; McCairns, R. J. Scott; Merilä, Juha; Nikinmaa, Mikko; Primmer, Craig R.; Leder, Erica H.

2016-01-01

Much adaptive evolutionary change is underlain by mutational variation in regions of the genome that regulate gene expression rather than in the coding regions of the genes themselves. An understanding of the role of gene expression variation in facilitating local adaptation will be aided by an understanding of underlying regulatory networks. Here, we characterize the genetic architecture of gene expression variation in the threespine stickleback (Gasterosteus aculeatus), an important model in the study of adaptive evolution. We collected transcriptomic and genomic data from 60 half-sib families using an expression microarray and genotyping-by-sequencing, and located expression quantitative trait loci (eQTL) underlying the variation in gene expression in liver tissue using an interval mapping approach. We identified eQTL for several thousand expression traits. Expression was influenced by polymorphism in both cis- and trans-regulatory regions. Trans-eQTL clustered into hotspots. We did not identify master transcriptional regulators in hotspot locations: rather, the presence of hotspots may be driven by complex interactions between multiple transcription factors. One observed hotspot colocated with a QTL recently found to underlie salinity tolerance in the threespine stickleback. However, most other observed hotspots did not colocate with regions of the genome known to be involved in adaptive divergence between marine and freshwater habitats. PMID:27836907

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia an bipolar affective disorder

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

Rubinsztein, D.C.; Leggo, J.; Crow, T.J.

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close tomore » the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tract-lengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus. 22 refs., 1 tab.« less

A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes.

PubMed

Liu, H X; Cartegni, L; Zhang, M Q; Krainer, A R

2001-01-01

Point mutations can generate defective and sometimes harmful proteins. The nonsense-mediated mRNA decay (NMD) pathway minimizes the potential damage caused by nonsense mutations. In-frame nonsense codons located at a minimum distance upstream of the last exon-exon junction are recognized as premature termination codons (PTCs), targeting the mRNA for degradation. Some nonsense mutations cause skipping of one or more exons, presumably during pre-mRNA splicing in the nucleus; this phenomenon is termed nonsense-mediated altered splicing (NAS), and its underlying mechanism is unclear. By analyzing NAS in BRCA1, we show here that inappropriate exon skipping can be reproduced in vitro, and results from disruption of a splicing enhancer in the coding sequence. Enhancers can be disrupted by single nonsense, missense and translationally silent point mutations, without recognition of an open reading frame as such. These results argue against a nuclear reading-frame scanning mechanism for NAS. Coding-region single-nucleotide polymorphisms (cSNPs) within exonic splicing enhancers or silencers may affect the patterns or efficiency of mRNA splicing, which may in turn cause phenotypic variability and variable penetrance of mutations elsewhere in a gene.

Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.

PubMed

Jones, Siân; Zhang, Xiaosong; Parsons, D Williams; Lin, Jimmy Cheng-Ho; Leary, Rebecca J; Angenendt, Philipp; Mankoo, Parminder; Carter, Hannah; Kamiyama, Hirohiko; Jimeno, Antonio; Hong, Seung-Mo; Fu, Baojin; Lin, Ming-Tseh; Calhoun, Eric S; Kamiyama, Mihoko; Walter, Kimberly; Nikolskaya, Tatiana; Nikolsky, Yuri; Hartigan, James; Smith, Douglas R; Hidalgo, Manuel; Leach, Steven D; Klein, Alison P; Jaffee, Elizabeth M; Goggins, Michael; Maitra, Anirban; Iacobuzio-Donahue, Christine; Eshleman, James R; Kern, Scott E; Hruban, Ralph H; Karchin, Rachel; Papadopoulos, Nickolas; Parmigiani, Giovanni; Vogelstein, Bert; Velculescu, Victor E; Kinzler, Kenneth W

2008-09-26

There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 10(6) single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.

Mutation detection in the human HSP70B′ gene by denaturing high-performance liquid chromatography

PubMed Central

Hecker, Karl H.; Asea, Alexzander; Kobayashi, Kaoru; Green, Stacy; Tang, Dan; Calderwood, Stuart K.

2000-01-01

Variances, particularly single nucleotide polymorphisms (SNP), in the genomic sequence of individuals are the primary key to understanding gene function as it relates to differences in the susceptibility to disease, environmental influences, and therapy. In this report, the HSP70B′ gene is the target sequence for mutation detection in biopsy samples from human prostate cancer patients undergoing combined hyperthermia and radiation therapy at the Dana-Farber Cancer Institute, using temperature-modulated heteroduplex analysis (TMHA). The underlying principles of TMHA for mutation detection using DHPLC technology are discussed. The procedures involved in amplicon design for mutation analysis by DHPLC are detailed. The melting behavior of the complete coding sequence of the target gene is characterized using WAVEMAKERTM software. Four overlapping amplicons, which span the complete coding region of the HSP70B′ gene, amenable to mutation detection by DHPLC were identified based on the software-predicted melting profile of the target sequence. TMHA was performed on PCR products of individual amplicons of the HSP70B′ gene on the WAVE® Nucleic Acid Fragment Analysis System. The criteria for mutation calling by comparing wild-type and mutant chromatographic patterns are discussed. PMID:11189446

Mutation detection in the human HSP7OB' gene by denaturing high-performance liquid chromatography.

PubMed

Hecker, K H; Asea, A; Kobayashi, K; Green, S; Tang, D; Calderwood, S K

2000-11-01

Variances, particularly single nucleotide polymorphisms (SNP), in the genomic sequence of individuals are the primary key to understanding gene function as it relates to differences in the susceptibility to disease, environmental influences, and therapy. In this report, the HSP70B' gene is the target sequence for mutation detection in biopsy samples from human prostate cancer patients undergoing combined hyperthermia and radiation therapy at the Dana-Farber Cancer Institute, using temperature-modulated heteroduplex analysis (TMHA). The underlying principles of TMHA for mutation detection using DHPLC technology are discussed. The procedures involved in amplicon design for mutation analysis by DHPLC are detailed. The melting behavior of the complete coding sequence of the target gene is characterized using WAVEMAKER software. Four overlapping amplicons, which span the complete coding region of the HSP70B' gene, amenable to mutation detection by DHPLC were identified based on the software-predicted melting profile of the target sequence. TMHA was performed on PCR products of individual amplicons of the HSP70B' gene on the WAVE Nucleic Acid Fragment Analysis System. The criteria for mutation calling by comparing wild-type and mutant chromatographic patterns are discussed.

Brief review of the chicken Major Histocompatibility Complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance

PubMed Central

Miller, Marcia M.; Taylor, Robert L.

2016-01-01

Nearly all genes presently mapped to chicken chromosome 16 (GGA 16) have either a demonstrated role in immune responses or are considered to serve in immunity by reason of sequence homology with immune system genes defined in other species. The genes are best described in regional units. Among these, the best known is the polymorphic major histocompatibility complex-B (MHC-B) region containing genes for classical peptide antigen presentation. Nearby MHC-B is a small region containing two CD1 genes, which encode molecules known to bind lipid antigens and which will likely be found in chickens to present lipids to specialized T cells, as occurs with CD1 molecules in other species. Another region is the MHC-Y region, separated from MHC-B by an intervening region of tandem repeats. Like MHC-B, MHC-Y is polymorphic. It contains specialized class I and class II genes and c-type lectin-like genes. Yet another region, separated from MHC-Y by the single nucleolar organizing region (NOR) in the chicken genome, contains olfactory receptor genes and scavenger receptor genes, which are also thought to contribute to immunity. The structure, distribution, linkages and patterns of polymorphism in these regions, suggest GGA 16 evolves as a microchromosome devoted to immune defense. Many GGA 16 genes are polymorphic and polygenic. At the moment most disease associations are at the haplotype level. Roles of individual MHC genes in disease resistance are documented in only a very few instances. Provided suitable experimental stocks persist, the availability of increasingly detailed maps of GGA 16 genes combined with new means for detecting genetic variability will lead to investigations defining the contributions of individual loci and more applications for immunogenetics in breeding healthy poultry. PMID:26740135

Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).

PubMed

Dossus, Laure; McKay, James D; Canzian, Federico; Wilkening, Stefan; Rinaldi, Sabina; Biessy, Carine; Olsen, Anja; Tjønneland, Anne; Jakobsen, Marianne U; Overvad, Kim; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Fournier, Agnes; Linseisen, Jakob; Lukanova, Annekatrin; Boeing, Heiner; Fisher, Eva; Trichopoulou, Antonia; Georgila, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Quirós, José Ramon; Sala, Núria; Martínez-García, Carmen; Dorronsoro, Miren; Chirlaque, Maria-Dolores; Barricarte, Aurelio; van Duijnhoven, Fränzel J B; Bueno-de-Mesquita, H B; van Gils, Carla H; Peeters, Petra H M; Hallmans, Göran; Lenner, Per; Bingham, Sheila; Khaw, Kay Tee; Key, Tim J; Travis, Ruth C; Ferrari, Pietro; Jenab, Mazda; Riboli, Elio; Kaaks, Rudolf

2008-07-01

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between <0.01 and 0.04). The false-positive report probability (FPRP) approach suggests that these results are noteworthy (FPRP < 0.20). The results presented here add to a growing body of evidence that GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.

Correlation between the development of calcium oxalate stones and polymorphisms in the fibronectin gene in the Uighur population of the Xinjiang region of China.

PubMed

Murat, M; Aekeper, A; Yuan, L Y; Alim, T; Du, G J; Abdusamat, A; Wu, G W; Aniwer, Y

2015-10-29

Here, we have investigated the correlation between calcium oxalate stone formation and Fn gene polymorphisms in urinary calculi patients among the Uighur population (Xinjiang region). In this case control study, genomic DNA extracted from the peripheral blood of 129 patients with calcium oxalate stones (patient group) and 94 normal people (control group) was used to genotype polymorphisms in the rs6725958, rs10202709, and rs35343655 sites of the Fn gene by polymerase chain reaction-restriction fragment length polymorphism. Subsequently, the association between different genotypes and susceptibility to calcium oxalate stone formation was compared among the patient and control groups. Single nucleotide polymorphisms (SNPs) were detected in the rs6725958, rs10202709, and rs35343655 sites of the Fn gene among the patient and control groups. The genotype distributions of the three loci complied with the Hardy-Weinberg equilibrium. The results of allele frequencies of the patient/control group for polymorphisms in the rs6725958 site of the Fn gene were C = 179 (69.92%)/119 (63.30%) and A = 77 (30.08%)/69 (36.70%), in the rs10202709 site were C = 245 (95.70%)/176 (93.63%) and T = 11 (4.30%)/12 (6.38%), and in the rs35343655 site of the Fn gene were A = 139 (54.30%)/87 (46.28%) and G = 117 (45.70%)/101 (53.72%). We observed no significant differences between the three SNPs and development of calcium oxalate stones. Polymorphisms in rs6725958, rs10202709, and rs35343655 of the Fn gene had no obvious effect on the susceptibility to the development of calcium oxalate stones in the Uighur population, residing in the Xinjiang region of China.

T-cell receptor V sub. alpha. and C sub. alpha. alleles associated with multiple sclerosis and myasthenia gravis

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

Oksenberg, J.R.; Cavalli-Sforza, L.L.; Steinman, L.

1989-02-01

Polymorphic markers in genes encoding the {alpha} chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, the authors amplified selected sequences derived from the full-length TcR {alpha} cDNA probe. These PcR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of themore » polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, the authors have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic V{sub {alpha}} and C{sub {alpha}} markers were identified between patients and healthy individuals.« less

Patterns of genetic diversity in the polymorphic ground snake (Sonora semiannulata).

PubMed

Cox, Christian L; Chippindale, Paul T

2014-08-01

We evaluated the genetic diversity of a snake species with color polymorphism to understand the evolutionary processes that drive genetic structure across a large geographic region. Specifically, we analyzed genetic structure of the highly polymorphic ground snake, Sonora semiannulata, (1) among populations, (2) among color morphs (3) at regional and local spatial scales, using an amplified fragment length polymorphism dataset and multiple population genetic analyses, including FST-based and clustering analytical techniques. Based upon these methods, we found that there was moderate to low genetic structure among populations. However, this diversity was not associated with geographic locality at either spatial scale. Similarly, we found no evidence for genetic divergence among color morphs at either spatial scale. These results suggest that despite dramatic color polymorphism, this phenotypic diversity is not a major driver of genetic diversity within or among populations of ground snakes. We suggest that there are two mechanisms that could explain existing genetic diversity in ground snakes: recent range expansion from a genetically diverse founder population and current or recent gene flow among populations. Our findings have further implications for the types of color polymorphism that may generate genetic diversity in snakes.

