Selection, subdivision and extinction and recolonization.

PubMed

Cherry, Joshua L

2004-02-01

In a subdivided population, the interaction between natural selection and stochastic change in allele frequency is affected by the occurrence of local extinction and subsequent recolonization. The relative importance of selection can be diminished by this additional source of stochastic change in allele frequency. Results are presented for subdivided populations with extinction and recolonization where there is more than one founding allele after extinction, where these may tend to come from the same source deme, where the number of founding alleles is variable or the founders make unequal contributions, and where there is dominance for fitness or local frequency dependence. The behavior of a selected allele in a subdivided population is in all these situations approximately the same as that of an allele with different selection parameters in an unstructured population with a different size. The magnitude of the quantity N(e)s(e), which determines fixation probability in the case of genic selection, is always decreased by extinction and recolonization, so that deleterious alleles are more likely to fix and advantageous alleles less likely to do so. The importance of dominance or frequency dependence is also altered by extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations.

The population genetics of X-autosome synthetic lethals and steriles.

PubMed

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

Evolutionary dynamics of sporophytic self-incompatibility alleles in plants.

PubMed

Schierup, M H; Vekemans, X; Christiansen, F B

1997-10-01

The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model of gametophytic self-incompatibility, but the selection intensity is stronger. With dominance, dominant alleles invade the population more easily than recessive alleles and have a lower frequency at equilibrium. In the SSIdom model, recessive alleles have both a higher allele frequency and higher expected life span. In the SSIdomcod model, however, loss due to drift occurs more easily for pollen-recessive than for pollen-dominant alleles, and therefore, dominant alleles have a higher expected life span than the more recessive alleles. The process of allelic turnover in the SSIdomcod and SSIdom models is closely approximated by a random walk on a dominance ladder. Implications of the results for experimental studies of sporophytic self-incompatibility in natural populations are discussed.

Distinguishing two types of gray mullet, Mugil cephalus L. (Mugiliformes: Mugilidae), by using glucose-6-phosphate isomerase (GPI) allozymes with special reference to enzyme activities.

PubMed

Huang, C S; Weng, C F; Lee, S C

2001-06-01

The resident and migratory types of gray mullet, Mugil cephalus, on the coast of Taiwan can not be separated morphologically. Allozyme analysis was applied to estimate genetic variation between the two types of gray mullet and to test whether they belong to different populations. After starch gel electrophoresis, different allelic frequency spectra of glucose-6-phosphate isomerase-A (GPI-A) between stocks was observed. The resident stock contained Gpi-A(135) and Gpi-A(100), whereas the migratory type contained Gpi-A(100) only. In addition, GPI activities of locus A showed two distinct profiles between the two alleles. The results broadly revealed that Gpi-A allelic frequency was not regulated by temperature changes even after 6 months of thermal acclimation. This suggests that natural selection may play a role in shaping the allelic frequency change during the migratory journey. These findings suggest that the Gpi-A allelic difference can be used for population discrimination.

Genetic variation in caribou and reindeer (Rangifer tarandus).

PubMed

Cronin, M A; Patton, J C; Balmysheva, N; MacNeil, M D

2003-02-01

Genetic variation at seven microsatellite DNA loci was quantified in 19 herds of wild caribou and domestic reindeer (Rangifer tarandus) from North America, Scandinavia and Russia. There is an average of 2.0-6.6 alleles per locus and observed individual heterozygosity of 0.33-0.50 in most herds. A herd on Svalbard Island, Scandinavia, is an exception, with relatively few alleles and low heterozygosity. The Central Arctic, Western Arctic and Porcupine River caribou herds in Alaska have similar allele frequencies and comprise one breeding population. Domestic reindeer in Alaska originated from transplants from Siberia, Russia, more than 100 years ago. Reindeer in Alaska and Siberia have different allele frequencies at several loci, but a relatively low level of genetic differentiation. Wild caribou and domestic reindeer in Alaska have significantly different allele frequencies at the seven loci, indicating that gene flow between reindeer and caribou in Alaska has been limited.

267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation.

PubMed

Dopazo, Joaquín; Amadoz, Alicia; Bleda, Marta; Garcia-Alonso, Luz; Alemán, Alejandro; García-García, Francisco; Rodriguez, Juan A; Daub, Josephine T; Muntané, Gerard; Rueda, Antonio; Vela-Boza, Alicia; López-Domingo, Francisco J; Florido, Javier P; Arce, Pablo; Ruiz-Ferrer, Macarena; Méndez-Vidal, Cristina; Arnold, Todd E; Spleiss, Olivia; Alvarez-Tejado, Miguel; Navarro, Arcadi; Bhattacharya, Shomi S; Borrego, Salud; Santoyo-López, Javier; Antiñolo, Guillermo

2016-05-01

Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalog of local variability motivated the whole-exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one-third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including ∼10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes, and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies to distinguish real disease associations from population-specific polymorphisms. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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

PubMed

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

2000-03-01

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

Haptoglobin gene subtypes in three Brazilian population groups of different ethnicities

PubMed Central

2009-01-01

Haptoglobin is a plasma hemoglobin-binding protein that limits iron loss during normal erythrocyte turnover and hemolysis, thereby preventing oxidative damage mediated by iron excess in the circulation. Haptoglobin polymorphism in humans, characterized by the Hp*1 and Hp *2 alleles, results in distinct phenotypes known as Hp1-1, Hp2-1 and Hp2-2, whose frequencies vary according to the ethnic origin of the population. The Hp*1 allele has two subtypes, Hp *1F and Hp *1S , that also vary in their frequencies among populations worldwide. In this work, we examined the distribution frequencies of haptoglobin subtypes in three Brazilian population groups of different ethnicities. The haptoglobin genotypes of Kayabi Amerindians (n = 56), Kalunga Afro-descendants (n = 70) and an urban population (n = 132) were determined by allele-specific PCR. The Hp*1F allele frequency was highest in Kalunga (29.3%) and lowest in Kayabi (2.6%). The Hp*1F/Hp*1S allele frequency ratios were 0.6, 1.0 and 0.26 for the Kayabi, Kalunga and urban populations, respectively. This variation was attributable largely to the Hp*1F allele. However, despite the large variation in Hp*1F frequencies, results of F ST (0.0291) indicated slight genetic differentiation among subpopulations of the general Brazilian population studied here. This is the first Brazilian report of variations in the Hp*1F and Hp*1S frequencies among non-Amerindian Brazilians. PMID:21637505

Haptoglobin gene subtypes in three Brazilian population groups of different ethnicities.

PubMed

Miranda-Vilela, Ana L; Akimoto, Arthur K; Alves, Penha C Z; Hiragi, Cássia O; Penalva, Guilherme C; Oliveira, Silviene F; Grisolia, Cesar K; Klautau-Guimarães, Maria N

2009-07-01

Haptoglobin is a plasma hemoglobin-binding protein that limits iron loss during normal erythrocyte turnover and hemolysis, thereby preventing oxidative damage mediated by iron excess in the circulation. Haptoglobin polymorphism in humans, characterized by the Hp(*1) and Hp (*2) alleles, results in distinct phenotypes known as Hp1-1, Hp2-1 and Hp2-2, whose frequencies vary according to the ethnic origin of the population. The Hp(*1) allele has two subtypes, Hp (*1F) and Hp (*1S) , that also vary in their frequencies among populations worldwide. In this work, we examined the distribution frequencies of haptoglobin subtypes in three Brazilian population groups of different ethnicities. The haptoglobin genotypes of Kayabi Amerindians (n = 56), Kalunga Afro-descendants (n = 70) and an urban population (n = 132) were determined by allele-specific PCR. The Hp(*1F) allele frequency was highest in Kalunga (29.3%) and lowest in Kayabi (2.6%). The Hp(*1F)/Hp(*1S) allele frequency ratios were 0.6, 1.0 and 0.26 for the Kayabi, Kalunga and urban populations, respectively. This variation was attributable largely to the Hp(*1F) allele. However, despite the large variation in Hp(*1F) frequencies, results of F (ST) (0.0291) indicated slight genetic differentiation among subpopulations of the general Brazilian population studied here. This is the first Brazilian report of variations in the Hp(*1F) and Hp(*1S) frequencies among non-Amerindian Brazilians.

[Relationship between the Fnu4HI site polymorphism of monoamine oxidase A gene and Parkinson's disease].

PubMed

Jiang, Xiao-hua; Yang, Hui; Yang, Jing-fang; Dong, Xiu-min; Xu, Qun-yuan; Chen, Biao

2003-06-01

To study the association between the polymorphism of human monoamine oxidase type A (MAO-A) gene and Parkinson's disease(PD). Fnu4HI restriction fragment length polymorphism(RFLP) and PCR-RFLP were used to detect the mutation of MAO-A gene. The frequencies of alleles and genotypes at the MAO-A Fnu4HI locus on the X chromosome in different PD group were compared with those of the control group. It was found that the frequencies of G allele in the patients with PD and controls were 0.613 and 0.527 respectively, P=0.039 "the frequencies of TT genotype were 0.303 and 0.415(P=0.014), and the frequencies of GG genotype were 0.564 and 0.451 respectively(P=0.021). When the patients were divided into two groups by age-onset, significant difference in the allelic and genotypic frequencies was observed only between early-onset PD group and control group. And when the PD patients were grouped by sex, significant difference was observed only between male PD group and male control group (the frequencies of G allele being 0.669 and 0.500 respectively, P=0.005). This study revealed significant differences between PD group and control group in allelic and genotypic frequencies. The findings supported the hypothesis about an association between MAO-A gene and PD, suggesting that age at onset of PD and gender predisposition might be related to the putative association, and Fnu4HI SNP be a risk factor for PD.

Robust Identification of Local Adaptation from Allele Frequencies

PubMed Central

Günther, Torsten; Coop, Graham

2013-01-01

Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of “standardized allele frequencies” that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools—a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org. PMID:23821598

Association between diabetes type 1 and DQB1 alleles in a case-control study conducted in Montevideo, Uruguay.

PubMed

Mimbacas, Adriana; Pérez-Bravo, Francisco; Hidalgo, Pedro C; Javiel, Gerardo; Pisciottano, Carmen; Grignola, Rosario; Jorge, Ana María; Gallino, Juan Pablo; Gasagoite, Jackeline; Cardoso, Horacio

2003-03-31

We studied HLA DQB1 allele frequencies and the relative risk (RR) of various genotypes in 72 type 1 diabetic patients and 40 control individuals in Uruguay. This is a tri-racial (Caucasian, Black and Indo-American) mixed population. The products of the polymerase chain reaction amplifications were hybridized with oligonucleotides by allele-specific oligonucleotide reverse or dot blot methods. Significant differences between these two groups were observed only for allele DQB1*0302 (35%, RR = 7.34, P<0.001). The frequency of the alleles carrying a non-aspartic acid residue at position 57 was significantly higher in the diabetic patients (85 vs 53%, P<0.001). In contrast, the frequency of Asp alleles was negatively associated with type 1 diabetes (RR = 0.20, P<0.001). The genotype DQB1*0302/DQB1*0201 (33%, RR = 5.41, P<0.05) was positively associated with this disease. The genotype frequencies associated with type 1 diabetes in our population were significantly different from what is known for Caucasian and Black populations as well as compared with another admixed population, from Chile.

Marker selection for the transmission/disequilibrium test, in recently admixed populations.

PubMed Central

Kaplan, N L; Martin, E R; Morris, R W; Weir, B S

1998-01-01

Recent admixture between genetically differentiated populations can result in high levels of association between alleles at loci that are <=10 cM apart. The transmission/disequilibrium test (TDT) proposed by Spielman et al. (1993) can be a powerful test of linkage between disease and marker loci in the presence of association and therefore could be a useful test of linkage in admixed populations. The degree of association between alleles at two loci depends on the differences in allele frequencies, at the two loci, in the founding populations; therefore, the choice of marker is important. For a multiallelic marker, one strategy that may improve the power of the TDT is to group marker alleles within a locus, on the basis of information about the founding populations and the admixed population, thereby collapsing the marker into one with fewer alleles. We have examined the consequences of collapsing a microsatellite into a two-allele marker, when two founding populations are assumed for the admixed population, and have found that if there is random mating in the admixed population, then typically there is a collapsing for which the power of the TDT is greater than that for the original microsatellite marker. A method is presented for finding the optimal collapsing that has minimal dependence on the disease and that uses estimates either of marker allele frequencies in the two founding populations or of marker allele frequencies in the current, admixed population and in one of the founding populations. Furthermore, this optimal collapsing is not always the collapsing with the largest difference in allele frequencies in the founding populations. To demonstrate this strategy, we considered a recent data set, published previously, that provides frequency estimates for 30 microsatellites in 13 populations. PMID:9497257

5-HTTLPR polymorphism: analysis in South African autistic individuals.

PubMed

Arieff, Zainunisha; Kaur, Mandeep; Gameeldien, Hajirah; van der Merwe, Lize; Bajic, Vladimir B

2010-06-01

The serotonin transporter promoter length polymorphism (5-hydroxytryptamine transporter length polymorphism; 5-HTTLPR) has long been implicated in autism and other psychiatric disorders. The use of selective serotonin reuptake inhibitors (SSRIs) has a positive effect on treating some symptoms of autism. The effects of these drugs vary in individuals because of the presence of the S or L allele of 5-HTTLPR. Studies performed on various autistic populations have found different allele frequencies for the L and S alleles. Allele frequencies and genotypes of the South African autistic populations (African, mixed, and Caucasian) were compared with matching South African ethnic control populations. The *S/*S genotype was found to be highly significantly associated with all the South African autistic ethnic populations. In the South African African population the *S/*S genotype was present in 7 (33%) of the autistic individuals but in none of the control subjects, yielding infinitely large odds of developing autism. The odds of developing autism with the *S/*S genotype compared to the *L/*L genotype increased 10.15-fold in the South African mixed group and 2.74-fold in the South African Caucasian population. The allele frequency of the South African autistic population was also compared with studies of other autistic populations around the world, and highly significant differences were found with the Japanese, Korean, and Indian population groups. The difference was not significant for the French, German, Israeli, Portuguese, and American groups. This is the first South African study of autistic individuals of different ethnic backgrounds that shows significant differences in allele and genotype frequencies of 5-HTTLPR. The results of this study open new avenues for investigating the role of transmission of the L and S alleles in families with autism in South Africa.

[Study on correlation between HLA-A, B, DR alleles and Duchenne muscular dystrophy].

PubMed

Chen, Wei; Xiao, Lulu; Zhang, Cheng; Wu, Hong-ling

2007-10-01

To analyze the polymorphism of HLA-A, B and DR alleles of Duchenne muscular dystrophy (DMD) patients in Han nationality of South China and to discuss the role of immune and genetic factors in the pathogenesis of DMD and muscular fiber necrosis. Polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO) and National Marrow Donor Program (NMDP) were used to analyze the polymorphism of HLA-A,B and DR alleles of 113 DMD patients and 406 normal controls in Han nationality of South China. The frequencies of HLA-A24, A30 alleles in DMD group were 11.25% and 5.46% respectively, indicating notable difference (P=0.001, < 0.01) from 22.16% and 0.87% of control group; the frequencies of HLA-B13, B15, B61 and B62 alleles in DMD group were 12.26%, 16.92%, 0.44% and 0.44%, indicating a notable difference (P=0.016, < 0.01, 0.001) from 6.76%, 1.49%, 4.79% and 5.05% of control group; the frequencies of HLA-DR04, DR07, DR12 alleles in DMD group were 17.45%, 6.40% and 19.62%, indicating a notable difference (P=0.018, < 0.01, 0.012) from 10.67%, 2.24% and 11.92% of control group. There are significant differences in the HLA gene frequencies between DMD patients and normal controls. These results suggest that HLA genotype relates to the muscular necrosis and the pathogenesis of DMD.

Allele frequency distribution of 1691G >A F5 (which confers Factor V Leiden) across Europe, including Slavic populations.

PubMed

Clark, Jeremy S C; Adler, Grażyna; Salkic, Nermin N; Ciechanowicz, Andrzej

2013-11-01

The allele 1691A F5, conferring Factor V Leiden, is a common risk factor in venous thromboembolism. The frequency distribution for this allele in Western Europe has been well documented; but here data from Central, Eastern and South-Eastern Europe has been included. In order to assess the significance of the collated data, a chi-squared test was applied, and Tukey tests and z-tests with Bonferroni correction were compared. A distribution with a North-Southeast band of high frequency of the 1691A F5 allele was discovered with a pocket including some Southern Slavic populations with low frequency. European countries/regions can be arbitrarily delimited into low (group 1, <2.8 %, mean 1.9 % 1691A F5 allele) or high (group 2, ≥2.8 %, mean 4.0 %) frequency groups, with many significant differences between groups, but only one intra-group difference (the Tukey test is suggested to be superior to the z-tests). In Europe a North-Southeast band of 1691A F5 high frequency has been found, clarified by inclusion of data from Central, Eastern and South-Eastern Europe, which surrounds a pocket of low frequency in the Balkans which could possibly be explained by Slavic migration. There seem to be no indications of variation in environmental selection due to geographical location.

Allele frequency data of 15 autosomal STR loci in four major population groups of South Africa.

PubMed

Lucassen, Anton; Ehlers, Karen; Grobler, Paul J; Shezi, Adeline L

2014-03-01

Allele frequency distributions for 15 tetrameric short tandem repeat (STR) loci were determined using the AmpFlSTR® Identifiler Plus™ PCR amplification kit. There was little evidence of departures from Hardy-Weinberg equilibrium or association of alleles of different loci in the population samples. The probability of identity values for the different populations range from 1/3.3 × 10(17) (White) to 1/1.88 × 10(18) (Coloured). The combined probability of paternal exclusion for the different population groups ranges from 0.9995858 (Coloured) to 0.9997874 (Indian).

Failure to Replicate a Genetic Association May Provide Important Clues About Genetic Architecture

PubMed Central

Greene, Casey S.; Penrod, Nadia M.; Williams, Scott M.; Moore, Jason H.

2009-01-01

Replication has become the gold standard for assessing statistical results from genome-wide association studies. Unfortunately this replication requirement may cause real genetic effects to be missed. A real result can fail to replicate for numerous reasons including inadequate sample size or variability in phenotype definitions across independent samples. In genome-wide association studies the allele frequencies of polymorphisms may differ due to sampling error or population differences. We hypothesize that some statistically significant independent genetic effects may fail to replicate in an independent dataset when allele frequencies differ and the functional polymorphism interacts with one or more other functional polymorphisms. To test this hypothesis, we designed a simulation study in which case-control status was determined by two interacting polymorphisms with heritabilities ranging from 0.025 to 0.4 with replication sample sizes ranging from 400 to 1600 individuals. We show that the power to replicate the statistically significant independent main effect of one polymorphism can drop dramatically with a change of allele frequency of less than 0.1 at a second interacting polymorphism. We also show that differences in allele frequency can result in a reversal of allelic effects where a protective allele becomes a risk factor in replication studies. These results suggest that failure to replicate an independent genetic effect may provide important clues about the complexity of the underlying genetic architecture. We recommend that polymorphisms that fail to replicate be checked for interactions with other polymorphisms, particularly when samples are collected from groups with distinct ethnic backgrounds or different geographic regions. PMID:19503614

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

PubMed

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

2016-10-01

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

ACE and ACTN3 genes polymorphisms among female Hungarian athletes in the aspect of sport disciplines.

PubMed

Bosnyák, E; Trájer, E; Udvardy, A; Komka, Z; Protzner, A; Kováts, T; Györe, I; Tóth, M; Pucsok, J; Szmodis, M

2015-12-01

The aim of the study was to determine the importance of two sport-associated gene polymorphisms, alpha-actinin-3 R577X (ACTN3) and angiotensin-converting enzyme I/D (ACE), among Hungarian athletes in different sports. The examination was carried out only on women (n = 100). Sport-specific groups were formed in order to guarantee the most homogeneous clusters. Human genomic DNA was isolated from blood, and genotyping was performed by polymerase chain reaction. To measure the differences between the participating groups, Chi-squared test was performed using Statistica 9.0 for Windows® (significance level: p < 0.05). In comparing the ACE I/D allele frequencies, significant difference was detected between water polo (I = 61.11%; D = 38.89%) and combat sports (I = 35.71%, D = 64.29%) athletes (p < 0.03). There was no statistical difference when ACE I/D alleles in combat sports and kayaking/rowing (p > 0.05) were compared. A similarity was detectable in the I allele frequencies of the water polo (61.11%) and kayaking/rowing (56.67%) groups. The ACTN3 R/X polymorphism showed no differences in comparison with the sport groups. R allele frequencies were higher in every group compared to the X allele. The potential significance of the ACE I allele in sports of an aerobic nature was not clearly confirmed among Hungarian athletes.

Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

PubMed

Urrutia, Inés; Martínez, Rosa; López-Euba, Tamara; Velayos, Teresa; Martínez de LaPiscina, Idoia; Bilbao, José Ramón; Rica, Itxaso; Castaño, Luis

2017-01-01

The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY. 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4). Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96) and OR 0.06 (95% CI: 0.02-0.18), respectively. The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

Frequency of interleukin 28B rs12979860 C>T variants in Filipino patients chronically infected with hepatitis B virus.

PubMed

Baclig, Michael O; Reyes, Karen G; Mapua, Cynthia A; Gopez-Cervantes, Juliet; Natividad, Filipinas F

2015-03-01

Hepatitis B virus (HBV) is one of the most prevalent viral infections worldwide. Nearly 400 million individuals are chronic carriers of HBV. The aim of the present study was to determine the frequency of human interleukin 28B (IL28B) variants among treatment naive Filipino patients clinically diagnosed with chronic hepatitis B (CHB), and to compare the IL28B frequency distribution with various ethnic populations. Fifty-seven CHB patients and 43 normal controls were enrolled in this study. Real-time PCR was performed using the TaqMan genotyping assay for IL28B rs12979860. The allelic frequencies among normal controls were 0.94 and 0.06 for the IL28B rs12979860 C and T alleles, respectively. Eighty-eight percent were identified as homozygous for the IL28B C/C genotype and 12% were identified as heterozygous for the IL28B C/T genotype. Among CHB patients, the allelic frequencies were 0.90 for the IL28B C allele and 0.10 for the IL28B T allele. No IL28B T/T genotype was observed between the two groups. No significant difference in the distribution of IL28B genotypes was observed between normal controls and CHB patients. Allelic frequencies of IL28B among Filipinos were similar with other Asian populations but significantly different from Caucasians. The frequency of rs12979860 C>T variants among Filipino CHB patients has not yet been reported. These data provided new insight into the geographical frequency distribution of IL28B variants. Further studies are needed to determine the possible association between IL28B variants and response to pegylated-interferon-α plus ribavirin combination therapy among Filipino patients chronically infected with HBV.

Research on the relativity between gene polymorphism and children cardiac insufficiency.

PubMed

He, X-H; Li, C-L; Ling, N; Wang, Q-W; Wang, Z-Z; An, X-J

2017-08-01

We analyzed the relationship between Mink-S27 gene polymorphism and children with cardiac insufficiency. From April 2013 to April 2015, we enrolled 73 cases of children with cardiac insufficiency for this study, and all 73 were placed in the observation group. 76 normal cases were selected for the control group. Restriction fragment length polymorphism (RFLP) was used to make polymorphism analysis of the Mink-S27. Our results showed no significant differences in Mink-S27 genotype and allele distribution in both observation and control groups (p>0.05). In lesion samples collected from children with cardiac insufficiency, we detected significant difference in AA, CC genotype frequency and allele frequency between the observation group and the control group (p< 0.05) (X2 = 15.43, p<0.05; X2  = 16.27, p<0.05). Further studies on samples obtained from both groups revealed certain differences of AA, CC, AC genotype frequency and allele frequency in the observation group. The proportion of homozygote (AA, CC) in children with severe cardiac insufficiency was relatively high. GNAS2 gene polymorphism was associated with the prevalence of cardiac insufficiency in children. And also the patients' condition was correlated to the frequency of different genotypes and alleles.

Angiotensin-converting enzyme (ACE) alleles in the Quechua, a high altitude South American native population.

PubMed

Rupert, J L; Devine, D V; Monsalve, M V; Hochachka, P W

1999-01-01

Recently it was reported that an allelic variant of the gene encoding angiotensin-converting enzyme (ACE) was significantly over-represented in a cohort of elite British mountaineers. It was proposed that this may be evidence for a specific genetic factor influencing the human capacity for physical performance. The implication that this allele could enhance performance at high altitude prompted us to determine its frequency in Quechua speaking natives living at altitudes greater than 3000m on the Andean Altiplano in South America. We found that the frequency of the putative performance allele in the Quechuas, although significantly higher than in Caucasians, was not different from lowland Native American populations. This observation suggests that, although the higher frequency of the 'performance allele' may have facilitated the migration of the ancestral Quechua to the highlands, the ACE insertion allele has not been subsequently selected for in this high altitude population.

The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population.

PubMed

Werneck, Lineu Cesar; Lorenzoni, Paulo José; Arndt, Raquel Cristina; Kay, Cláudia Suemi Kamoi; Scola, Rosana Herminia

2016-08-01

To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil. We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.

Estimating the number, frequency, and dominance of S-alleles in a natural population of Arabidopsis lyrata(Brassicaceae) with sporophytic control of self-incompatibility.

PubMed

Mable, B K; Schierup, M H; Charlesworth, D

2003-06-01

In homomorphic plant self-incompatibility (SI) systems, large numbers of alleles may be maintained at a single Mendelian locus. Most estimators of the number of alleles present in natural populations are designed for gametophytic self-incompatibility systems (GSI) in which the recognition phenotype of the pollen is determined by its own haploid genotype. In sporophytic systems (SSI), the recognition phenotype of the pollen is determined by the diploid genotype of its parent, and dominance differs among alleles. We describe research aimed at estimates of S-allele numbers in a natural population of Arabidopsis lyrata (Brassicaceae), whose SSI system has recently been described. Using a combination of pollination studies and PCR-based identification of alleles at a locus equivalent to the Brassica SRK gene, we identified and sequenced 11 putative alleles in a sample of 20 individuals from different maternal seed sets. The pollination results indicate that we have not amplified all alleles that must be present. Extensive partial incompatibility, nonreciprocal compatibility differences, and evidence of weakened expression of SI in some genotypes, prevent us from determining the exact number of missing alleles based only on cross-pollination data. Although we show that none of the theoretical models currently proposed is completely appropriate for estimating the number of alleles in this system, we estimate that there are between 13 and 16 different S-alleles in our sample, probably between 16 and 25 alleles in the population, and discuss the relative frequency of alleles in relation to dominance.

Estimated frequency of the canine hyperuricosuria mutation in different dog breeds.

PubMed

Karmi, N; Brown, E A; Hughes, S S; McLaughlin, B; Mellersh, C S; Biourge, V; Bannasch, D L

2010-01-01

Hyperuricosuria is a condition that predisposes dogs to urate urolithiasis. A mutation that causes canine hyperuricosuria was previously identified in 3 unrelated dog breeds. The occurrence of the mutation in additional breeds was not determined. Identify additional breeds that have the hyperuricosuria mutation and estimate the mutant allele frequency in those breeds. Three thousand five hundred and thirty dogs from 127 different breeds were screened for the hyperuricosuria mutation. DNA samples were genotyped by pyrosequencing and allele-specific polymerase chain reaction methods. Mutant allele frequencies that range from 0.001 to 0.15 were identified in the American Staffordshire Terrier, Australian Shepherd, German Shepherd Dog, Giant Schnauzer, Parson (Jack) Russell Terrier, Labrador Retriever, Large Munsterlander, Pomeranian, South African Boerboel, and Weimaraner breeds. The hyperuricosuria mutation has been identified in several unrelated dog breeds. The mutant allele frequencies vary among breeds and can be used to determine an appropriate breeding plan for each breed. A DNA test is available and may be used by breeders to decrease the mutant allele frequency in breeds that carry the mutation. In addition, veterinarians may use the test as a diagnostic tool to identify the cause of urate urolithiasis. Copyright © 2010 by the American College of Veterinary Internal Medicine.

Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences

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

Sachse, C.; Brockmoeller, J.; Bauer, S.

Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324, .018, and .015,more » respectively. By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of.005 (*1 x 2), .013 (* 2 x 2), and .001 (*4 x 2). Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001 (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found. All 41 PMs (7.0%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity. Three novel variants of known CYP2D6 alleles were discovered: *1C (T{sub 1957}C), *2B (additional C{sub 2558}T), and *4E (additional C{sub 2938}T). Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EN/PM (mean MR = .006) and IM/PM (mean MR = .014) alleles and between carriers of one (mean MR = .009) and two (mean MR = .003) functional alleles. The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment. 35 refs., 4 figs., 5 tabs.« less

Brief communication: Molecular characterization of O alleles at the ABO locus in Chilean Aymara and Huilliche Indians.

PubMed

Llop, Elena; Henríquez, Hugo; Moraga, Mauricio; Castro, Mario; Rothhammer, Francisco

2006-12-01

A molecular characterization of alleles O1, O1variant (O1v), and the mutation G542A of the ABO blood group was performed in two Amerindian populations of Chile, the Aymara (n = 84) and the Huilliche (n = 75). In addition, a sample of 82 individuals of Santiago belonging to the mixed Chilean population was typed for comparative purposes. The polymorphisms which allow for molecular differentiation of different alleles of the O blood group were studied in genomic DNA. The mutations G188, G261-, G542A, T646A, and C771T, described for alleles O1, O1v, and G542A, were determined using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique. All individuals studied were group O homozygotes for the deletion G261-, which defines the O1 alleles. Results obtained indicate that allele O1v exhibits frequencies of 0.65, 0.81, and 0.60 in Aymara, Huilliche, and Santiago populations, respectively. The frequencies of allele O1(G542A) were 0.119, 0.113, and 0.079 in the same populations. Frequencies for alleles O1 and O1v obtained in the Chilean populations studied concur with the results obtained by other authors, respecting the greater frequency of allele O1v as well as with its heterogeneous distribution in aboriginal South American populations. In Chilean populations, Allele G542A exhibits lower frequencies than those described for indigenous populations from Brazil and may be used as an Amerind admixture marker. 2006 Wiley-Liss, Inc.