Chloroplast Genome Differences between Asian and American Equisetum arvense (Equisetaceae) and the Origin of the Hypervariable trnY-trnE Intergenic Spacer

PubMed Central

Kim, Hyoung Tae; Kim, Ki-Joong

2014-01-01

Comparative analyses of complete chloroplast (cp) DNA sequences within a species may provide clues to understand the population dynamics and colonization histories of plant species. Equisetum arvense (Equisetaceae) is a widely distributed fern species in northeastern Asia, Europe, and North America. The complete cp DNA sequences from Asian and American E. arvense individuals were compared in this study. The Asian E. arvense cp genome was 583 bp shorter than that of the American E. arvense. In total, 159 indels were observed between two individuals, most of which were concentrated on the hypervariable trnY-trnE intergenic spacer (IGS) in the large single-copy (LSC) region of the cp genome. This IGS region held a series of 19 bp repeating units. The numbers of the 19 bp repeat unit were responsible for 78% of the total length difference between the two cp genomes. Furthermore, only other closely related species of Equisetum also show the hypervariable nature of the trnY-trnE IGS. By contrast, only a single indel was observed in the gene coding regions: the ycf1 gene showed 24 bp differences between the two continental individuals due to a single tandem-repeat indel. A total of 165 single-nucleotide polymorphisms (SNPs) were recorded between the two cp genomes. Of these, 52 SNPs (31.5%) were distributed in coding regions, 13 SNPs (7.9%) were in introns, and 100 SNPs (60.6%) were in intergenic spacers (IGS). The overall difference between the Asian and American E. arvense cp genomes was 0.12%. Despite the relatively high genetic diversity between Asian and American E. arvense, the two populations are recognized as a single species based on their high morphological similarity. This indicated that the two regional populations have been in morphological stasis. PMID:25157804

Templated sequence insertion polymorphisms in the human genome

NASA Astrophysics Data System (ADS)

Onozawa, Masahiro; Aplan, Peter

2016-11-01

Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including 1) target-site duplication (TSD), 2) polyadenylation 10-30 nucleotides downstream of a “cryptic” polyadenylation signal, and 3) preference for insertion at a 5’-TTTT/A-3’ sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break via insertion of a DNA “patch” that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25-30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases.

Adaptive divergence in the monkey flower Mimulus guttatus is maintained by a chromosomal inversion

PubMed Central

Twyford, Alex D.; Friedman, Jannice

2015-01-01

Organisms exhibit an incredible diversity of life history strategies as adaptive responses to environmental variation. The establishment of novel life history strategies involves multilocus polymorphisms, which will be challenging to establish in the face of gene flow and recombination. Theory predicts that adaptive allelic combinations may be maintained and spread if they occur in genomic regions of reduced recombination, such as chromosomal inversion polymorphisms, yet empirical support for this prediction is lacking. Here, we use genomic data to investigate the evolution of divergent adaptive ecotypes of the yellow monkey flower Mimulus guttatus. We show that a large chromosomal inversion polymorphism is the major region of divergence between geographically widespread annual and perennial ecotypes. In contrast, ∼40,000 single nucleotide polymorphisms in collinear regions of the genome show no signal of life history, revealing genomic patterns of diversity have been shaped by localized homogenizing gene flow and large‐scale Pleistocene range expansion. Our results provide evidence for an inversion capturing and protecting loci involved in local adaptation, while also explaining how adaptive divergence can occur with gene flow. PMID:25879251

Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China.

PubMed

Jin, Tianbo; Yang, Hua; Zhang, Jiayi; Yunus, Zulfiya; Sun, Qiang; Geng, Tingting; Chen, Chao; Yang, Jie

2015-01-01

Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5'UTR, promoters, exons, introns, and 3'UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. Twenty-one genetic polymorphisms in CYP3A4, and nine of them were novel. We detected CYP3A4*8, a putative poor-metabolizer allele, with the frequency of 0.5% in Uygur population. Tfsitescan revealed that the density of transcription factor varied in the different promoter regions, among which some were key regions for transcription factor binding. our results provide basic information about CPY3A4 alleles in Uygur and suggest that the enzymatic activities of CPY3A4 may differ among the diverse ethnic populations of China.

Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China

PubMed Central

Jin, Tianbo; Yang, Hua; Zhang, Jiayi; Yunus, Zulfiya; Sun, Qiang; Geng, Tingting; Chen, Chao; Yang, Jie

2015-01-01

Purpose: Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. Methods: The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5’UTR, promoters, exons, introns, and 3’UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. Results: Twenty-one genetic polymorphisms in CYP3A4, and nine of them were novel. We detected CYP3A4*8, a putative poor-metabolizer allele, with the frequency of 0.5% in Uygur population. Tfsitescan revealed that the density of transcription factor varied in the different promoter regions, among which some were key regions for transcription factor binding. Conclusion: our results provide basic information about CPY3A4 alleles in Uygur and suggest that the enzymatic activities of CPY3A4 may differ among the diverse ethnic populations of China. PMID:26261601

Polymorphisms at the 3' untranslated region of SLC11A1 gene are associated with protection to Brucella infection in goats.

PubMed

Iacoboni, Paola A; Hasenauer, Flavia C; Caffaro, M Eugenia; Gaido, Analia; Rossetto, Cristina; Neumann, Roberto D; Salatin, Antonio; Bertoni, Emiliano; Poli, Mario A; Rossetti, Carlos A

2014-08-15

Goats are susceptible to brucellosis and the detection of Brucella-infected animals is carried out by serological tests. In other ruminant species, polymorphisms in microsatellites (Ms) of 3' untranslated region (3'UTR) of the solute carrier family 11 member A1 (SLC11A1) gene were associated with resistance to Brucella abortus infection. Goats present two polymorphic Ms at the 3'UTR end of SLC11A1 gene, called regions A and B. Here, we evaluated if polymorphisms in regions A and/or B are associated with Brucella infection in goats. Serum (for the detection of Brucella-specific antibodies) and hair samples (for DNA isolation and structure analysis of the SLC11A1 gene) were randomly collected from 229 adult native goats from the northwest of Argentina. Serological status was evaluated by buffer plate antigen test (BPAT) complemented by the fluorescent polarization assay (FPA), and the genotype of the 3'UTR of the SLC11A1 gene was determined by capillary electrophoresis and confirmed by sequence analysis. Polymorphisms in regions A and B of the 3'UTR SLC11A1 gene were found statistically significant associated with protection to Brucella infection. Specifically, the association study indicates statistical significance of the allele A15 and B7/B7 genotype with absence of Brucella-specific antibodies (p=0.0003 and 0.0088, respectively). These data open a promising opportunity for limiting goat brucellosis through selective breeding of animals based on genetic markers associated with natural resistance to B. melitensis infection. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium vivax Myanmar isolates

PubMed Central

2012-01-01

Background Plasmodium vivax Duffy binding protein (PvDBP) plays an essential role in erythrocyte invasion and a potential asexual blood stage vaccine candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly amino terminal cysteine-rich region (PvDBPII), represents a major impediment to the successful design of a protective vaccine against vivax malaria. In this study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P. vivax isolates were analysed. Methods Fifty-four P. vivax infected blood samples collected from patients in Myanmar were used. The region flanking PvDBPII was amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic characters and natural selection of the region were analysed using the DnaSP and MEGA4 programs. Results Thirty-two point mutations (28 non-synonymous and four synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were identified in Myanmar P. vivax isolates and that the region has evolved under positive natural selection. High selective pressure preferentially acted on regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also be played a role in the resulting genetic diversity of PvDBPII. Conclusions PvDBPII of Myanmar P. vivax isolates displays a high level of genetic polymorphism and is under selective pressure. Myanmar P. vivax isolates share distinct types of PvDBPII alleles that are different from those of other geographical areas. These results will be useful for understanding the nature of the P. vivax population in Myanmar and for development of PvDBPII-based vaccine. PMID:22380592

Novel mutations of TCOF1 gene in European patients with treacher Collins syndrome

PubMed Central

2011-01-01

Background Treacher Collins syndrome (TCS) is one of the most severe autosomal dominant congenital disorders of craniofacial development and shows variable phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in 50.000 live births. The TCS distinguishing characteristics are represented by down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present. TCS results from mutations in the TCOF1 gene located on chromosome 5, which encodes a serine/alanine-rich nucleolar phospho-protein called Treacle. However, alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases. Methods In this study, the entire coding regions of the TCOF1 gene, including newly described exons 6A and 16A, were sequenced in 46 unrelated subjects suspected of TCS clinical indication. Results Fifteen mutations were reported, including twelve novel and three already described in 14 sporadic patients and in 3 familial cases. Moreover, seven novel polymorphisms were also described. Most of the mutations characterised were microdeletions spanning one or more nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop mutation. The deletions and the insertion described cause a premature termination of translation, resulting in a truncated protein. Conclusion This study confirms that almost all the TCOF1 pathogenic mutations fall in the coding region and lead to an aberrant protein. PMID:21951868

Novel mutations of TCOF1 gene in European patients with Treacher Collins syndrome.

PubMed

Conte, Chiara; D'Apice, Maria Rosaria; Rinaldi, Fabrizio; Gambardella, Stefano; Sangiuolo, Federica; Novelli, Giuseppe

2011-09-27

Treacher Collins syndrome (TCS) is one of the most severe autosomal dominant congenital disorders of craniofacial development and shows variable phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in 50.000 live births. The TCS distinguishing characteristics are represented by down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present. TCS results from mutations in the TCOF1 gene located on chromosome 5, which encodes a serine/alanine-rich nucleolar phospho-protein called Treacle. However, alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases. In this study, the entire coding regions of the TCOF1 gene, including newly described exons 6A and 16A, were sequenced in 46 unrelated subjects suspected of TCS clinical indication. Fifteen mutations were reported, including twelve novel and three already described in 14 sporadic patients and in 3 familial cases. Moreover, seven novel polymorphisms were also described. Most of the mutations characterised were microdeletions spanning one or more nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop mutation. The deletions and the insertion described cause a premature termination of translation, resulting in a truncated protein. This study confirms that almost all the TCOF1 pathogenic mutations fall in the coding region and lead to an aberrant protein.

Population genetic implications from sequence variation in four Y chromosome genes.

PubMed

Shen, P; Wang, F; Underhill, P A; Franco, C; Yang, W H; Roxas, A; Sung, R; Lin, A A; Hyman, R W; Vollrath, D; Davis, R W; Cavalli-Sforza, L L; Oefner, P J

2000-06-20

Some insight into human evolution has been gained from the sequencing of four Y chromosome genes. Primary genomic sequencing determined gene SMCY to be composed of 27 exons that comprise 4,620 bp of coding sequence. The unfinished sequencing of the 5' portion of gene UTY1 was completed by primer walking, and a total of 20 exons were found. By using denaturing HPLC, these two genes, as well as DBY and DFFRY, were screened for polymorphic sites in 53-72 representatives of the five continents. A total of 98 variants were found, yielding nucleotide diversity estimates of 2.45 x 10(-5), 5. 07 x 10(-5), and 8.54 x 10(-5) for the coding regions of SMCY, DFFRY, and UTY1, respectively, with no variant having been observed in DBY. In agreement with most autosomal genes, diversity estimates for the noncoding regions were about 2- to 3-fold higher and ranged from 9. 16 x 10(-5) to 14.2 x 10(-5) for the four genes. Analysis of the frequencies of derived alleles for all four genes showed that they more closely fit the expectation of a Luria-Delbrück distribution than a distribution expected under a constant population size model, providing evidence for exponential population growth. Pairwise nucleotide mismatch distributions date the occurrence of population expansion to approximately 28,000 years ago. This estimate is in accord with the spread of Aurignacian technology and the disappearance of the Neanderthals.

Isolated familial somatotropinomas: clinical features and analysis of the MEN1 gene.

PubMed

De Menis, Ernesto; Prezant, Toni R

2002-01-01

Isolated familial somatotropinomas (IFS) rarely occurs in the absence of multiple endocrine neoplasia type I (MEN1) or the Carney complex. In the present study we report two Italian siblings affected by GH-secreting adenomas. There was no history of parental consanguinity. The sister presented at 18 years of age with secondary amenorrhea and acromegalic features and one of her two brothers presented with gigantism at the same age. Endocrinological investigations confirmed GH hypersecretion in both cases. Although a pituitary microadenoma was detected in both patients, transsphenoidal surgery was not successful. The sister received conventional radiotherapy and acromegaly is now considered controlled; the brother is being treated with octreotide LAR 30 mg monthly and the disease is considered clinically active. Patients, their parents and the unaffected brother underwent extensive evaluation, and no features of MEN1 or Carney complex were found. Analysis of polymorphic microsatellite markers from chromosome 11q13 (D11S599, D11S4945, D11S4939, D11S4938 and D11S987) showed that the acromegalic siblings had inherited different maternal chromosomes and shared the paternal chromosome. No pathogenic MEN1 sequence changes were detected by sequencing or dideoxy fingerprinting of the coding sequence (exons 2-10) and exon/intron junctions. Although mutations in the promoter, introns or untranslated regions of the MEN1 gene cannot be excluded, germline mutations within the coding region of this gene do not appear responsible for IFS in this family.

DNA polymorphism in recombining and non-recombing mating-type-specific loci of the smut fungus Microbotryum

PubMed Central

Votintseva, A A; Filatov, D A

2011-01-01

The population-genetic processes leading to the genetic degeneration of non-recombining regions have mainly been studied in animal and plant sex chromosomes. Here, we report population genetic analysis of the processes in the non-recombining mating-type-specific regions of the smut fungus Microbotryum violaceum. M. violaceum has A1 and A2 mating types, determined by mating-type-specific ‘sex chromosomes' that contain 1–2 Mb long non-recombining regions. If genetic degeneration were occurring, then one would expect reduced DNA polymorphism in the non-recombining regions of this fungus. The analysis of DNA diversity among 19 M. violaceum strains, collected across Europe from Silene latifolia flowers, revealed that (i) DNA polymorphism is relatively low in all 20 studied loci (π∼0.15%), (ii) it is not significantly different between the two mating-type-specific chromosomes nor between the non-recombining and recombining regions, (iii) there is substantial population structure in M. violaceum populations, which resembles that of its host species, S. latifolia, and (iv) there is significant linkage disequilibrium, suggesting that widespread selfing in this species results in a reduction of the effective recombination rate across the genome. We hypothesise that selfing-related reduction of recombination across the M. violaceum genome negates the difference in the level of DNA polymorphism between the recombining and non-recombining regions, and may possibly lead to similar levels of genetic degeneration in the mating-type-specific regions of the non-recombining ‘sex chromosomes' and elsewhere in the genome. PMID:21081967

MHC class II B diversity in blue tits: a preliminary study.

PubMed

Aguilar, Juan Rivero-de; Schut, Elske; Merino, Santiago; Martínez, Javier; Komdeur, Jan; Westerdahl, Helena

2013-07-01

In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were investigated using both PCR-based methods and unamplified genomic DNA with restriction fragment length polymorphism (RFLP) and southern blots. A total of 13 different exon 2 sequences were obtained independently from DNA and/or RNA, thus confirming gene transcription and likely functionality of the genes. Nine out of 13 alleles were found in more than one country, and two alleles appeared in all countries. Positive selection was detected in the region coding for the peptide binding region (PBR). A maximum of three alleles per individual was detected by sequencing and the RFLP pattern consisted of 4-7 fragments, indicating a minimum number of 2-4 loci per individual. A phylogenetic analysis, demonstrated that the blue tit sequences are divergent compared to sequences from other passerines resembling a different MHC lineage than those possessed by most passerines studied to date.

MHC class II B diversity in blue tits: a preliminary study

PubMed Central

Aguilar, Juan Rivero-de; Schut, Elske; Merino, Santiago; Martínez, Javier; Komdeur, Jan; Westerdahl, Helena

2013-01-01

In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were investigated using both PCR-based methods and unamplified genomic DNA with restriction fragment length polymorphism (RFLP) and southern blots. A total of 13 different exon 2 sequences were obtained independently from DNA and/or RNA, thus confirming gene transcription and likely functionality of the genes. Nine out of 13 alleles were found in more than one country, and two alleles appeared in all countries. Positive selection was detected in the region coding for the peptide binding region (PBR). A maximum of three alleles per individual was detected by sequencing and the RFLP pattern consisted of 4–7 fragments, indicating a minimum number of 2–4 loci per individual. A phylogenetic analysis, demonstrated that the blue tit sequences are divergent compared to sequences from other passerines resembling a different MHC lineage than those possessed by most passerines studied to date. PMID:23919136

The Genetics of the Thyroid Stimulating Hormone Receptor: History and Relevance

PubMed Central

Yin, Xiaoming; Latif, Rauf

2010-01-01

Background The thyroid stimulating hormone receptor (TSHR) is the key regulator of thyrocyte function. The gene for the TSHR on chromosome 14q31 has been implicated as coding for the major autoantigen in the autoimmune hyperthyroidism of Graves' disease (GD) to which T cells and autoantibodies are directed. Summary The TSHR is a seven-transmembrane domain receptor that undergoes complex posttranslational processing. In this brief review, we look at the genetics of this important autoantigen and its influence on a variety of tissue functions in addition to its role in the induction of GD. Conclusions There is convincing evidence that the TSH receptor gene confers increased susceptibility for GD, but not Hashimoto's thyroiditis. GD is associated with polymorphisms in the intron 1 gene region. How such noncoding nucleotide changes influence disease susceptibility remains uncertain, but is likely to involve TSHR splicing variants and/or microRNAs arising from this gene region. Whether such influences are confined to the thyroid gland or whether they influence cell function in the many extrathyroidal sites of TSHR expression remains unknown. PMID:20578897

Polymorphisms and Tissue Expression of the Feline Leukocyte Antigen Class I Loci FLAI-E, -H and -K

PubMed Central

Holmes, Jennifer C.; Holmer, Savannah G.; Ross, Peter; Buntzman, Adam S.; Frelinger, Jeffrey A.; Hess, Paul R.

2013-01-01

Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the Feline Leukocyte Antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, 3 loci - FLAI-E, -H and -K – are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, -H, and -K alleles from 12 cats of various breeds, identifying, for the first time, alleles across 3 distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the α1/α2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and -K. Only FLAI-E, -H and -K-origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, -H, and -K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats. PMID:23812210

HTR1B gene variants associate with the susceptibility of Raynauds' phenomenon in workers exposed hand-arm vibration.

PubMed

Chen, Qingsong; Lang, Li; Xiao, Bin; Lin, Hansheng; Yang, Aichu; Li, Hongling; Tang, Shichuan; Huang, Hanlin

2016-10-05

To explore whether polymorphic variants of the HTR1B gene are associated with the susceptibility of Raynauds' Phenomenon (RP) coursed by vibration. 148 subjects exposed to vibration for more than 2 years were classified into either induced white finger (VWF) group (n = 72), or non-VWF group (n = 76). Vibration exposure levels were measured and assessed following ISO 5349-1:2001 protocol. All workers were genotyped by sequencing for the single nucleotide polymorphisms (SNPs) in the 5'-flanking and coding region of HTR1B. Genetic characteristics and linkage disequilibrium (LD) were analyzed with Haploview. Serum serotonin levels of each subject were detected using ELISA. The association between the susceptibility of vascular damage and genotype was analyzed via logistic regression. 7 known SNPs were obtained and their allele frequencies were inserted into the Hardy-Weinberg equilibrium. rs6297 variant genotype had an increased risk of VWF compared with wild genotype (OR = 2.14, 95% CI = 1.04- 4.58, P < 0.05). rs6298 mutant type (AG+GG) was found to have a significant interaction on vibration exposure LN(CEI), accounting for VWF occurrence. LN(5-HT) level is significantly different between the VWF group (x¯±s= 1.99±1.09 ng/mL) and the non-VWF group (x¯±s= 2.72±1.47 ng/mL). Serotonin levels may affect the progression of secondary RP. Polymorphic variants of the HTR1B gene are associated with the susceptibility of secondary RP in vibration-exposed occupational populations of Chinese Han people.

Paraoxonase 1 (Q192R) gene polymorphism, coronary heart disease and the risk of a new acute coronary event.

PubMed

Martínez-Quintana, Efrén; Rodríguez-González, Fayna; Medina-Gil, José María; Garay-Sánchez, Paloma; Tugores, Antonio

Paraoxonase 1 (PON1) plays a major role in the oxidation of low density lipoprotein and in the prevention of coronary atherogenesis. In this context, coding region polymorphisms of PON1 gene, responsible for the enzyme activity, has become of interest as a marker for atherogenesis. A study and follow-up was conducted on 529 patients with an acute coronary event in order to assess the association between the PON1 Q192R (rs662;A/G) polymorphism, the type of acute coronary syndrome, cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidaemia, and smoking), the extent and severity of coronary atherosclerosis, and the medium-term clinical follow-up. The QQ genotype was found in 245 (46.3%) patients, with 218 (41.2%) patients showing the QR genotype, and 66 (14.5%) patients had the RR genotype. No significant differences were found between the QQ and QR/RR genotypes as regards the clinical characteristics, the analytical data, and the angiographic variables. Similarly, Kaplan-Meier survival analysis showed no significant differences in presenting with a new acute coronary event (p=0.598), cardiac mortality (p=0.701), stent thrombosis (p=0.508), or stent re-stenosis (p=0.598) between QQ and QR/RR genotypes during the follow-up period (3.3±2.2 years). In patients with an acute coronary syndrome, the PON1 Q192R genotypes did not influence the risk of suffering a new acute coronary event during the medium-term follow-up. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Cannabinoid Receptor 1 Gene Polymorphisms and Marijuana Misuse Interactions On White Matter and Cognitive Deficits in Schizophrenia

PubMed Central

Ho, Beng-Choon; Wassink, Thomas H.; Ziebell, Steven; Andreasen, Nancy C.

2011-01-01

Marijuana exposure during the critical period of adolescent brain maturation may disrupt neuro-modulatory influences of endocannabinoids and increase schizophrenia susceptibility. Cannabinoid receptor 1 (CB1/CNR1) is the principal brain receptor mediating marijuana effects. No study to-date has systematically investigated the impact of CNR1 on quantitative phenotypic features in schizophrenia and inter-relationships with marijuana misuse. We genotyped 235 schizophrenia patients using 12 tag single nucleotide polymorphisms (tSNPs) that account for most of CB1 coding region genetic variability. Patients underwent a high-resolution anatomic brain magnetic resonance scan and cognitive assessment. Almost a quarter of the sample met DSM marijuana abuse (14%) or dependence (8%) criteria. Effects of CNR1 tSNPs and marijuana abuse/dependence on brain volumes and neurocognition were assessed using ANCOVA, including co-morbid alcohol/non-marijuana illicit drug misuse as covariates. Significant main effects of CNR1 tSNPs (rs7766029, rs12720071, and rs9450898) were found in white matter (WM) volumes. Patients with marijuana abuse/dependence had smaller fronto-temporal WM volumes than patients without heavy marijuana use. More interestingly, there were significant rs12720071 genotype-by-marijuana use interaction effects on WM volumes and neurocognitive impairment; suggestive of gene-environment interactions for conferring phenotypic abnormalities in schizophrenia. In this comprehensive evaluation of genetic variants distributed across the CB1 locus, CNR1 genetic polymorphisms were associated with WM brain volume variation among schizophrenia patients. Our findings suggest that heavy cannabis use in the context of specific CNR1 genotypes may contribute to greater WM volume deficits and cognitive impairment, which could in turn increase schizophrenia risk. PMID:21420833

Fatty Acid Profile and Unigene-Derived Simple Sequence Repeat Markers in Tung Tree (Vernicia fordii)

PubMed Central

Zhang, Lin; Jia, Baoguang; Tan, Xiaofeng; Thammina, Chandra S.; Long, Hongxu; Liu, Min; Wen, Shanna; Song, Xianliang; Cao, Heping

2014-01-01

Tung tree (Vernicia fordii) provides the sole source of tung oil widely used in industry. Lack of fatty acid composition and molecular markers hinders biochemical, genetic and breeding research. The objectives of this study were to determine fatty acid profiles and develop unigene-derived simple sequence repeat (SSR) markers in tung tree. Fatty acid profiles of 41 accessions showed that the ratio of α-eleostearic acid was increasing continuously with a parallel trend to the amount of tung oil accumulation while the ratios of other fatty acids were decreasing in different stages of the seeds and that α-eleostearic acid (18∶3) consisted of 77% of the total fatty acids in tung oil. Transcriptome sequencing identified 81,805 unigenes from tung cDNA library constructed using seed mRNA and discovered 6,366 SSRs in 5,404 unigenes. The di- and tri-nucleotide microsatellites accounted for 92% of the SSRs with AG/CT and AAG/CTT being the most abundant SSR motifs. Fifteen polymorphic genic-SSR markers were developed from 98 unigene loci tested in 41 cultivated tung accessions by agarose gel and capillary electrophoresis. Genbank database search identified 10 of them putatively coding for functional proteins. Quantitative PCR demonstrated that all 15 polymorphic SSR-associated unigenes were expressed in tung seeds and some of them were highly correlated with oil composition in the seeds. Dendrogram revealed that most of the 41 accessions were clustered according to the geographic region. These new polymorphic genic-SSR markers will facilitate future studies on genetic diversity, molecular fingerprinting, comparative genomics and genetic mapping in tung tree. The lipid profiles in the seeds of 41 tung accessions will be valuable for biochemical and breeding studies. PMID:25167054

CRAWview: for viewing splicing variation, gene families, and polymorphism in clusters of ESTs and full-length sequences.