Epistatic selection of a sequence 5{prime} of the gene responsible for cystic fibrosis may account for the high frequency of this disease in the Caucasian population

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

Macek, M. Jr.; Nash, E.; Cutting, G.R.

1994-09-01

Cystic fibrosis (CF) is one of the more common lethal autosomal recessive disorders in Caucasian populations. Numerous hypotheses including genetic drift, founder effect, sex ratio, segregation distortions and various forms of heterozygote advantage have been proposed to explain the relatively high frequency of CF alleles. The observation of high linkage disequilibrium between markers at the 5{prime} end of CFTR and mutations that cause CF raised the possibility of epistatic selection. CF-linked marker allele frequencies were determined in 417 elderly individuals from a stable Czech population that survived high levels of infant and childhood mortality in the pre-antibiotic era. These datamore » were compared with allele frequencies of 646 contemporary newborns and 345 young adults drawn from the same population who had significantly lower mortality rates in the antibiotic era. Allele frequencies of markers CS7/Hhal and KM19/Pstl from the D7S23 locus are significantly different (p<0.05) between elderly female and male subjects in this population. Furthermore, there is a significant difference in the allele frequencies of marker CS7/Hhal when newborn females and elderly women are compared (p<0.05). Taken together, these data suggest that the allele status at the CS7 region influenced female survival in the period of high infant and childhood mortality in the pre-antibiotic era. Under this selective pressure, CFTR mutations that occurred on the {open_quotes}favorable{close_quotes} background would marginally increase in frequency in each successive generation and more ancient mutations residing on this background would become the most frequent in the general population.« less

CYP2D6 genotype and phenotype in Amerindians of Tepehuano origin and Mestizos of Durango, Mexico.

PubMed

Sosa-Macías, Martha; Elizondo, Guillermo; Flores-Pérez, Carmen; Flores-Pérez, Janet; Bradley-Alvarez, Francisco; Alanis-Bañuelos, Ruth E; Lares-Asseff, Ismael

2006-05-01

Although the drug-metabolizing enzyme CYP2D6 has been studied extensively in subjects of differing ethnicities, limited CYP2D6 pharmacogenetic data are available for the Amerindian population and Mestizos of Mexico. Dextromethorphan hydroxylation phenotype was studied in Tepehuano Amerindian (n = 58) and Mestizo (n = 88) subjects, and 195 individuals (85 Tepehuano Amerindians and 110 Mestizos) were genotyped by polymerase chain reaction-restriction fragment length polymorphism methods to identify the frequencies of the CYP2D6*3, *4, *6, and *10 alleles. Tepehuano Amerindian subjects lacked the poor metabolizer (PM) phenotype, whereas in Mestizos the PM phenotype frequency was 6.8%. The CYP2D6*3, *6, and *10 alleles were not found in Tepehuano Amerindians. The CYP2D6*4 allele had a low frequency (0.006) in this Amerindian group. In the Mestizo group, the CYP2D6*3, *4, and *10 alleles had frequencies of 0.009, 0.131, and 0.023, respectively. The CYP2D6*6 allele was not found in Mestizos. The genotype-phenotype association was strongly statistically significant (r(2) = .45; P = .005) in Mestizos. The Tepehuano population was found to have a low phenotypic and genotypic CYP2D6 diversity and differed from other Amerindian groups. On the other hand, the frequencies of the CYP2D6 variant alleles in Mestizos were similar to those reported for whites.

Empirical Distributions of F ST from Large-Scale Human Polymorphism Data

PubMed Central

Elhaik, Eran

2012-01-01

Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright’s F ST that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-F ST may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically F ST analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global F ST distribution closely follows an exponential distribution. Third, although the overall F ST distribution is similarly shaped (inverse J), F ST distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-F ST of these groups is linear in allele frequency. These results suggest that investigating the extremes of the F ST distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection. PMID:23185452

Empirical distributions of F(ST) from large-scale human polymorphism data.

PubMed

Elhaik, Eran

2012-01-01

Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright's F(ST) that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-F(ST) may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically F(ST) analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global F(ST) distribution closely follows an exponential distribution. Third, although the overall F(ST) distribution is similarly shaped (inverse J), F(ST) distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-F(ST) of these groups is linear in allele frequency. These results suggest that investigating the extremes of the F(ST) distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection.

The association between oxcarbazepine-induced maculopapular eruption and HLA-B alleles in a Northern Han Chinese population

PubMed Central

2013-01-01

Background We investigated the association between oxcarbazepine (OXC)-induced maculopapular eruption (MPE) and HLA-B alleles in a northern Han Chinese population, and conducted an analysis of clinical risk factors for OXC-MPE. Methods Forty-two northern Han Chinese patients who had been treated with OXC in Changchun, China were genotyped. Among them were 14 cases with OXC-induced MPE; the remaining 28 were OXC-tolerant. The HLA-B allele frequencies of the normal control group were found in the Allele Frequency Net Database. Polymerase chain reaction-sequence specific primer( PCR-SSP )was used for HLA-B*1502 testing and direct sequencing for four-digit genotype determination. Results Four-digit allele sequencing showed that there was no statistically significant difference in the frequency of the HLA-B*1502 allele between the OXC-MPE and OXC-tolerant controls (3.6% versus 7.5%, OR = 0.38, 95% CI = 0.04–3.40, P = 0.65), as well as between OXC-MPE and normal controls (3.6% versus 2.4%, OR = 1.54, 95% CI = 0.20–11.73, P = 0.49). However, a significant difference in the frequency of HLA-B*3802 alleles was found between the MPE group and normal controls (10.7% versus 1.9%, OR = 6.329, 95% CI = 1.783-22.460, P = 0.018). There was no significant difference in terms of age, gender, or final OXC dose between the OXC-MPE and OXC-tolerant groups. Conclusions There was no significant association between OXC-MPE and HLA-B*1502 in the northern Han Chinese population in our study. Instead, HLA-B*3802 was found to be a potential risk factor for OXC-MPE. PMID:23829937

The association of 22 Y chromosome short tandem repeat loci with initiative-aggressive behavior.

PubMed

Yang, Chun; Ba, Huajie; Zhang, Wei; Zhang, Shuyou; Zhao, Hanqing; Yu, Haiying; Gao, Zhiqin; Wang, Binbin

2018-05-15

Aggressive behavior represents an important public concern and a clinical challenge to behaviorists and psychiatrists. Aggression in humans is known to have an important genetic basis, so to investigate the association of Y chromosome short tandem repeat (Y-STR) loci with initiative-aggressive behavior, we compared allelic and haplotypic distributions of 22 Y-STRs in a group of Chinese males convicted of premeditated extremely violent crimes (n = 271) with a normal control group (n = 492). Allelic distributions of DYS533 and DYS437 loci differed significantly between the two groups (P < 0.05). The case group had higher frequencies of DYS533 allele 14, DYS437 allele 14, and haplotypes 11-14 of DYS533-DYS437 compared with the control group. Additionally, the DYS437 allele 15 frequency was significantly lower in cases than controls. No frequency differences were observed in the other 20 Y-STR loci between these two groups. Our results indicate a genetic role for Y-STR loci in the development of initiative aggression in non-psychiatric subjects. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.

PubMed

Shahmoradi, Somayeh; Ahmadalipour, Ali; Salehi, Mansoor

2014-01-01

Angiotensin converting enzyme (ACE) is an important gene, which is associated with the successful physical activity. The ACE gene has a major polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In this study, we aimed to determine whether there is an association between this polymorphism and sports performance in our studied population including elite athletes of different sports disciplines. We investigated allele frequency and genotype distribution of the ACE gene in 156 Iranian elite athletes compared to 163 healthy individuals. We also investigated this allele frequency between elite athletes in three functional groups of endurance, power, and mixed sports performances. DNA was extracted from peripheral blood, and polymerase chain reaction (PCR) method was performed on intron 16 of the ACE gene. The ACE genotype was determined for each subject. Statistical analysis was performed by SPSS 15, and results were analyzed by Chi-Square test. There was a significant difference in genotype distribution and allele frequency of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively). There was also a significant difference in allele frequency of the ACE gene in 3 groups of athletes with different sports disciplines (P = 0.045). Proportion of the ACE gene D allele was greater in elite endurance athletes (37 high-distance cyclists) than two other groups. Findings of the present study demonstrated that there is an association between the ACE gene I/D polymorphism and sports performance in Iranian elite athletes.

Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8.

PubMed

Fujinami, Kaoru; Strauss, Rupert W; Chiang, John Pei-Wen; Audo, Isabelle S; Bernstein, Paul S; Birch, David G; Bomotti, Samantha M; Cideciyan, Artur V; Ervin, Ann-Margret; Marino, Meghan J; Sahel, José-Alain; Mohand-Said, Saddek; Sunness, Janet S; Traboulsi, Elias I; West, Sheila; Wojciechowski, Robert; Zrenner, Eberhart; Michaelides, Michel; Scholl, Hendrik P N

2018-06-20

To describe the genetic characteristics of the cohort enrolled in the international multicentre progression of Stargardt disease 1 (STGD1) studies (ProgStar) and to determine geographic differences based on the allele frequency. 345 participants with a clinical diagnosis of STGD1 and harbouring at least one disease-causing ABCA4 variant were enrolled from 9 centres in the USA and Europe. All variants were reviewed and in silico analysis was performed including allele frequency in public databases and pathogenicity predictions. Participants with multiple likely pathogenic variants were classified into four national subgroups (USA, UK, France, Germany), with subsequent comparison analysis of the allele frequency for each prevalent allele. 211 likely pathogenic variants were identified in the total cohort, including missense (63%), splice site alteration (18%), stop (9%) and others. 50 variants were novel. Exclusively missense variants were detected in 139 (50%) of 279 patients with multiple pathogenic variants. The three most prevalent variants of these patients with multiple pathogenic variants were p.G1961E (15%), p.G863A (7%) and c.5461-10 T>C (5%). Subgroup analysis revealed a statistically significant difference between the four recruiting nations in the allele frequency of nine variants. There is a large spectrum of ABCA4 sequence variants, including 50 novel variants, in a well-characterised cohort thereby further adding to the unique allelic heterogeneity in STGD1. Approximately half of the cohort harbours missense variants only, indicating a relatively mild phenotype of the ProgStar cohort. There are significant differences in allele frequencies between nations, although the three most prevalent variants are shared as frequent variants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Frequencies of apolipoprotein E polymorphism in a healthy Kurdish population from Kermanshah, Iran.

PubMed

Vaisi-Raygani, Asad; Kharrazi, Hadi; Rahimi, Zohreh; Pourmotabbed, Tayebeh

2007-10-01

The molecular polymorphism displayed by apolipoprotein E (APOE) has been listed as a risk factor for susceptibility to various disorders, such as those associated with lipid metabolism, arteriosclerosis, coronary artery disease (CAD), and Alzheimer disease. To evaluate the role of APOE genotypes as risk factors for Alzheimer disease, CAD, and atherosclerosis in the Kurdish population of Kermanshah, Iran, we studied the frequencies of APOE alleles *2, *3, and *4 and genotypes in 914 healthy Kurdish subjects (514 men and 400 women). The highest frequency of APOE in the Kurdish population was found for APOE*3 (87.87%). The APOE*2 and APOE*4 allele frequencies were 6.66% and 5.45%, respectively. Distribution of APOE genotypes and alleles was not significantly different between male and female subjects (p > 0.05). Interestingly, the order of the frequency of APOE alleles (*3-->*2-->*4) in the Kurdish population was quite different from that reported for most populations in the world (*3-->*4-->*2). The findings of the present study can be used to identify individuals with high risk of CAD and atherosclerosis and suggest a preventive measure to reduce their susceptibility.

Lack of association between TaqI A1 Allele of dopamine D2 receptor gene and alcohol-use disorders in Atayal natives of Taiwan

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

Chia-Hsiang Chen; Shih-Hsiang Chien; Hai-Gwo Hwu

1996-09-20

Association studies between the A1 allele of the dopamine D2 receptor (DRD2) gene TaqI A polymorphism and alcoholism remain controversial. A recent study from Japan demonstrated that the A1 allele is associated with severe alcoholism in the Japanese population. We were interested in knowing if this association also exists in the Atayals of Taiwan, who were found to have a higher prevalence of alcohol-use disorders than the Han Chinese in Taiwan. Genotype and allele frequencies were determined in alcohol-abusing, alcohol-dependent, and nonalcoholic control Atayal natives in Taiwan. A1 allele frequencies in alcohol-dependent, alcohol-abusing, and normal control Atayals were 0.39, 0.42,more » and 0.39, respectively. No difference in A1 allele frequency was found among these three groups. Our data do not support the hypothesis that the A1 allele of the TaqI A polymorphism of the DRD2 gene increases susceptibility to alcohol-use disorders in the Atayals of Taiwan. 18 refs., 1 tab.« less

Is the -174 C/G polymorphism of the IL6 gene associated with elite power performance? A replication study with two different Caucasian cohorts.

PubMed

Eynon, Nir; Ruiz, Jonatan R; Meckel, Yoav; Santiago, Catalina; Fiuza-Luces, Carmen; Gómez-Gallego, Félix; Oliveira, José; Lucia, Alejandro

2011-02-01

A functional -174 C/G polymorphism in the interleukin-6 gene (IL6) is a candidate to explain individual variations in exercise-related phenotypes. To replicate recent findings showing an association between the G allele and GG genotype of elite power sports performance in European (Spanish) Caucasian males, we compared allelic and genotypic frequencies of the IL6 -174 C/G polymorphism among elite endurance athletes (n = 74) and power athletes (n = 81) and non-athletic control subjects (n = 205) of both sexes from Israel. All subjects were Israeli Caucasians (with an equivalent ratio of non-Ashkenazi and Ashkenazi descent in each group; 2:1). We found no differences in the genotype or allele frequencies among groups (all P > 0.3). We further compared the genotype and allele frequencies between national- (n = 109) and international-level Israeli athletes (n = 46) in the endurance and power group, and found no significant genotype or allele differences after adjusting for multiple comparisons. We repeated all the analyses after pooling the Israeli and Spanish control subjects, endurance and power elite athletes, and found no genotypic and allelic differences among groups. The results did not change when the analyses were repeated including only the best Israeli athletes (i.e. the international-level group) together with the group of elite Spanish athletes (P > 0.2). In conclusion, the results of the present study did not show an association between the G allele of the IL6 -174 G/C polymorphism and power sports performance in the Israeli (Caucasian) population. Our findings support the need to replicate association results between genetic polymorphisms and athletic status in populations of different ethnic backgrounds with the largest possible population samples.

Detection of MPLW515L/K Mutations and Determination of Allele Frequencies with a Single-Tube PCR Assay

PubMed Central

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner. PMID:25144224

Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

PubMed

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

The allele frequency of two single nucleotide polymorphisms in the von Hippel-Lindau (VHL) tumor suppressor gene in the Taiwanese population.

PubMed

Wang, Wen-Chung; Chen, Hui-Ju; Shu, Wei-Pang; Tsai, Yi-Chang; Lai, Yen-Chein

2011-10-01

The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551. In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations. The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I. Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles. We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects. Copyright © 2011. Published by Elsevier B.V.

The HLA-C*04: 01/KIR2DS4 gene combination and human leukocyte antigen alleles with high population frequency drive rate of HIV disease progression.

PubMed

Olvera, Alex; Pérez-Álvarez, Susana; Ibarrondo, Javier; Ganoza, Carmela; Lama, Javier R; Lucchetti, Aldo; Cate, Steven; Hildebrand, William; Bernard, Nicole; Gomez, Lupe; Sanchez, Jorge; Brander, Christian

2015-03-13

The objective of this study is to identify human leukocyte antigen (HLA) class I and killer-cell immunoglobulin-like receptor (KIR) genotypes associated with different risks for HIV acquisition and HIV disease progression. A cross-sectional study of a cohort of 468 high-risk individuals (246 HIV-positive and 222 HIV-negative) from outpatient clinics in Lima (Perú). The cohort was high-resolution HLA and KIR-typed and analysed for potential differences in single-allele frequencies and allele combinations between HIV-positive and HIV-negative individuals and for associations with HIV viral load and CD4 cell counts in infected individuals. HLA class I alleles associated with a lack of viral control had a significantly higher population frequency than relatively protective alleles (P = 0.0093), in line with a rare allele advantage. HLA-A02 : 01 and HLA-C04 : 01 were both associated with high viral loads (P = 0.0313 and 0.0001, respectively) and low CD4 cell counts (P = 0.0008 and 0.0087, respectively). Importantly, the association between HLA-C04 : 01 and poor viral control was not due to its linkage disequilibrium with other HLA alleles. Rather, the coexpression of its putative KIR ligand KIR2DS4f was critically linked to elevated viral loads. These results highlight the impact of population allele frequency on viral control and identify a novel association between HLA-C04 : 01 in combination with KIR2DS4f and uncontrolled HIV infection. Our data further support the importance of the interplay of markers of the adaptive and innate immune system in viral control.

Linking Y-chromosomal short tandem repeat loci to human male impulsive aggression.

PubMed

Yang, Chun; Ba, Huajie; Cao, Yin; Dong, Guoying; Zhang, Shuyou; Gao, Zhiqin; Zhao, Hanqing; Zhou, Xianju

2017-11-01

Men are more susceptible to impulsive behavior than women. Epidemiological studies revealed that the impulsive aggressive behavior is affected by genetic factors, and the male-specific Y chromosome plays an important role in this behavior. In this study, we investigated the association between the impulsive aggressive behavior and Y-chromosomal short tandem repeats (Y-STRs) loci. The collected biologic samples from 271 offenders with impulsive aggressive behavior and 492 healthy individuals without impulsive aggressive behavior were amplified by PowerPlex R Y23 PCR System and the resultant products were separated by electrophoresis and further genotyped. Then, comparisons in allele and haplotype frequencies of the selected 22 Y-STRs were made in the two groups. Our results showed that there were significant differences in allele frequencies at DYS448 and DYS456 between offenders and controls ( p  < .05). Univariate analysis further revealed significant frequency differences for alleles 18 and 22 at DYS448 (0.18 vs 0.27, compared to the controls, p  = .003, OR=0.57,95% CI=0.39-0.82; 0.03 vs 0.01, compared to the controls, p  = .003, OR=7.45, 95% CI=1.57-35.35, respectively) and for allele 17 at DYS456 (0.07 vs 0.14, compared to the controls, p  = .006, OR=0.48, 95% CI =0.28-0.82) between two groups. Interestingly, the frequency of haploid haplotype 22-15 on the DYS448-DYS456 (DYS448-DYS456-22-15) was significantly higher in offenders than in controls (0.033 vs 0.004, compared to the control, p  = .001, OR = 8.42, 95%CI =1.81-39.24). Moreover, there were no significant differences in allele frequencies of other Y-STRs loci between two groups. Furthermore, the unconditional logistic regression analysis confirmed that alleles 18 and 22 at DYS448 and allele 17 at DYS456 are associated with male impulsive aggression. However, the DYS448-DYS456-22-15 is less related to impulsive aggression. Our results suggest a link between Y-chromosomal allele types and male impulsive aggression.

Allele frequency data for 15 autosomal STR loci in eight Indonesian subpopulations.

PubMed

Venables, Samantha J; Daniel, Runa; Sarre, Stephen D; Soedarsono, Nurtami; Sudoyo, Herawati; Suryadi, Helena; van Oorschot, Roland A H; Walsh, Simon J; Widodo, Putut T; McNevin, Dennis

2016-01-01

Evolutionary and cultural history can affect the genetic characteristics of a population and influences the frequency of different variants at a particular genetic marker (allele frequency). These characteristics directly influence the strength of forensic DNA evidence and make the availability of suitable allele frequency information for every discrete country or jurisdiction highly relevant. Population sub-structure within Indonesia has not been well characterised but should be expected given the complex geographical, linguistic and cultural architecture of the Indonesian population. Here we use forensic short tandem repeat (STR) markers to identify a number of distinct genetic subpopulations within Indonesia and calculate appropriate population sub-structure correction factors. This data represents the most comprehensive investigation of population sub-structure within Indonesia to date using these markers. The results demonstrate that significant sub-structure is present within the Indonesian population and must be accounted for using island specific allele frequencies and corresponding sub-structure correction factors in the calculation of forensic DNA match statistics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts.

PubMed

Bazrgar, Masood; Karimi, Mehran; Fathzadeh, Mohsen; Senemar, Sara; Peiravian, Farah; Shojaee, Ashraf; Saadat, Mostafa

2008-12-01

Apolipoprotein E (apoE) with three major alleles E2, E3 and E4 is one of the critical genes in lipid metabolism. Common apoE alleles are in association with an increase in risk for central nervous and cardiovascular diseases such as Alzheimer's disease, dementia, multiple sclerosis, atherosclerosis, coronary heart disease, hyperlipoproteinemia and stroke. ApoE3 is known as the most frequent allele in all populations, while association of apoE gene polymorphism with reported diseases have mostly been related to other two major alleles especially apoE4. To determine of apoE alleles frequencies in Southern Iran and comparison of those frequencies with other populations. DNA was extracted from the whole blood of 198 healthy unrelated candidates from population of Fars Province, Southern Iran, for apoE genotyping who were checked up by a physician. The frequencies of apoE alleles were compared with other populations by chi(2) test. The frequencies of E2, E3 and E4 were 0.063, 0.886 and 0.051 respectively. These values were similar to those reported from populations of Kuwait, Oman, Lebanon, India, Turkey, Greece, Spain, Sardinia Islands of Italy and two Iranian populations but were different from South of Italy and Caucasians in other Europe regions, American, American-Indian, African, East Asian and Saudi populations (P < 0.05). The frequency of E4 allele as a genetic risk factor for some multifactorial diseases in the population of Southern Iran is in the lowest reported amounts in the world. Iranian population has Caucasoid origin but differs from some Caucasian populations in Europe and America. The results of present study are in agreement with the historical evidences which show admixture of Iranian population with other populations and some studies based on genetic polymorphisms in the population of Southern Iran.

CYP2C19 polymorphism frequency in Russian patients in Central Russia and Siberia with acute coronary syndrome

PubMed Central

Mirzaev, Karin B; Zelenskaya, Elena M; Barbarash, Olga L; Ganyukov, Vladimir I; Apartsin, Konstantin A; Saraeva, Natalya O; Nikolaev, Konstantin Y; Ryzhikova, Kristina A; Lifshits, Galina I; Sychev, Dmitry A

2017-01-01

Purpose The aim of this study is to investigate the frequency of CYP2C19*2, *3 allelic variants, associated with poor response to clopidogrel, and CYP2C19*17, associated with excessive response to clopidogrel, in patients with acute coronary syndrome (ACS) from Siberia and Moscow regions of Russia. Patients and methods The study included 512 ACS patients who were subsequently treated with coronary arterial stenting. The subjects assigned were from the cities of Central (Novosibirsk, Kemerovo), Eastern (Irkutsk), Northern (Surgut) Siberia regions and from Moscow region. The mean age of patients enrolled was 63.9±10.9 years. Among the assigned subjects, the proportion of men accounted for 80% and women 20%. Results According to the results obtained in the present study, from 16% up to 27.5% of patients in different regions of Russia have at least one CYP2C19 “poor metabolizer” (PM) allele variant affecting clopidogrel metabolism and, therefore, suppressing its antiplatelet activity. CYP2C19*17 allele variant was identified with the frequency of 15.4% up to 33.3%. The study revealed the presence of statistically significant differences in CYP2C19*3 allele frequency between the Russian ethnic group patients from Eastern and Central Siberia (p=0.001; odds ratio=1.05 [95% confidence interval 1.01–1.09]). Conclusion The study revealed statistically significant differences between the allele frequencies in Eastern and Central Siberia, which can probably be caused by a considerable number of Buryats inhabiting Eastern Siberia. PMID:28442925

Calpain-10 gene polymorphisms and risk of type 2 diabetes mellitus in Mexican mestizos.

PubMed

Picos-Cárdenas, V J; Sáinz-González, E; Miliar-García, A; Romero-Zazueta, A; Quintero-Osuna, R; Leal-Ugarte, E; Peralta-Leal, V; Meza-Espinoza, J P

2015-03-27

The calpain-10 gene is expressed primarily in tissues important in glucose metabolism; thus, some of its polymorphisms have been associated with type 2 diabetes. In this study, we examined the association between the calpain-10 single-nucleotide polymorphism (SNP)-43, SNP-19, and SNP-63 and type 2 diabetes in Mexican mestizos. We included 211 patients and 152 non-diabetic subjects. Polymerase chain reaction was used to identify alleles. We compared allele, genotype, haplotype, and diplotype frequencies between both groups and used the chi-square test to calculate the risk. The allele frequency of SNP-43 allele 1 was 70% in controls and 72% in patients; the GG, GA, and AA genotype frequencies were 48.7, 42.8, and 8.5% in controls and 51.2, 41.7, and 7.1% in patients, respectively. For SNP- 19, the prevalence of allele 1 (2R) was 32% in controls and 39% in patients. In controls, homozygosity (2R/2R) was 10.5%, heterozygosity was 42.8%, and 3R/3R was 46.7%; in cases, these values were 13.3, 50.7, and 36.0%, respectively. For SNP-63, the frequency of allele 1 was 87% in controls and 83% in patients; genotype frequencies in controls were 75.7% (CC), 23% (CT), and 1.3% (TT), and were 69.7, 27.5, and 2.8%, respectively for the cases. Genotype distributions were consistent with Hardy-Weinberg equilibrium. No significant intergroup differences for allele, genotype, haplotype, or diplotype frequencies were observed. We found no association between these polymorphisms and diabetes. However, our sample size was small, so the role of calpain-10 risk alleles should be further examined.

Biallelic and Triallelic 5-Hydroxytyramine Transporter Gene-Linked Polymorphic Region (5-HTTLPR) Polymorphisms and Their Relationship with Lifelong Premature Ejaculation: A Case-Control Study in a Chinese Population

PubMed Central

Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Li, Chao; Liu, Weiqun; Liang, Chaozhao

2016-01-01

Background This study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications. Material/Methods A total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as having lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. We evaluated the associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, as well as the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients. Results The patients and controls did not differ significantly in terms of any characteristic except age. The results showed no significant difference regarding biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found when comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG, and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L’L’ genotype (OR=0.37; 95%CI=0.15–0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes. Conclusions Contrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research in PE to avoid false-negative results in future studies. PMID:27311544

Diversity of alleles encoding HLA-B40: relative frequencies in united states populations and description of five novel alleles.

PubMed

Pimtanothai, N; Rizzuto, G A; Slack, R; Steiner, N K; Kosman, C A; Jones, P F; Koester, R; Ng, J; Hartzman, R J; Katovich Hurley, C

2000-08-01

The frequency of each B*40 allele was determined by DNA sequencing in four major United States populations: Caucasians, African Americans, Asians/Pacific Islanders, and Hispanics. Thirty-two individuals from each ethnic group, who were previously described serologically as B40, B60, or B61, were randomly selected out of a pool of 82,979 unrelated individuals for allele characterization. Out of nine different B*40 alleles identified in this study, B*4001 and B*4002 were the two most frequent B*40 alleles in all the population groups. B*4001 was the primary B*40 allele seen in Caucasians (83%) and African Americans (76%), while B*4002 was found in the majority of Hispanics (62%). The distributions of both alleles were comparable in the Asian/Pacific Islander population. These two alleles were the only B*40 alleles detected in Caucasians while four to five additional B*40 alleles were seen in the other population groups. The other B*40 alleles detected in this study included: B*4003 and B*4010 in Asian/Pacific Islanders; B*4012 and B*4016 in African Americans; and B*4004, B*4006, and B*4027 in Hispanics. Analysis revealed significant differences between Hispanics and all other groups as well as between African Americans and Asian/Pacific Islanders. This report also describes five novel B*40 alleles: B*4019, B*4020, B*4024, B*4027, and B*4028.

Genetic polymorphisms in warfarin and tacrolimus-related genes VKORC1, CYP2C9 and CYP3A5 in the Greek-Cypriot population

PubMed Central

2014-01-01

Background Two variants in the gene encoding the cytochrome P450 2C9 enzyme (CYP2C9) are considered the most significant genetic risk factors associated with bleeding after warfarin prescription. A variant in the vitamin K epoxide reductase (VKORC1) has been also associated by several studies with warfarin response. Another variant in the P450 3A5 enzyme (CYP3A5) gene is known to affect the metabolism of many drugs, including tacrolimus. Findings We conducted a population genetic study in 148 unrelated healthy Greek-Cypriot volunteers (through PCR-RFLP assays), in order to determine the frequencies of the above pharmacogenetics variants and to compare allele frequencies with those in other major ethnic groups. The allele frequencies of CYP2C9*2, CYP2C9*3 and CYP3A5*3 were found to be 0.162, 0.112 and 0.943 respectively, whereas VKORC1 - 1639A was 0.534. The latter frequency differs significantly when compared with Caucasians, Asians and Africans (p < 0.001) and is still significant when compared with the geographically and culturally closely related to Greek-Cypriots, Hellenes of Greece (p = 0.01). Interestingly ~18% of our population are carriers of four or three risk alleles regarding warfarin sensitivity, therefore they have a high predisposition for bleeding after taking high or even normal warfarin doses. Conclusions Our data show no significant difference in the frequency of CYP2C9 and CYP3A5 allelic variants when compared to the Caucasian population, but differ significantly when compared with Africans and Asians (p < 0.001). Also, the frequency of variant VKORC1 - 1639A differs between Greek-Cypriots and every other population we compared. Finally, about 1/5 Greek-Cypriots carry three or four risk alleles and ~50% of them carry at least two independent risk alleles regarding warfarin sensitivity, a potentially high risk for over-anticoagulation. PMID:24593903

[Association of methionine synthase reductase gene polymorphism with unexplained recurrent spontaneous abortion].

PubMed

Guo, Qian-nan; Liao, Shi-xiu; Kang, Bing; Zhang, Ju-xin; Wang, Rui-li; Ding, Xue-bing; Zhang, Wei-hua

2012-10-01

To explore the relationship between the polymorphism of methionine synthase reductase (MTRR) A66G and the susceptibility to unexplained repeated spontaneous abortion (URSA). Total of 200 Henan Han couples with URSA (URSA group) and 76 Henan Han healthy couples without URSA (control group) were enrolled in this study. Their MTRR A66G genotypes were determined by PCR restriction fragment length polymorphism (PCR-RFLP). (1) The allele frequencies of MTRR A66G: the frequencies of allele A and allele G in URSA group were 76.5% (153/200) in husband and 72.8% (146/200) in wife, 23.5% (47/200) in husband and 27.2% (54/200) in wife, respectively. The frequencies of allele A and allele G in control group were 78.9% (60/76) in husband and 78.3% (59/76) in wife, 21.1% (16/76) in husband and 21.7% (16/76) in wife, respectively. The frequencies of allele A and allele G were not significantly different between female and male subjects within the same experimental group (P > 0.05), and also there were not significantly different between the same gender subjects at URAS and control groups (P > 0.05). (2) The genotype frequencies of MTRR A66G: the frequencies of genotype AA, AG and GG in URSA group were 57.0% (114/200) in husband and 52.0% (104/200) in wife, 39.0% (78/200) in husband and 41.5% (83/200) in wife, 4.0% (8/200) in husband and 6.5% (13/200) in wife, prepectively. The frequencies of genotype AA, AG and GG in control group were 59.2% (45/76) in husband and 59.2% (50/76) in wife, 39.5% (30/76) in husband and 38.2% (29/76) in wife; 1.3% (1/76) in husband and 2.6% (2/76) in wife, prepectively. The frequencies of genotype AA, AG and GG were not significantly different between female and male subjects within the same group (P > 0.05), and also there were not significantly different between the same gender subjects at URSA and control groups (P > 0.05).(3)Combined genotype of couples: the combined genotype frequencies of GG + GG, GG + AG, GG + AA, AG + AG, AG + AA and AA + AA in URSA group were 1.0% (2/200), 2.5% (5/200), 6.0% (12/200), 20.0% (40/200), 38.0% (76/200), and 32.5% (65/200), prepectively; the combined genotype frequencies in control group were 0, 1.3% (1/76), 2.6% (2/76), 17.1% (13/76), 42.1% (32/76), 36.8% (28/76), prepectively. The combined genotype analysis between the two groups were also not significantly different (P > 0.05). The polymorphism of MTRR A66G gene was not associated with the susceptibility to URSA (P > 0.05), and so it was not the inherited genetic risk factor of URSA.

[Genetic aspects of species structure of the compost worm Eisenia foetida (Sav.) (Oligochaeta, Lumbricidae)].

PubMed

Bolotetskiĭ, N M; Kodolova, O P

2002-01-01

Distribution of frequencies alleles of polymorphous loci of peroxidase (Pox), leucineaminopeptidase (Lap), phosphoglucomutase (Pgm) and octanoldehydrogenase (Odh) were studied by electrophoresis in polyacrylamide gel in 22 local samples of Esenia foetida in Russia (European part), Ukraine, Kazakhstan and Kirghizia. The samples form two spatial groups--"northern" and "southern", distinguished by set of alleles in every studied locus. The "northern" groups is formed by local populations of European Russia from Murmansk region on the north to Smolensk region on the south, and also by cultivated population of selection line "red California hybrid". The "southern" group is formed by local populations on the territory of Russia from middle Volga to the North Caucasus, Ukraine, Kazakhstan, Kirghizia, cultivated populations from Kirghizia and Portugal. High degree of genetic difference between samples and independence of alleles frequencies distribution from geographical location and habitat allows to consider almost all studied groups as separate populations. Statistical processing of Nei genetic distances (Nei, 1972) revealed reliable differences between averages of within- and intergroup distances. Besides, discrete differences between intervals of significance of genetic distances were revealed. The results indicate that on the studied territory E. foetida has hierarchical two level structure. The first level is formed by local populations differed by frequency of the same alleles. The second level is formed by local populations, united into spatial groups, that are qualitatively distinguished by the set of alleles in the same loci.

Detection of Allelic Frequency Differences between the Sexes in Humans: A Signature of Sexually Antagonistic Selection.

PubMed

Lucotte, Elise A; Laurent, Romain; Heyer, Evelyne; Ségurel, Laure; Toupance, Bruno

2016-06-02

Sexually antagonistic (SA) selection, a form of selection that can occur when both sexes have different fitness optima for a trait, is a major force shaping the evolution of organisms. A seminal model developed by Rice (Rice WR. 1984. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38:735-742.) predicts that the X chromosome should be a hotspot for the accumulation of loci under SA selection as compared with the autosomes. Here, we propose a methodological framework designed to detect a specific signature of SA selection on viability, differences in allelic frequencies between the sexes. Applying this method on genome-wide single nucleotide polymorphism (SNP) data in human populations where no sex-specific population stratification could be detected, we show that there are overall significantly more SNPs exhibiting differences in allelic frequencies between the sexes on the X chromosome as compared with autosomes, supporting the predictions of Rice's model. This pattern is consistent across populations and is robust to correction for potential biases such as differences in linkage disequilibrium, sample size, and genotyping errors between chromosomes. Although SA selection is not the only factor resulting in allelic frequency differences between the sexes, we further show that at least part of the identified X-linked loci is caused by such a sex-specific processes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Association of polymorphisms G(-174)C in IL-6 gene and G(-1082)A in IL-10 gene with traditional cardiovascular risk factors in patients with coronary artery disease.

PubMed

Elsaid, Afaf; Abdel-Aziz, A F; Elmougy, Rehab; Elwaseef, A M

2014-08-01

Interleukin-6 (IL-6) polymorphism has been associated with the genetic susceptibility to coronary artery disease (CAD) and also with the lipid profile in different populations. The present work aimed at studying the association, if any between the IL-6 (174) G/C and IL-10 (1082) G/A genes with hypertension or hyperlipidimia in Egyptian patients with CAD and the association of the IL-6 -174 G/C polymorphism with serum IL-6 levels. 108 Egyptian patients with CAD and 143 unrelated healthy subjects were included in the study. The different genotypes of IL-6 and IL-10 were detected by polymerase chain reaction. Serum levels of lipoprotein(a) [Lp(a)] and IL-6 were estimated in the patients, as well as in the healthy subjects. Increased frequency of G allele, GG and GC genotypes in IL-6, as well as decreased frequency of C allele and CC genotype were found in CAD patients, compared to healthy subjects [P = < 0.0001, OR = 3.95, 95% CI (2.16-7.22) for GG and GC vs CC genotype], [P = < 0.0001, OR = 3.44, 95% CI (2.26-5.23) for G allele]. There was an increased frequency of G allele vs A allele in IL-10 genotype in CAD patients, compared to healthy subjects [P = 0.005, OR = 1.866, 95% CI (1.2-2.9]. Higher levels of both Lp(a) and IL-6 were observed in CAD patients, compared to control subjects (P = 0.0012, P = 0.0346, respectively). Increased frequency of IL-6 -174 G-allele was implicated in a greater cardiovascular risk and the presence of G allele or homozygosity for G allele of IL-10 G/A (1082) was associated with an increased prevalence of CAD. The GC genotype and G allele in IL-6 had significant correlation with hyperlipidimic CAD patients; however, G allele in IL-6 and IL-10 showed significant association with hypertension. Thus, G allele in IL-6 and IL-10 was considered as an independent risk factor in hypertensive CAD patients.

Association between anal sac gland carcinoma and dog leukocyte antigen-DQB1 in the English Cocker Spaniel.

PubMed

Aguirre-Hernández, J; Polton, G; Kennedy, L J; Sargan, D R

2010-12-01

Anal sac gland carcinomas occur frequently in English Cocker Spaniels and, to a lesser extent, in other spaniel breeds. The disease typically presents in dogs aged 8 years or older and frequently metastasises to the local lymph nodes. The association between anal sac gland carcinoma in English Cocker Spaniels and the major histocompatibility complex class II loci (the dog leukocyte antigen loci DLA-DRB1, -DQA1, -DQB1) was investigated in 42 cases and 75 controls. Based on a corrected error rate of 0.017 for each test, the allele distribution in DLA-DRB1 showed no significant difference between cases and controls (P value = 0.019), while a significant difference was obtained for DLA-DQA1 and -DQB1 alleles (P values are 0.010 and 3.3 × 10⁻⁵). The DLA-DQB1*00701 allele was the most common in both cases and controls, but it had a higher frequency among the former (0.89) than in the latter (0.61), while the second most common allele had a higher frequency in the controls (0.23) than in the cases (0.07). Haplotype distributions were also significantly different between the two groups (P value = 1.61 × 10⁻⁴). This is the second disease in English Cocker Spaniels for which the most common DLA-DQB1 allele in the breed has been shown to have a higher frequency in cases than controls, while the second most common allele in the breed (*02001) has a significantly higher frequency in the controls, compared with the cases. © 2010 John Wiley & Sons A/S.

Apolipoprotein E type epsilon4 allele, heritability and age at onset in twins with Alzheimer disease and vascular dementia.

PubMed

Bergem, A L; Lannfelt, L

1997-11-01

The apolipoprotein E (APOE) epsilon4 allele is a risk factor in Alzheimer disease (AD), but not in vascular dementia (VaD). We have investigated whether the epsilon4 allele is more common in twin pairs concordant for AD, compared with those discordant for AD, and whether the epsilon4 allele is more common in AD twins than in VaD twins. In addition, we have investigated the relationship of the epsilon4 allele and the age at onset in AD and VaD. APOE genotype was analysed in 29 senile demented twin pairs. The epsilon4 allele was associated with AD and not with VaD. However, there was no difference in the frequency of the APOE epsilon4 allele in concordant (33.3%) and discordant (31.3%) AD dizygotic twin pairs. Age at onset in AD was significantly lower in epsilon4 homozygotes than in individuals with one or no copies of epsilon4 (62.4 vs. 73.5, p<0.01). In concordant AD twin pairs, the epsilon4 allele frequency was somewhat higher in the twins with earlier onset (41.7% vs. 25%), but the difference was not statistically significant. In the VaD group the age at onset was not significantly different between individuals with or without epsilon4 in their genotypes.

Comparison of oxidative stress and the frequency of polymorphisms in the HFE gene between hemoglobin S trait blood donors and sickle cell disease patients.

PubMed

Viana-Baracioli, L M S; Tukamoto Junior, N C; Ricci Junior, O; Mattos, L C; Ângulo, I L; Bonini-Domingos, C R

2011-12-08

It is well documented that Hb S and iron affect blood cells, and trigger oxidative processes and generation of free radicals with potential for lipid peroxidation. We evaluated the frequency of polymorphisms in the HFE gene in Hb AS blood donors and how these polymorphisms influenced lipid peroxidation and antioxidant capacity. Blood samples were collected from 211 Hb AS blood donors, 119 Hb AA blood donors as a control group, and 28 sickle cell disease patients (Hb SS). The H63D allele was found at a frequency of 10.5% in the Hb AS samples, and the C282Y allele frequency was 0.7%. In the control group, the frequencies of the H63D and C282Y alleles were 13.4 and 2.1%, respectively. In the sickle-cell disease patients, the H63D and the C282Y allele frequencies were 10.7 and 3.5%, respectively. The frequencies of the C282Y and H63D polymorphisms in Hb AS blood donors are similar to those reported for the Brazilian population. Serum malondialdehyde values, indicative of lipid peroxidation, were highest in sickle cell patients, independent of the polymorphisms in the HFE gene, with significant differences, showing the influence of Hb S allele in the levels of lipid peroxidation. However, the trolox equivalent antioxidant capacity average levels, indicative of the antioxidant capacity, were reduced with significant differences, indicating that in spite of a lipid peroxidation raise, this is not followed by the increased of the antioxidant capacity, leading to oxidative stress.

Temporal Stability of Genetic Variability and Differentiation in the Three-Spined Stickleback (Gasterosteus aculeatus)

PubMed Central

DeFaveri, Jacquelin; Merilä, Juha

2015-01-01

Temporal variation in allele frequencies, whether caused by deterministic or stochastic forces, can inform us about interesting demographic and evolutionary phenomena occurring in wild populations. In spite of the continued surge of interest in the genetics of three-spined stickleback (Gasterosteus aculeatus) populations, little attention has been paid towards the temporal stability of allele frequency distributions, and whether there are consistent differences in effective size (Ne) of local populations. We investigated temporal stability of genetic variability and differentiation in 15 microsatellite loci within and among eight collection sites of varying habitat type, surveyed twice over a six-year time period. In addition, Nes were estimated with the expectation that they would be lowest in isolated ponds, intermediate in larger lakes and largest in open marine sites. In spite of the marked differences in genetic variability and differentiation among the study sites, the temporal differences in allele frequencies, as well as measures of genetic diversity and differentiation, were negligible. Accordingly, the Ne estimates were temporally stable, but tended to be lower in ponds than in lake or marine habitats. Hence, we conclude that allele frequencies in putatively neutral markers in three-spined sticklebacks seem to be temporally stable – at least over periods of few generations – across a wide range of habitat types differing markedly in levels of genetic variability, effective population size and gene flow. PMID:25853707

Temporal stability of genetic variability and differentiation in the three-spined stickleback (Gasterosteus aculeatus).

PubMed

DeFaveri, Jacquelin; Merilä, Juha

2015-01-01

Temporal variation in allele frequencies, whether caused by deterministic or stochastic forces, can inform us about interesting demographic and evolutionary phenomena occurring in wild populations. In spite of the continued surge of interest in the genetics of three-spined stickleback (Gasterosteus aculeatus) populations, little attention has been paid towards the temporal stability of allele frequency distributions, and whether there are consistent differences in effective size (Ne) of local populations. We investigated temporal stability of genetic variability and differentiation in 15 microsatellite loci within and among eight collection sites of varying habitat type, surveyed twice over a six-year time period. In addition, Nes were estimated with the expectation that they would be lowest in isolated ponds, intermediate in larger lakes and largest in open marine sites. In spite of the marked differences in genetic variability and differentiation among the study sites, the temporal differences in allele frequencies, as well as measures of genetic diversity and differentiation, were negligible. Accordingly, the Ne estimates were temporally stable, but tended to be lower in ponds than in lake or marine habitats. Hence, we conclude that allele frequencies in putatively neutral markers in three-spined sticklebacks seem to be temporally stable - at least over periods of few generations - across a wide range of habitat types differing markedly in levels of genetic variability, effective population size and gene flow.

A search for association between schizophrenia and dopamine-related alleles.

PubMed

Jönsson, E; Brené, S; Geijer, T; Terenius, L; Tylec, A; Persson, M L; Sedvall, G

1996-01-01

Dopamine receptor dysfunction and altered tyrosine hydroxylase activity have both been implicated in the pathophysiology of schizophrenia. Schizophrenic patients and control subjects were examined for allele frequencies in the tyrosine hydroxylase and dopamine D2 and D4 receptor genes. No significant differences of allele or genotype frequencies were found between the two groups after adjustment for multiple comparisons. Neither were any significant relationships observed between allele frequencies and a number of clinical variables within the schizophrenic subsample. When no adjustment was made for multiple testing a few significant tendencies were obtained which warrant further research in extended patient and control materials. The results are compatible with the view that the tyrosine hydroxylase, dopamine receptor D2 and D4 gene polymorphisms examined are not of major importance in the aetiology or pathophysiology of schizophrenia.

The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease

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

Yu, Chang-En; Nemens, E.; Olson, J.M.

1994-04-01

The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset <60 years), and late-onset families. A genetic association was observed between apolipoprotein E (ApoE) allele E4 and FAD in late-onset families; the E4 allele frequency was .51 in affected subjects, .37 in at-risk subjects, .11 in spouses, and .19 in unrelated controls. The differences between the E4 frequencies in affected subjects versus controls and in at-risk subjects versus controls were highly significant. No association betweenmore » the E4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between E4 and AD was also observed in a group of unrelated subjects; the E4 frequency was .26 in affected subjects, versus .19 in controls (Z[sub SND] = 2.20, P < .03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained. For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls or allele frequencies from the families were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased. For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree-member analysis gave significant results for the late-onset kindreds, for ApoE, when control allele frequencies were used but not when allele frequencies were derived from the families. 58 refs., 6 tabs.« less

REVIEW-ARTICLE Intermediate alleles of Huntington's disease HTT gene in different populations worldwide: a systematic review.

PubMed

Apolinário, T A; Paiva, C L A; Agostinho, L A

2017-04-05

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). The considered normal alleles have less than 27 CAG repeats. Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. The IAs apparently have shown a normal phenotype. However, there are some reported associations between individuals that bear an IA and clinical HD signs, such as behavioral disturbs. The association of IAs with the presence of clinical signs gives clinical relevance to these patients. We emphasized the importance of determining the frequency of IA alleles in the general population as well as in HD families. Therefore, the aim of this study was to conduct a systematic review, in order to investigate the frequency of IAs in the overall chromosomes of different ethnic groups and of families with HD history worldwide as well as the frequency of individuals who bear the intermediate alleles. We searched indexed articles from the following electronic databases: U.S. National Library of Medicine and the National Institutes of Health (PubMed), Pubmed Central (PMC) and Virtual Health Library (VHL). Therefore, 488 articles were obtained and, of these, 33 had been published in more than one database. We accepted the article of only one database and ended up with 455 articles for this review. The frequency of IAs within the chromosomes of the general population ranged from 0.45 to 8.7% and of individuals with family history of HD ranged from 0.05 to 5.1%. The higher frequency of IAs in the general population (8.7%) was found in one Brazilian cohort.

[Distribution of DRD4 and DAT1 alleles from dopaminergic system in a mixed Chilean population].

PubMed

Vieyra, Gonzalo; Moraga, Mauricio; Henríquez, Hugo; Aboitiz, Francisco; Rothhammer, Francisco

2003-02-01

Genes for dopamine receptor DRD4 and dopamine transporter DAT1 are highly polymorphic. Two alleles of these genes, namely the DRD4.7 and the DAT1*9 are frequently associated to the attention deficit disorder with hyperactivity. In Europe, the allele for DRD4 receptor with four repetitions (DRD4.4) has the highest frequency, with a median of 69%, followed by DRD4.7, with a frequency of 15%. South American indigenous populations have higher frequencies for DRD4.7 (61%) than for DRD4.4 (29%). The ten repetition allele for DAT1 transporter has a high frequency among Europeans (72%) and Amerindians (100%). The allele DAT1*9 is the second most frequent allele. To study the frequency of DRD4 and DAT1 alleles in a Chilean population sample. One hundred serum samples were obtained from blood donors in two public hospitals in Santiago. Polymorphic regions for DRD4 and DAT1 were amplified by polymerase chain reaction. The allele DRD4.4 had a frequency of 59% and DRD4.7 a frequency of 27%. The allele DAT1*10 had a frequency of 74%, followed by DAT 1*9, with a frequency of 23%. In a Chilean population sample, the frequency of DRD4 and DAT1 alleles was very similar to that of European populations.

Diversity of HLA-B61 alleles and haplotypes in East Asians and Spanish Gypsies.

PubMed

Ogawa, A; Tokunaga, K; Lin, L; Kashiwase, K; Tanaka, H; Herrero, M J; Vilches, C; Park, M H; Jia, G J; Chimge, N O; Sideltseva, E W; Ishikawa, Y; Akaza, T; Tadokoro, K; Juji, T

1998-04-01

The distribution of HLA-B61 alleles and their association with HLA-C and DRB1 alleles were investigated in six East Asian populations (South Korean, Chinese Korean, Man (Manchu), Northern Han, Mongolian and Buryat) and Spanish Gypsies and compared to our previous report on the Japanese population. The alleles were identified using a group-specific polymerase chain reaction (PCR) and genomic DNA followed by hybridization with sequence-specific oligonucleotide probes (SSOP). Both HLA-B*4002 and B*4006 were commonly detected in the South Korean, Chinese Korean, Man, Northern Han and Japanese populations, while HLA-B*4002 was predominant in the Mongolian and Buryat populations. Strong associations of B*4002 with Cw*0304 and of B*4006 with Cw*0801 were commonly observed in these East Asian populations. In contrast, in Spanish Gypsies, only HLA-B*4006 was found and the allele exhibited a strong association with Cw*1502. HLA-B*4003 was also identified in the South Korean, Chinese Korean, Northern Han, Mongolian and Japanese populations at relatively low frequencies, and exhibited an association with Cw*0304. Moreover, the association of these B61 alleles with the DRB1 alleles revealed considerable diversity among the different populations. HLA-B*4004 and B*4009 were not observed in these populations. Consequently, the frequencies of the B61 alleles varied among the different East Asian populations, but the individual B61 alleles were carried by specific haplotypes often regardless of the ethnic differences.

Frequency of genetic polymorphisms of PXR gene in the Brazilian population.

PubMed

Moreira, Ricardo P P; Jorge, Alexander A L; Mendonca, Berenice B; Bachega, Tânia A S S

2011-01-01

PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913 C>T and -6994T>C occurred at a higher frequency comparedtothe Africanalleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C>T allele was found at a similar frequency to those described in Caucasians and Africans (p > 0.05). We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians.

Association Study of Klotho Gene Polymorphism With Calcium Oxalate Stones in The Uyghur Population of Xinjiang, China.

PubMed

Ali, Abdusamat; Tursun, Halmurat; Talat, Alim; Abla, Akpar; Muhtar, Erpan; Zhang, Tao; Mahmut, Murat

2017-01-18

The aim of the present study was to investigate the correlation between Klotho gene polymorphisms andcalcium oxalate stones in Xinjiang Uyghur people. We compared 128 patients with calcium oxalate stones (case group) and 94 healthypeople (control group), detected the genotype and allele distributions of single-nucleotide polymorphisms (SNPs)of the Klotho gene (rs3752472, rs650439, and rs1207568) by reverse transcription polymerase chain reaction. The distributions of the genotype and allele frequencies of the SNPs were consistent with the Hardy-Weinberg equilibrium in the two groups. There were statistically significant differences between the genotype andallele distributions of rs3752472 between the case and control groups; the allele frequencies in the case/controlgroups were C = 240 (93.7%)/151 (80.3%) and T = 16 (6.3%)/37 (19.7%). There was no statistically significantdifference in the genotype distribution of rs650439 between the case and control groups, but there was a differencein the allele distribution; the allele frequencies in the case/control groups were A = 202 (78.9%)/143 (57.2%) andT = 54 (21.1%)/107 (42.8%). There were no statistically significant differences in genotype and allele distributionsbetween the case and control groups of rs1207568; the allele frequencies in the case/control groups were C = 194(71.3%)/145 (77.1%) and T = 78 (28.7%)/43 (22.9%). In rs3752472, the risk for patients with the C and A allelesincreased by 3.675 and 2.799 times, respectively. The rs3752472 and rs650439 SNPs are related to the risk of calcium oxalate stones in Xinjiang Uyghurpeople, and might be one of the risk factors.

Geographic distributions of Idh-1 alleles in a cricket are linked to differential enzyme kinetic performance across thermal environments

PubMed Central

Huestis, Diana L; Oppert, Brenda; Marshall, Jeremy L

2009-01-01

Background Geographic clines within species are often interpreted as evidence of adaptation to varying environmental conditions. However, clines can also result from genetic drift, and these competing hypotheses must therefore be tested empirically. The striped ground cricket, Allonemobius socius, is widely-distributed in the eastern United States, and clines have been documented in both life-history traits and genetic alleles. One clinally-distributed locus, isocitrate dehydrogenase (Idh-1), has been shown previously to exhibit significant correlations between allele frequencies and environmental conditions (temperature and rainfall). Further, an empirical study revealed a significant genotype-by-environmental interaction (GxE) between Idh-1 genotype and temperature which affected fitness. Here, we use enzyme kinetics to further explore GxE between Idh-1 genotype and temperature, and test the predictions of kinetic activity expected under drift or selection. Results We found significant GxE between temperature and three enzyme kinetic parameters, providing further evidence that the natural distributions of Idh-1 allele frequencies in A. socius are maintained by natural selection. Differences in enzyme kinetic activity across temperatures also mirror many of the geographic patterns observed in allele frequencies. Conclusion This study further supports the hypothesis that the natural distribution of Idh-1 alleles in A. socius is driven by natural selection on differential enzymatic performance. This example is one of several which clearly document a functional basis for both the maintenance of common alleles and observed clines in allele frequencies, and provides further evidence for the non-neutrality of some allozyme alleles. PMID:19460149

Ancient DNA Investigation of a Medieval German Cemetery Confirms Long-Term Stability of CCR5-Δ32 Allele Frequencies in Central Europe.

PubMed

Bouwman, Abigail; Shved, Natallia; Akgül, Gülfirde; Rühli, Frank; Warinner, Christina

2017-04-01

The CCR5-Δ32 mutation present in European populations is among the most prominently debated cases of recent positive selection in humans. This allele, a 32-bp deletion that renders the T-cell CCR5 receptor nonfunctional, has important epidemiological and public health significance, as homozygous carriers are resistant to several HIV strains. However, although the function of this allele in preventing HIV infection is now well described, its human evolutionary origin is poorly understood. Initial attempts to determine the emergence of the CCR5-Δ32 allele pointed to selection during the 14th-century Black Death pandemic; however, subsequent analyses suggest that the allele rose in frequency more than 5,000 years ago, possibly through drift. Recently, three studies have identified populations predating the 14th century CE that are positive for the CCR5-Δ32 allele, supporting the claim for a more ancient origin. However, these studies also suggest poorly understood regional differences in the recent evolutionary history of the CCR5-Δ32 allele. Here a new hydrolysis-probe-based real-time PCR assay was designed to ascertain CCR5 allele frequency in 53 individuals from a 10th- to 12th-century CE church and convent complex in central Germany that predates outbreaks of the Black Death pandemic. High-confidence genotypes were obtained for 32 individuals, and results show that CCR5-Δ32 allele frequency has remained unchanged in this region of Central Europe over the last millennium, suggesting that there has been no strong positive selective pressure over this time period and confirming a more ancient origin for the allele.

Polymorphisms of alcohol metabolizing enzymes in indigenous Mexican population: unusual high frequency of CYP2E1*c2 allele.

PubMed

Gordillo-Bastidas, Elizabeth; Panduro, Arturo; Gordillo-Bastidas, Daniela; Zepeda-Carrillo, Eloy A; García-Bañuelos, Jesús J; Muñoz-Valle, José F; Bastidas-Ramírez, Blanca E

2010-01-01

Alcohol abuse represents the major identified etiological factor of cirrhosis in México. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out. One hundred and one HUI and 331 MES subjects were studied. Genotype and allele frequency were assessed through polymerase chain reaction-restriction fragment length polymorphism after DNA isolation from peripheral leukocytes. Commercial kits for lipid and hepatic determinations were used. Polymorphic allele distribution in HUI was: 0%ADH1B*2, 0.5%ALDH2*2, 51.5%CYP2E1*c2; in MES: 3.4%ADH1B*2, 0%ALDH2*2, 16.1%CYP2E1*c2. Frequency of ADH1B*2 was statistically (p < 0.001) lower in HUI than MES. CYP2E1*c2 polymorphic allele was significantly higher (p < 0.0001) in HUI than MES. Hepatic profile was normal in both groups. HUI showed a better lipid profile than MES independently of genotype. Huichols exhibited the highest CYP2E1*c2 allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and ALDH2*2 were practically absent. This feature could be useful in the understanding of Mexican population gene composition, alcohol metabolism, and alcoholic liver disease development. However, further association studies are necessary. The heterogeneity of Mexican population was evidenced by the significantly different distribution of CYP2E1*c2 allele observed among different regions of the country. Lipid and hepatic values were not associated to genotype. This report constitutes the first study dealing with gene polymorphisms of alcohol metabolizing enzymes conducted in HUI.

Association of the HLA-B*52 allele with non-progression to AIDS in Brazilian HIV-1-infected individuals.

PubMed

Teixeira, S L M; de Sá, N B R; Campos, D P; Coelho, A B; Guimarães, M L; Leite, T C N F; Veloso, V G; Morgado, M G

2014-04-01

Several human leukocyte antigen (HLA) class I alleles are associated with the susceptibility to human immunodeficiency virus-1 (HIV-1) infection and/or AIDS progression. Of these, the HLA-B alleles are considered the strongest genetic determinant of disease outcome. We evaluated the influence of the HLA-B alleles on AIDS progression among HIV-1-positive individuals from Rio de Janeiro, Brazil, who were categorized as rapid progressors (RPs), typical progressors (TPs) or long-term non-progressors (LTNPs). In this study, significant differences in HLA-B allele frequencies were observed among the three progression groups for the B*48, B*49 and B*52 alleles. After controlling for other factors associated with AIDS progression, the presence of the B*52 allele was shown to be a significant protective factor (hazard ratio (HR) 0.49 (95% confidence interval (CI) 0.27-0.90) P<0.03). Although no direct association was observed between the presence of the B*27 or B*57 allele and the LTNP profile compared with the TP or RP groups, the adjusted model confirmed that these alleles are protective factors against AIDS progression (HR 0.62 (95% CI 0.38-0.99) P<0.05), as previously described. These data corroborate the existence of significant differences in HLA-B allele frequencies among the distinct AIDS progression profiles and further elucidate the role of HLA alleles in the outcome of HIV infections in diverse populations.

Frequency analysis of the delta32ccr5 HIV resistance allele in a medieval plague mass grave.