PubMed

Chou, A; Burke, J

1999-05-01

DNA sequence clustering has become a valuable method in support of gene discovery and gene expression analysis. Our interest lies in leveraging the sequence diversity within clusters of expressed sequence tags (ESTs) to model gene structure for the study of gene variants that arise from, among other things, alternative mRNA splicing, polymorphism, and divergence after gene duplication, fusion, and translocation events. In previous work, CRAW was developed to discover gene variants from assembled clusters of ESTs. Most importantly, novel gene features (the differing units between gene variants, for example alternative exons, polymorphisms, transposable elements, etc.) that are specialized to tissue, disease, population, or developmental states can be identified when these tools collate DNA source information with gene variant discrimination. While the goal is complete automation of novel feature and gene variant detection, current methods are far from perfect and hence the development of effective tools for visualization and exploratory data analysis are of paramount importance in the process of sifting through candidate genes and validating targets. We present CRAWview, a Java based visualization extension to CRAW. Features that vary between gene forms are displayed using an automatically generated color coded index. The reporting format of CRAWview gives a brief, high level summary report to display overlap and divergence within clusters of sequences as well as the ability to 'drill down' and see detailed information concerning regions of interest. Additionally, the alignment viewing and editing capabilities of CRAWview make it possible to interactively correct frame-shifts and otherwise edit cluster assemblies. We have implemented CRAWview as a Java application across windows NT/95 and UNIX platforms. A beta version of CRAWview will be freely available to academic users from Pangea Systems (http://www.pangeasystems.com). Contact :

Haplotype Detection from Next-Generation Sequencing in High-Ploidy-Level Species: 45S rDNA Gene Copies in the Hexaploid Spartina maritima

PubMed Central

Boutte, Julien; Aliaga, Benoît; Lima, Oscar; Ferreira de Carvalho, Julie; Ainouche, Abdelkader; Macas, Jiri; Rousseau-Gueutin, Mathieu; Coriton, Olivier; Ainouche, Malika; Salmon, Armel

2015-01-01

Gene and whole-genome duplications are widespread in plant nuclear genomes, resulting in sequence heterogeneity. Identification of duplicated genes may be particularly challenging in highly redundant genomes, especially when there are no diploid parents as a reference. Here, we developed a pipeline to detect the different copies in the ribosomal RNA gene family in the hexaploid grass Spartina maritima from next-generation sequencing (Roche-454) reads. The heterogeneity of the different domains of the highly repeated 45S unit was explored by identifying single nucleotide polymorphisms (SNPs) and assembling reads based on shared polymorphisms. SNPs were validated using comparisons with Illumina sequence data sets and by cloning and Sanger (re)sequencing. Using this approach, 29 validated polymorphisms and 11 validated haplotypes were reported (out of 34 and 20, respectively, that were initially predicted by our program). The rDNA domains of S. maritima have similar lengths as those found in other Poaceae, apart from the 5′-ETS, which is approximately two-times longer in S. maritima. Sequence homogeneity was encountered in coding regions and both internal transcribed spacers (ITS), whereas high intragenomic variability was detected in the intergenic spacer (IGS) and the external transcribed spacer (ETS). Molecular cytogenetic analysis by fluorescent in situ hybridization (FISH) revealed the presence of one pair of 45S rDNA signals on the chromosomes of S. maritima instead of three expected pairs for a hexaploid genome, indicating loss of duplicated homeologous loci through the diploidization process. The procedure developed here may be used at any ploidy level and using different sequencing technologies. PMID:26530424

Arg25Pro polymorphism of transforming growth factor-beta1 and its role in the pathogenesis of essential hypertension in Russian population of the Central Chernozem Region.

PubMed

Ivanov, V P; Solodilova, M A; Polonnikov, A V; Belugin, D A; Shestakov, A M; Ushachev, D V; Khoroshaya, I V; Katargina, L N; Kozhukhov, M A; Kolesnikova, O E

2007-07-01

We studied the relationship between Arg25Pro polymorphism of TGFbeta1 gene and predisposition to essential hypertension in the Russian population of Central Chernozem Region (n=402). An association was found between 25Pro allele and 25ArgPro genotype with low risk of essential hypertension in male individuals.

High-resolution human/goat comparative map of the goat polled/intersex syndrome (PIS): the human homologue is contained in a human YAC from HSA3q23.

PubMed

Vaiman, D; Schibler, L; Oustry-Vaiman, A; Pailhoux, E; Goldammer, T; Stevanovic, M; Furet, J P; Schwerin, M; Cotinot, C; Fellous, M; Cribiu, E P

1999-02-15

The genetic and cytogenetic map around the chromosome 1 region shown to be linked with polledness and intersexuality (PIS) in the domestic goat (Capra hircus) was refined. For this purpose, a goat BAC library was systematically screened with primers from human coding sequences, scraped chromosome 1 DNA, bovine microsatellites from the region, and BAC ends. All the BACs (n = 30) were mapped by fluorescence in situ hybridization (FISH) on goat chromosome 1q41-q45. The genetic mapping of 30 new goat polymorphic markers, isolated from these BACs, made it possible to reduce the PIS interval to a region of less than 1 cM on goat chromosome 1q43. The PIS locus is now located between the two genes ATP1B and COP, which both map to 3q23 in humans. Genetic, cytogenetic, and comparative data suggest that the PIS region is now probably circumscribed to an approximately 1-Mb DNA segment for which construction of a BAC contig is in progress. In addition, a human YAC contig encompassing the blepharophimosis-ptosis-epicanthus-inversus region was mapped by FISH to goat chromosome 1q43. This human disease, mapped to HSA 3q23 and affecting the development and maintenance of ovarian function, could be a potential candidate for goat PIS. Copyright 1999 Academic Press.

A second locus for very-late-onset Alzheimer disease: a genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region.

PubMed

Olson, Jane M; Goddard, Katrina A B; Dudek, Doreen M

2002-07-01

We used a covariate-based linkage method to reanalyze genome scan data from affected sibships collected by the Alzheimer Disease (AD) Genetics Initiative of the National Institute of Mental Health. As reported in an earlier article, the amyloid-beta precursor protein (APP) region is strongly linked to affected sib pairs of the oldest current age (i.e., age either at last exam or at death) who lack E4 alleles at the apolipoprotein E (ApoE) locus. We now report that a region on 20p shows the same pattern. A model that includes current age and the number of E2 alleles as covariates gives a LOD score of 4.1. The signal on 20p is near the location of the gene coding for cystatin-C, previously shown to be associated with late-onset AD and to codeposit with APP in the brains of patients with AD. Two-locus analysis provides evidence of strong epistasis between 20p and the APP region, limited to the oldest age group and to those lacking ApoE4 alleles. We speculate that high-risk polymorphisms in both regions produce a biological interaction between these two proteins that increases susceptibility to a very-late-onset form of AD.

Physical and transcriptional map in the CMT 1A region

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

Chevillard, C.; Passage, E.; Cudrey, C.

1994-09-01

The Charcot-Marie-Tooth disease type 1A (CMT1A) has been mapped to the proximal short arm of chromosome 17. CMT1A is the most frequent of the motor and sensory peripheral neuropathies and is associated with a duplication of a 1.5 Mb fragment in proximal 17p12. Several groups have proposed that the gene coding for peripheral myelin protein-22 (PMP-22) as the candidate gene for CMT1A. We have recently published a {open_quote}MegaYAC{close_quote} contig of 6 Mb which covers the CMT1A critical region. In order to isolate new genes localized in this region, we used a {open_quote}physical trapping {close_quote} strategy derived from the direct cDNAmore » selection technique developed by Parimoo et al. This approach has allowed us to construct cDNA {open_quotes}minilibraries{close_quotes} using YAC DNA from the CMT1A region. One of the clones in these minilibraries has been mapped back to the CMT1A duplication. Other potentially interesting clones are in the process of further characterization. Furthermore, we have mapped several Genethon microsatellites in the 6 Mb YAC contig and some are located in the CMT1A duplicated region. These highly polymorphic markers should prove useful for diagnostic testing in CMT1A.« less

A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer.

PubMed

Sharifi, Nima; Hamada, Akinobu; Sissung, Tristan; Danesi, Romano; Venzon, David; Baum, Caitlin; Gulley, James L; Price, Douglas K; Dahut, William L; Figg, William D

2008-08-05

To determine if patients with advanced prostate cancer carrying a polymorphism that codes for a more active testosterone transporter have less durable responses to androgen-deprivation therapy (ADT) than patients not carrying this polymorphism. We previously determined that a polymorphism in SLCO1B3 affects testosterone transport and that those men who have at least one wild-type T allele at the 334 T > G polymorphism in this gene have a shorter survival. We hypothesized that the T allele which increases testosterone transport would be associated with a shorter interval from ADT to androgen independence. We examined the association between this SLCO1B3 polymorphism and time from ADT to androgen independence, ADT to prostate-specific antigen (PSA) nadir and PSA nadir to androgen independence in 68 Caucasian patients with advanced prostate cancer who were treated with ADT with metastatic disease (D2) or biochemical failure with no metastatic disease (D0). When examined separately, patients in the individual stages tended to have a shorter time to androgen independence with the T allele in the D0 (P = 0.11) and D2 (P = 0.18) groups. Combining these groups and stratifying by stage yielded a statistically significant shorter time to androgen independence with the T allele (P = 0.048). A polymorphism in a transporter that increases testosterone import is associated with a shorter time to androgen independence in patients with prostate cancer who are treated with ADT.

Asymmetric Dispersal Can Maintain Larval Polymorphism: A Model Motivated by Streblospio benedicti

PubMed Central

Zakas, Christina; Hall, David W.

2012-01-01

Polymorphism in traits affecting dispersal occurs in a diverse variety of taxa. Typically, the maintenance of a dispersal polymorphism is attributed to environmental heterogeneity where parental bet-hedging can be favored. There are, however, examples of dispersal polymorphisms that occur across similar environments. For example, the estuarine polychaete Streblospio benedicti has a highly heritable offspring dimorphism that affects larval dispersal potential. We use analytical models of dispersal to determine the conditions necessary for a stable dispersal polymorphism to exist. We show that in asexual haploids, sexual haploids, and in sexual diploids in the absence of overdominance, asymmetric dispersal is required in order to maintain a dispersal polymorphism when patches do not vary in intrinsic quality. Our study adds an additional factor, dispersal asymmetry, to the short list of mechanisms that can maintain polymorphism in nature. The region of the parameter space in which polymorphism is possible is limited, suggesting why dispersal polymorphisms within species are rare. PMID:22576818

Phytomonas: analysis of polymorphism and genetic relatedness between isolates from plants and phytophagous insects from different geographic regions by RAPD fingerprints and synapomorphic markers.