PubMed

Kremeyer, Barbara; Hummel, Susanne; Herrmann, Bernd

2005-03-01

The 32 basepair deletion in the gene for the human chemokine receptor CCR5 (delta32ccr5) conferring resistance against HIV-1 infection is present in Caucasian populations. The mutant allele is believed to have originated by a single mutational event in historic times and to have reached its present population frequency of an average 10 % in Europe through selective pressure by a pathogenic agent. Because of their great impact on European populations, the medieval Plague epidemics have been considered as a possible candidate. To test this hypothesis, we studied the delta32ccr5-frequency in 35 individuals from a mass grave containing victims of the 14th century Plague pandemic in Lübeck, Northern Germany, and compared them to the frequency in a control group from the same burial site, dating from the time before the first Plague pandemic. If the delta32ccr5 allele conferred an at least partial resistance against the medieval Plague, its frequency would be expected to be lower in those that died in the pandemic, than it was in the local population before the arrival of the Plague. The CCR5 locus could be typed successfully for 14 Plague victims and for 20 individuals from the medieval control group. We found a delta32ccr5 allelic frequency of 14.2% and 12.5%, respectively. The difference between these figures is not statistically significant. Furthermore, they are comparable to the delta32ccr5 frequency for nowadays Northern Europe. We therefore conclude that the medieval Plague pandemic has not contributed to an increase in the allelic frequency of the mutant delta32ccr5 allele and that, if there has been a positive selection of this allele, it is likely to have occurred before the 14th century and thus before the arrival of the Plague in Europe.

Allele frequency and genotype distribution of polymorphisms within disease-related genes is influenced by ethnic population sub-structuring in Sudan.

PubMed

Bereir, R E H; Mohamed, H S; Seielstad, M; El Hassani, A M; Khalil, E A G; Peacock, C S; Blackwell, J M; Ibrahim, M E

2003-09-01

Four single nucleotide polymorphisms (SNPs) and a variable number of tandem repeats (VNTR) polymorphism located within disease associated/causing genes were typed in four populations of different tribal and ethnic affiliation from the Sudan. The genotype and allele frequencies were compared with those of other groups from published and unpublished data of world populations. The combined Sudanese sample conformed with Hardy-Weinberg equilibrium (HWE) expectation. However, population sub-structuring according to ethnic/linguistic group indicated at least two SNPs in departure from HWE. Differences in allele frequencies and genotype distribution between groups was also noted in three of the four SNPs. The other loci were distributed homogeneously within the populations studied with genotype frequencies in agreement with HWE expectation. These results highlight the importance of inter-population stratification for polymorphic markers, as well as the potential influence of evolutionary history and ethnic variation of loci, in the general distribution of SNPs and other polymorphisms.

Transethnic differences in GWAS signals: A simulation study.

PubMed

Zanetti, Daniela; Weale, Michael E

2018-05-07

Genome-wide association studies (GWASs) have allowed researchers to identify thousands of single nucleotide polymorphisms (SNPs) and other variants associated with particular complex traits. Previous studies have reported differences in the strength and even the direction of GWAS signals across different populations. These differences could be due to a combination of (1) lack of power, (2) allele frequency differences, (3) linkage disequilibrium (LD) differences, and (4) true differences in causal variant effect sizes. To determine whether properties (1)-(3) on their own might be sufficient to explain the patterns previously noted in strong GWAS signals, we simulated case-control data of European, Asian and African ancestry, applying realistic allele frequencies and LD from 1000 Genomes data but enforcing equal causal effect sizes across populations. Much of the observed differences in strong GWAS signals could indeed be accounted for by allele frequency and LD differences, enhanced by the Euro-centric SNP bias and lower SNP coverage found in older GWAS panels. While we cannot rule out a role for true transethnic effect size differences, our results suggest that strong causal effects may be largely shared among human populations, motivating the use of transethnic data for fine-mapping. © 2018 John Wiley & Sons Ltd/University College London.

Y-STR INRA189 polymorphisms in Chinese yak breeds.

PubMed

Ma, Z J; Chen, S M; Sun, Y G; Xi, Y L; Li, R Z; Xu, J T; Lei, C Z

2015-12-29

To further explore Y-STR INRA189 polymorphisms in the yak, and to determine the genetic differences among yak breeds, genotyping analysis of INRA189 in 102 male yak individuals from three yak breeds in Qinghai Province of China was performed. Genotyping revealed the presence of four alleles, with sizes of 149, 155, 157, and 159 bp, respectively. Of these, the 157-bp allele, which was found with the highest frequency in the three yak breeds, was the dominant allele. Interestingly, the 149-bp allele was only detected in the Gaoyuan breed, and the 159-bp allele was only found in the Huanhu and Datong breeds. Only the 157- and 155-bp alleles were found in all three yak breeds. Taking the three yak breeds as a single population, the frequency of these four alleles was 0.0294, 0.0686, 0.8628, and 0.0392, respectively. The average polymorphism information content in the three yak breeds was 0.2379, indicating that the INRA189 was a low polymorphic Y-STR marker in yak.

Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS).

PubMed

Rajender, Singh; Carlus, Silas Justin; Bansal, Sandeep Kumar; Negi, Mahendra Pal Singh; Negi, Mahendra Pratap Singh; Sadasivam, Nirmala; Sadasivam, Muthusamy Narayanan; Thangaraj, Kumarasamy

2013-01-01

Polycystic ovarian syndrome (PCOS) refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR) CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk. CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003) inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls. CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43) repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29) repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles) did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles) showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2) = 4.41; P = 0.036), which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short/extreme-sized alleles in the cases may be a chance finding without any true association with PCOS risk.

Vascular endothelial growth factor-A gene polymorphism is associated with congenital renal lesions in children with urinary tract infections.

PubMed

Bimpaki, Eirini; Bitsori, Maria; Choulaki, Christiana; Galanakis, Emmanouil

2017-08-01

This study investigated the relationship between vascular endothelial growth factor-A (VEGF-A)-460C/T functional gene polymorphism and renal parenchymal lesions, vesicoureteral reflux and other urinary tract abnormalities in children with a urinary tract infection (UTI). VEGF-A-460C/T gene polymorphism was investigated with restriction length polymorphism analysis in 76 children with their first UTI and in 63 controls without infections. Genotype and allele frequencies were compared between children with UTIs and controls and between different groups with UTIs. The VEGF-A-460C/T genotype frequencies differed significantly between those with and without renal parenchymal lesions in the UTI cohort. Allele C homozygosity was significantly more common in those with renal parenchymal lesions (36.6% versus 8.7%, p = 0.007). A separate analysis showed that allele C was associated with lesions compatible with hypodysplasia, rather than with focal ones associated with infections, with an odds ratio of 11.55 and 95% confidence interval of 3.03-43.9 (p = 0.0001). No significant differences in genotypes or allele frequencies were found between children with and without reflux or other urinary tract anomalies. In children with UTIs, C allele polymorphism of the VEGF-A gene was associated with hypodysplastic renal parenchymal lesions, which were possibly congenital and existed before the infection. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Association of STin2 Variable Number of Tandem Repeat (VNTR) Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects

PubMed Central

Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Peng, Dangwei; Liang, Chaozhao

2016-01-01

Background The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). Material/Methods We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. Results The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31–0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. Conclusions Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers. PMID:27713390

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

PubMed

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

2013-12-01

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

Glypican-4 gene polymorphism (rs1048369) and susceptibility to Epstein-Barr virus-associated and -negative gastric carcinoma.

PubMed

Zhao, Danrui; Liu, Shuzhen; Sun, Lingling; Zhao, Zhenzhen; Liu, Song; Kuang, Xiaojing; Shu, Jun; Luo, Bing

2016-07-15

Gastric cancer (GC) is one of the most common malignant tumors in China and single nucleotide polymorphisms (SNPs) have been found to be highly related to GC carcinogenesis. Glypican-4 (GPC4), a member of the heparan sulphate proteoglycan family, plays an important role in the regulation of cell growth and differentiation. However, little is known about polymorphisms of GPC4 gene and their associated susceptibility to GC, especially to Epstein-Barr virus-associated GC (EBVaGC). Here we studied the GPC4 polymorphism (rs1048369) in GC individuals, especially those with EBVaGC, and we explored an association between the GPC4 gene polymorphism (rs1048369) and susceptibility to EBVaGC and Epstein-Barr virus-negative GC (EBVnGC) in a population from Northern China. The GPC4 gene polymorphism (rs1048369) was detected in 54 cases of EBVaGC and 73 cases of EBVnGC using polymerase chain reaction (PCR). One hundred and seven peripheral blood samples from healthy individuals were also measured as a control group. There were significant differences in both the genotype and allelic frequency of GPC4 gene (rs1048369) between the EBVaGC and EBVnGC patients. Meanwhile, the distribution of genotype and allelic frequency of GPC4 (rs1048369) differed between EBVaGC and control groups. Distribution of the GPC4 genotype also revealed differences between EBVnGC and control groups, no significant differences in the allelic frequency of the GPC4 gene (rs1048369) were observed. The frequency of the T allele in EBVaGC group was significantly higher than that in control and EBVnGC groups. The GPC4 gene polymorphism and the allele of GPC4 are both associated with susceptibility to EBVaGC. The T allele of GPC4 may represent a risk factor for EBVaGC. Copyright © 2016 Elsevier B.V. All rights reserved.

Significant genotype difference in the CYP2E1 PstI polymorphism of indigenous groups in Sabah, Malaysia with Asian and non-Asian populations.

PubMed

Goh, Lucky Poh Wah; Chong, Eric Tzyy Jiann; Chua, Kek Heng; Chuah, Jitt Aun; Lee, Ping-Chin

2014-01-01

CYP2E1 PstI polymorphism G-1259C (rs3813867) genotype distributions vary significantly among different populations and are associated with both diseases, like cancer, and adverse drug effects. To date, there have been limited genotype distributions and allele frequencies of this polymorphism reported in the three major indigenous ethnic groups (KadazanDusun, Bajau, and Rungus) in Sabah, also known as North Borneo. The aim of this study was to investigate the genotype distributions and allele frequencies of the CYP2E1 PstI polymorphism G-1259C in these three major indigenous peoples in Sabah. A total of 640 healthy individuals from the three dominant indigenous groups were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at G-1259C polymorphic site of CYP2E1 gene was performed using the Pst I restriction enzyme. Fragments were analyzed using agarose gel electrophoresis and confirmed by direct sequencing. Overall, the allele frequencies were 90.3% for c1 allele and 9.7% for c2 allele. The genotype frequencies for c1/c1, c1/c2 and c2/c2 were observed as 80.9%, 18.8%, and 0.3%, respectively. A highly statistical significant difference (p<0.001) was observed in the genotype distributions between indigenous groups in Sabah with all Asian and non-Asian populations. However, among these three indigenous groups, there was no statistical significant difference (p>0.001) in their genotype distributions. The three major indigenous ethnic groups in Sabah show unique genotype distributions when compared with other populations. This finding indicates the importance of establishing the genotype distributions of CYP2E1 PstI polymorphism in the indigenous populations.

Allele frequencies for 12 autosomal short tandem repeat loci in two Bolivian populations.

PubMed

Cifuentes, L; Jorquera, H; Acuña, M; Ordóñez, J; Sierra, A L

2008-03-18

Two hundred and sixty unrelated subjects who asked for paternity testing at two Bolivian Laboratories in La Paz and Santa Cruz were studied. The loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, and CSF1PO were typed from blood samples, amplifying DNA by polymerase chain reactions and electrophoresis. Allele frequencies were estimated by simple counting and the unbiased heterozygosity was calculated. Hardy-Weinberg equilibrium was studied and gene frequencies were compared between the two samples. All loci conformed to the Hardy-Weinberg law and allele frequencies were similar in samples from the two cities. The Bolivian gene frequencies estimated were significantly different from those described for Chile and the United States Hispanic-Americans for most of the loci.

Human local adaptation of the TRPM8 cold receptor along a latitudinal cline

PubMed Central

Mundry, Roger; Peter, Benjamin M.; Sekar, Aarthi; D’Amato, Mauro; Dennis, Megan Y.; Andrés, Aida M.

2018-01-01

Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on this question, we exploit the fact that humans are a cosmopolitan species that inhabit territories under a wide range of temperatures. Focusing on cold perception–which is central to thermoregulation and survival in cold environments–we show evidence of recent local adaptation on TRPM8. This gene encodes for a cation channel that is, to date, the only temperature receptor known to mediate an endogenous response to moderate cold. The upstream variant rs10166942 shows extreme population differentiation, with frequencies that range from 5% in Nigeria to 88% in Finland (placing this SNP in the 0.02% tail of the FST empirical distribution). When all populations are jointly analyzed, allele frequencies correlate with latitude and temperature beyond what can be explained by shared ancestry and population substructure. Using a Bayesian approach, we infer that the allele originated and evolved neutrally in Africa, while positive selection raised its frequency to different degrees in Eurasian populations, resulting in allele frequencies that follow a latitudinal cline. We infer strong positive selection, in agreement with ancient DNA showing high frequency of the allele in Europe 3,000 to 8,000 years ago. rs10166942 is important phenotypically because its ancestral allele is protective of migraine. This debilitating disorder varies in prevalence across human populations, with highest prevalence in individuals of European descent–precisely the population with the highest frequency of rs10166942 derived allele. We thus hypothesize that local adaptation on previously neutral standing variation may have contributed to the genetic differences that exist in the prevalence of migraine among human populations today. PMID:29723195

Human local adaptation of the TRPM8 cold receptor along a latitudinal cline.

PubMed

Key, Felix M; Abdul-Aziz, Muslihudeen A; Mundry, Roger; Peter, Benjamin M; Sekar, Aarthi; D'Amato, Mauro; Dennis, Megan Y; Schmidt, Joshua M; Andrés, Aida M

2018-05-01

Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on this question, we exploit the fact that humans are a cosmopolitan species that inhabit territories under a wide range of temperatures. Focusing on cold perception-which is central to thermoregulation and survival in cold environments-we show evidence of recent local adaptation on TRPM8. This gene encodes for a cation channel that is, to date, the only temperature receptor known to mediate an endogenous response to moderate cold. The upstream variant rs10166942 shows extreme population differentiation, with frequencies that range from 5% in Nigeria to 88% in Finland (placing this SNP in the 0.02% tail of the FST empirical distribution). When all populations are jointly analyzed, allele frequencies correlate with latitude and temperature beyond what can be explained by shared ancestry and population substructure. Using a Bayesian approach, we infer that the allele originated and evolved neutrally in Africa, while positive selection raised its frequency to different degrees in Eurasian populations, resulting in allele frequencies that follow a latitudinal cline. We infer strong positive selection, in agreement with ancient DNA showing high frequency of the allele in Europe 3,000 to 8,000 years ago. rs10166942 is important phenotypically because its ancestral allele is protective of migraine. This debilitating disorder varies in prevalence across human populations, with highest prevalence in individuals of European descent-precisely the population with the highest frequency of rs10166942 derived allele. We thus hypothesize that local adaptation on previously neutral standing variation may have contributed to the genetic differences that exist in the prevalence of migraine among human populations today.

Frequencies of apolipoprotein E alleles in depressed patients undergoing hemodialysis--a case-control study.

PubMed

Su, Yan-yan; Zhang, Yun-fang; Yang, Shen; Wang, Jie-lin; Hua, Bao-jun; Luo, Jie; Wang, Qi; Zeng, De-wang; Lin, Yan-qun; Li, Hong-yan

2015-06-01

To explore the relation between the frequencies of apolipoprotein E (ApoE) alleles and the occurrence of depression in patients undergoing hemodialysis in a Chinese population. We examined the ApoE alleles in a sample of 288 subjects: 72 patients with depression under hemodialysis, 74 patients without depression under hemodialysis, 75 patients with depression under nondialytic treatment and 67 patients without depression under nondialytic treatment. The depression state was assessed using the Center for Epidemiological Studies Depression (CES-D) scale. Associations between the occurrence of depression and the frequencies of ApoE alleles were examined using multinomial logistic regression models with adjustment of relevant covariates. Information about sociodemographics, clinical data, vascular risk factors and cognitive function was also collected and evaluated. The frequencies of ApoE-ɛ2 were significantly different between depressed and non-depressed patients irrespective of dialysis (p < 0.05), but no significant difference was found in the frequencies of ApoE-ɛ4 (p > 0.05). Serum ApoE levels were significantly different between depressed and non-depressed patients in the whole sample (p < 0.05). Multinomial logistic regression models showed significant association between the frequency of ApoE-ɛ2 and the occurrence of depression in the Chinese population after control of relevant covariates, including age, sex, educational level, history of smoking and drinking, vascular risk factors and cognitive function. No association between the frequency of ApoE-ɛ4 and the occurrence of depression was found in patients undergoing hemodialysis. Further research is needed to find out if ApoE-ɛ2 acts as a protective factor in Chinese dialysis population since it might decrease the prevalence of depression and delay the onset age.

Correlation between NFATC1 gene polymorphisms and congenital heart disease in children.

PubMed

Li, C-L; Niu, L; Fu, M-Y; Tian, J; Wang, Q-W; An, X-J

2017-08-01

To analyze the links between NFATC1 gene polymorphism and congenital heart disease in children. In the present study, we selected 85 children patients with congenital heart disease who were hospitalized from February 2013 to February 2015 as research subjects (observation group), and 92 healthy subjects as control group. Restriction fragment length polymorphism (RFLP) was used for analysis of NFATC1 gene in samples from each group. The distribution of NFATC1 genotype and allele between the observation group (children with congenital heart disease) and the control group showed no significant difference (p >0.05), but AA, GG genotypes, and allele frequency between pathological samples of children with congenital heart disease and the control group displayed significant difference (p <0.05) (X2 = 16.04, p <0.05; X2 = 16.29, p <0.05). Further analyses showed that AA, GG, AG genotype and allele frequency among children with congenital heart disease in observation group also showed a difference, i.e., homozygote (AA, GG) ratio in children with severe congenital heart disease is relatively high. There is a correlation between NFATC1 genes and the incidence of congenital heart disease in children, and a correlation between different genotypes and allele frequency and the incidence of the disease.

Beta2-adrenergic receptor allele frequencies in the Quechua, a high altitude native population.

PubMed

Rupert, J L; Monsalve, M V; Devine, D V; Hochachka, P W

2000-03-01

The beta2-adrenergic receptor is involved in the control of numerous physiological processes and, as the primary catecholamine receptor in the lungs, is of particular importance in the regulation of pulmonary function. There are several polymorphic loci in the beta2-adrenergic receptor gene that have alleles that alter receptor function, including two (A/G46, G/C79) that increase agonist sensitivity. As such a phenotype may increase vaso and bronchial dilation, thereby facilitating air and blood flow through the lungs, we hypothesized that selection may have favoured these alleles in high altitude populations as part of an adaptive strategy to deal with the hypoxic conditions characteristic of such environments. We tested this hypothesis by determining the allele frequencies for these two polymorphisms, as well one additional missense mutation (C/T491) and two silent mutations (G/A252 and C/A523) in 63 Quechua speaking natives from communities located between 3200 and 4200 m on the Peruvian altiplano. These frequencies were compared with those of two lowland populations, one native American (Na-Dene from the west coast of Canada) and one Caucasian of Western European descent. The Quechua manifest many of the pulmonary characteristics of high altitude populations and differences in allele frequencies between the Quechua and lowlanders could be indicative of a selective advantage conferred by certain genotypes in high altitude environments. Allele frequencies varied between populations at some loci and patterns of linkage disequilibrium differed between the old-world and new-world samples; however, as these populations are not closely related, significant variation would be expected due to stochastic effects alone. Neither of the alleles associated with increased receptor sensitivity (A46, G79) was significantly over-represented in the Quechua compared with either lowland group. The Quechua were monomorphic for the C allele at base 79. This variant has been associated with body mass index; however no clearly defined metabolic phenotype has been established. In addition, we sequenced the coding region of the gene in three unrelated Quechua to determine if there were any other polymorphisms common in this population. None were detected.

Patterns of gene variation in central and marginal populations of Drosophila robusta.

PubMed

Prakash, S

1973-10-01

The central and marginal populations of D. robusta differ greatly in the level of inversion polymorphism; the marginal populations are monomorphic or nearly so and the central populations are highly polymorphic. This paper presents the frequencies of alleles at forty gene loci in various populations of D. robusta, studied by electrophoresis of proteins and enzymes. Population samples were obtained from eight widely separated populations of D. robusta which included the central, the extreme marginal and the intervening populations between the center and the margins. We find that the proportion of polymorphic loci and average heterozygosity per individual is slightly higher in the marginal populations than the central populations. In D. robusta on an average, 39% of the loci are polymorphic and the average proportion of loci heterozygous per individual is 11%. A breakdown of loci in three categories, viz, hydrolytic enzymes and some other enzymes, larval proteins and glycolytic and Kreb's cycle enzymes, shows that in all populations the level of polymorphism is highest in the hydrolytic enzymes, intermediate in larval proteins and least in the glycolytic and Kreb's cycle enzymes. On the average, the proportion of loci heterozygous per individual for three groups of loci is: hydrolytic enzymes and others (.164), larval proteins (.115) and glycolytic and Kreb's cycle enzymes (.037). We also observe that in all populations the level of polymorphism on the X chromosome is far less than the expected 38%; in salivary gland cells the euchromatic length of the X chromosome is 38% of the entire genome. Lower levels of polymorphism for the X chromosome loci are explained due to low probability of balanced polymorphisms for the X-linked loci since the conditions for establishment of balanced polymorphism for X-linked loci are more restrictive than for the autosomal loci.-The polymorphic loci can be grouped according to pattern of allele frequencies in different populations as follows: (1) The allele frequencies are similar in all populations at the XDH, Pep-1 and Hex-1 loci. (2) The alleles at the Est-1, Est-2, Amy loci and the AP-4(1.0) and the LAP-1(.90) alleles show north south clinal change in frequency. (3) There is north south and east west differentiation at the Pt-5, Pt-8 and Pt-9 loci and the allele AP-4(.81). (4) Polymorphism at loci such as Fum, B.Ox, Hex-8, Pep-2 and Pep-3 are restricted to only one or two of the populations. (5) Allele frequencies at the MDH and ODH loci fluctuate between populations. (6) Allele frequencies at many polymorphic loci such as Est-1, Est-2, LAP-1, AP-4, Pt-5, Pt-8, Pt-9, Pt-16, MDH, Fum change clinally within a gene arrangement. The pattern of gene variation in D. robusta is very complex and cannot be easily explained due to migration of neutral alleles between once-isolated populations or to semi-isolation of neutral alleles. The observations of the pattern of allele variation in different populations, high levels of polymorphism in the marginal populations which have small population size and low levels of polymorphism of the X chromosome loci all support the argument in favor of balancing selection as the main mechanism for the maintenance of these polymorphisms. Environmental factors must play a role in the maintenance of a great deal of these polymorphisms, since we observe clinal allele frequency changes even within a given inversion type.

Patterns of Gene Variation in Central and Marginal Populations of DROSOPHILA ROBUSTA

PubMed Central

Prakash, Satya

1973-01-01

The central and marginal populations of D. robusta differ greatly in the level of inversion polymorphism; the marginal populations are monomorphic or nearly so and the central populations are highly polymorphic. This paper presents the frequencies of alleles at forty gene loci in various populations of D. robusta, studied by electrophoresis of proteins and enzymes. Population samples were obtained from eight widely separated populations of D. robusta which included the central, the extreme marginal and the intervening populations between the center and the margins. We find that the proportion of polymorphic loci and average heterozygosity per individual is slightly higher in the marginal populations than the central populations. In D. robusta on an average, 39% of the loci are polymorphic and the average proportion of loci heterozygous per individual is 11%. A breakdown of loci in three categories, viz, hydrolytic enzymes and some other enzymes, larval proteins and glycolytic and Kreb's cycle enzymes, shows that in all populations the level of polymorphism is highest in the hydrolytic enzymes, intermediate in larval proteins and least in the glycolytic and Kreb's cycle enzymes. On the average, the proportion of loci heterozygous per individual for three groups of loci is: hydrolytic enzymes and others (.164), larval proteins (.115) and glycolytic and Kreb's cycle enzymes (.037). We also observe that in all populations the level of polymorphism on the X chromosome is far less than the expected 38%; in salivary gland cells the euchromatic length of the X chromosome is 38% of the entire genome. Lower levels of polymorphism for the X chromosome loci are explained due to low probability of balanced polymorphisms for the X-linked loci since the conditions for establishment of balanced polymorphism for X-linked loci are more restrictive than for the autosomal loci.—The polymorphic loci can be grouped according to pattern of allele frequencies in different populations as follows: (1) The allele frequencies are similar in all populations at the XDH, Pep-1 and Hex-1 loci. (2) The alleles at the Est-1, Est-2, Amy loci and the AP-41.0 and the LAP-1.90 alleles show north south clinal change in frequency. (3) There is north south and east west differentiation at the Pt-5, Pt-8 and Pt-9 loci and the allele AP-4.81. (4) Polymorphism at loci such as Fum, B.Ox, Hex-8, Pep-2 and Pep-3 are restricted to only one or two of the populations. (5) Allele frequencies at the MDH and ODH loci fluctuate between populations. (6) Allele frequencies at many polymorphic loci such as Est-1, Est-2, LAP-1, AP-4, Pt-5, Pt-8, Pt-9, Pt-16, MDH, Fum change clinally within a gene arrangement. The pattern of gene variation in D. robusta is very complex and cannot be easily explained due to migration of neutral alleles between once-isolated populations or to semi-isolation of neutral alleles. The observations of the pattern of allele variation in different populations, high levels of polymorphism in the marginal populations which have small population size and low levels of polymorphism of the X chromosome loci all support the argument in favor of balancing selection as the main mechanism for the maintenance of these polymorphisms. Environmental factors must play a role in the maintenance of a great deal of these polymorphisms, since we observe clinal allele frequency changes even within a given inversion type. PMID:4203580

Social causes of correlational selection and the resolution of a heritable throat color polymorphism in a lizard.

PubMed

Sinervo, B; Bleay, C; Adamopoulou, C

2001-10-01

When selection acts on social or behavioral traits, the fitness of an individual depends on the phenotypes of its competitors. Here, we describe methods and statistical inference for measuring natural selection in small social groups. We measured selection on throat color alleles that arises from microgeographic variation in allele frequency at natal sites of side-blotched lizards (Uta stansburiana). Previous game-theoretic analysis indicates that two color morphs of female side-blotched lizards are engaged in an offspring quantity-quality game that promotes a density- and frequency-dependent cycle. Orange-throated females are r-strategists. They lay large clutches of small progeny, which have poor survival at high density, but good survival at low density. In contrast, yellow-throated females are K-strategists. They lay small clutches of large progeny, which have good survival at high density. We tested three predictions of the female game: (1) orange progeny should have a fitness advantage at low density; (2) correlational selection acts to couple color alleles and progeny size; and (3) this correlational selection arises from frequency-dependent selection in which large hatchling size confers an advantage, but only when yellow alleles are rare. We also confirmed the heritability of color, and therefore its genetic basis, by producing progeny from controlled matings. A parsimonious cause of the high heritability is that three alleles (o, b, y) segregate as one genetic factor. We review the physiology of color formation to explain the possible genetic architecture of the throat color trait. Heritability of color was nearly additive in our breeding study, allowing us to compute a genotypic value for each individual and thus predict the frequency of progeny alleles released on 116 plots. Rather than study the fitness of individual progeny, we studied how the fitness of their color alleles varied with allele frequency on plots. We confirmed prediction 1: When orange alleles are present in female progeny, they have higher fitness at low density when compared to other alleles. Even though the difference in egg size of the female morphs was small (0.02 g), it led to knife-edged survival effects for their progeny depending on local social context. Selection on hatchling survival was not only dependent on color alleles, but on a fitness interaction between color alleles and hatchling size, which confirmed prediction 2. Sire effects, which are not confounded by maternal phenotype, allowed us to resolve the frequency dependence of correlational selection on egg size and color alleles and thereby confirmed prediction 3. Selection favored large size when yellow sire alleles were rare, but small size when they were common. Correlational selection promotes the formation of a self-reinforcing genetic correlation between the morphs and life-history variation, which causes selection in the next density and frequency cycle to be exacerbated. We discuss general conditions for the evolution of self-reinforcing genetic correlations that arise from social selection associated with frequency-dependent sexual and natural selection.

Distribution of HLA-DQB1 in Czech Patients with Central Hypersomnias.

PubMed

Vrana, Milena; Siffnerova, Vera; Pecherkova, Pavla; Ratajova, Eva; Sonka, Karel

2016-12-01

The aim of our study was to analyze the distribution of HLA-DQB1 in Czech patients with central hypersomnias and differences between diagnostic groups of narcolepsy type 1 (NT1), type 2 (NT2), idiopathic hypersomnia (IH) and no central hypersomnia subjects (no-CH). Statistical analysis of DQB1 genotyping was performed on the cohort of 716 patients (375 men, 341 women) with reported excessive daytime sleepiness. DQB1*06:02 allele was present in 94% of the NT1 patients. The decrease of DQB1*06:03 allele was also confirmed. No other DQB1*06 allele nor any other DQB1 allele group was differently distributed in the NT1. In the cohort of NT2 patients DQB1*06:02 allele was present in 43%. Allele group DQB*05 was detected with a significantly higher frequency in this diagnostic unit. Any differences in presence of DQB1*05 alleles in NT2 patients were not reported so far. The cohort of patients with IH did not show any difference in allele distribution of DQB1 alleles/allele groups comparing to healthy controls. DQB1*06:02 allele was significantly increased in the no hypersomnia group. No other DQB1 allele/allele group had any difference in distribution in patients comparing to healthy controls. The different distribution of DQB1*06:02 and other DQB1 alleles/allele groups was detected in analyzed diagnostic groups. These results indicate that DQB1 contributes to the genetic predisposition to NT1, NT2, IH and no-CH in different manners.

[High frequency of ancestral allele of the TJP1 polymorphism rs2291166 in Mexican population, conformational effect and applications in surgery and medicine].

PubMed

Ramirez-Garcia, Sergio Alberto; Flores-Alvarado, Luis Javier; Topete-González, Luz Rosalba; Charles-Niño, Claudia; Mazariegos-Rubi, Manuel; Dávalos-Rodríguez, Nory Omayra

2016-01-01

TJP1 gene encodes a ZO-1 protein that is required for the recruitment of occludins and claudins in tight junction, and is involved in cell polarisation. It has different variations, the frequency of which has been studied in different populations. In Mexico there are no studies of this gene. These are required because their polymorphisms can be used in studies associated with medicine and surgery. Therefore, the aim of this study was to estimate the frequency of alleles and genotypes of rs2291166 gene polymorphism TJP1 in Mexico Mestizos population, and to estimate the conformational effect of an amino acid change. A total of 473 individuals were included. The rs2291166 polymorphism was identified PASA PCR-7% PAGE, and stained with silver nitrate. The conformational effect of amino acid change was performed in silico, and was carried out with servers ProtPraram Tool and Search Database with Fasta. The most frequent allele in the two populations is the ancestral allele (T). A genotype distribution similar to other populations was found. The polymorphism is in Hardy-Weinberg, p>0.05. Changing aspartate to alanine produced a conformational change. The study reveals a high frequency of the ancestral allele at rs2291166 polymorphism in the Mexican population. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

The Distribution of Genotype and Allelic Frequency of IL28B Gene Polymorphism in Andhra Pradesh, India

PubMed Central

Sivaprasad, Siddapuram; Rao, Padaki Nagaraja; Gupta, Rajesh; Ashwini, Kaitha; Reddy, Duvvuru Nageshwar

2012-01-01

Background The single nucleotide polymorphism (SNP) of IL28B gene on chromosome 19, encoding for the interferon (IFN)-λ-3 is strongly associated with treatment response to pegylated-IFN and ribavirin in patients infected with different genotypes of hepatitis C virus (HCV). Difference between ethnicity and treatment response rates suggesting a key role of host genetics. The IL28B polymorphism (rs12979860C/T) shows a marked differential distribution between racial groups. Aim The present study is aimed to evaluate genotype and allelic frequency of IL28B gene polymorphism (rs12979860C/T) in Andhra Pradesh, India. Methods A total of 220 healthy controls were recruited for the study. The genotyping of SNP rs12979860C/T on IL28B gene was performed by polymerase chain reaction-direct sequencing method. Result The frequency of CC genotype was found to be significantly (59.09%) higher compared to CT (34.09%) and TT (6.81%) genotypes, respectively. The frequency of major allele C is 0.762 whereas minor allele T is 0.238. Conclusion The higher distribution of genotype ‘CC’ of SNP, rs12979860C/T of IL28B gene in study subjects is suggestive of better response of HCV patients to standard anti-HCV therapy. PMID:25755419

Functional PMS2 Hybrid Alleles Containing a Pseudogene-Specific Missense Variant Trace Back to a Single Ancient Intrachromosomal Recombination Event

PubMed Central

Ganster, Christina; Wernstedt, Annekatrin; Kehrer-Sawatzki, Hildegard; Messiaen, Ludwine; Schmidt, Konrad; Rahner, Nils; Heinimann, Karl; Fonatsch, Christa; Zschocke, Johannes; Wimmer, Katharina

2012-01-01

Sequence exchange between PMS2 and its pseudogene PMS2CL, embedded in an inverted duplication on chromosome 7p22, has been reported to be an ongoing process that leads to functional PMS2 hybrid alleles containing PMS2- and PMS2CL-specific sequence variants at the 5′-and the 3′-end, respectively. The frequency of PMS2 hybrid alleles, their biological significance, and the mechanisms underlying their formation are largely unknown. Here we show that overall hybrid alleles account for one-third of 384 PMS2 alleles analyzed in individuals of different ethnic backgrounds. Depending on the population, 14–60% of hybrid alleles carry PMS2CL-specific sequences in exons 13–15, the remainder only in exon 15. We show that exons 13–15 hybrid alleles, named H1 hybrid alleles, constitute different haplotypes but trace back to a single ancient intrachromosomal recombination event with crossover. Taking advantage of an ancestral sequence variant specific for all H1 alleles we developed a simple gDNA-based polymerase chain reaction (PCR) assay that can be used to identify H1-allele carriers with high sensitivity and specificity (100 and 99%, respectively). Because H1 hybrid alleles harbor missense variant p.N775S of so far unknown functional significance, we assessed the H1-carrier frequency in 164 colorectal cancer patients. So far, we found no indication that the variant plays a major role with regard to cancer susceptibility. PMID:20186689

Functional PMS2 hybrid alleles containing a pseudogene-specific missense variant trace back to a single ancient intrachromosomal recombination event.

PubMed

Ganster, Christina; Wernstedt, Annekatrin; Kehrer-Sawatzki, Hildegard; Messiaen, Ludwine; Schmidt, Konrad; Rahner, Nils; Heinimann, Karl; Fonatsch, Christa; Zschocke, Johannes; Wimmer, Katharina

2010-05-01

Sequence exchange between PMS2 and its pseudogene PMS2CL, embedded in an inverted duplication on chromosome 7p22, has been reported to be an ongoing process that leads to functional PMS2 hybrid alleles containing PMS2- and PMS2CL-specific sequence variants at the 5'-and the 3'-end, respectively. The frequency of PMS2 hybrid alleles, their biological significance, and the mechanisms underlying their formation are largely unknown. Here we show that overall hybrid alleles account for one-third of 384 PMS2 alleles analyzed in individuals of different ethnic backgrounds. Depending on the population, 14-60% of hybrid alleles carry PMS2CL-specific sequences in exons 13-15, the remainder only in exon 15. We show that exons 13-15 hybrid alleles, named H1 hybrid alleles, constitute different haplotypes but trace back to a single ancient intrachromosomal recombination event with crossover. Taking advantage of an ancestral sequence variant specific for all H1 alleles we developed a simple gDNA-based polymerase chain reaction (PCR) assay that can be used to identify H1-allele carriers with high sensitivity and specificity (100 and 99%, respectively). Because H1 hybrid alleles harbor missense variant p.N775S of so far unknown functional significance, we assessed the H1-carrier frequency in 164 colorectal cancer patients. So far, we found no indication that the variant plays a major role with regard to cancer susceptibility. (c) 2010 Wiley-Liss, Inc.

Identification of the sequence variations of 15 autosomal STR loci in a Chinese population.

PubMed

Chen, Wenjing; Cheng, Jianding; Ou, Xueling; Chen, Yong; Tong, Dayue; Sun, Hongyu

2014-01-01

DNA sequence variation including base(s) changes and insertion or deletion in the primer binding region may cause a null allele and, if this changes the length of the amplified fragment out of the allelic ladder, off-ladder (OL) alleles may be detected. In order to provide accurate and reliable DNA evidence for forensic DNA analysis, it is essential to clarify sequence variations in prevalently used STR loci. Suspected null alleles and OL alleles of PlowerPlex16® System from 21,934 unrelated Chinese individuals were verified by alternative systems and sequenced. A total of 17 cases with null alleles were identified, including 12 kinds of point mutations in 16 cases and a 19-base deletion in one case. The total frequency of null alleles was 7.751 × 10(-4). Eight hundred and forty-four OL alleles classified as being of 97 different kinds were observed at 15 STR loci of the PowerPlex®16 system except vWA. All the frequencies of OL alleles were under 0.01. Null alleles should be confirmed by alternative primers and OL alleles should be named appropriately. Particular attention should be paid to sequence variation, since incorrect designation could lead to false conclusions.

[Immunogenetic characteristics of the population of the Transcarpathian region of the UkrSSR ABO system erythrocyte antigen findings].

PubMed

Levaniuk, V F

1977-01-01

The phenotypes with their respective alleles frequencies of the ABO system were studied in 33 230 individuals of 9 ethnic groups of the Transcarpathian Region population. Statistically significant differences in allele frequencies were found in Gypsies, Germans and Slovaks as compared to those in the main Ukrainian population. There are significant differences between Hungarians and Gypsies of the Transcarpathian Region and analogous populations beyond the region. Absence of a reliable difference between gene pools of the Slav groups of the population and of Hungarians may point to the local origin of the later.

Population-specific documentation of pharmacogenomic markers and their allelic frequencies in FINDbase.

PubMed

Georgitsi, Marianthi; Viennas, Emmanouil; Gkantouna, Vassiliki; Christodoulopoulou, Elena; Zagoriti, Zoi; Tafrali, Christina; Ntellos, Fotios; Giannakopoulou, Olga; Boulakou, Athanassia; Vlahopoulou, Panagiota; Kyriacou, Eva; Tsaknakis, John; Tsakalidis, Athanassios; Poulas, Konstantinos; Tzimas, Giannis; Patrinos, George P

2011-01-01

Population and ethnic group-specific allele frequencies of pharmacogenomic markers are poorly documented and not systematically collected in structured data repositories. We developed the Frequency of Inherited Disorders Pharmacogenomics database (FINDbase-PGx), a separate module of the FINDbase, aiming to systematically document pharmacogenomic allele frequencies in various populations and ethnic groups worldwide. We critically collected and curated 214 scientific articles reporting pharmacogenomic markers allele frequencies in various populations and ethnic groups worldwide. Subsequently, in order to host the curated data, support data visualization and data mining, we developed a website application, utilizing Microsoft™ PivotViewer software. Curated allelic frequency data pertaining to 144 pharmacogenomic markers across 14 genes, representing approximately 87,000 individuals from 150 populations worldwide, are currently included in FINDbase-PGx. A user-friendly query interface allows for easy data querying, based on numerous content criteria, such as population, ethnic group, geographical region, gene, drug and rare allele frequency. FINDbase-PGx is a comprehensive database, which, unlike other pharmacogenomic knowledgebases, fulfills the much needed requirement to systematically document pharmacogenomic allelic frequencies in various populations and ethnic groups worldwide.

Impact and quantification of the sources of error in DNA pooling designs.

PubMed

Jawaid, A; Sham, P

2009-01-01

The analysis of genome wide variation offers the possibility of unravelling the genes involved in the pathogenesis of disease. Genome wide association studies are also particularly useful for identifying and validating targets for therapeutic intervention as well as for detecting markers for drug efficacy and side effects. The cost of such large-scale genetic association studies may be reduced substantially by the analysis of pooled DNA from multiple individuals. However, experimental errors inherent in pooling studies lead to a potential increase in the false positive rate and a loss in power compared to individual genotyping. Here we quantify various sources of experimental error using empirical data from typical pooling experiments and corresponding individual genotyping counts using two statistical methods. We provide analytical formulas for calculating these different errors in the absence of complete information, such as replicate pool formation, and for adjusting for the errors in the statistical analysis. We demonstrate that DNA pooling has the potential of estimating allele frequencies accurately, and adjusting the pooled allele frequency estimates for differential allelic amplification considerably improves accuracy. Estimates of the components of error show that differential allelic amplification is the most important contributor to the error variance in absolute allele frequency estimation, followed by allele frequency measurement and pool formation errors. Our results emphasise the importance of minimising experimental errors and obtaining correct error estimates in genetic association studies.

Apolipoprotein B and E genetic polymorphisms in the Cayapa Indians of Ecuador.

PubMed

Scacchi, R; Corbo, R M; Rickards, O; Mantuano, E; Guevara, A; De Stefano, G F

1997-06-01

Three DNA polymorphisms (XbaI, EcoRI, and Ins/Del) of the apolipoprotein B (APOB) gene and the CfoI polymorphism of the APOE gene were investigated in a sample of 96 Cayapa Indians from Ecuador. The frequencies of the X+ (0.182), R+ (1.000), and Del alleles (0.432) at the three APOB sites were found to be higher than and to differ significantly from those reported for East Asians. No comparisons could be made between the Cayapa and other native Americans because of the lack of data on these sites. We observed in our sample that, like native American populations but unlike East Asians, the APOE allele frequencies were characterized by the absence of the APOE*2 allele and by a high frequency of the APOE*4 allele (0.280). Besides a probable drift effect, the high APOE*4 value was tentatively attributed to an effect of selection. Because this allele enhances the absorption of cholesterol by the intestine, it could confer an advantage to carriers in an unfavorable environment (i.e., diet poor in cholesterol).

Benzimidazole resistance in equine cyathostomins in India.

PubMed

Kumar, Sunil; Garg, Rajat; Kumar, Saroj; Banerjee, P S; Ram, Hira; Prasad, A

2016-03-15

Benzimidazole resistance is a major hindrance to the control of equine cyathostominosis throughout the world. There is a paucity of knowledge on the level of benzimidazole resistance in small strongyles of horses in India. In the present study, allele-specific PCR (AS-PCR) that detects F200Y mutation of the isotype 1 β-tubulin gene and faecal egg count reduction test (FECRT) were used for detecting benzimidazole resistance in equine cyathostomin populations in different agro-climatic zones of Uttar Pradesh, India. Results of the FECRT revealed prevalence of benzimidazole resistance in cyathostomins in an intensively managed equine farm in the mid-western plain (FECR=27.5%, LCI=0) and in working horses (extensively managed) at three locations in central plains of Uttar Pradesh (FECR=75.7-83.6%, LCI=29-57%). Post-treatment larval cultures revealed the presence of exclusively cyathostomin larvae. Genotyping of cyathostomin larvae by AS-PCR revealed that the frequency of homozygous resistant (rr) individuals and the resistant allele frequency was significantly higher (p<0.001) in the intensively managed farm in the mid-western plain and in working horses at two locations in central plains of the state. The resistant allele (r) frequency in cyathostomins was significantly higher (p<0.05) in Vindhyan and Tarai and Bhabar zones of Uttar Pradesh. The prevalence of benzimidazole resistant allele (r) was significantly higher (p<0.05) in cyathostomins of intensively managed horses (allelic frequency-0.35) as compared to extensively managed horses (allelic frequency-0.22). The widespread prevalence of benzimidazole resistant alleles in equine cyathostomins in Uttar Pradesh, India, necessitates immediate replacement of the drugs of benzimidazole group with other unrelated effective anthelmintics for management and control of equine cyathostomins. Copyright © 2016 Elsevier B.V. All rights reserved.

Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) - a narrative literature review.

PubMed

Bamm, Vladimir V; Geist, Arielle M; Harauz, George

2017-02-01

We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.

Intracellular population genetics: evidence for random drift of mitochondrial allele frequencies in Saccharomyces cerevisiae and Schizosaccharomyces pombe.

PubMed

Thrailkill, K M; Birky, C W

1980-09-01

We report evidence for random drift of mitochondrial allele frequencies in zygote clones of Saccharomyces cerevisiae and Schizosaccharomyces pombe. Monofactorial and bifactorial crosses were done, using strains resistant or sensitive to erythromycin (alleles Er, Es), oligomycin (Or, Os), or diuron (Dr, Ds). The frequencies of resistant and sensitive cells (and thus the frequencies of the resistant and sensitive alleles) were determined for each of a number of clones of diploid cells arising from individual zygotes. Allele frequencies were extremely variable among these zygote clones; some clones were "uniparental," with mitochondrial alleles from only one parent present. These observations suggest random drift of the allele frequencies in the population of mitochondrial genes within an individual zygote and its diploid progeny. Drift would cease when all the cells in a clone become homoplasmic, due to segregation of the mitochondrial genomes during vegetative cell divisions. To test this, we delayed cell division (and hence segregation) for varying times by starving zygotes in order to give drift more time to operate. As predicted, delaying cell division resulted in an increase in the variance of allele frequencies among the zygote clones and an increase in the proportion of uniparental zygote clones. The changes in form of the allele frequency distributions resembled those seen during random drift in finite Mendelian populations. In bifactorial crosses, genotypes as well as individual alleles were fixed or lost in some zygote clones. However, the mean recombination frequency for a large number of clones did not increase when cell division was delayed. Several possible molecular mechanisms for intracellular random drift are discussed.

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

PubMed

Browning, B L; Annese, V; Barclay, M L; Bingham, S A; Brand, S; Büning, C; Castro, M; Cucchiara, S; Dallapiccola, B; Drummond, H; Ferguson, L R; Ferraris, A; Fisher, S A; Gearry, R B; Glas, J; Henckaerts, L; Huebner, C; Knafelz, D; Lakatos, L; Lakatos, P L; Latiano, A; Liu, X; Mathew, C; Müller-Myhsok, B; Newman, W G; Nimmo, E R; Noble, C L; Palmieri, O; Parkes, M; Petermann, I; Rutgeerts, P; Satsangi, J; Shelling, A N; Siminovitch, K A; Török, H-P; Tremelling, M; Vermeire, S; Valvano, M R; Witt, H

2008-01-01

DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. DLG5 30Q is associated with a small reduction in risk of CD in women.

Prevalence of the rs1801282 single nucleotide polymorphism of the PPARG gene in patients with metabolic syndrome.

PubMed

Rocha, Renato Marano; Barra, Gustavo Barcelos; Rosa, Érica Carine Campos Caldas; Garcia, Érica Correa; Amato, Angélica Amorim; Azevedo, Monalisa Ferreira

2015-08-01

This study aimed to get the genotypic and allelic frequencies of rs1801282 in 179 volunteer donors and 154 patients with Metabolic syndrome (MetS) in Brasilia, Brazil and also examine the association with anthropometric, biochemical and hemodynamic variables in the latter group. MetS comprises a group of diseases resulting from insulin resistance, in-creased risk of type 2 diabetes and atherosclerotic cardiovascular disease. MetS is defined by the presence of increased visceral fat, atherogenic dyslipidemia (elevated triglycerides (TGL)), with decreased high density lipoprotein (HDL) and increased low density lipoprotein (LDL) levels, hypertension (BPH) and disturbances in glucose homeostasis representing a significant burden across the world due to the alarming increase in the incidence over the last decades besides their significant morbidity and mortality. Peroxisome proliferator activated receptor-gamma (PPARg) has been mentioned as a candidate gene for determining the risk of MetS. It is a member of the nuclear receptors superfamily and a ligand-activated transcription factor, which regulates the expression of genes involved in the network lipogenesis and adipogenesis, insulin sensitivity, energy balance, inflammation, angiogenesis and atherosclerosis. Among the PPARG genetic variants, single nucleotide polymorphism rs1801282 has been the most extensively studied one since it was first described by Yen and cols. in 1997. This polymorphism is characterized by the replacement of a proline (CCC) to an alanine (GCA) at codon 12 of exon B, due to the exchange of a cytosine with a guanine. The Ala allele frequency varies in different ethnic groups. DNA was extracted using Chelex-100 method and determinations of genotypes were performed by allele-specific chain reaction. The distribution of genotype frequency of the MetS group was not statistically different from the frequency in the donor population at large. In the first group, genotype frequency was CC to 0.869 and 0.103 for CG, while allelic frequencies were 0.948 for C and 0.052 for G allele. In the group of donors, the genotype and allele frequencies were 0.882 for CC, 0.117 to CG; and 0.941 to 0.059 for G and C, respectively. GG genotype was not found in any of the two groups. The genotype distribution and allele frequencies were in Hardy-Weinberg equilibrium. No marker could be detected from the analysis of anthropometric, biochemical and hemodynamic variables in the MetS group. Our data suggest that this polymorphism is not correlated with predisposition to MetS. The results obtained on a small sample of the population of Brasilia, corroborate the data reported in the literature on the prevalence of this polymorphism in PPAR in populations of different ethnic origins.

Multiplex pyrosequencing method to determine CYP2C9*3, VKORC1*2, and CYP4F2*3 polymorphisms simultaneously: its application to a Korean population and comparisons with other ethnic groups.

PubMed

Kim, Kyoung-Ah; Song, Wan-Geun; Lee, Hae-Mi; Joo, Hyun-Jin; Park, Ji-Young

2014-11-01

Warfarin is an anticoagulant that is difficult to administer because of the wide variation in dose requirements to achieve a therapeutic effect. CYP2C9, VKROC1, and CYP4F2 play important roles in warfarin metabolism, and their genetic polymorphisms are related to the variability in dose determination. In this study we describe a new multiplex pyrosequencing method to identify CYP2C9*3 (rs1057910), VKORC1*2 (rs9923231), and CYP4F2*3 (rs2108661) simultaneously. A multiplex pyrosequencing method to simultaneously detect CYP2C9*3, VKORC1*2, and CYP4F2*3 alleles was designed. We assessed the allele frequencies of the polymorphisms in 250 Korean subjects using the multiplex pyrosequencing method. The results showed 100 % concordance between single and multiplex pyrosequencing methods, and the polymorphisms identified by pyrosequencing were also validated with the direct sequencing method. The allele frequencies of these polymorphisms in this population were as follows: 0.040 for CYP2C9*3, 0.918 for VKORC1*2, and 0.416 for CYP4F2*3. Although the allele frequencies of the CYP2C9*3 and VKROC1*2 were comparable to those in Japanese and Chinese populations, their frequencies in this Korean population differed from those in other ethnic groups; the CYP4F2*3 frequency was the highest among other ethnic populations including Chinese and Japanese populations. The pyrosequencing methods developed were rapid and reliable for detecting CYP2C9*3, VKORC1*2, and CYP4F2*3. Large ethnic differences in the frequency of these genetic polymorphisms were noted among ethnic groups. CYP4F2*3 exhibited its highest allele frequency among other ethnic populations compared to that in a Korean population.

The Crossveinless Polygenes in an Iowa Population

PubMed Central

Boyer, Bradford J.; Parris, Deborah L.; Milkman, Roger

1973-01-01

A natural population of Drosophila melanogaster was tested for the presence of crossveinless (cve) alleles over the course of a summer. Approximately 8% of the wild-caught females tested carried enough cve alleles to produce true-breeding crossveinless lines. In some cases, different isofemale lines produced identical cve strains. Also, differences were sometimes observed among independently selected cve sublines of a given isofemale line.—The cv-2 allele was found to occur with a frequency of about 1% to 2%. PMID:4202772

Genetic structure of the gentle Africanized honey bee population (gAHB) in Puerto Rico.

PubMed

Galindo-Cardona, Alberto; Acevedo-Gonzalez, Jenny P; Rivera-Marchand, Bert; Giray, Tugrul

2013-08-06

The Africanized honey bee is one of the most spectacular invasions in the Americas. African bees escaped from apiaries in Brazil in 1956, spread over Americas and by 1994 they were reported in Puerto Rico. In contrast to other places, the oceanic island conditions in Puerto Rico may mean a single introduction and different dynamics of the resident European and new-coming Africanized bees.To examine the genetic variation of honey bee feral populations and colonies from different locations in Puerto Rico, we used eight known polymorphic microsatellite loci. In Puerto Rico, gAHB population does not show any genetic structure (Fst = 0.0783), and is best described as one honey bee population, product of hybridization of AHB and EHB. The genetic variability in this Africanized population was similar to that reported in studies from Texas. We observed that European private allele frequencies are high in all but one locus. This contrasts with mainland Africanized populations, where European allele frequencies are diminished. Two loci with European private alleles, one on Linkage Group 7, known to carry two known defensiveness Quantitative Trait Loci (QTLs), and the other on Linkage Group 1, known to carry three functionally studied genes and 11 candidate genes associated with Varroa resistance mechanisms were respectively, significantly greater or lower in European allele frequency than the other loci with European private alleles. Genetic structure of Puerto Rico gAHB differs from mainland AHB populations, probably representing evolutionary processes on the island.

Genetic structure of the gentle Africanized honey bee population (gAHB) in Puerto Rico

PubMed Central

2013-01-01

Background The Africanized honey bee is one of the most spectacular invasions in the Americas. African bees escaped from apiaries in Brazil in 1956, spread over Americas and by 1994 they were reported in Puerto Rico. In contrast to other places, the oceanic island conditions in Puerto Rico may mean a single introduction and different dynamics of the resident European and new-coming Africanized bees. To examine the genetic variation of honey bee feral populations and colonies from different locations in Puerto Rico, we used eight known polymorphic microsatellite loci. Results In Puerto Rico, gAHB population does not show any genetic structure (Fst = 0.0783), and is best described as one honey bee population, product of hybridization of AHB and EHB. The genetic variability in this Africanized population was similar to that reported in studies from Texas. We observed that European private allele frequencies are high in all but one locus. This contrasts with mainland Africanized populations, where European allele frequencies are diminished. Two loci with European private alleles, one on Linkage Group 7, known to carry two known defensiveness Quantitative Trait Loci (QTLs), and the other on Linkage Group 1, known to carry three functionally studied genes and 11 candidate genes associated with Varroa resistance mechanisms were respectively, significantly greater or lower in European allele frequency than the other loci with European private alleles. Conclusions Genetic structure of Puerto Rico gAHB differs from mainland AHB populations, probably representing evolutionary processes on the island. PMID:23915100

Genotype distribution and allele frequencies of the genes associated with body composition and locomotion traits in Myanmar native horses.

PubMed

Okuda, Yu; Moe, Hla Hla; Moe, Kyaw Kyaw; Shimizu, Yuki; Nishioka, Kenji; Shimogiri, Takeshi; Mannen, Hideyuki; Kanemaki, Misao; Kunieda, Tetsuo

2017-08-01

Myanmar native horses are small horses used mainly for drafting carts or carriages in rural areas and packing loads in mountainy areas. In the present study, we investigated genotype distributions and allele frequencies of the LCORL/NCAPG, MSTN and DMRT3 genes, which are associated with body composition and locomotion traits of horses, in seven local populations of Myanmar native horses. The genotyping result of LCORL/NCAPG showed that allele frequencies of C allele associated with higher withers height ranged from 0.08 to 0.27, and 0.13 in average. For MSTN, allele frequencies of C allele associated with higher proportion of Type 2B muscular fiber ranged from 0.05 to 0.23, and 0.09 in average. For DMRT3, allele frequencies of A allele associated with ambling gait ranged from 0 to 0.04, and 0.01 in average. The presences of the minor alleles of these genes at low frequencies suggest a possibility that these horse populations have not been under strong selection pressure for particular locomotion traits and body composition. Our findings of the presence of these minor alleles in Southeast Asian native horses are also informative for considering the origins of these minor alleles associated with body composition and locomotion traits in horse populations. © 2016 Japanese Society of Animal Science.

Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world

PubMed Central

Morrison, Margaux A.; Magalhaes, Tiago R.; Ramke, Jacqueline; Smith, Silvia E.; Ennis, Sean; Simpson, Claire L.; Portas, Laura; Murgia, Federico; Ahn, Jeeyun; Dardenne, Caitlin; Mayne, Katie; Robinson, Rosann; Morgan, Denise J.; Brian, Garry; Lee, Lucy; Woo, Se J.; Zacharaki, Fani; Tsironi, Evangelia E.; Miller, Joan W.; Kim, Ivana K.; Park, Kyu H.; Bailey-Wilson, Joan E.; Farrer, Lindsay A.; Stambolian, Dwight; DeAngelis, Margaret M.

2015-01-01

We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus. PMID:26217379

VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

PubMed Central

Avidan, Nili; Le Panse, Rozen; Harbo, Hanne F; Bernasconi, Pia; Poulas, Konstantinos; Ginzburg, Elizabeta; Cavalcante, Paola; Colleoni, Lara; Baggi, Fulvio; Antozzi, Carlo; Truffault, Frédérique; Horn-Saban, Shirley; Pöschel, Simone; Zagoriti, Zoi; Maniaol, Angelina; Lie, Benedicte A; Bernard, Isabelle; Saoudi, Abdelhadi; Illes, Zsolt; Casasnovas Pons, Carlos; Melms, Arthur; Tzartos, Socrates; Willcox, Nicholas; Kostera-Pruszczyk, Anna; Tallaksen, Chantal; Mantegazza, Renato; Berrih-Aknin, Sonia; Miller, Ariel

2014-01-01

Objective To identify novel genetic loci that predispose to early-onset myasthenia gravis (EOMG) applying a two-stage association study, exploration, and replication strategy. Methods Thirty-four loci and one confirmation loci, human leukocyte antigen (HLA)-DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, B-cell activating factor (BAFF), and tumor necrosis factor-alpha (TNF-α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA-DRA and TNF-α loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T- and B-cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B-cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor-kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG. PMID:25356403

[Prevalence of Variants in the Apolipoprotein E (APOE) Gene in a General Population of Adults from an Urban Area of Medellin (Antioquia)].

PubMed

Arango Viana, Juan Carlos; Valencia, Ana Victoria; Páez, Ana Lucía; Montoya Gómez, Nilton; Palacio, Carlos; Arbeláez, María Patricia; Bedoya Berrío, Gabriel; García Valencia, Jenny

2014-01-01

To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

PubMed

He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

2016-02-26

BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility.

The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

PubMed

Wan, Ji-Peng; Wang, Hong; Li, Chang-Zhong; Zhao, Han; You, Li; Shi, Dong-Hong; Sun, Xiu-Hua; Lv, Hong; Wang, Fei; Wen, Ze-Qing; Wang, Xie-Tong; Chen, Zi-Jiang

2014-11-01

Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. © The Author(s) 2014.

Distribution of HLA-DRB1 and HLA-DQB1 alleles in Lak population of Iran.