PubMed

Serrano, M G; Camargo, E P; Teixeira, M M

1999-01-01

The random amplification of polymorphic DNA was used for easy, quick and sensitive assessment of genetic polymorphism within Phytomonas to discriminate isolates and determine genetic relationships within the genus. We examined 48 Phytomonas spp., 31 isolates from plants and 17 from insects, from different geographic regions. Topology of the dendrogram based on randomly amplified polymorphic DNA fingerprints segregated the Phytomonas spp. into 5 main clusters, despite the high genetic variability within this genus. Similar clustering could also be obtained by both visual and cross-hybridization analysis of randomly amplified synapomorphic DNA fragments. There was some concordance between the genetic relationship of isolates and their plant tissue tropism. Moreover, Phytomonas spp. from plants and insects were grouped according to geographic origin, thus revealing a complex structure of this taxon comprising several clusters of very closely related organisms.

Color differences among feral pigeons (Columba livia) are not attributable to sequence variation in the coding region of the melanocortin-1 receptor gene (MC1R)

PubMed Central

2013-01-01

Background Genetic variation at the melanocortin-1 receptor (MC1R) gene is correlated with melanin color variation in many birds. Feral pigeons (Columba livia) show two major melanin-based colorations: a red coloration due to pheomelanic pigment and a black coloration due to eumelanic pigment. Furthermore, within each color type, feral pigeons display continuous variation in the amount of melanin pigment present in the feathers, with individuals varying from pure white to a full dark melanic color. Coloration is highly heritable and it has been suggested that it is under natural or sexual selection, or both. Our objective was to investigate whether MC1R allelic variants are associated with plumage color in feral pigeons. Findings We sequenced 888 bp of the coding sequence of MC1R among pigeons varying both in the type, eumelanin or pheomelanin, and the amount of melanin in their feathers. We detected 10 non-synonymous substitutions and 2 synonymous substitution but none of them were associated with a plumage type. It remains possible that non-synonymous substitutions that influence coloration are present in the short MC1R fragment that we did not sequence but this seems unlikely because we analyzed the entire functionally important region of the gene. Conclusions Our results show that color differences among feral pigeons are probably not attributable to amino acid variation at the MC1R locus. Therefore, variation in regulatory regions of MC1R or variation in other genes may be responsible for the color polymorphism of feral pigeons. PMID:23915680

Adaptive Evolution Is Substantially Impeded by Hill-Robertson Interference in Drosophila.

PubMed

Castellano, David; Coronado-Zamora, Marta; Campos, Jose L; Barbadilla, Antonio; Eyre-Walker, Adam

2016-02-01

Hill-Robertson interference (HRi) is expected to reduce the efficiency of natural selection when two or more linked selected sites do not segregate freely, but no attempt has been done so far to quantify the overall impact of HRi on the rate of adaptive evolution for any given genome. In this work, we estimate how much HRi impedes the rate of adaptive evolution in the coding genome of Drosophila melanogaster. We compiled a data set of 6,141 autosomal protein-coding genes from Drosophila, from which polymorphism levels in D. melanogaster and divergence out to D. yakuba were estimated. The rate of adaptive evolution was calculated using a derivative of the McDonald-Kreitman test that controls for slightly deleterious mutations. We find that the rate of adaptive amino acid substitution at a given position of the genome is positively correlated to both the rate of recombination and the mutation rate, and negatively correlated to the gene density of the region. These correlations are robust to controlling for each other, for synonymous codon bias and for gene functions related to immune response and testes. We show that HRi diminishes the rate of adaptive evolution by approximately 27%. Interestingly, genes with low mutation rates embedded in gene poor regions lose approximately 17% of their adaptive substitutions whereas genes with high mutation rates embedded in gene rich regions lose approximately 60%. We conclude that HRi hampers the rate of adaptive evolution in Drosophila and that the variation in recombination, mutation, and gene density along the genome affects the HRi effect. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

DNA fingerprinting of Chinese melon provides evidentiary support of seed quality appraisal.

PubMed

Gao, Peng; Ma, Hongyan; Luan, Feishi; Song, Haibin

2012-01-01

Melon, Cucumis melo L. is an important vegetable crop worldwide. At present, there are phenomena of homonyms and synonyms present in the melon seed markets of China, which could cause variety authenticity issues influencing the process of melon breeding, production, marketing and other aspects. Molecular markers, especially microsatellites or simple sequence repeats (SSRs) are playing increasingly important roles for cultivar identification. The aim of this study was to construct a DNA fingerprinting database of major melon cultivars, which could provide a possibility for the establishment of a technical standard system for purity and authenticity identification of melon seeds. In this study, to develop the core set SSR markers, 470 polymorphic SSRs were selected as the candidate markers from 1219 SSRs using 20 representative melon varieties (lines). Eighteen SSR markers, evenly distributed across the genome and with the highest contents of polymorphism information (PIC) were identified as the core marker set for melon DNA fingerprinting analysis. Fingerprint codes for 471 melon varieties (lines) were established. There were 51 materials which were classified into17 groups based on sharing the same fingerprint code, while field traits survey results showed that these plants in the same group were synonyms because of the same or similar field characters. Furthermore, DNA fingerprinting quick response (QR) codes of 471 melon varieties (lines) were constructed. Due to its fast readability and large storage capacity, QR coding melon DNA fingerprinting is in favor of read convenience and commercial applications.

DNA Fingerprinting of Chinese Melon Provides Evidentiary Support of Seed Quality Appraisal

PubMed Central

Gao, Peng; Ma, Hongyan; Luan, Feishi; Song, Haibin

2012-01-01

Melon, Cucumis melo L. is an important vegetable crop worldwide. At present, there are phenomena of homonyms and synonyms present in the melon seed markets of China, which could cause variety authenticity issues influencing the process of melon breeding, production, marketing and other aspects. Molecular markers, especially microsatellites or simple sequence repeats (SSRs) are playing increasingly important roles for cultivar identification. The aim of this study was to construct a DNA fingerprinting database of major melon cultivars, which could provide a possibility for the establishment of a technical standard system for purity and authenticity identification of melon seeds. In this study, to develop the core set SSR markers, 470 polymorphic SSRs were selected as the candidate markers from 1219 SSRs using 20 representative melon varieties (lines). Eighteen SSR markers, evenly distributed across the genome and with the highest contents of polymorphism information (PIC) were identified as the core marker set for melon DNA fingerprinting analysis. Fingerprint codes for 471 melon varieties (lines) were established. There were 51 materials which were classified into17 groups based on sharing the same fingerprint code, while field traits survey results showed that these plants in the same group were synonyms because of the same or similar field characters. Furthermore, DNA fingerprinting quick response (QR) codes of 471 melon varieties (lines) were constructed. Due to its fast readability and large storage capacity, QR coding melon DNA fingerprinting is in favor of read convenience and commercial applications. PMID:23285039

[Effect of TNF-alpha gene polymorphism on outcome of thalidomide-based regimens for multiple myeloma].

PubMed

DU, Juan; Yuan, Zhen-Gang; Zhang, Chun-Yang; Fu, Wei-Jun; Jiang, Hua; Chen, Bao-An; Hou, Jian

2009-10-01

To evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM). The polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis. In TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049). The TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.

Sequence divergence of the red and green visual pigments in great apes and humans.

PubMed Central

Deeb, S S; Jorgensen, A L; Battisti, L; Iwasaki, L; Motulsky, A G

1994-01-01

We have determined the coding sequences of red and green visual pigment genes of the chimpanzee, gorilla, and orangutan. The deduced amino acid sequences of these pigments are highly homologous to the equivalent human pigments. None of the amino acid differences occurred at sites that were previously shown to influence pigment absorption characteristics. Therefore, we predict the spectra of red and green pigments of the apes to have wavelengths of maximum absorption that differ by < 2 nm from the equivalent human pigments and that color vision in these nonhuman primates will be very similar, if not identical, to that in humans. A total of 14 within-species polymorphisms (6 involving silent substitutions) were observed in the coding sequences of the red and green pigment genes of the great apes. Remarkably, the polymorphisms at 6 of these sites had been observed in human populations, suggesting that they predated the evolution of higher primates. Alleles at polymorphic sites were often shared between the red and green pigment genes. The average synonymous rate of divergence of red from green sequences was approximately 1/10th that estimated for other proteins of higher primates, indicating the involvement of gene conversion in generating these polymorphisms. The high degree of homology and juxtaposition of these two genes on the X chromosome has promoted unequal recombination and/or gene conversion that led to sequence homogenization. However, natural selection operated to maintain the degree of separation in peak absorbance between the red and green pigments that resulted in optimal chromatic discrimination. This represents a unique case of molecular coevolution between two homologous genes that functionally interact at the behavioral level. PMID:8041777

Extensive 5.8S nrDNA polymorphism in Mammillaria (Cactaceae) with special reference to the identification of pseudogenic internal transcribed spacer regions.

PubMed

Harpke, Doerte; Peterson, Angela

2008-05-01

The internal transcribed spacer (ITS) region (ITS1, 5.8S rDNA, ITS2) represents the most widely applied nuclear marker in eukaryotic phylogenetics. Although this region has been assumed to evolve in concert, the number of investigations revealing high degrees of intra-individual polymorphism connected with the presence of pseudogenes has risen. The 5.8S rDNA is the most important diagnostic marker for functionality of the ITS region. In Mammillaria, intra-individual 5.8S rDNA polymorphisms of up to 36% and up to nine different types have been found. Twenty-eight of 30 cloned genomic Mammillaria sequences were identified as putative pseudogenes. For the identification of pseudogenic ITS regions, in addition to formal tests based on substitution rates, we attempted to focus on functional features of the 5.8S rDNA (5.8S motif, secondary structure). The importance of functional data for the identification of pseudogenes is outlined and discussed. The identification of pseudogenes is essential, because they may cause erroneous phylogenies and taxonomic problems.

Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups.

PubMed

Lee, Su-Jun; Usmani, Khawja A; Chanas, Brian; Ghanayem, Burhan; Xi, Tina; Hodgson, Ernest; Mohrenweiser, Harvey W; Goldstein, Joyce A

2003-08-01

Genetic polymorphisms of cytochromes P450 (CYPs) are a principal reason for inter-individual variations in the metabolism of therapeutic drugs and environmental chemicals in humans. The present study identifies 34 single nucleotide polymorphisms (SNPs) of CYP3A5 including 27 previously unidentified SNPs by direct sequencing of the exons, intron-exon junctions and 5'-upstream region of CYP3A5 from 92 racially diverse individuals (24 Caucasians, 24 Africans, 24 Asians, and 20 individuals of unknown racial origin). Four new CYP3A5 SNPs produced coding changes: R28C, L82R, A337T, and F446S. CYP3A5 R28C occurred in African populations (allelic frequency of 4%). CYP3A5 A337T occurred in Asians (2% allelic frequency), CYP3A5 L82R (occurred in the racially unidentified group) and CYP3A5 F446S (identified in Caucasians with a 2% allelic frequency) were on an allele containing the splice change g.6986A>G known as CYP3A5*3. The newly identified allelic proteins were constructed by site-directed mutagenesis, expressed in Escherichia coli and purified. CYP3A5 L82R was expressed only as denatured CYP420, suggesting it may be unstable. CYP3A5*1 exhibited the highest maximal clearance for testosterone followed by CYP3A5 A337T > CYP3A5 R28C > CYP3A5 F446S. CYP3A5*1 exhibited a higher V(max) for nifedipine oxidation than CYP3A5 A337T > CYP3A5 R28C > CYP3A5 F446S. CYP3A5 A337T and CYP3A5 R28C exhibited a 42-64% lower V(max) for nifedipine oxidation than CYP3A5*1. CYP3A5 F446S exhibited a > 95% decrease in the intrinsic clearance for both 6beta-hydroxytestosterone and nifedipine oxidation. This study identifies four new potentially defective coding alleles. CYP3A5 F446S is predicted to be more catalytically defective than the splice change alone.

Analysis of some polymorphic markers of the CFTR gene in cystic fibrosis patients and healthy donors from the Moscow region

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

Amosenko, F.A.; Sazonova, M.A.; Kapranov, N.I.