PubMed

Varzi, Ali Mohammad; Shahsavar, Farhad; Tarrahi, Mohammad Javad

2016-07-01

Human leukocyte antigen (HLA) genes are the most polymorphic loci in the human genome and encode the highly polymorphic molecules critically involved in immune responses. Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine the HLA-DRB1 and HLA-DQB1 allele frequencies in 100 unrelated Lak individuals from Lorestan province of Iran. Finally, we compared the results with those previously described in four other Iranian populations. Commercial HLA-Type kits were used for determination of the HLA-DRB1 and HLA-DQB1 allele frequencies. Differences between populations in the distribution of HLA-DRB1 and HLA-DQB1 alleles were estimated by χ2 test with Yate's correction and Fisher's exact test. The most frequent HLA-DRB1 alleles were (*)1103=4 (23%), (*)1502 (9.5%), (*)0701 (9%), (*)0301 (8.5%), (*)1101 (7.5%) and (*)1501 (6%) while HLA-DQB1(*)0301 (40%), (*)0201 (15%), (*)0502 (10.5%), (*)0303 (10%), (*)0602=3 (9.5%), and (*)0501 (7.5%) were the most frequent alleles in Lak population. HLA-DRB1(*)0409, (*)0804, (*)1102, (*)1112, (*)1405, and HLA-DQB1(*)0503, (*)0604 were the least observed frequencies in Lak population. Our results based on HLA-DRB1 and HLA-DQB1 allele frequencies showed that the Lak population possesses the previously reported general features of the Lur and Kurd populations but still with unique, decreased or increased frequencies of several alleles. In other words, the Lak population is close to Lurs Khorramabadi and Kurd but far from Lurs Kohkiloyeh/Boyerahmad and Bakhtiari. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Measuring Ambiguity in HLA Typing Methods

PubMed Central

Madbouly, Abeer; Freeman, John; Maiers, Martin

2012-01-01

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

Stabilizing selection on microsatellite allele length at arginine vasopressin 1a receptor and oxytocin receptor loci

PubMed Central

Kallio, Eva R.; Koskela, Esa; Lonn, Eija

2017-01-01

The loci arginine vasopressin receptor 1a (avpr1a) and oxytocin receptor (oxtr) have evolutionarily conserved roles in vertebrate social and sexual behaviour. Allelic variation at a microsatellite locus in the 5′ regulatory region of these genes is associated with fitness in the bank vole Myodes glareolus. Given the low frequency of long and short alleles at these microsatellite loci in wild bank voles, we used breeding trials to determine whether selection acts against long and short alleles. Female bank voles with intermediate length avpr1a alleles had the highest probability of breeding, while male voles whose avpr1a alleles were very different in length had reduced probability of breeding. Moreover, there was a significant interaction between male and female oxtr genotypes, where potential breeding pairs with dissimilar length alleles had reduced probability of breeding. These data show how genetic variation at microsatellite loci associated with avpr1a and oxtr is associated with fitness, and highlight complex patterns of selection at these loci. More widely, these data show how stabilizing selection might act on allele length frequency distributions at gene-associated microsatellite loci. PMID:29237850

[Analysis of HLA-B locus gene polymorphism in Sichuan Yi ethnic group and Xinjiang Uygur ethnic group].

PubMed

Xu, Ming-Yan; Hong, Kun-Xue; Ma, Jun; Deng, Xiao-Ling; Li, Jun; Peng, Hong; Ruan, Yu-Hua; Qin, Guan-Ming; Zhang, Yuan-Zhi; Xing, Hui; Xu, Xiao-Hu; Shao, Yi-Ming

2006-08-01

The polymorphism of HLA-B alleles in Sichuan Yi and Xinjiang Uygur population was investigated using the PCR-SSP method. Twenty one alleles were detected in HLA-B loci in 106 Sichuan unrelated Yi healthy subjects. Of them, B*40, B*15 and B*51 were the most common alleles with an allele frequency of 0.1981, 0.1368, 0.1274, respectively; while B*47, B*44, B*18, B*57 and B*78 were the rare alleles with an allele frequency of 0.0189, 0.0142, 0.0094, 0.0047 and 0.0047, respectively. The distribution of HLA-B allele frequencies in Sichuan Yis was between Southern Han and Northern Han. In 110 Xinjiang unrelated healthy Uygur subjects, 27 alleles were detected in HLA-B loci. Of them, B*35 and B*51 were the most common alleles with an allele frequency of 0.1136 and 0.1136, respectively; while B*41, B*56 and B*78 were the rare alleles with a frequency of 0.0045, 0.0045 and 0.0091, respectively. Frequencies of "Caucasoid origin" HLA alleles such as B*08, B*35 and B*50 in Xinjiang Uygurs were higher than other ethnic groups in China. The result of chi2 tests showed that the distributions of HLA-B alleles in Yi and Uygur ethnic groups were in Hardy-Weinberg equilibrium. Heterozygosity (H), discrimination power (DP) and probability of paternity exclusion (EP) of HLA-B locus from Sichuan Yi ethnic group were computed to be 0.8977, 0.9661 and 0.8009; and those from Xinjiang Uygur ethnic group were 0.9372, 0.9857 and 0.8732. The data obtained in this study on the distributions of HLA-B alleles in the Sichuan Yi and Xinjiang Uygur population provide important group genetics information for forensic and paternity tests to estimate the frequency of a DNA profile in these two populations, and can be used in transplant matching, anthropological and disease association studies.

Exploring the genetic role of the HLA-DPB1 locus in Chileans with intrahepatic cholestasis of pregnancy.

PubMed

Mella, J G; Roschmann, E; Glasinovic, J C; Alvarado, A; Scrivanti, M; Volk, B A

1996-03-01

Intrahepatic cholestasis of pregnancy is a rare disease of unknown etiology, with a strikingly higher prevalence in Chile than in most other countries. Although several studies suggest that a genetic predisposition is involved in the pathogenesis, no genetic disease-marker has so far been identified. Using a recently developed HLA-genotyping technique, we performed an association study with a highly polymorphic HLA class II gene in patients with recurrent intrahepatic cholestasis of pregnancy and normal control patients. Genomic DNA was extracted from 26 unrelated patients with recurrent ICP and 30 unrelated multiparous women without a personal or family history of this disease among a Chilean population. The polymorphic second exon of the HLA-DPB1 gene was amplified by the polymerase chain reaction and hybridized with 25 sequence-specific oligonucleotide probes to assign the HLA-DPB1 alleles on the basis of known sequence variations. Out of more than 50 HLA-DPB1 alleles presently known, 13 were represented in the analyzed groups. Patients with ICP had a higher frequency of the allele DPB*0402 when compared to controls (69% vs 43%). This difference failed to reach statistical significance (x2 = 2.81, corrected p > 0.5). No significant differences were observed between the frequencies of other detected HLA-DPB1 alleles in the analyzed groups. In this study, we observed a high frequency of the allele HLA-DPB1*0402 among Chilean patients with recurrent ICP, but no association of the disease with HLA-DPB1 alleles. Therefore, HLA-DPB1 alleles do not play a major role in determining susceptibility or resistance to intrahepatic cholestasis of pregnancy.

Spectrum of hemoglobinopathies among the primitive tribes: a multicentric study in India.

PubMed

Mohanty, Dipika; Mukherjee, Malay B; Colah, Roshan B; Wadia, Mahrukh; Ghosh, Kanjaksha; Chottray, Guru Prasad; Jain, Dipty; Italia, Yazdi; Ashokan, Kumar S; Kaul, Rajni; Shukla, Deepak K; Muthuswamy, Vasantha

2015-03-01

We evaluated the spectrum of hemoglobinopathies among the primitive tribal groups from 4 states in India. A total of 15,200 individuals from 14 primitive tribal groups were studied by automated high-performance liquid chromatography. The hemoglobin S (HbS) allele frequency varied from 0.011 to 0.120 and the β-thalassemia allele frequency from 0.005 to 0.024. It is interesting to note that a very high HbS allele frequency was observed among the Dravidian (0.060-0.120) and Indo-European (0.060-0.076) as compared with Austro-Asiatic (0.011-0.022) speaking tribal groups. Although statistical analysis of the data did not show any ethnic differences within the states, regional differences were observed between the states for both HbS and β-thalassemia traits. HbS was found to be the most common hemoglobinopathy followed by β-thalassemia. A health plan for identifying sickle-cell homozygotes in the neonatal period with proper medical intervention is desirable. © 2013 APJPH.

[Study on the correlation between chronic asymptomatic HBV carriers of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles].

PubMed

Guo, Jian-chun; Xiao, Li-na; Xun, Yun-hao

2012-08-01

To study on the correlation between chronic asymptomatic HBV carriers (ASC) of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles. Totally 105 ASC were assigned to two groups according to their constitutions, i.e., the yin asthenia group (47 cases) and the non-yin asthenia group (58 cases). The genotypes of HLA-DRB1 and HLA DQA1 alleles were determined using PCR-SSP. The gene frequency of HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele (being 12.1% and 19.1%) were obviously lower in the yin asthenia group than in the non-yin asthenia group (being 27.8% and 39.7%, P < 0.05). The gene frequency of HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele were obviously higher in the yin asthenia group (being 12.1% and 28.7%) than in the non-yin asthenia group (4.3% and 9.5%), showing statistical difference (P < 0.05, P < 0.01). HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele might be the molecular bases for non-yin asthenia patients with ASC. HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele might be the molecular bases for yin asthenia patients with ASC.

Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies.

PubMed

Solmi, M; Gallicchio, D; Collantoni, E; Correll, C U; Clementi, M; Pinato, C; Forzan, M; Cassina, M; Fontana, F; Giannunzio, V; Piva, I; Siani, R; Salvo, P; Santonastaso, P; Tenconi, E; Veronese, N; Favaro, A

2016-06-01

Objectives Growing interest focuses on the association between 5-HTTLPR polymorphism and eating disorders (ED), but published findings have been conflicting. Methods The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. We conducted a literature search of studies published up to 1 April 2015, including studies reporting on 5HTTLPR genotype and allele frequencies in obesity and/or ED. We ran a meta-analysis, including data from BIO.VE.D.A. - comparing low and high-functioning genotype and allele frequencies in ED vs. Results Data from 21 studies, plus BIO.VE.D.A., were extracted providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and triallelic models, differed from control groups. After sensitivity analysis, results were the same in AN vs. Results remained unaltered when investigating recessive and dominant models. Conclusions 5HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Future studies in ED should explore the role of ethnicity and psychiatric comorbidity as a possible source of bias.

Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations

PubMed Central

Hubácek, Jaroslav A.; Adámková, Věra; Šedová, Lenka; Olišarová, Věra; Adámek, Václav; Tóthová, Valérie

2017-01-01

Abstract Lactase non-persistence (leading to primary lactose intolerance) is a genetically dependent inability to digest lactose in adulthood. As part of the human adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates adult expression of lactase) developed, spread and participated in the adaptation to dairying. This variant is associated with lactase activity persistence, and its carriers are able to digest lactose. We compared the frequencies of lactase 13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma (N = 300), two ethnically different groups where this polymorphism has not yet been analysed. Allelic frequencies significantly differed between the populations (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in 76% of the individuals, which is in agreement with frequencies among geographically neighbouring populations. In the Czech Gypsy/Roma population, only 27% of the adults were carriers of at least one lactase persistence allele, similar to the Indian population. In agreement with this result, dairy product consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs populations, the presence of carriers of the lactase persistence allele was similar in subjects self-reporting the consumption of unfermented/fresh milk, in comparison to the others. PMID:28497837

Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations.

PubMed

Hubácek, Jaroslav A; Adámková, Věra; Šedová, Lenka; Olišarová, Věra; Adámek, Václav; Tóthová, Valérie

2017-01-01

Lactase non-persistence (leading to primary lactose intolerance) is a genetically dependent inability to digest lactose in adulthood. As part of the human adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates adult expression of lactase) developed, spread and participated in the adaptation to dairying. This variant is associated with lactase activity persistence, and its carriers are able to digest lactose. We compared the frequencies of lactase 13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma (N = 300), two ethnically different groups where this polymorphism has not yet been analysed. Allelic frequencies significantly differed between the populations (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in 76% of the individuals, which is in agreement with frequencies among geographically neighbouring populations. In the Czech Gypsy/Roma population, only 27% of the adults were carriers of at least one lactase persistence allele, similar to the Indian population. In agreement with this result, dairy product consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs populations, the presence of carriers of the lactase persistence allele was similar in subjects self-reporting the consumption of unfermented/fresh milk, in comparison to the others.

Toll-like receptor polymorphisms in malaria-endemic populations

PubMed Central

Greene, Jennifer A; Moormann, Ann M; Vulule, John; Bockarie, Moses J; Zimmerman, Peter A; Kazura, James W

2009-01-01

Background Toll-like receptors (TLR) and related downstream signaling pathways of innate immunity have been implicated in the pathogenesis of Plasmodium falciparum malaria. Because of their potential role in malaria pathogenesis, polymorphisms in these genes may be under selective pressure in populations where this infectious disease is endemic. Methods A post-PCR Ligation Detection Reaction-Fluorescent Microsphere Assay (LDR-FMA) was developed to determine the frequencies of TLR2, TLR4, TLR9, MyD88-Adaptor Like Protein (MAL) single nucleotide polymorphisms (SNPs), and TLR2 length polymorphisms in 170 residents of two regions of Kenya where malaria transmission is stable and high (holoendemic) or episodic and low, 346 residents of a malaria holoendemic region of Papua New Guinea, and 261 residents of North America of self-identified ethnicity. Results The difference in historical malaria exposure between the two Kenyan sites has significantly increased the frequency of malaria protective alleles glucose-6-phoshpate dehydrogenase (G6PD) and Hemoglobin S (HbS) in the holoendemic site compared to the episodic transmission site. However, this study detected no such difference in the TLR2, TLR4, TLR9, and MAL allele frequencies between the two study sites. All polymorphisms were in Hardy Weinberg Equilibrium in the Kenyan and Papua New Guinean populations. TLR9 SNPs and length polymorphisms within the TLR2 5' untranslated region were the only mutant alleles present at a frequency greater than 10% in all populations. Conclusion Similar frequencies of TLR2, TLR4, TLR9, and MAL genetic polymorphisms in populations with different histories of malaria exposure suggest that these innate immune pathways have not been under strong selective pressure by malaria. Genotype frequencies are consistent with Hardy-Weinberg Equilibrium and the Neutral Theory, suggesting that genetic drift has influenced allele frequencies to a greater extent than selective pressure from malaria or any other infectious agents in these populations. PMID:19317913

Linkage disequilibrium levels in Bos indicus and Bos taurus cattle using medium and high density SNP chip data and different minor allele frequency distributions

USDA-ARS?s Scientific Manuscript database

Linkage disequilibrium (LD), the observed correlation between alleles at different loci in the genome, is a determinant parameter in many applications of molecular genetics. With the wider use of genomic technologies in animal breeding and animal genetics, it is worthwhile revising and improving the...

Genetic polymorphisms of enzyme proteins and transporters related to methotrexate response and pharmacokinetics in a Japanese population.

PubMed

Hashiguchi, Masayuki; Shimizu, Mikiko; Hakamata, Jun; Tsuru, Tomomi; Tanaka, Takanori; Suzaki, Midori; Miyawaki, Kumika; Chiyoda, Takeshi; Takeuchi, Osamu; Hiratsuka, Jiro; Irie, Shin; Maruyama, Junya; Mochizuki, Mayumi

2016-01-01

Methotrexate (MTX) is currently the anchor drug widely used worldwide in the treatment of rheumatoid arthritis (RA). However, the therapeutic response to MTX has been shown to vary widely among individuals, genders and ethnic groups. The reason for this has been not clarified but it is considered to be partially due to several mechanisms in the cellular pathway of MTX including single-nucleotide polymorphisms (SNPs). The purpose of this study was to investigate the allelic frequencies in different ethnic and/or population groups in the 10 polymorphisms of enzyme proteins and transporters related to the MTX response and pharmacokinetics including MTHFR, TYMS, RFC1, FPGS, GGH, ABCB1, ABCC2 and ABCG2 in unrelated healthy Japanese adults and patients with RA. Ten polymorphisms, methylenetetrahydrofolate reductase (MTHFR) 1298, thymidylate synthase (TYMS) 3'-UTR, reduced folate carrier 1 (RFC1) 80 and-43, folypolyglutamyl synthase (FPGS) 1994, γ-glutamyl hydrolase (GGH) 452 and-401, the ABC transporters (ABCB1 3435, ABCC2 IVS23 + 56, ABCG2 914) of enzyme proteins and transporters related to MTX response and pharmacokinetics in 299 unrelated healthy Japanese adults and 159 Japanese patients with RA were investigated to clarify their contributions to individual variations in response and safety to MTX and establish personalized MTX therapy. SNPs were evaluated using real-time polymerase chain reaction (PCR). Comparison of allelic frequencies in our study with other ethnic/population groups of healthy adults and RA patients showed significant differences in 10 polymorphisms among healthy adults and 7 among RA patients. Allelic frequencies of MTHFR 1298 C, FPGS 1994A and ABCB1 3435 T were lower in Japanese than in Caucasian populations and those of ABCC2 IVS23 + 56 C and ABCG2 914A were higher in Japanese than in Caucasian/European populations in both healthy adults and RA patients. Allelic frequencies of MTHFR 1298 C, GGH-401 T, ABCB1 3435 T, and ABCG2 914A were higher in healthy Japanese adults than in an African population, and those of RFC1 80A, RFC1-43C and ABCC2 IVS23 + 56 C in healthy Japanese adults were lower than in Africans. However, no significant differences were seen in the distribution of allelic frequencies between healthy Japanese adults and RA patients. The variations in allelic frequencies in different ethnic and/or population groups in healthy adults and RA patients may contribute to individual variations in MTX response and toxicity.

Distribution and genotype frequency of the C1431T and pro12ala polymorphisms of the peroxisome proliferator activator receptor gamma gene in an Iranian population

PubMed Central

Rooki, Hassan; Haerian, Monir-Sadat; Azimzadeh, Pedram; Ebrahimi, Mahmoud; Mirhafez, Reza; Ferns, Gordon; Ghayour-Mobarhan, Majid; Zali, Mohammad-Reza

2013-01-01

BACKGROUND: Peroxisome proliferator activator receptor gamma (PPARγ) is a nuclear transcription factor regulating multiple genes involved in cell growth, differentiation, carbohydrate and lipid metabolism and energy production. Several genetic variations in the PPARγ gene have been identified to be associated with diabetes, obesity, dyslipidemia, insulin resistance, metabolic syndrome and coronary artery disease. The present study was designed to explore the distribution of two common single nucleotide polymorphisms of the PPARγ gene (C1431T and Pro12Ala) in an Iranian population. MATERIALS AND METHODS: Genotype frequencies for these two polymorphisms were compared for 160 healthy Iranian individuals with reports from other populations. The Genotyping was performed using real-time polymerase chain reaction. RESULTS: The genotype distribution of the C1431T PPARγ polymorphism was 0.869 for the CC genotype, 0.119 for the CT genotype and 0.013 for uncommon TT genotype. Allelic frequencies were 0.93 for C and 0.07 for T allele respectively. For the Pro12Ala polymorphism of PPARγ gene, genotypic distributions and allelic frequencies were, 0.813 for CC, 0.181 for CG and 0.06 for GG and 0.903 for C and 0.097 for G respectively. Allelic and genotypic frequencies for both polymorphisms of PPARγ gene were in Hardy-Weinberg equilibrium. CONCLUSIONS: Iran is a country with an ethnically diverse population and a comparison of allelic and genotypic frequencies of PPARγ C1431T and Pro12Ala polymorphisms between our population and others showed significant differences. PMID:24497707

Genetic profiling of GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in an Argentinian population.

PubMed

Galván, Cristian A; Elbarcha, Osvaldo C; Fernández, Eduardo J; Beltramo, Dante M; Soria, Néstor W

2011-09-01

To determine the frequencies of relevant allelic variants in oncology for the GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in a population from Central Argentina. To compare the allelic distribution found with the frequencies reported for other ethnic groups. Genotyping was carried out in a total of 102 unrelated Argentinian subjects. FCGR3A (rs396991) was detected using allele specific polymerase chain reaction (PCR) assay, while GSTP1 (rs1695), DPYD (rs3918290), FCGR2A (rs1801274) and CCND1 (rs9344) variants were assessed by PCR-restriction fragment length polymorphism (PCR-RFLP). The allele frequencies for GSTP*1B, DPYD*2A, FCGR2A (131R), FCGR3A (158F) and CCND1 (870G) in Argentinians were 0.35, 0.005, 0.41, 0.77 and 0.47, respectively. We found that the Argentinian population tested resembles other Caucasians populations, especially Spaniards; yet the differences in allele distribution with other Caucasian groups, uncover population admixture with native Amerindian and other ethnic groups, consistent with the well documented immigration flows landing Argentina from several countries. Copyright © 2011. Published by Elsevier Inc.

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

PubMed

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

2016-05-06

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

Extreme Population Differences in the Human Zinc Transporter ZIP4 (SLC39A4) Are Explained by Positive Selection in Sub-Saharan Africa

PubMed Central

Pybus, Marc; Andrews, Glen K.; Lalueza-Fox, Carles; Comas, David; Sekler, Israel; de la Rasilla, Marco; Rosas, Antonio; Stoneking, Mark; Valverde, Miguel A.; Vicente, Rubén; Bosch, Elena

2014-01-01

Extreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution (Leu372Val) in the human intestinal zinc uptake transporter, ZIP4, yet no further evidence was found for a selective sweep around the ZIP4 gene (SLC39A4). By interrogating allele frequencies in more than 100 diverse human populations and resequencing Neanderthal DNA, we confirmed the ancestral state of this locus and found a strong geographical gradient for the derived allele (Val372), with near fixation in West Africa. In extensive coalescent simulations, we show that the extreme differences in allele frequency, yet absence of a classical sweep signature, can be explained by the effect of a local recombination hotspot, together with directional selection favoring the Val372 allele in Sub-Saharan Africans. The possible functional effect of the Leu372Val substitution, together with two pathological mutations at the same codon (Leu372Pro and Leu372Arg) that cause acrodermatitis enteropathica (a disease phenotype characterized by extreme zinc deficiency), was investigated by transient overexpression of human ZIP4 protein in HeLa cells. Both acrodermatitis mutations cause absence of the ZIP4 transporter cell surface expression and nearly absent zinc uptake, while the Val372 variant displayed significantly reduced surface protein expression, reduced basal levels of intracellular zinc, and reduced zinc uptake in comparison with the Leu372 variant. We speculate that reduced zinc uptake by the ZIP4-derived Val372 isoform may act by starving certain pathogens of zinc, and hence may have been advantageous in Sub-Saharan Africa. Moreover, these functional results may indicate differences in zinc homeostasis among modern human populations with possible relevance for disease risk. PMID:24586184

The maintenance of single-locus polymorphism. IV. Models with mutation from existing alleles.

PubMed

Spencer, H G; Marks, R W

1992-01-01

The ability of viability selection to maintain allelic polymorphism is investigated using a constructionist approach. In extensions to the models we have previously proposed, a population is bombarded with a series of mutations whose fitnesses in conjunction with other alleles are functions of the corresponding fitnesses with a particular allele, the parent allele, already in the population. Allele frequencies are iterated simultaneously, thus allowing alleles to be driven to extinction by selection. Such models allow very high levels of polymorphism to evolve: up to 38 alleles in one case. Alleles that are lethal as homozygotes can evolve to surprisingly high frequencies. The joint evolution of allele frequencies and viabilities highlights the necessity to consider more than the current morphology of a population. Comparisons are made with the neutral theory of evolution and it is suggested that failure to reject neutrality using the Ewens-Watterson test cannot be regarded as evidence for the neutral theory.

Allelic Diversity and Geographical Distribution of the Gene Encoding Plasmodium falciparum Merozoite Surface Protein-3 in Thailand

PubMed Central

Sawaswong, Vorthon; Simpalipan, Phumin; Siripoon, Napaporn; Harnyuttanakorn, Pongchai; Pattaradilokrat, Sittiporn

2015-01-01

Merozoite surface proteins (MSPs) of malaria parasites play critical roles during the erythrocyte invasion and so are potential candidates for malaria vaccine development. However, because MSPs are often under strong immune selection, they can exhibit extensive genetic diversity. The gene encoding the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum displays 2 allelic types, K1 and 3D7. In Thailand, the allelic frequency of the P. falciparum msp-3 gene was evaluated in a single P. falciparum population in Tak at the Thailand and Myanmar border. However, no study has yet looked at the extent of genetic diversity of the msp-3 gene in P. falciparum populations in other localities. Here, we genotyped the msp-3 alleles of 63 P. falciparum samples collected from 5 geographical populations along the borders of Thailand with 3 neighboring countries (Myanmar, Laos, and Cambodia). Our study indicated that the K1 and 3D7 alleles coexisted, but at different proportions in different Thai P. falciparum populations. K1 was more prevalent in populations at the Thailand-Myanmar and Thailand-Cambodia borders, whilst 3D7 was more prevalent at the Thailand-Laos border. Global analysis of the msp-3 allele frequencies revealed that proportions of K1 and 3D7 alleles of msp-3 also varied in different continents, suggesting the divergence of malaria parasite populations. In conclusion, the variation in the msp-3 allelic patterns of P. falciparum in Thailand provides fundamental knowledge for inferring the P. falciparum population structure and for the best design of msp-3 based malaria vaccines. PMID:25925176

Allelic Diversity and Geographical Distribution of the Gene Encoding Plasmodium falciparum Merozoite Surface Protein-3 in Thailand.

PubMed

Sawaswong, Vorthon; Simpalipan, Phumin; Siripoon, Napaporn; Harnyuttanakorn, Pongchai; Pattaradilokrat, Sittiporn

2015-04-01

Merozoite surface proteins (MSPs) of malaria parasites play critical roles during the erythrocyte invasion and so are potential candidates for malaria vaccine development. However, because MSPs are often under strong immune selection, they can exhibit extensive genetic diversity. The gene encoding the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum displays 2 allelic types, K1 and 3D7. In Thailand, the allelic frequency of the P. falciparum msp-3 gene was evaluated in a single P. falciparum population in Tak at the Thailand and Myanmar border. However, no study has yet looked at the extent of genetic diversity of the msp-3 gene in P. falciparum populations in other localities. Here, we genotyped the msp-3 alleles of 63 P. falciparum samples collected from 5 geographical populations along the borders of Thailand with 3 neighboring countries (Myanmar, Laos, and Cambodia). Our study indicated that the K1 and 3D7 alleles coexisted, but at different proportions in different Thai P. falciparum populations. K1 was more prevalent in populations at the Thailand-Myanmar and Thailand-Cambodia borders, whilst 3D7 was more prevalent at the Thailand-Laos border. Global analysis of the msp-3 allele frequencies revealed that proportions of K1 and 3D7 alleles of msp-3 also varied in different continents, suggesting the divergence of malaria parasite populations. In conclusion, the variation in the msp-3 allelic patterns of P. falciparum in Thailand provides fundamental knowledge for inferring the P. falciparum population structure and for the best design of msp-3 based malaria vaccines.

Analysis of TNF-α (-308) polymorphism and gingival crevicular fluid TNF-α levels in aggressive and chronic periodontitis: A preliminary report.

PubMed

Özer Yücel, Özlem; Berker, Ezel; Mesci, Lütfiye; Eratalay, Kenan; Tepe, Eser; Tezcan, İlhan

2015-04-01

The purpose of this study was to determine the differences in the distribution of TNF-α (-308) gene polymorphism among aggressive periodontitis, chronic periodontitis and periodontally healthy individuals and also to investigate whether this polymorphism is associated with gingival crevicular fluid TNF-α levels and periodontal disease severity. A total of 93 individuals were enrolled in the study including 38 aggressive periodontitis, 29 chronic periodontitis patients, and 26 healthy controls. Single nucleotide polymorphism at TNF-α (-308) is analyzed by PCR-RFLP method. Gingival crevicular fluid samples were analyzed for TNF-α, using ELISA. The distribution of genotypes and allele frequencies for TNF-α (-308) were similar among the groups. After stratification of patients with respect to attachment level, aggressive periodontitis patients with clinical attachment level ⩾4mm was observed to have a higher frequency of TNF-α (-308) allele 2 compared to the chronic periodontitis patients with clinical attachment level ⩾4mm. No significant differences were found between the TNF-α levels of the different genotypes in spite of an insignificant increase in patient groups carrying TNF-α (-308) allele 2. The results of this study revealed an association between TNF-α (-308) allele 2 frequency and aggressive periodontitis patients with clinical attachment level ⩾4mm in the population studied. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of Polymorphisms in Genes (AGT, MTHFR, GPIIIa, and GSTP1) Associated with Hypertension, Thrombophilia and Oxidative Stress in Mestizo and Amerindian Populations of México

PubMed Central

Juárez-Velázquez, Rocio; Canto, Patricia; Canto-Cetina, Thelma; Rangel-Villalobos, Hector; Rosas-Vargas, Haydee; Rodríguez, Maricela; Canizales-Quinteros, Samuel; Velázquez Wong, Ana Claudia; Ordoñez-Razo, Rosa María; Vilchis-Dorantes, Guadalupe; Coral-Vázquez, Ramón Mauricio

2010-01-01

Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1) polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using χ2 tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups. PMID:20592457

Plasmodium falciparum msp1 and msp2 genetic diversity and allele frequencies in parasites isolated from symptomatic malaria patients in Bobo-Dioulasso, Burkina Faso.

PubMed

Somé, Anyirékun Fabrice; Bazié, Thomas; Zongo, Issaka; Yerbanga, R Serge; Nikiéma, Frédéric; Neya, Cathérine; Taho, Liz Karen; Ouédraogo, Jean-Bosco

2018-05-30

In Burkina Faso, malaria remains the overall leading cause of morbidity and mortality accounting for 35.12% of consultations, 40.83% of hospitalizations and 37.5% of deaths. Genotyping of malaria parasite populations remains an important tool to determine the types and number of parasite clones in an infection. The present study aimed to evaluate the merozoite surface protein 1 (msp1) and merozoite surface protein 2 (msp2) genetic diversity and allele frequencies in Bobo-Dioulasso, Burkina Faso. Dried blood spots (DBS) were collected at baseline from patients with uncomplicated malaria in urban health centers in Bobo-Dioulasso. Parasite DNA was extracted using chelex-100 and species were identified using nested PCR. Plamodium falciparum msp1 and msp2 genes were amplified by nested polymerase chain reaction (PCR) and PCR products were analyzed by electrophoresis on a 2.5% agarose gel. Alleles were categorized according to their molecular weight. A total of 228 blood samples were analyzed out of which 227 (99.9%) were confirmed as P. falciparum-positive and one sample classified as mixed infection for P. malaria and P. falciparum. In msp1, the K1 allelic family was predominant with 77.4% (162/209) followed respectively by the MAD20 allelic family with 41.3% and R033 allelic family with 36%. In msp2, the 3D7 allelic family was the most frequently detected with 93.1 % compared to FC27 with 41.3%. Twenty-one different alleles were observed in msp1 with 9 alleles for K1, 8 alleles for MAD20 and 4 alleles for R033. In msp2, 25 individual alleles were detected with 10 alleles for FC27 and 15 alleles for 3D7. The mean multiplicity of falciparum infection was 1.95 with respectively 1.8 (1.76-1.83) and 2.1 (2.03-2.16) for msp1 and msp2 (P = 0.01). Our study showed high genetic diversity and allelic frequencies of msp1 and msp2 in Plasmodium falciparum isolates from symptomatic malaria patients in Bobo-Dioulasso.