1995-04-01

Allelic frequencies of three polymorphic markers in the CFTR gene were estimated on chromosomes derived from cystic fibrosis (CF) patients and healthy donors from Moscow and the Moscow region. These polymorphic markers are tetranucleotide tandem repeats GATT in intron 6B, M470V in exon 10, and T854T in exon 14 (fragment A). Frequencies at allele 1 of the M470V marker, along with allele 2 of GATT and T854T, are two times higher for CF patients without {Delta}F508 mutation than for healthy donors, and there is linkage disequilibrium of these alleles of the polymorphic markers analyzed with the CF gene. Allele 1more » of M470V and T854T markers, as well as allele 2 of the GATT marker (six repeats), are absolutely linked to mutation F508 of the CFTR gene. Using the polymorphic markers studied, family analysis of CF was carried out in two families. 10 refs., 1 fig., 1 tab.« less

Possible association between serotonin transporter promoter region polymorphism and extremely violent crime in Chinese males.

PubMed

Liao, Ding-Lieh; Hong, Chen-Jee; Shih, Hao-Ling; Tsai, Shih-Jen

2004-01-01

The neurotransmitter, serotonin, has been implicated in aggressive behavior. The serotonin transporter (5-HTT), which reuptakes serotonin into the nerve terminal, plays a critical role in the regulation of serotonergic function. Previous western reports have demonstrated that the low-activity short (S) allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with aggressive behavior and associated personality traits. In the present study, we investigated this 5-HTTLPR genetic polymorphism in a group of Chinese males who had been convicted for extremely violent crime (n = 135) and a normal control group (n = 111). The proportion of S-allele carriers was significantly higher in the criminal group than in the controls (p = 0.006). A significant association was not demonstrated for the relationship between the 5-HTTLPR polymorphism and antisocial personality disorder, substance abuse or alcohol abuse in the criminal group. Our findings demonstrate that carriage of the low-activity S allele is associated with extremely violent criminal behavior in Chinese males, and suggests that the 5-HTT may be implicated in the mechanisms underlying violent behaviors.

Candidate genes associated with testicular development, sperm quality, and hormone levels of inhibin, luteinizing hormone, and insulin-like growth factor 1 in Brahman bulls.

PubMed

Fortes, Marina R S; Reverter, Antonio; Hawken, Rachel J; Bolormaa, Sunduimijid; Lehnert, Sigrid A

2012-09-01

Bull fertility is an important target for genetic improvement, and early prediction using genetic markers is therefore a goal for livestock breeding. We performed genome-wide association studies to identify genes associated with fertility traits measured in young bulls. Data from 1118 Brahman bulls were collected for six traits: blood hormone levels of inhibin (IN) at 4 mo, luteinizing hormone (LH) following a gonadotropin-releasing hormone challenge at 4 mo, and insulin-like growth factor 1 (IGF1) at 6 mo, scrotal circumference (SC) at 12 mo, ability to produce sperm (Sperm) at 18 mo, and percentage of normal sperm (PNS) at 24 mo. All the bulls were genotyped with the BovineSNP50 chip. Sires and dams of the bull population (n = 304) were genotyped with the high-density chip (∼800 000 polymorphisms) to allow for imputation, thereby contributing detail on genome regions of interest. Polymorphism associations were discovered for all traits, except for Sperm. Chromosome 2 harbored polymorphisms associated with IN. For LH, associated polymorphisms were located in five different chromosomes. A region of chromosome 14 contained polymorphisms associated with IGF1 and SC. Regions of the X chromosome showed associations with SC and PNS. Associated polymorphisms yielded candidate genes in chromosomes 2, 14, and X. These findings will contribute to the development of genetic markers to help select cattle with improved fertility and will lead to better annotation of gene function in the context of reproductive biology.

Genetic Diversity of Pinus Roxburghii Sarg. Collected from Different Himalayan Regions of India Assessed by Random Amplified Polymorphic DNA Analysis

PubMed Central

Sinha, Dwaipayan; Singh, Jyotsna; Tandon, P. K.; Kakkar, Poonam

2013-01-01

Present study was aimed at molecular genetic fingerprint profile of 15 genotypes of three populations of Pinus roxburghii Sarg. from Himalayan regions of India using random amplified polymorphic DNA (RAPD) based markers. Needles of Pinus roxburghii Sarg. were collected from Dharamshala, Himachal Pradesh (HP), Nainital, Uttarakhand (UK) and Darjeeling, West Bengal (WB) regions of India. The samples were subjected to DNA extraction and RAPD analysis using oligonucleotide purification cartridge (OPC) primers. Out of 15 primers tested, nine primers gave scorable bands. Altogether 48 bands were obtained, out of which 43 were found to be polymorphic. Number of amplified fragments with RAPD primers ranged from four to eight with the size of amplicon ranging from 500 to 7,000bp. Investigation of natural diversity at intraspecies level was performed with 15 genotypes. Forty-eight amplification products were scored by RAPD and showed 89.58% polymorphism with a mean intrapopulation genetic diversity (Hpop) of 0.2754. A significant inter- and intrapopulation diversity was observed, with the percentage of polymorphic loci (Pp) ranging from 50.09 to 70.83%, Shannon's information index (I) from 0.3262 to 0.4689 and Nei's gene diversity (h) from 0.2032 to 0.3335 with mean Nei's gene diversity 0.377 and the overall estimate of gene flow being (Nm) 1.3555. Unweighted pair-group method with arithmetic average (UPGMA) analysis based Dendrogram showed single cluster. The variation amongst the samples of the three ecological regions can be attributed to varied climatic conditions and may help in conservation/future cultivation of these species. PMID:24403729

The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review.

PubMed

Ghalandari, Hamid; Hosseini-Esfahani, Firoozeh; Mirmiran, Parvin

2015-07-01

Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review. The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships. In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association.

Polymorphisms in GSTM1, GSTT1, GSTP1, and GSTM3 genes and breast cancer risk in northeastern Mexico.

PubMed

Jaramillo-Rangel, G; Ortega-Martínez, M; Cerda-Flores, R M; Barrera-Saldaña, H A

2015-06-11

Glutathione S-transferases (GSTs) are a family of phase II metabolizing enzymes involved in carcinogen detoxification and the metabolism of various bioactive compounds. Several genes that code for these enzymes are polymorphic in an ethnicity-dependent manner, with particular genotypes previously associated with an increased risk of breast cancer. The purpose of this study was to determine the frequencies of polymorphisms in the genes GSTM1, GSTT1, GSTP1, and GSTM3 and to investigate whether an association exists between these genes and breast cancer risk in subjects from northeastern Mexico. Genotypes were determined for 243 women with histologically confirmed breast cancer and 118 control subjects. Gene polymorphisms were analyzed using a DNA microarray. We found an increased breast cancer risk associated with the GSTM1 gene deletion polymorphism (OR = 2.19; 95%CI = 1.50-3.21; P = 0.001). No associations between the GSTT1, GSTP1, and GSTM3 genotypes and neoplasia risk were observed. In conclusion, we determined the genotype distribution of GST polymorphisms in control subjects and breast cancer patients from northeastern Mexico. The GSTM1 null genotype was associated with breast cancer risk. Our findings may be used to individualize breast cancer screening and therapeutic intervention in our population, which displays ethnic characteristics that differentiate it from other populations in Mexico.

Association of I-FABP gene polymorphism and the risk of coronary heart disease.

PubMed

Yuan, Dong; Yu, Changqing; Zeng, Chunyu

2015-01-01

The study aimed to investigate the association between polymorphism of I-FABP gene and coronary heart disease (CHD). 225 patients with CHD were randomly recruited into the case group, and 196 healthy elderly volunteers were recruited from Medical Examination Center of our hospital as control. General clinical data were collected and plasma TC, TG, LDL-C, HDL-C levels were measured. Besides, polymerase chain reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technology were used to detect the polymorphism of Hha-I enzyme cleavage sites in I-FABP gene in the study population. Hha-I cleavage sites occurred at codon 54 in exon in the coding sequencing of I-FABP gene in all participants. After cleavage with Hha-I enzyme, the genotypes were identified as wild-type A/A, heterozygous mutant A/T and homozygous mutant T/T. In case group, A/T and T/T genetic carriers had significantly higher levels of TC, TG and LDL-C than A/A carriers (P<0.05). However, in control group, similar differences were not observed (P>0.05). BMI, dietary habits and I-FABP alleles were independent risk factors of CHD. The polymorphism of I-FABP gene existed in the study population. And this genetic variation had influence on lipid metabolism, which was associated with the risk of developing CHD. I-FABP gene polymorphism may contribute to the increased genetic susceptibility to CHD.

Methodology for fast detection of false sharing in threaded scientific codes

DOEpatents

Chung, I-Hsin; Cong, Guojing; Murata, Hiroki; Negishi, Yasushi; Wen, Hui-Fang

2014-11-25

A profiling tool identifies a code region with a false sharing potential. A static analysis tool classifies variables and arrays in the identified code region. A mapping detection library correlates memory access instructions in the identified code region with variables and arrays in the identified code region while a processor is running the identified code region. The mapping detection library identifies one or more instructions at risk, in the identified code region, which are subject to an analysis by a false sharing detection library. A false sharing detection library performs a run-time analysis of the one or more instructions at risk while the processor is re-running the identified code region. The false sharing detection library determines, based on the performed run-time analysis, whether two different portions of the cache memory line are accessed by the generated binary code.

Markers and mapping revisited: finding your gene.

PubMed

Jones, Neil; Ougham, Helen; Thomas, Howard; Pasakinskiene, Izolda

2009-01-01

This paper is an update of our earlier review (Jones et al., 1997, Markers and mapping: we are all geneticists now. New Phytologist 137: 165-177), which dealt with the genetics of mapping, in terms of recombination as the basis of the procedure, and covered some of the first generation of markers, including restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNA (RAPDs), simple sequence repeats (SSRs) and quantitative trait loci (QTLs). In the intervening decade there have been numerous developments in marker science with many new systems becoming available, which are herein described: cleavage amplification polymorphism (CAP), sequence-specific amplification polymorphism (S-SAP), inter-simple sequence repeat (ISSR), sequence tagged site (STS), sequence characterized amplification region (SCAR), selective amplification of microsatellite polymorphic loci (SAMPL), single nucleotide polymorphism (SNP), expressed sequence tag (EST), sequence-related amplified polymorphism (SRAP), target region amplification polymorphism (TRAP), microarrays, diversity arrays technology (DArT), single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE) and methylation-sensitive PCR. In addition there has been an explosion of knowledge and databases in the area of genomics and bioinformatics. The number of flowering plant ESTs is c. 19 million and counting, with all the opportunity that this provides for gene-hunting, while the survey of bioinformatics and computer resources points to a rapid growth point for future activities in unravelling and applying the burst of new information on plant genomes. A case study is presented on tracking down a specific gene (stay-green (SGR), a post-transcriptional senescence regulator) using the full suite of mapping tools and comparative mapping resources. We end with a brief speculation on how genome analysis may progress into the future of this highly dynamic arena of plant science.

Presence of the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease.

PubMed

Clark-Feoktistova, Y; Ruenes-Domech, C; García-Bacallao, E F; Roblejo-Balbuena, H; Feoktistova, L; Clark-Feoktistova, I; Jay-Herrera, O; Collazo-Mesa, T

2018-06-10

Wilson's disease is characterized by the accumulation of copper in different organs, mainly affecting the liver, brain, and cornea, and is caused by mutations in the ATP7B gene. More than 120 polymorphisms in the ATP7B gene have been reported in the medical literature. The aim of the present study was to identify the conformational changes in the exon 3 region of the ATP7B gene and detect the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease. A descriptive study was conducted at the Centro Nacional de Genética Médica and the Instituto Nacional de Gastroenterología within the time frame of 2007-2012 and included 105 patients with a clinical diagnosis of Wilson's disease. DNA extraction was performed through the salting-out method and the fragment of interest was amplified using the polymerase chain reaction technique. The conformational shift changes in the exon 3 region and the presence of the p.L456V polymorphism were identified through the Single-Strand Conformation Polymorphism analysis. The so-called b and c conformational shift changes, corresponding to the p.L456V polymorphism in the heterozygous and homozygous states, respectively, were identified. The allelic frequency of the p.L456V polymorphism in the 105 Cuban patients that had a clinical diagnosis of Wilson's disease was 41% and liver-related symptoms were the most frequent in the patients with that polymorphism. The p.L456V polymorphism was identified in 64 Cuban patients clinically diagnosed with Wilson's disease, making future molecular study through indirect methods possible. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Toll like receptor 2 and 4 polymorphisms in malaria endemic populations of India.

PubMed

Bali, Prerna; Pradhan, Sabyasachi; Sharma, Divya; Adak, Tridibes

2013-02-01

Toll like receptors (TLRs) play a pivotal role in recognizing the invading malaria parasite Plasmodium, thus genetic makeup of the exposed population can be of utmost importance for its predisposition to malaria. In this study 264 malaria patients from seven different eco epidemiological regions of India were genotyped for TLR2 and TLR4 polymorphisms using DNA sequencing methods. No variation was observed at residue positions 677 and 753 in TLR2 whereas residue positions 299 and 399 in TLR4 were highly polymorphic. The GC haplotype (Asp299Gly/Thr399Thr) was observed at the highest frequency in populations of East Singhbhum, Vizianagaram and North Goa and absent in Kolkata, Dakshin Kannada and Nicobar district. All polymorphisms were in Hardy Weinberg equilibrium. Populations of Kolkata, Nicobar district, Sundergarh and Dakshin Kannada were observed to be closely related. TLR2 polymorphism was absent in the Indian population and an overall heterogeneous pattern of TLR4 polymorphism can be attributed to genetic drift. However it can be inferred that GC haplotype is under the process of natural selection in the Indian population and one of the factors contributing to its selection could be predominance of Plasmodium falciparum in these regions. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

A Trio of Human Molecular Genetics PCR Assays

ERIC Educational Resources Information Center

Reinking, Jeffrey L.; Waldo, Jennifer T.; Dinsmore, Jannett

2013-01-01

This laboratory exercise demonstrates three different analytical forms of the polymerase chain reaction (PCR) that allow students to genotype themselves at four different loci. Here, we present protocols to allow students to a) genotype a non-coding polymorphic Variable Number of Tandem Repeat (VNTR) locus on human chromosome 5 using conventional…

Genetic and epigenetic status of triple exotic consanguinity cotton introgression lines.

PubMed

He, S P; Sun, J L; Du, X M

2011-10-03

Introgression lines are some of the most important germplasm for breeding applications and other research conducted on cotton crops. The DNA methylation level among 10 introgression lines of cotton (Gossypium hirsutum) and three exotic parental species (G. arboreum, G. thurberi and G. barbadense) were assessed by methylation-sensitive amplified polymorphism (MSAP) technology. The methylation level in the introgression lines ranged from 33.3 to 51.5%. However, the lines PD0111 and PD0113 had the lowest methylation level (34.6 and 33.3%, respectively) due to demethylation of most non-coding sequences. Amplified fragment length polymorphism (AFLP) was used to evaluate the genetic polymorphism in the cotton introgression lines. A high degree of polymorphism was observed in all introgression lines (mean 47.2%) based on AFLP and MSAP analyses. This confirmed the effects of genetic improvement on cotton introgression lines. The low methylation varieties, PD0111 and PD0113 (introgression lines), clustered outside of the introgression lines based on MSAP data, which was incongruent with an AFLP-based dendrogram. This phenomenon could be caused by environmental changes or introgression of exotic DNA fragments.

Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children1234

PubMed Central

Cole, Shelley A; Voruganti, V Saroja; Cai, Guowen; Haack, Karin; Kent, Jack W; Blangero, John; Comuzzie, Anthony G; McPherson, John D; Gibbs, Richard A

2010-01-01

Background: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain. Objective: The aim was to identify and characterize the effects of MC4R variants in Hispanic children. Design: MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits. Results: Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81. Conclusion: This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure. PMID:19889825

Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes.

PubMed

Pueyo, Neus; Ortega, Francisco J; Mercader, Josep M; Moreno-Navarrete, José M; Sabater, Monica; Bonàs, Sílvia; Botas, Patricia; Delgado, Elías; Ricart, Wifredo; Martinez-Larrad, María T; Serrano-Ríos, Manuel; Torrents, David; Fernández-Real, José M

2013-01-01

Surfactant protein-D (SP-D) is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs) affecting SP-D with insulin resistance and type 2 diabetes (T2D). We evaluated a common genetic variant located in the SP-D coding region (rs721917, Met(31)Thr) in a sample of T2D patients and non-diabetic controls (n = 2,711). In a subset of subjects (n = 1,062), this SNP was analyzed in association with circulating SP-D concentrations, insulin resistance, and T2D. This SNP and others were also screened in the publicly available Genome Wide Association (GWA) database of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). We found the significant association of rs721917 with circulating SP-D, parameters of insulin resistance and T2D. Indeed, G carriers showed decreased circulating SP-D (p = 0.004), decreased fasting glucose (p = 0.0002), glycated hemoglobin (p = 0.0005), and 33% (p = 0.002) lower prevalence of T2D, estimated under a dominant model, especially among women. Interestingly, these differences remained significant after controlling for origin, age, gender, and circulating SP-D. Moreover, this SNP and others within the SP-D genomic region (i.e. rs10887344) were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC. SP-D gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations.

Balancing Selection on a Regulatory Region Exhibiting Ancient Variation That Predates Human–Neandertal Divergence

PubMed Central

Iskow, Rebecca C.; Austermann, Christian; Scharer, Christopher D.; Raj, Towfique; Boss, Jeremy M.; Sunyaev, Shamil; Price, Alkes; Stranger, Barbara; Simon, Viviana; Lee, Charles

2013-01-01

Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10−15). Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human–Neandertal divergence and is evolving under balancing selection, especially among European populations. PMID:23593015

Association Analysis of the Ephrin-B2 Gene in African-Americans with End-Stage Renal Disease

PubMed Central

Hicks, Pamela J.; Staten, Jennifer L.; Palmer, Nicholette D.; Langefeld, Carl D.; Ziegler, Julie T.; Keene, Keith L.; Sale, Michele M.; Bowden, Donald W.; Freedman, Barry I.

2008-01-01

Background Genome scans in African-Americans with end-stage renal disease (ESRD) identified linkage on chromosome 13q33 in the region containing the ephrin-B2 ligand (EFNB2) genes. Interactions between the ephrin-B2 receptor and ephrin-B2 ligand play essential roles in renal angiogenesis, blood vessel maturation, and kidney disease. Methods The EFNB2 gene was evaluated as a positional candidate for non-diabetic and diabetic ESRD susceptibility in 1,071 unrelated African-American subjects; 316 with non-diabetic etiologies of ESRD, 394 with type 2 diabetes-associated ESRD and 361 healthy controls. Single nucleotide polymorphism (SNP) genotyping was performed on the Sequenom Mass Array System. Statistical analyses were computed using Dandelion version 1.26, Snpaddmix version 1.4 and Haploview version 3.32. Results Twenty-eight HapMap tag SNPs were genotyped spanning the 39 kilobases (kb) of the EFNB2 coding region, with average spacing of 1.43 kb. Analysis of 710 ESRD patient samples and 361 controls provided no evidence of single SNP associations in either diabetic or non-diabetic ESRD; although nominal evidence of association with all-cause ESRD was observed with a two SNP (p = 0.022) and three SNP (p = 0.023) haplotype, both containing SNPs rs7490924 and rs2391335 in intron 1. Conclusions Although an attractive positional candidate gene, polymorphisms in the EFNB2 gene do not appear to contribute in a substantial way to non-diabetic, diabetic or all-cause ESRD susceptibility in African-Americans. Additional genes within the chromosome 13q33 linkage interval are likely contributors to African-American non-diabetic ESRD. PMID:18580054

Fine Mapping Identifies SmFAS Encoding an Anthocyanidin Synthase as a Putative Candidate Gene for Flower Purple Color in Solanum melongena L.

PubMed Central

Chen, Mengqiang; Xu, Mengyun; Xiao, Yao; Cui, Dandan; Qin, Yongqiang; Wu, Jiaqi; Wang, Wenyi; Wang, Guoping

2018-01-01

Anthocyanins are the main pigments in flowers and fruits. These pigments are responsible for the red, red-purple, violet, and purple color in plants, and act as insect and animal attractants. In this study, phenotypic analysis of the purple flower color in eggplant indicated that the flower color is controlled by a single dominant gene, FAS. Using an F2 mapping population derived from a cross between purple-flowered ‘Blacknite’ and white-flowered ‘Small Round’, Flower Anthocyanidin Synthase (FAS) was fine mapped to an approximately 165.6-kb region between InDel marker Indel8-11 and Cleaved Amplified Polymorphic Sequences (CAPS) marker Efc8-32 on Chromosome 8. On the basis of bioinformatic analysis, 29 genes were subsequently located in the FAS target region, among which were two potential Anthocyanidin Synthase (ANS) gene candidates. Allelic sequence comparison results showed that one ANS gene (Sme2.5_01638.1_g00003.1) was conserved in promoter and coding sequences without any nucleotide change between parents, whereas four single-nucleotide polymorphisms were detected in another ANS gene (Sme2.5_01638.1_g00005.1). Crucially, a single base pair deletion at site 438 resulted in premature termination of FAS, leading to the loss of anthocyanin accumulation. In addition, FAS displayed strong expression in purple flowers compared with white flowers and other tissues. Collectively, our results indicate that Sme2.5_01638.1_g00005.1 is a good candidate gene for FAS, which controls anthocyanidin synthase in eggplant flowers. The present study provides information for further potential facilitate genetic engineering for improvement of anthocyanin levels in plants. PMID:29522465

Resequencing of IRS2 reveals rare variants for obesity but not fasting glucose homeostasis in Hispanic children.

PubMed

Butte, Nancy F; Voruganti, V Saroja; Cole, Shelley A; Haack, Karin; Comuzzie, Anthony G; Muzny, Donna M; Wheeler, David A; Chang, Kyle; Hawes, Alicia; Gibbs, Richard A

2011-09-22

Our objective was to resequence insulin receptor substrate 2 (IRS2) to identify variants associated with obesity- and diabetes-related traits in Hispanic children. Exonic and intronic segments, 5' and 3' flanking regions of IRS2 (∼14.5 kb), were bidirectionally sequenced for single nucleotide polymorphism (SNP) discovery in 934 Hispanic children using 3730XL DNA Sequencers. Additionally, 15 SNPs derived from Illumina HumanOmni1-Quad BeadChips were analyzed. Measured genotype analysis tested associations between SNPs and obesity and diabetes-related traits. Bayesian quantitative trait nucleotide analysis was used to statistically infer the most likely functional polymorphisms. A total of 140 SNPs were identified with minor allele frequencies (MAF) ranging from 0.001 to 0.47. Forty-two of the 70 coding SNPs result in nonsynonymous amino acid substitutions relative to the consensus sequence; 28 SNPs were detected in the promoter, 12 in introns, 28 in the 3'-UTR, and 2 in the 5'-UTR. Two insertion/deletions (indels) were detected. Ten independent rare SNPs (MAF = 0.001-0.009) were associated with obesity-related traits (P = 0.01-0.00002). SNP 10510452_139 in the promoter region was shown to have a high posterior probability (P = 0.77-0.86) of influencing BMI, fat mass, and waist circumference in Hispanic children. SNP 10510452_139 contributed between 2 and 4% of the population variance in body weight and composition. None of the SNPs or indels were associated with diabetes-related traits or accounted for a previously identified quantitative trait locus on chromosome 13 for fasting serum glucose. Rare but not common IRS2 variants may play a role in the regulation of body weight but not an essential role in fasting glucose homeostasis in Hispanic children.

Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross

PubMed Central

Ferris, Martin T.; Aylor, David L.; Bottomly, Daniel; Whitmore, Alan C.; Aicher, Lauri D.; Bell, Timothy A.; Bradel-Tretheway, Birgit; Bryan, Janine T.; Buus, Ryan J.; Gralinski, Lisa E.; Haagmans, Bart L.; McMillan, Leonard; Miller, Darla R.; Rosenzweig, Elizabeth; Valdar, William; Wang, Jeremy; Churchill, Gary A.; Threadgill, David W.; McWeeney, Shannon K.; Katze, Michael G.; Pardo-Manuel de Villena, Fernando; Baric, Ralph S.; Heise, Mark T.

2013-01-01

Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss. PMID:23468633

Identification of a QTL in Mus musculus for Alcohol Preference, Withdrawal, and Ap3m2 Expression Using Integrative Functional Genomics and Precision Genetics

PubMed Central

Bubier, Jason A.; Jay, Jeremy J.; Baker, Christopher L.; Bergeson, Susan E.; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C.; Chesler, Elissa J.

2014-01-01

Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits. PMID:24923803

Major histocompatibility complex and other allergy-related candidate genes associated with insect bite hypersensitivity in Icelandic horses.