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

PubMed

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

2011-01-01

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

Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in a Chinese Tibetan population

PubMed Central

Wang, Li; Ren, Guoxia; Li, Jingjie; Zhu, Linhao; Niu, Fanglin; Yan, Mengdan; Li, Jing; Yuan, Dongya; Jin, Tianbo

2017-01-01

Abstract Cytochrome P4502E1 (CYP2E1) gene genetic polymorphisms vary markedly in frequency among different ethnic and racial groups. We studied the genotype distributions and allele frequencies of 3 CYP2E1 polymorphisms: CYP2E1∗1A, CYP2E1∗7A, and CYP2E1∗7C by polymerase chain reaction technique in a sample of 100 healthy subjects representing Tibetan population. The frequencies of CYP2E1∗1A, ∗7A, and ∗7C alleles were 0.705, 0.125, and 0.170, respectively. Compared with other populations, we found that the allele frequencies of the variants −352A>G (rs2070672) and −333A>T (rs2070673) in this Tibetan population have significant differences compared with European-American, African-American, Japanese, Korean, and other different geographic areas in Chinese Han population. Furthermore, the results of protein prediction revealed that the variant 6397G>A (rs61710826) could influence the protein structure and function. These findings in this study would be valuable for pharmacogenetics for drug therapy and drug discovery. However, further studies in larger samples are warranted to confirm our results. PMID:29381998

Polymorphic admixture typing in human ethnic populations

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

Dean, M.; Stephens, J.C.; Boaze, R.

1994-10-01

A panel of 257 RFLP loci was selected on the basis of high heterozygosity in Caucasian DNA surveys and equivalent spacing throughout the human genome. Probes from each locus were used in a Southern blot survey of allele frequency distribution for four human ethnic groups: Caucasian, African American, Asian (Chinese), and American Indian (Cheyenne). Nearly all RFLP loci were polymorphic in each group, albeit with a broad range of differing allele frequencies ({delta}). The distribution of frequency differences ({delta} values) was used for three purposes: (1) to provide estimates for genetic distance (differentiation) among these ethnic groups, (2) to revisitmore » with a large data set the proportion of human genetic variation attributable to differentiation within ethnic groups, and (3) to identify loci with high {delta} values between recently admixed populations of use in mapping by admixture linkage disequilibrium (MALD). Although most markers display significant allele frequency differences between ethnic groups, the overall genetic distances between ethnic groups were small (.066-.098), and <10% of the measured overall molecular genetic diversity in these human samples can be attributed to {open_quotes}racial{close_quotes} differentiation. The median {delta} values for pairwise comparisons between groups fell between .15 and .20, permitting identification of highly informative RFLP loci for MALD disease association studies. 43 refs., 5 figs., 5 tabs.« less

Examination of Allelic Variation at the Hexokinase Loci of DROSOPHILA PSEUDOOBSCURA and D. PERSIMILIS by Different Methods

PubMed Central

Beckenbach, Andrew T.; Prakash, Satya

1977-01-01

Recently a number of electrophoretic techniques have been applied to reveal the presence of additional genetic variation among the electrophoretic mobility classes of the highly polymorphic xanthine dehydrogenase (XDH ) and esterase-5 (est-5) loci. We examined the hexokinase loci of Drosophila pseudoobscura and D. persimilis using a variety of techniques to determine whether further allelic variation could be revealed for these much less polymorphic loci and to analyze the nature of the known variation at the hexokinase-1 (hex-1) locus. The following studies were conducted: 135 strains of the two species from six localities were examined with buffer pH ranging from 5.5 to 10.0; 40 strains of D. pseudoobscura and 9 strains of D. persimilis from Mather were studied using starch gel concentrations ranging from 8.5 to 15.5% and were examined for differences in heat stability and reactivity to the thiol reagent pCMSA; strains were also tested for susceptibility to urea denaturation and differences in relative activities. Major findings of the work are: (1) No additional allelic variation could be detected at any of the hexokinase loci by applying these techniques. The finding of abundant hidden genetic variation in XDH and est-5 does not extend to all enzyme loci. (2) Evidence from studies using pCMSA indicates that the hex-1 alleles 0.6, 0.8, 1.0 and 1.2 of the two species form a series of unit charge steps. Since the 0.94 allele of D. persimilis has mobility intermediate between 0.8 and 1.0, it is argued that routine electrophoretic techniques are sensitive to at least some conservative amino acid substitutions. (3) Strong correlations were found at the hex-1 locus between low allelic frequency, reduced relative activity and reduced stability to heat and urea denaturation. Since the three sibling species, D. pseudoobscura, D. persimilis and D. miranda, all appear to share a common high frequency allele (1.0) at that locus, these findings are taken as evidence that the observed allelic frequencies are a result of directional selection and mutation, rather than any form of balancing selection. PMID:17248785

Short alleles revealed by PCR demonstrate no heterozygote deficiency at minisatellite loci D1S7, D7S21, and D12S11

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

Alonso, S.; Castro, A.; Fernandez-Fernandez, I.

1997-02-01

Short VNTR alleles that go undetected after conventional Southern blot hybridization may constitute an alternative explanation for the heterozygosity deficiency observed at some minisatellite loci. To examine this hypothesis, we have employed a screening procedure based on PCR amplification of those individuals classified as homozygotes in our databases for the loci D1S7, D7S21, and D12S11. The results obtained indicate that the frequency of these short alleles is related to the heterozygosity deficiency observed. For the most polymorphic locus, D1S7, {approximately}60% of those individuals previously classified as homozygotes were in fact heterozygotes for a short allele. After the inclusion of thesemore » new alleles, the agreement between observed and expected heterozygosity, along with other statistical tests employed, provide additional evidence for lack of population substructuring. Comparisons of allele frequency distributions reveal greater differences between racial groups than between closely related populations. 45 refs., 3 figs., 6 tabs.« less

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

PubMed

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

2000-09-01

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

Quechua Amerindian population characterized by HLA-DQ alpha, YNZ22, 3'APO B, HUMTH01, and HUMVWA31A polymorphisms.

PubMed

Gené, M; Fuentes, M; Huguet, E; Piqué, E; Bert, F; Corella, A; Pérez-Pérez, A; Corbella, J; Moreno, P

1998-03-01

Allele and genotype frequencies of DNA polymorphisms were determined in a population sample of Quechua (n = 113) using the polymerase chain reaction (PCR). We report data on the frequencies of HLA-DQ alpha, YNZ22, 3'ApoB, HUMTH01 and HUMVWA31A alleles and the distribution of the different genotypes. No significant deviations between observed and expected numbers were found, thus assuming the Hardy-Weinberg equilibrium.

Null alleles are ubiquitous at microsatellite loci in the Wedge Clam (Donax trunculus)

PubMed Central

Cuesta, Jose Antonio; Drake, Pilar; Macpherson, Enrique; Bernatchez, Louis

2017-01-01

Recent studies have reported an unusually high frequency of nonamplifying alleles at microsatellite loci in bivalves. Null alleles have been associated with heterozygous deficits in many studies. While several studies have tested for its presence using different analytical tools, few have empirically tested for its consequences in estimating population structure and differentiation. We characterised 16 newly developed microsatellite loci and show that null alleles are ubiquitous in the wedge clam, Donax trunculus. We carried out several tests to demonstrate that the large heterozygous deficits observed in the newly characterised loci were most likely due to null alleles. We tested the robustness of microsatellite genotyping for population assignment by showing that well-recognised biogeographic regions of the south Atlantic and south Mediterranean coast of Spain harbour genetically different populations. PMID:28439464

Type 2 Diabetes Risk Alleles Demonstrate Extreme Directional Differentiation among Human Populations, Compared to Other Diseases

PubMed Central

Chen, Rong; Corona, Erik; Sikora, Martin; Dudley, Joel T.; Morgan, Alex A.; Moreno-Estrada, Andres; Nilsen, Geoffrey B.; Ruau, David; Lincoln, Stephen E.; Bustamante, Carlos D.; Butte, Atul J.

2012-01-01

Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed disparity in T2D incidence rates across ethnic populations. PMID:22511877

Genetic variation of the angiotensin-converting enzyme gene: increased frequency of the insertion allele in Koreans.

PubMed

Hong, S H; Kang, B Y; Park, W H; Kim, J Q; Lee, C C

1997-01-01

In view of the clinical importance of angiotensin-converting enzyme (ACE) as a major marker for cardiovascular diseases, we investigated insertion/deletion (I/D) polymorphism of the ACE gene in Koreans. Genotype frequencies were examined by polymerase chain reaction in 171 patients with coronary artery disease (CAD) and 120 healthy subjects. Allele frequencies of ACE polymorphism in Koreans were not significantly different between patient and control groups. In addition, association between ACE genotypes and the number of stenosed coronary arteries was not detected. ACE genotypes in the CAD group were not associated with body mass index and plasma lipid levels. Thus, our results suggest that, at least in Koreans, I/D polymorphism of the gene is unlikely to be a useful marker for CAD subjects. However, the I allele frequency of Koreans (0.58) was higher than that of Caucasian populations (0.47) but lower than that of Samoan (0.91) and Yanomami (0.85) populations. Here, we discuss the clinical and ethnic importance of ACE polymorphism.

Genetic variability in biochemical characters of Brazilian field populations of the Leishmania vector, Lutzomyia longipalpis (Diptera: Psychodidae).

PubMed

Mukhopadhyay, J; Ghosh, K; Rangel, E F; Munstermann, L E

1998-12-01

The phlebotomine sand fly Lutzomyia longipalpis is the insect vector of visceral leishmaniasis, a protozoan disease of increasing incidence and distribution in Central and South America. Electrophoretic allele frequencies of 15 enzyme loci were compared among the L. longipalpis populations selected across its distribution range in Brazil. The mean heterozygosity of two colonized geographic strains (one each from Colombia and Brazil) were 6% and 13% respectively, with 1.6-1.9 alleles detected per locus. In contrast, among the seven widely separated field populations, the mean heterozygosity ranged from 11% to 16% with 2.1-2.9 alleles per locus. No locus was recovered that was diagnostic for any of the field populations. Allelic frequency differences among five field strains from the Amazon basin and eastern coastal Brazil were very low, with Nei's genetic distances of less than 0.01 separating them. The two inland and southerly samples from Minas Gerais (Lapinha) and Bahia (Jacobina) states were more distinctive with genetic distances of 0.024-0.038 and 0.038-0.059, respectively, when compared with the five other samples. These differences were the consequence of several high frequency alleles (glycerol-3-phosphate dehydrogenase [Gpd1.69] and phosphoglucomutase [Pgm1.69]) relatively uncommon in other strains. The low genetic distances, absence of diagnostic loci, and the distribution of genes in geographic space indicate L. longipalpis of Brazil to be a single, but genetically heterogeneous, polymorphic species.

[Variation of CAG repeats in coding region of ATXN2 gene in different ethnic groups].

PubMed

Chen, Xiao-Chen; Sun, Hao; Mi, Dong-Qing; Huang, Xiao-Qin; Lin, Ke-Qin; Yi, Wen; Yu, Liang; Shi, Lei; Shi, Li; Yang, Zhao-Qing; Chu, Jia-You

2011-04-01

Toinvestigate CAG repeats variation of ATXN2 gene coding region in six ethnic groups that live in comparatively different environments, to evaluate whether these variations are under positive selection, and to find factors driving selection effects, 291 unrelated healthy individuals were collected from six ethnic groups and their STR geneotyping was performed. The frequencies of alleles and genotypes were counted and thereby Slatkin's linearized Fst values were calculated. The UPGMA tree against this gene was constructed. The MDS analysis among these groups was carried out as well. The results from the linearized Fst values indicated that there were significant evolutionary differences of the STR in ATXN2 gene between Hui and Yi groups, but not among the other 4 groups. Further analysis was performed by combining our data with published data obtained from other groups. These results indicated that there were significant differences between Japanese and other groups including Hui, Hani, Yunnan Mongolian, and Inner Mongolian. Both Hui and Mongolian from Inner Mongolia were significantly different from Han. In conclusion, the six ethnic groups had their own distribution characterizations of allelic frequencies of ATXN2 STR, and the potential cause of frequency changes in rare alleles could be the consequence of positive selection.

PrP genotype frequencies and risk evaluation for scrapie in dairy sheep breeds from southern Italy.

PubMed

Martemucci, Giovanni; Iamartino, Daniela; Blasi, Michele; D'Alessandro, Angela Gabriella

2015-12-01

Concerns regarding scrapie in sheep breeding have increased in the last few decades. The present study was carried out in dairy sheep breeds from southern Italy. In order to find breeding animals resistant to scrapie, the PrP genes of 1,205 animals from entire flocks of dairy native Apulian Leccese and Altamurana breeds, and Sicilian Comisana breed, were analysed for polymorphisms at codons 136, 154, and 171 related to scrapie resistance/susceptibility. The Altamurana breed was considered as two populations (Alt-Cav and Alt-Cra-Zoe), based on presumed cross-breeding. A total of five alleles and ten different genotypes were found. The ARQ allele was predominant for all breeds followed by ARR, the most resistant allele to scrapie, which was highly prevalent in Comisana (50%) and in native Alt-Cav (42.4%). The VRQ allele, associated with the highest susceptibility to scrapie, was detected at not negligeable levels in allocthonous Comisana (3.5%), at a low frequency (0.2%) in native Leccese and Alt-Cra-Zoe, while it was absent in Alt-Cav. The frequencies of PrP genotypes with a very low susceptibility risk to scrapie (R1) was higher in Comisana and Alt-Cav. The most susceptible genotype, ARQ/VRQ, was found only in Comisana. Within the Altamurana breed, there were notable differences between Alt-Cav and Alt-Cra-Zoe sheep. The Alt-Cav was characterised by the absence of VRQ and AHQ alleles and by the higher frequency of the ARR/ARR genotype (18.7%). Breeding programs, mainly in endangered breeds such as Altamurana, should be conducted gradually, combining resistance to scrapie, maintenance of genetic variability, and production. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-05-01

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

Allele frequency changes due to hitch-hiking in genomic selection programs

PubMed Central

2014-01-01

Background Genomic selection makes it possible to reduce pedigree-based inbreeding over best linear unbiased prediction (BLUP) by increasing emphasis on own rather than family information. However, pedigree inbreeding might not accurately reflect loss of genetic variation and the true level of inbreeding due to changes in allele frequencies and hitch-hiking. This study aimed at understanding the impact of using long-term genomic selection on changes in allele frequencies, genetic variation and level of inbreeding. Methods Selection was performed in simulated scenarios with a population of 400 animals for 25 consecutive generations. Six genetic models were considered with different heritabilities and numbers of QTL (quantitative trait loci) affecting the trait. Four selection criteria were used, including selection on own phenotype and on estimated breeding values (EBV) derived using phenotype-BLUP, genomic BLUP and Bayesian Lasso. Changes in allele frequencies at QTL, markers and linked neutral loci were investigated for the different selection criteria and different scenarios, along with the loss of favourable alleles and the rate of inbreeding measured by pedigree and runs of homozygosity. Results For each selection criterion, hitch-hiking in the vicinity of the QTL appeared more extensive when accuracy of selection was higher and the number of QTL was lower. When inbreeding was measured by pedigree information, selection on genomic BLUP EBV resulted in lower levels of inbreeding than selection on phenotype BLUP EBV, but this did not always apply when inbreeding was measured by runs of homozygosity. Compared to genomic BLUP, selection on EBV from Bayesian Lasso led to less genetic drift, reduced loss of favourable alleles and more effectively controlled the rate of both pedigree and genomic inbreeding in all simulated scenarios. In addition, selection on EBV from Bayesian Lasso showed a higher selection differential for mendelian sampling terms than selection on genomic BLUP EBV. Conclusions Neutral variation can be shaped to a great extent by the hitch-hiking effects associated with selection, rather than just by genetic drift. When implementing long-term genomic selection, strategies for genomic control of inbreeding are essential, due to a considerable hitch-hiking effect, regardless of the method that is used for prediction of EBV. PMID:24495634

Prolonged P300 latency in children with the D[sub 2] dopamine receptor A1 allele

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

Noble, E.P.; Berman, S.M.; Ozkaragoz, T.Z.

1994-04-01

Previous studies have indicated the presence of a hereditary component in the generation of the P300, or P3, a late positive component of the event-related potential. Moreover, the dopaminergic system has been implicated in the P3. In the present study, 98 healthy Caucasian boys, mean age of 12.5 years and of above-average intelligence, were studied. The sample was composed of 32 sons of active alcoholic (SAA) fathers, 36 sons of recovering alcoholic (SRA) fathers, and 30 sons of social drinker (SSD) fathers, with none of them having yet begun to consume alcohol or other drugs. TaqI A D[sub 2] dopaminemore » receptor alleles (A1 and A2) were determined. A significant difference in the frequency of the A1 allele was found among these three groups of boys, with the SAA group having the highest A1 allele frequency (.313), followed by the SRA (.139) and the SSD (.133) groups. The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between boys with the A1 and A2 allele. However, P3 latency was significantly longer in the total sample of boys with the A1 allele compared with those carrying the A2 allele. These findings suggest that polymorphism of the D[sub 2] dopamine receptor gene is an important determinant of P3 latency. 84 refs., 2 figs., 3 tabs.« less

Molecular diversity of HLA-Cw alleles in the Maratha community of Mumbai, Maharashtra, western India.

PubMed

Shankarkumar, U; Ghosh, K; Mohanty, D

2005-08-01

Recent advances suggest a significant role for the HLA-C locus as a target of alloreactions after bone marrow transplantation. The biological importance of products of the HLA-C locus, both as transplant antigens and as ligands for natural killer (NK) cells, is well established. A total of 10 different serologically defined HLA-Cw antigen specificities (Cw1-Cw10) are encoded by the C locus; however, there are now 151 different alleles that can be identified by molecular methods. Serological definition of Cw alleles therefore includes 20-50% blanks, which cannot be detected by the available antisera. We used the molecular method of polymerase chain reaction (PCR)-based sequence-specific amplification and probe hybridization to define Cw alleles in 91 individuals from the Maratha community, and compared the data with data for 92 serologically typed Maratha individuals from India. We identified Cw*12, Cw*14, Cw*15, Cw*16 and Cw*18, along with the serologically identified Cw*01, Cw*02, Cw*03, Cw*04, Cw*06 and Cw*07 alleles. The HLA-Cw blank allele frequency in the Maratha was reduced from 0.5706 to 0.00. Furthermore, by using a molecular technique, it was possible to identify novel allele subtypes, such as Cw*0104, Cw*0203 and Cw*0707, and a high frequency of Cw* 1801 in the Maratha community compared with other Indian and world populations. Our results will have clinical implications in related and unrelated HLA-matched bone marrow transplantation in India.

Screening of Two ADH4 Variations in a Swedish Cluster Headache Case–Control Material

PubMed Central

Fourier, Carmen; Ran, Caroline; Steinberg, Anna; Sjöstrand, Christina; Waldenlind, Elisabet

2016-01-01

Background Cluster headache (CH) is a severe neurovascular disorder and an increasing amount of evidence points to a genetic contribution to this disease. When CH was first described, it was observed that alcohol may precipitate an attack during the active phase of the disease. The alcohol dehydrogenase 4 (ADH4) gene encodes an enzyme which contributes to the metabolization of alcohol and is, therefore, an interesting candidate gene for CH. Two Italian groups have reported association of the single nucleotide polymorphism (SNP) rs1126671 located in the ADH4 gene with an increased risk of CH in Italy. In addition, one of the groups found an association between the ADH4 SNP rs1800759 and CH. Objective To perform a replication study on the ADH4 SNPs rs1126671 and rs1800759 in a large homogeneous Swedish case–control cohort in order to further investigate the possible contribution of ADH4 to CH. Methods A total of 390 unrelated patients diagnosed with CH and 389 controls representing a general Swedish population were recruited to the study. DNA samples from patients and controls were genotyped for the two ADH4 SNPs rs1126671 and rs1800759 using quantitative real‐time polymerase chain reaction. Statistical analyses of genotype, allele and haplotype frequencies for the two SNPs were performed and compared between patients and controls. Results For rs1126671, the minor allele frequency (A allele) was 32.8% (n = 254) in controls compared with 31.9% (n = 249) in CH patients. The minor allele frequency (A allele) of rs1800759 was 42.3% (n = 324) in controls and 41.9% (n = 327) in CH patients. Statistical analysis showed no significant differences in allele as well as in genotype or haplotype frequencies between the patient and control group for either SNP. This was also seen after stratifying the patient group for experiencing alcohol as a trigger factor. Conclusions The data did not support an association of the ADH4 SNPs rs1126671 and rs1800759 with CH. A comparison with previous studies revealed variance in genotype, allele, and haplotype frequencies among the different populations which might contribute to the contradictory results. Although a significant association with CH in Swedish case–control group was not found, ADH4 as a candidate gene for CH could not be excluded. PMID:27041676

THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites

PubMed Central

Chang, Hsiao-Han; Worby, Colin J.; Yeka, Adoke; Nankabirwa, Joaniter; Kamya, Moses R.; Staedke, Sarah G.; Hubbart, Christina; Amato, Roberto; Kwiatkowski, Dominic P.

2017-01-01

As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available. Estimates limited to monogenomic infections may not be representative, however, and when the average COI is high, they can be difficult or impossible to obtain. Therefore, we developed THE REAL McCOIL, Turning HEterozygous SNP data into Robust Estimates of ALelle frequency, via Markov chain Monte Carlo, and Complexity Of Infection using Likelihood, to incorporate polygenomic samples and simultaneously estimate allele frequency and COI. This approach was tested via simulations then applied to SNP data from cross-sectional surveys performed in three Ugandan sites with varying malaria transmission. We show that THE REAL McCOIL consistently outperforms COIL on simulated data, particularly when most infections are polygenomic. Using field data we show that, unlike with COIL, we can distinguish epidemiologically relevant differences in COI between and within these sites. Surprisingly, for example, we estimated high average COI in a peri-urban subregion with lower transmission intensity, suggesting that many of these cases were imported from surrounding regions with higher transmission intensity. THE REAL McCOIL therefore provides a robust tool for understanding the molecular epidemiology of malaria across transmission settings. PMID:28125584

Population data of six STR loci using hexaplex PCR amplification and typing system, "Midi-6" in four regional populations in Japan.

PubMed

Uchihi, Rieko; Yamamoto, Toshimichi; Yoshimoto, Takashi; Inoue, Chikako; Kishida, Tetsuko; Yoshioka, Naofumi; Katsumata, Yoshinao

2007-07-04

The genetic differences of the allele frequency distributions for six STR loci (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290) among regions in Japan were examined using our recently designed hexaplex amplification and typing system, "Midi-6" newly named, to construct a database in the Japanese population. Genotypes at six loci were analyzed in 198, 200, 175, and 196 individuals from the area of Akita, Nagoya, Oita, and Okinawa, respectively, in Japan. The allele frequency distributions were significantly different (p<0.05) at from one to five loci among the four populations when compared pairwise. Significant differences were also observed at two or three loci between Oita- or Okinawa-Japanese and the "pooled" population (n=769), respectively. However, since F(ST) (theta) values were extremely low (<0.05), ranging from 0.0020 to 0.0118 for six loci, genetic differentiation within the pooled Japanese population was negligible. Therefore, it suggested that the data of the allele frequencies at six loci in the pooled population would be employed as the base of calculation for statistical probabilities.

Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos.

PubMed

Dai, D; Tang, J; Rose, R; Hodgson, E; Bienstock, R J; Mohrenweiser, H W; Goldstein, J A

2001-12-01

CYP3A4 is the most abundant isoform of cytochrome P450 (CYP) in adult human liver. It metabolizes numerous clinically, physiologically, and toxicologically important compounds. The expression of CYP3A4 varies 40-fold in individual human livers, and metabolism of CYP3A4 substrates varies at least 10-fold in vivo. Single nucleotide polymorphisms (SNPs) in CYP3A4 were identified by direct sequencing of genomic DNA in 72 individuals from three different ethnic groups, including Caucasians, Blacks (African-Americans and African pygmies), and Asians. A total of 28 SNPs were identified, including five which produced coding changes M445T (CYP3A4*3), R162Q (CYP3A4*15), F189S (CYP3A4*17), L293P (CYP3A4*18), and P467S (CYP3A4*19). The latter four represent new alleic variants. Racial variability was observed for the frequency of individual SNPs. CYP3A R162Q was identified only in Black populations with an allelic frequency of 4%. CYP3A4 F189S and CYP3A4 M445T were identified in Caucasians with allelic frequencies 2% and 4%, respectively. L293P and P467S were only observed in Asians at allelic frequencies of 2%. The cDNAs for the F189S, L293P, M445T, and P467S mutant alleles were constructed by site-directed mutagenesis and expressed in an Escherichia coli expression system. Testosterone and the insecticide chlorpyrifos were used to assess the catalytic activities of the most common CYP3A4 allele (CYP3A4*1) and its allelic variants. CYP3A4 F189S exhibited lower turnover numbers for testosterone and chlorpyrifos, while CYP3A4 L293P had higher turnover numbers for both substrates. The turnover numbers of the CYP3A4 M445T and P467S alleles to metabolize these compounds were not significantly different from those of wild-type CYP3A4.

Are ‘Endurance’ Alleles ‘Survival’ Alleles? Insights from the ACTN3 R577X Polymorphism

PubMed Central

Fiuza-Luces, Carmen; Ruiz, Jonatan R.; Rodríguez-Romo, Gabriel; Santiago, Catalina; Gómez-Gallego, Félix; Yvert, Thomas; Cano-Nieto, Amalia; Garatachea, Nuria

2011-01-01

Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100–108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain ‘survival’ advantage brought about by α-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition. PMID:21407828

HLA-DRB1 shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population.

PubMed

Konda Mohan, Vasanth; Ganesan, Nalini; Gopalakrishnan, Rajasekhar; Venkatesan, Vettriselvi

2017-10-01

To investigate the presence of the 'shared epitope' (SE) in the HLA-DRB1 alleles in patients with RA and to ascertain the frequency of the HLA-DRB1 alleles with autoantibodies (anti-cyclic citrullinated peptide [anti-CCP] rheumatoid factor [RF]) and disease severity. A total of 200 RA patients and 200 apparently healthy subjects participated in the study. HLA-DRB1 were genotyped using polymerase chain reaction with sequence-specific primer (PCR-SSP). Anti-CCP and RF in serum were determined by in vitro quantitative enzyme-linked immunosorbent assay (ELISA) method. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. Disease activity was assessed by using the disease activity score-28 (DAS-28). Chi-square test and Student's t-test were used in the statistical analysis. A significant increase in the frequency of HLA-DRB1*01, *04, *10 and *14 were identified in RA patients and showed a strong association with the disease susceptibility. While the frequencies of HLA-DRB1*03, *07, *11 and *13 were significantly lower in RA patients than in controls. The other HLA-DRB1 alleles *08, *09, *12, *15 and *16 showed no significant difference. The frequency of anti-CCP and RF antibodies did not showed significant difference in SE-positive patients compared with SE-negative patients. DAS-28 values of RA patients showed no significant difference between SE-positive and SE-negative groups. Our results indicate that HLA-DRB1*01, *04, *10 and *14 alleles are related with RA, while HLA-DRB1*03, *07, *11 and *13 protect against RA in our population. On the other hand, we failed to provide evidence for the association of the autoantibodies and DAS-28 with SE-positive RA patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Association of human leukocyte antigen polymorphism with outcomes of hepatitis B virus infection.

PubMed

Ramezani, Amitis; Hasanjani Roshan, Mohammad Reza; Kalantar, Ebrahim; Eslamifar, Ali; Banifazl, Mohammad; Taeb, Jaleh; Aghakhani, Arezoo; Gachkar, Latif; Velayati, Ali Akbar

2008-11-01

Host genetic and environmental factors are viewed as a common basis of the different outcomes of hepatitis B virus (HBV) infection. Human leukocyte antigen (HLA) plays an important role in immunological reaction to HBV infection. In this study, we aimed to determine the association between HBV infection and HLA-A, B, and DRB1 alleles in northern Iran. HLA-A, B, and DRB1 alleles in 33 patients with chronic hepatitis B (CHB) and 31 healthy carriers as the persistent group, and 30 subjects who had spontaneously recovered from HBV infection were analyzed by using the polymerase chain reaction (PCR)-sequence-specific primer (PCR-SSP) technique. The frequency of the HLA-A*33 allele was higher in the persistent group than in the recovered group (10.16% vs 0%, P < 0.008); the frequency of the DRB1*13 allele was lower in the persistent group than in the recovered group (3.13% vs 11.67%, P < 0.03). The frequency of the B*52 allele was higher in CHB patients than healthy carriers (7.58% vs 0%, P < 0.05). The logistic regression model showed that the presence of the HLA-DRB1*13 allele was the significant factor associated with protection against the persistency of HBV. There were significant differences between the HBV recovered group, CHB patients, and healthy carriers regarding age, hepatitis B e antigen, and anti-hepatitis B e positivity. HLA-A*33 was closely related with susceptibility to persisting hepatitis B infection, and HLA-DRB1*13 was closely related with protection against persisting hepatitis B in an Iranian population. These findings emphasized that the host HLA polymorphism is an important factor in determining the outcome of HBV infection.

[Relationship between interleukin-17A gene polymorphisms and the susceptibility to childhood asthma].