PubMed

Klumplerova, Marie; Vychodilova, Leona; Bobrova, Olga; Cvanova, Michaela; Futas, Jan; Janova, Eva; Vyskocil, Mirko; Vrtkova, Irena; Putnova, Lenka; Dusek, Ladislav; Marti, Eliane; Horin, Petr

2013-04-01

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by bites of insects. IBH is a multifactorial disease with contribution of genetic and environmental factors. Candidate gene association analysis of IBH was performed in a group of 89 Icelandic horses all born in Iceland and imported to Europe. Horses were classified in IBH-affected and non-affected based on clinical signs and history of recurrent dermatitis, and on the results of an in vitro sulfidoleukotriene (sLT)-release assay with Culicoides nubeculosus and Simulium vittatum extract. Different genetic markers were tested for association with IBH by the Fisher's exact test. The effect of the major histocompatibility complex (MHC) gene region was studied by genotyping five microsatellites spanning the MHC region (COR112, COR113, COR114, UM011 and UMN-JH34-2), and exon 2 polymorphisms of the class II Eqca-DRA gene. Associations with Eqca-DRA and COR113 were identified (p < 0.05). In addition, a panel of 20 single nucleotide polymorphisms (SNPs) in 17 candidate allergy-related genes was tested. During the initial screen, no marker from the panel was significantly (p < 0.05) associated with IBH. Five SNPs associated with IBH at p < 0.10 were therefore used for analysis of combined genotypes. Out of them, SNPs located in the genes coding for the CD14 receptor (CD14), interleukin 23 receptor (IL23R), thymic stromal lymphopoietin (TSLP) and transforming growth factor beta 3 (TGFB3) molecules were associated with IBH as parts of complex genotypes. These results are supported by similar associations and by expression data from different horse populations and from human studies.

Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and Ap3m2 expression using integrative functional genomics and precision genetics.

PubMed

Bubier, Jason A; Jay, Jeremy J; Baker, Christopher L; Bergeson, Susan E; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C; Chesler, Elissa J

2014-08-01

Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits. Copyright © 2014 by the Genetics Society of America.

Comparison of space flight and heavy ion radiation induced genomic/epigenomic mutations in rice (Oryza sativa)

NASA Astrophysics Data System (ADS)

Shi, Jinming; Lu, Weihong; Sun, Yeqing

2014-04-01

Rice seeds, after space flight and low dose heavy ion radiation treatment were cultured on ground. Leaves of the mature plants were obtained for examination of genomic/epigenomic mutations by using amplified fragment length polymorphism (AFLP) and methylation sensitive amplification polymorphism (MSAP) method, respectively. The mutation sites were identified by fragment recovery and sequencing. The heritability of the mutations was detected in the next generation. Results showed that both space flight and low dose heavy ion radiation can induce significant alterations on rice genome and epigenome (P < 0.05). For both genetic and epigenetic assays, while there was no significant difference in mutation rates and their ability to be inherited to the next generation, the site of mutations differed between the space flight and radiation treated groups. More than 50% of the mutation sites were shared by two radiation treated groups, radiated with different LET value and dose, while only about 20% of the mutation sites were shared by space flight group and radiation treated group. Moreover, in space flight group, we found that DNA methylation changes were more prone to occur on CNG sequence than CG sequence. Sequencing results proved that both space flight and heavy ion radiation induced mutations were widely spread on rice genome including coding region and repeated region. Our study described and compared the characters of space flight and low dose heavy ion radiation induced genomic/epigenomic mutations. Our data revealed the mechanisms of application of space environment for mutagenesis and crop breeding. Furthermore, this work implicated that the nature of mutations induced under space flight conditions may involve factors beyond ion radiation.

Two polymorphs of safinamide, a selective and reversible inhibitor of monoamine oxidase B.

PubMed

Ravikumar, Krishnan; Sridhar, Balasubramanian

2010-06-01

Two polymorphs of safinamide {systematic name: (2S)-2-[4-(3-fluorobenzyloxy)benzylamino]propionamide}, C(17)H(19)FN(2)O(2), a potent selective and reversible monoamine oxidase B (MAO-B) inhibitor, are described. Both forms are orthorhombic and regarded as conformational polymorphs due to the differences in the orientation of the 3-fluorobenzyloxy and propanamide groups. Both structures pack with layers in the ac plane. In polymorph (I), the layers have discrete wide and narrow regions which are complementary when located next to adjacent layers. In polymorph (II), the layer has long flanges protruding from each side, which interdigitate when packed with the adjacent layers. N-H...O hydrogen bonds are present in both structures, whereas N-H...F hydrogen bonding is seen in polymorph (I), while N-H...N hydrogen bonding is seen in polymorph (II).

Common Polymorphisms in GSTA1, GSTM1 and GSTT1 Are Associated with Susceptibility to Urinary Bladder Cancer in Individuals from Balkan Endemic Nephropathy Areas of Serbia.

PubMed

Matic, Marija; Dragicevic, Biljana; Pekmezovic, Tatjana; Suvakov, Sonja; Savic-Radojevic, Ana; Pljesa-Ercegovac, Marija; Dragicevic, Dejan; Smiljic, Jelena; Simic, Tatjana

2016-09-01

Balkan endemic nephropathy (BEN) is a chronic familial form of interstitial nephritis that might eventually lead to end stage renal disease. This nephropathy affects individuals living along of the Danube River and its tributaries in Serbia, Bosnia, Croatia, Bulgaria and Romania. The increased incidence of urinary tract tumors in the BEN areas is well described, but its specific genetic predisposition is still unclear. Certain nephrocarcinogenic compounds, including those associated with BEN, are metabolized by glutathione S-transferase (GST) superfamily of phase II detoxication enzymes. Importantly, the GST-mediated detoxification may result in formation of more toxic compounds. We examined the association of common GST polymorphisms and bladder cancer (BC) risk in individuals from BEN areas in Serbia. A hospital-based case-control study included 201 BC cases (67 from BEN region) and 122 controls. Each polymorphism was identified by a PCR-based method. Individuals from BEN region with low-expression GSTA1 genotype (AB+BB) exhibited a 2.6-fold higher BC risk compared to those with GSTA1 (AA) genotype who were from non-BEN region (OR = 2.60, p = 0.015). In contrast, carriers of GSTM1-active genotype from BEN region had a 2.9-fold increased BC risk compared to those with GSTM1-active genotype from non-BEN region (OR = 2.90, p = 0.010). Likewise, carriers with GSTT1-active genotype from BEN region exhibited 2.1-fold higher BC risk compared to those from non-BEN region with GSTT1-active genotype (OR = 2.10, p = 0.027). Thus, common polymorphisms in GSTA1, GSTM1 and GSTT1 are associated with susceptibility to BC in individuals from BEN areas of Serbia.

Pressure-tuning micro-Raman spectra of artists' pigments: α- and β-copper phthalocyanine polymorphs.

PubMed

Beaulieu-Houle, Guillaume; Gilson, Denis F R; Butler, Ian S

2014-01-03

The two polymorphs of copper phthalocyanine, α- and β-CuPc, have been examined by micro-Raman spectroscopy at pressures approaching 5.0 GPa. The metastable α-polymorph does not exhibit any structural changes, while the more thermodynamically stable β-polymorph does exhibit a reversible phase transition at 2.0 GPa. The pressure dependences (dν/dP) for a selected number of vibrational modes are reported. Two regions of the Raman spectra, 800-900 cm(-1) and 1100-1200 cm(-1), are sensitive to pressure such that they can be used as indicators of the polymorphic form. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetic polymorphisms related to efficacy and overuse of triptans in chronic migraine.

PubMed

Gentile, Giovanna; Borro, Marina; Lala, Noemi; Missori, Serena; Simmaco, Maurizio; Martelletti, Paolo

2010-10-01

Migraine is a common type of headache and its most severe attacks are usually treated with triptans, the efficacy of which is extremely variable. Several SNPs in genes involved in metabolism and target mechanisms of triptans have been described. To define an association between genetic profile and triptan response, we classified a migrainous population on the basis of triptan response and characterized it for polymorphisms in the genes coding for monoamine oxidase A, G protein β3 and the cytochrome CYP1A2. Analysis of the association between genotypic and allelic frequencies of the analyzed SNPs and the grade of response to triptan administration showed a significant correlation for MAOA uVNTR polymorphism. Further stratification of patients in abuser and non-abuser groups revealed a significant association with triptan overuse and, within the abusers, with drug response to the CYP1A2*1F variant.

GLYOXALASE I A111E, PARAOXONASE 1 Q192R AND L55M POLYMORPHISMS IN ITALIAN PATIENTS WITH SPORADIC CEREBRAL CAVERNOUS MALFORMATIONS: A PILOT STUDY.

PubMed

Rinaldi, C; Bramanti, P; Famà, A; Scimone, C; Donato, L; Antognelli, C; Alafaci, C; Tomasello, F; D'Angelo, R; Sidoti, A

2015-01-01

It is already known that the conditions of increased oxidative stress are associated to a greater susceptibility to vascular malformations including cerebral cavernous malformations (CCMs). These are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1(Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Polymorphisms in the genes encoding for enzymes involved in the antioxidant systems such as glyoxalase I (GLO I) and paraoxonase I (PON I) could influence individual susceptibility to the vascular malformations. A single nucleotide polymorphism was identified in the exon 4 of GLO 1 gene that causes an amino acid substitution of Ala for Glu (Ala111Glu). Two common polymorphisms have been described in the coding region of PON1, which lead to glutamine → arginine substitution at 192 (Q192R) and a leucine → methionine substitution at 55 (L55M). The polymorphisms were characterized in 59 patients without mutations in the CCM genes versus 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that the frequency of patients carrying the GLO1 A/E genotype among the case group (56%) was four-fold higher than among the controls (14.1%). In the cohort of CCM patients, an increase in the frequency of PON192 Q/R genotype was observed (39% in the CCM group versus 3.7% in the healthy controls). Similarly, an increase was observed in the proportion of individuals with the genotype R/R in the disease group (5%) in respect to the normal healthy cohort (0.5%). Finally, the frequency of the PON55 heterozygotes L/M genotype was 29% in patients with CCMs and 4% in the healthy controls. The same trend was observed in PON55 homozygous M/M genotype frequency (CCMs 20% vs controls 10%). The present study aimed to investigate the possible association of GLO1 A111E, PON1 Q192R and L55M polymorphisms with the risk of CCMs. We found that individuals with the GLO1 A /E genotype, PON192/QR-RR genotypes and PON55/LM-MM genotypes had a significantly higher risk of CCMs compared with the other genotypes. However, because CCM is a heterogeneous disease, other additional factors might be involved in the initiation and progression of CCM disease.

Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol

PubMed Central

Dastani, Zari; Ruel, Isabelle L; Engert, James C; Genest, Jacques; Marcil, Michel

2007-01-01

Background Niemann-Pick disease type A and B is caused by a deficiency of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Methods Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (< 5th percentile for age and gender-matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the 25th percentile. Results For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. Conclusion These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population. PMID:18088425

Identification of promoter polymorphisms in the cytochrome P450 CYP6AY1 linked with insecticide resistance in the brown planthopper, Nilaparvata lugens.

PubMed

Pang, R; Li, Y; Dong, Y; Liang, Z; Zhang, Y; Zhang, W

2014-12-01

Imidacloprid resistance in the brown planthopper, Nilaparvata lugens, is primarily the result of the over-expression of cytochrome P450 monooxygenases. Here, a field-collected strain of N. lugens was shown to be highly resistant to both imidacloprid and buprofezin. Insecticide exposure and quantitative real-time PCR revealed that its resistance was mainly associated with a cytochrome P450 gene, CYP6AY1. CYP6AY1 is known to metabolize imidacloprid but its effect on buprofezin is unclear. In the 5'-untranslated region of CYP6AY1, a novel alternative splicing was detected. After a 1990-bp promoter region was cloned, its basal luciferase activity was assessed. Furthermore, genotyping studies identified 12 variations in the promoter region that discriminated between the field-collected and control strain. Finally, survival bioassays revealed a single nucleotide polymorphism and an insertion-deletion polymorphism linked to buprofezin and imidacloprid resistance. Mutagenesis of these sites enhanced the promoter activity of CYP6AY1. These results suggest that promoter polymorphisms may affect P450-mediated multiple insecticide resistance of pests. © 2014 The Royal Entomological Society.