PubMed

Zhong, Fang-Fang; Zou, Yan; Liu, Chun-Yan; Liu, Wen-Jun

2016-12-01

To explore the relationship between polymorphisms of interleukin-17A (IL-17A) gene promoter (-197G/A and -692C/T) and the susceptibility to childhood asthma, to further identify the candidate genes for asthma, and to provide a basis for early prevention of asthma in high-risk children. Sixty-five outpatients or inpatients with childhood asthma between August 2013 and August 2015 were assigned to asthma group. Seventy healthy children within the same period were assigned to control group. Using peripheral venous blood from the two groups, PCR with sequence-specific primers was carried out to determine single nucleotide polymorphisms at positions -197G/A and -692C/T in IL-17A gene promoter. A statistical analysis was used to evaluate differences in genotype and allele frequencies between the two groups. Compared with the control group, the asthma group had significantly higher frequencies of TT genotype (29% vs 16%; P=0.012) and T allele (52% vs 42%; P=0.039) at position -692C/T of IL-17A gene. Children with T allele had 1.413-fold higher risk of childhood asthma than those with C allele (OR=1.413, 95%CI: 1.015-1.917). There were no significant differences in genotype and allele frequencies at position -197G/A in IL-17A gene between the two groups (p>0.05). Polymorphisms at position -692C/T in IL-17A gene promoter is associated with the susceptibility to childhood asthma. Children with -692T allele are more susceptible to childhood asthma. There is no significant relationship between polymorphisms at position -197G/A in IL-17A gene promoter and the susceptibility to childhood asthma.

The Maintenance of Single-Locus Polymorphism. IV. Models with Mutation from Existing Alleles

PubMed Central

Spencer, H. G.; Marks, R. W.

1992-01-01

The ability of viability selection to maintain allelic polymorphism is investigated using a constructionist approach. In extensions to the models we have previously proposed, a population is bombarded with a series of mutations whose fitnesses in conjunction with other alleles are functions of the corresponding fitnesses with a particular allele, the parent allele, already in the population. Allele frequencies are iterated simultaneously, thus allowing alleles to be driven to extinction by selection. Such models allow very high levels of polymorphism to evolve: up to 38 alleles in one case. Alleles that are lethal as homozygotes can evolve to surprisingly high frequencies. The joint evolution of allele frequencies and viabilities highlights the necessity to consider more than the current morphology of a population. Comparisons are made with the neutral theory of evolution and it is suggested that failure to reject neutrality using the Ewens-Watterson test cannot be regarded as evidence for the neutral theory. PMID:1732162

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage.

PubMed

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-07-01

Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele.

Analyses of Genetic Variations of Glutathione S-Transferase Mu1 and Theta1 Genes in Bangladeshi Tannery Workers and Healthy Controls.

PubMed

Akther, Jobaida; Ebihara, Akio; Nakagawa, Tsutomu; Islam, Laila N; Suzuki, Fumiaki; Hosen, Md Ismail; Hossain, Mahmud; Nabi, A H M Nurun

2016-01-01

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/-), 31.4% had GSTT1 (-/+) alleles, and 6.4% had null genotypes (-/-) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/-, 30.5% were -/+, and 8.4% were -/-. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes.

Association of HLA class I alleles with aloplecia areata in Chinese Hans.

PubMed

Xiao, Feng-Li; Yang, Sen; Yan, Kai-lin; Cui, Yong; Liang, Yan-Hua; Zhou, Fu-Sheng; Du, Wen-Hui; Gao, Min; Sun, Liang-Dan; Fan, Xing; Chen, Jian-Jun; Wang, Pei-Guang; Zhu, Ya-Gang; Zhou, Shun-Ming; Zhang, Xue-Jun

2006-02-01

Some studies suggested that human HLA status may potentiate development of the AA phenotype and exists ethic differences. No report has been published about HLA class I alleles associated with AA in Chinese Hans. To study the distribution of HLA class I alleles and haplotypes in Chinese Hans AA patients and the relation of HLA class I profile with age of onset, severity, duration of current attack, past history and family history. The polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA class I alleles in 192 patients with AA and 252 healthy controls in Chinese Hans. The frequencies of HLA-A*02, -A*03, -B*18, -B*27, -B*52 and -Cw*0704 were significantly higher in patients than in controls. The A*2-B*18, A*2-B*27, A*2-B*52, A*2-Cw*0704, B*18-Cw*0704, B*27-Cw*0704, B*52-Cw*0704 were found as high-risk haplotypes in developing AA in this study. The HLA-A*02 and -A*03 were observed increased frequencies in patients less than 50% hair loss, and HLA-B*27 equally in patients of 50-99% hair loss, alopecia totalis and alopecia universalis. The frequencies of HLA-A*02 and -B*27 were significantly raised in recurrent patients, and ones of HLA-A*02, -A*03 and -B*27 similarly in patients without a positive family history. This study demonstrated the positive association of HLA class I alleles and haplotypes with AA. There may be differences in genetic background in patients with different age of onset, grade of scalp hair loss, duration of current attack, a past history and a family history.

Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients.

PubMed

Heneberg, Petr; Kocková, Lucie; Čecháková, Marie; Daňková, Pavlína; Černá, Marie

2018-06-12

A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22. We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA. We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes). The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood. © 2018 S. Karger AG, Basel.

DD genotype of ACE gene in boys: may it be a risk factor for minimal change nephrotic syndrome?

PubMed

Alasehirli, Belgin; Balat, Ayşe; Büyükçelik, Mithat

2012-01-01

It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.

Identification of the third/extra allele for forensic application in cases with TPOX tri-allelic pattern.

PubMed

Picanço, Juliane Bentes; Raimann, Paulo Eduardo; Motta, Carlos Henrique Ares Silveira da; Rodenbusch, Rodrigo; Gusmão, Leonor; Alho, Clarice Sampaio

2015-05-01

Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.

PubMed

Marez, D; Legrand, M; Sabbagh, N; Lo Guidice, J M; Spire, C; Lafitte, J J; Meyer, U A; Broly, F

1997-06-01

The polymorphic cytochrome P450 CYP2D6 is involved in the metabolism of various drugs of wide therapeutic use and is a presumed susceptibility factor for certain environmentally-induced diseases. Our aim was to define the mutations and alleles of the CYP2D6 gene and to evaluate their frequencies in the European population. Using polymerase chain reaction-single strand conformation polymorphism analysis, 672 unrelated subjects were screened for mutations in the 9 exons of the gene and their exon-intron boundaries. A total of 48 point mutations were identified, of which 29 were novel. Mutations 1749 G-->C, 2938 C-->T and 4268 G-->C represented 52.6%, 34.3% and 52.9% of the mutations in the total population, respectively. Of the eight detrimental mutations detected, the 1934 G-->A, the 1795 Tdel and the 2637 Adel accounted for 65.8%, 6.2% and 4.8% respectively, within the poor metabolizer subgroup. Fifty-three different alleles were characterized from the mutation pattern and by allele-specific sequencing. They are derived from three major alleles, namely the wild-type CYP2D6*1A, the functional CYP2D6*2 and the null CYP2D6*4A. Five allelic variants (CYP2D6*1A, *2, *2B, *4A and *5) account for about 87% of all alleles, while the remaining alleles occur with a frequency of 0.1%-2.7%. These data provide a solid basis for future epidemiological, clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight that the described single strand conformation polymorphism method can be successfully used in designing such studies.

Lineage dynamics and mutation-selection balance in non-adapting asexual populations

NASA Astrophysics Data System (ADS)

Pénisson, Sophie; Sniegowski, Paul D.; Colato, Alexandre; Gerrish, Philip J.

2013-02-01

In classical population genetics, mutation-selection balance refers to the equilibrium frequency of a deleterious allele established and maintained under two opposing forces: recurrent mutation, which tends to increase the frequency of the allele; and selection, which tends to decrease its frequency. In a haploid population, if μ denotes the per capita rate of production of the deleterious allele by mutation and s denotes the selective disadvantage of carrying the allele, then the classical mutation-selection balance frequency of the allele is approximated by μ/s. This calculation assumes that lineages carrying the mutant allele in question—the ‘focal allele’—do not accumulate deleterious mutations linked to the focal allele. In principle, indirect selection against the focal allele caused by such additional mutations can decrease the frequency of the focal allele below the classical mutation-selection balance. This effect of indirect selection will be strongest in an asexual population, in which the entire genome is in linkage. Here, we use an approach based on a multitype branching process to investigate this effect, analyzing lineage dynamics under mutation, direct selection, and indirect selection in a non-adapting asexual population. We find that the equilibrium balance between recurrent mutation to the focal allele and the forces of direct and indirect selection against the focal allele is closely approximated by γμ/(s + U) (s = 0 if the focal allele is neutral), where γ ≈ eθθ-(ω+θ)(ω + θ)(Γ(ω + θ) - Γ(ω + θ,θ)), \\theta =U/\\tilde {s}, and \\omega =s/\\tilde {s}; U denotes the genomic deleterious mutation rate and \\tilde {s} denotes the geometric mean selective disadvantage of deleterious mutations elsewhere on the genome. This mutation-selection balance for asexual populations can remain surprisingly invariant over wide ranges of the mutation rate.

FREQ-Seq: A Rapid, Cost-Effective, Sequencing-Based Method to Determine Allele Frequencies Directly from Mixed Populations

PubMed Central

Delaney, Nigel F.; Marx, Christopher J.

2012-01-01

Understanding evolutionary dynamics within microbial populations requires the ability to accurately follow allele frequencies through time. Here we present a rapid, cost-effective method (FREQ-Seq) that leverages Illumina next-generation sequencing for localized, quantitative allele frequency detection. Analogous to RNA-Seq, FREQ-Seq relies upon counts from the >105 reads generated per locus per time-point to determine allele frequencies. Loci of interest are directly amplified from a mixed population via two rounds of PCR using inexpensive, user-designed oligonucleotides and a bar-coded bridging primer system that can be regenerated in-house. The resulting bar-coded PCR products contain the adapters needed for Illumina sequencing, eliminating further library preparation. We demonstrate the utility of FREQ-Seq by determining the order and dynamics of beneficial alleles that arose as a microbial population, founded with an engineered strain of Methylobacterium, evolved to grow on methanol. Quantifying allele frequencies with minimal bias down to 1% abundance allowed effective analysis of SNPs, small in-dels and insertions of transposable elements. Our data reveal large-scale clonal interference during the early stages of adaptation and illustrate the utility of FREQ-Seq as a cost-effective tool for tracking allele frequencies in populations. PMID:23118913

Frequency of APOE, MTHFR and ACE polymorphisms in the Zambian population

PubMed Central

2014-01-01

Background Polymorphisms within the apolipoprotein-E (APOE), Methylenetetrahydrofolate reductase (MTHFR) and Angiotensin I-converting enzyme (ACE) genes has been associated with cardiovascular and cerebrovascular disorders, Alzheimer’s disease and other complex diseases in various populations. The aim of the study was to analyze the allelic and genotypic frequencies of APOE, MTHFR C677T and ACE I/D gene polymorphisms in the Zambian population. Results The allele frequencies of APOE polymorphism in the Zambian populations were 13.8%, 59.5% and 26.7% for the ε2, ε3 and ε4 alleles respectively. MTHFR C677T and ACE I/D allele frequencies were 8.6% and 13.8% for the T and D minor alleles respectively. The ε2ε2 genotype and TT genotype were absent in the Zambian population. The genetic distances between Zambian and other African and non-African major populations revealed an independent variability of these polymorphisms. Conclusion We found that the APOE ε3 allele and the I allele of the ACE were significantly high in our study population while there were low frequencies observed for the MTHFR 677 T and ACE D alleles. Our analysis of the APOE, MTHFR and ACE polymorphisms may provide valuable insight into the understanding of the disease risk in the Zambian population. PMID:24679048

D1S80 (pMCT118) allele frequencies in a Malay population sample from Malaysia.

PubMed

Koh, C L; Lim, M E; Ng, H S; Sam, C K

1997-01-01

The D1S80 allele frequencies in 124 unrelated Malays from the Malaysian population were determined and 51 genotypes and 19 alleles were encountered. The D1S80 frequency distribution met Hardy-Weinberg expectations. The observed heterozygosity was 0.80 and the power of discrimination was 0.96.

Identification of contemporary selection signatures using composite log likelihood and their associations with marbling score in Korean cattle.

PubMed

Ryu, Jihye; Lee, Chaeyoung

2014-12-01

Positive selection not only increases beneficial allele frequency but also causes augmentation of allele frequencies of sequence variants in close proximity. Signals for positive selection were detected by the statistical differences in subsequent allele frequencies. To identify selection signatures in Korean cattle, we applied a composite log-likelihood (CLL)-based method, which calculates a composite likelihood of the allelic frequencies observed across sliding windows of five adjacent loci and compares the value with the critical statistic estimated by 50,000 permutations. Data for a total of 11,799 nucleotide polymorphisms were used with 71 Korean cattle and 209 foreign beef cattle. As a result, 147 signals were identified for Korean cattle based on CLL estimates (P < 0.01). The signals might be candidate genetic factors for meat quality by which the Korean cattle have been selected. Further genetic association analysis with 41 intragenic variants in the selection signatures with the greatest CLL for each chromosome revealed that marbling score was associated with five variants. Intensive association studies with all the selection signatures identified in this study are required to exclude signals associated with other phenotypes or signals falsely detected and thus to identify genetic markers for meat quality. © 2014 Stichting International Foundation for Animal Genetics.

Distribution of human leukocyte antigen alleles and haplotypes in Oroqen and Ewenki nationality minority in Inner Mongolia Autonomous Region of China.

PubMed

Zhang, H B; Wei, S G; Zheng, H B; Yu, B; Lai, J H

2010-10-01

The frequencies of the human leukocyte antigen alleles HLA-A,-B, DRB1 and the A-B, A-DRB1, B-DRB1, A-B-DRB1 haplotypes were investigated through means of PCR-based reverse line-strip sequence specific oligonucleotide hybridization on 108 Oroqen and 104 Ewenki nationality unrelated healthy individuals from the Inner Mongolia Autonomous Region of China. A total of thirteen different HLA-A alleles, 21 different HLA-B alleles and 13 different HLA-DRB1 alleles were detected in the Oroqen ethnic group and the most frequent HLA alleles found were A*24(35.65%), B*15(17.92%), and DRB1*09(17.59%), respectively. The common HLA-A-B-DRB1 haplotypes were A*24-B*40-DRB1*09(5.09%), A*24-B*48-DRB1*12(2.78%) and A*24-B*51-DRB1*04(2.78%); and the HLA-A*33-B*58, A*30-B*13, A*01-B*37, A*33-DRB1*03, A*01-DRB1*10, A*30-DRB1*07, B*37-DRB1*10, B*58-DRB1*03, B*38-DRB1*08, B*13-DRB1*07 were significant positive linkage disequilibrium in the Oroqen nationality group. In total, 14 different HLA-A alleles, 27 B alleles and 12 DRB1 alleles were found in Ewenki nationality group, and the most frequent HLA alleles found were A*24(24.49%), B*40(17.35%), and DRB1*04(14.80%), respectively. The common HLA-A-B-DRB1 haplotypes were A*33-B*58-DRB1*03(6.25%), A*01-B*51-DRB1*11(2.88%) and A*24-B*40-DRB1*09(2.88%); the HLA-A*33-B*58, A*29-B*44, A*03-B*52, A*33-DRB1*03, A*29-DRB1*07, A*24-DRB1*09, B*58-DRB1*03, B*08-DRB1*03, B*46-DRB1*09 were significant positive linkage disequilibrium in Ewenki nationality group. The distribution of HLA A,-B, DRB1, alleles haplotypes frequencies and phylogenetic tree indicated that the Oroqen and Ewenki population groups belongs to northern group of China, together as a group cluster. © 2010 Blackwell Publishing Ltd.

NaV channel variants in patients with painful and nonpainful peripheral neuropathy

PubMed Central

Wadhawan, Samir; Pant, Saumya; Golhar, Ryan; Kirov, Stefan; Thompson, John; Jacobsen, Leslie; Qureshi, Irfan; Ajroud-Driss, Senda; Freeman, Roy; Simpson, David M.; Smith, A. Gordon; Hoke, Ahmet

2017-01-01

Objective: To examine the incidence of nonsynonymous missense variants in SCN9A (NaV1.7), SCN10A (NaV1.8), and SCN11A (NaV1.9) in patients with painful and nonpainful peripheral neuropathy. Methods: Next-generation sequencing was performed on 457 patient DNA samples provided by the Peripheral Neuropathy Research Registry (PNRR). The patient diagnosis was as follows: 278 idiopathic peripheral neuropathy (67% painful and 33% nonpainful) and 179 diabetic distal polyneuropathy (77% painful and 23% nonpainful). Results: We identified 36 (SCN9A), 31 (SCN10A), and 15 (SCN11A) nonsynonymous missense variants, with 47.7% of patients carrying a low-frequency (minor allele frequency <5%) missense variant in at least 1 gene. The incidence of previously reported gain-of-function missense variants was low (≤3%), and these were detected in patients with and without pain. There were no significant differences in missense variant allele frequencies of any gene, or SCN9A haplotype frequencies, between PNRR patients with painful or nonpainful peripheral neuropathy. PNRR patient SCN9A and SCN11A missense variant allele frequencies were not significantly different from the Exome Variant Server, European American (EVS-EA) reference population. For SCN10A, there was a significant increase in the alternate allele frequency of the common variant p.V1073A and low-frequency variant pS509P in PNRR patients compared with EVS-EA and the 1000 Genomes European reference populations. Conclusions: These results suggest that identification of a genetically defined subpopulation for testing of NaV1.7 inhibitors in patients with peripheral neuropathy is unlikely and that additional factors, beyond expression of previously reported disease “mutations,” are more important for the development of painful neuropathy than previously discussed. PMID:29264398

Simulation of introgression of the polled allele into the Holstein breed via conventional breeding versus gene editing

USDA-ARS?s Scientific Manuscript database

The objective of this study was to simulate the introgression of the polled allele into a dairy cattle population and compare the impact of using the methods of conventional breeding versus gene editing to increase the frequency of the polled allele. The rate of minor allele frequency (MAF) change, ...

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

PubMed Central

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-01-01

Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

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

PubMed

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

2018-07-01

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

Frequency of alleles conferring resistance to a Bacillus thuringiensis toxin in a Philippine population of Scirpophaga incertulas (Lepidoptera: Pyralidae).

PubMed

Bentur, J S; Andow, D A; Cohen, M B; Romena, A M; Gould, F

2000-10-01

Using the F2 screen methodology, we estimated the frequency of alleles conferring resistance to the Cry1Ab toxin of Bacillus thuringiensis Berliner in a Philippine population of the stem borer Scirpophaga incertulas (Walker). Evaluation of >450 isofemale lines for survival of F2 larvae on cry1Ab plants did not detect the presence of an allele conferring a high level of resistance. The frequency of such an allele in the sampled population was conservatively estimated to be <3.6 x 10(-3) with 95% confidence and a detection probability of 94%. However, there was evidence of the presence of alleles conferring partial resistance to Cry1Ab. The frequency of alleles for partial resistance was estimated as 4.8 x 10(-3) with a 95% CI between 1.3 x 10(-3) and 1.04 x 10(-2) and a detection probability of 94%. Our results suggest that the frequency of alleles conferring resistance to Cry1Ab in the population of S. incertulas sampled is not too high to preclude successful implementation of the high dose/refuge resistance management strategy.

Polymorphism discovery and allele frequency estimation using high-throughput DNA sequencing of target-enriched pooled DNA samples

PubMed Central

2012-01-01

Background The central role of the somatotrophic axis in animal post-natal growth, development and fertility is well established. Therefore, the identification of genetic variants affecting quantitative traits within this axis is an attractive goal. However, large sample numbers are a pre-requisite for the identification of genetic variants underlying complex traits and although technologies are improving rapidly, high-throughput sequencing of large numbers of complete individual genomes remains prohibitively expensive. Therefore using a pooled DNA approach coupled with target enrichment and high-throughput sequencing, the aim of this study was to identify polymorphisms and estimate allele frequency differences across 83 candidate genes of the somatotrophic axis, in 150 Holstein-Friesian dairy bulls divided into two groups divergent for genetic merit for fertility. Results In total, 4,135 SNPs and 893 indels were identified during the resequencing of the 83 candidate genes. Nineteen percent (n = 952) of variants were located within 5' and 3' UTRs. Seventy-two percent (n = 3,612) were intronic and 9% (n = 464) were exonic, including 65 indels and 236 SNPs resulting in non-synonymous substitutions (NSS). Significant (P < 0.01) mean allele frequency differentials between the low and high fertility groups were observed for 720 SNPs (58 NSS). Allele frequencies for 43 of the SNPs were also determined by genotyping the 150 individual animals (Sequenom® MassARRAY). No significant differences (P > 0.1) were observed between the two methods for any of the 43 SNPs across both pools (i.e., 86 tests in total). Conclusions The results of the current study support previous findings of the use of DNA sample pooling and high-throughput sequencing as a viable strategy for polymorphism discovery and allele frequency estimation. Using this approach we have characterised the genetic variation within genes of the somatotrophic axis and related pathways, central to mammalian post-natal growth and development and subsequent lactogenesis and fertility. We have identified a large number of variants segregating at significantly different frequencies between cattle groups divergent for calving interval plausibly harbouring causative variants contributing to heritable variation. To our knowledge, this is the first report describing sequencing of targeted genomic regions in any livestock species using groups with divergent phenotypes for an economically important trait. PMID:22235840

[Polymorphism of alcohol dehydrogenase gene ADH1B in eastern Slavic and Iranian-speaking populations].

PubMed

2005-11-01

Frequencies of alleles and genotypes for alcohol dehydrogenase gene ADH1B (arg47his polymorphism), associated with alcohol tolerance/sensitivity, were determined. It was demonstrated that the frequency of allele ADH1B*47his, corresponding to atypical alcohol dehydrogenase variant in Russians, Ukrainians, Iranians, and mountain-dwellers of the Pamirs constituted 3, 7, 24, and 22%, respectively. The frequencies established were consistent with the allele frequency distribution pattern among the populations of Eurasia. Russians and Ukrainians were indistinguishable from other European populations relative to the frequency of allele ADH1B*47his, and consequently, relative to specific features of ethanol metabolic pathways. The data obtained provide refinement of the geographic pattern of ADH1B*47his frequency distribution in Eurasia.

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

PubMed

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

2018-06-01

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

Single step PCR for detection of allelic variation of MDR1 gene (P-glycoprotein) among three ethnic groups in Malaysia.

PubMed

Teh, L K; Lee, W L; Amir, J; Salleh, M Z; Ismail, R

2007-06-01

P-glycoprotein (PgP) is the most extensively studied ATP-binding cassette (ABC) coded by MDR1 gene. To date, 29 single nucleotide polymorphisms (SNPs) have been identified; but only SNP C3435T has been correlated with intestinal PgP expression levels and shown to influence the absorption of orally taken drugs that are PgP substrates. Individuals homozygous for the T allele have more than fourfold lower PgP expression compared with C/C individuals. We developed a one step primer based allele specific PCR method to detect SNP at C3435T to investigate the distribution of this genotype in the local population. DNA was extracted from 5 mL of whole blood using standard salting-out method. Primers were designed specific to 3' end which amplify the variants of C3435T. The method was validated by direct DNA sequencing. Seven hundred and sixty-three healthy blood donors comprising of three major ethnic groups in Malaysia were recruited and DNA subjected to genotyping of C3435T using this method. The method was found to be robust and reproducible in detecting SNP of C3435T. Interethnic variations in genotype and allele frequency were observed in PgP among the ethnic groups. In comparison to both the Caucasians and the other Asian countries, the Malay and Chinese showed a higher frequency of allele C (50-60%); while the Indian exhibits a lower frequency (40%), similar to other Indian populations. Using a new simple method to investigate the distribution of C3435T, we found that the allele frequency of MDR1 showed variablity between the different ethnic groups within the Malaysian population.

[Association study between 834+7G/A and +1332C/T polymorphisms in the growth arrest specific 6 gene and risk of severe preeclampsia in Chinese population].

PubMed

Ye, Liyan; Guan, Linbo; Fan, Ping; Liu, Xinghui; Liu, Rui; Chen, Jinxin; Zhu, Yue; Wei, Xin; Liu, Yu; Bai, Huai

2017-02-10

To investigate the relationship between polymorphisms of the growth arrest specific 6 (GAS6) gene and severe preeclampsia in a South West Han Chinese population. Blood samples from 167 patients with severe preeclampsia and 312 normal pregnant women as controls from Han Chinese in Chengdu area were analyzed by polymerase chain reaction-restriction fragment length polymorphisms. C and T allele frequencies for +1332C/T site were 85.63% and 14.37% in the patient group, respectively, and 78.04% and 21.96% in control group, respectively. The TT genotype and variant T allelic frequencies of the +1332C/T polymorphism were significantly lower in patients with severe preeclampsia than in the control group (both P<0.05), and the odds ratio for the risk of severe preeclampsia was 0.602 (95%CI: 0.401-0.904) in carriers for the variant T allele (χ 2 =6.045, P=0.014). G and A allele frequencies for 834+7G/A site were 72.75% and 27.25% in case group, respectively, and 74.36% and 25.64% in control group, respectively. The genotype and allele frequencies of the 834+7G/A polymorphism in patients with severe preeclampsia and controls showed no significant differences (both P>0.05). In addition, there was no significant association between the polymorphisms and blood pressure levels in the patient or control groups. The variant GAS6+1332 T allele is associated with a decreased risk for severe preeclampsia in a South West Han Chinese population. On the other hand, the 834+7G/A polymorphism has no effect on the severe preeclampsia.

[Pharmacogenomics study of 620 whole-exome sequencing: focusing on aspirin application].

PubMed

Yang, L; Lu, Y L; Wang, H J; Zhou, W H

2016-05-01

To investigate the allele frequencies of aspirin-response-related variants in different population. The allele frequencies of reported clinically significant aspirin-response-related variants were evaluated based on 620 whole exome sequencing (WES) data collected from 2013 to 2016 in Children's Hospital of Fudan University.Then the local allele frequencies were compared with 1 000 Genomes project database, and χ(2) test was used. Thirty-eight aspirin-response-related variants that had clinical significance had been detected in the 620 WES data.Ten (26%) of them were related with drug efficacy while 28 (74%) were related with toxicity or adverse drug reaction (ADR). These variants were distributed in 33 genes.There were 23 aspirin-related variants further analysised, and the frequency of 7 (rs1050891, rs6065, rs7862221, rs1065776, rs3818822, rs3775291 and rs1126643) had no significant difference compared with frequency of European and East Asian population of 1 000 Genome project (P>0.01 for both), 10 (rs2228079, rs1613662, rs4523, rs28360521, rs1131882, rs1047626, rs3856806, rs2768759, rs7572857 and rs1126510) of them had no significant difference compared with East Asian but were significantly different from European population, 1 (rs2075797) had no significant difference compared with frequency of European and different with frequency of East Asian, and 5 variants(rs10279545, rs730012, rs16851030, rs1353411, rs1800469)were different from frequency of both East Asian(0.019, 0.058, 0.167, 0.452, 0.340 vs. 0.100, 0.151, 0.396, 0.568, 0.453, χ(2)=21.798, 20.400, 67.543, 16.531, 15.807, P all<0.01) and European population(0.531, 0.312, 0.037, 0.179, 0.688, χ(2)=325.799, 92.877, 144.811, 156.471, 174.533, P all<0.01). Most variants that have clinical significance in aspirin response are related with drug efficacy or drug toxicity or ADR, indicating the urgency of variants screen in clinical practice.Significant population-specificity is detected in local 620 WES data in aspirin-response-related variants.

al mena: a comprehensive resource of human genetic variants integrating genomes and exomes from Arab, Middle Eastern and North African populations.

PubMed

Koshy, Remya; Ranawat, Anop; Scaria, Vinod

2017-10-01

Middle East and North Africa (MENA) encompass very unique populations, with a rich history and encompasses characteristic ethnic, linguistic and genetic diversity. The genetic diversity of MENA region has been largely unknown. The recent availability of whole-exome and whole-genome sequences from the region has made it possible to collect population-specific allele frequencies. The integration of data sets from this region would provide insights into the landscape of genetic variants in this region. We integrated genetic variants from multiple data sets systematically, available from this region to create a compendium of over 26 million genetic variations. The variants were systematically annotated and their allele frequencies in the data sets were computed and available as a web interface which enables quick query. As a proof of principle for application of the compendium for genetic epidemiology, we analyzed the allele frequencies for variants in transglutaminase 1 (TGM1) gene, associated with autosomal recessive lamellar ichthyosis. Our analysis revealed that the carrier frequency of selected variants differed widely with significant interethnic differences. To the best of our knowledge, al mena is the first and most comprehensive repertoire of genetic variations from the Arab, Middle Eastern and North African region. We hope al mena would accelerate Precision Medicine in the region.

Evaluation of 16 SNPs allele-specific to quantify post hSCT chimerism by SYBR green-based qRT-PCR.

PubMed

Almeida, Carlos Arthur Cardoso; Dreyfuss, Juliana Luporini; Azevedo-Shimmoto, Marily Maria; Figueiredo, Maria Stela; de Oliveira, José Salvador Rodrigues

2013-03-01

The importance of monitoring post haematopoietic stem cell transplantation (hSCT) chimerism has been defined in numerous publications. Single-nucleotide polymorphisms (SNPs) are molecular markers that vary significantly among different populations. Allied to a very sensible technique, SNP assays seem to be very sensitive (0.001%) when post hSCT chimerism is measured. However, well known SNP frequencies are limited to certain populations, mainly in countries where there is a high level of diversity in its population, therefore restricting their use worldwide. Amplification by SYBR green based quantitative real time PCR of eight pairs of allele-specific SNPs (MLH-1, PECAM-1, ICAM-1, SUR-1, HA-1, rs715405, rs713503, rs2296600) was conducted in 88 patient/donor pairs, who underwent allogeneic myeloablative or non-myeloablative hSCT. One informative allele was detected in at least 42% (n=37) of the samples; 20% (n=18) had at least two informative alleles; 10% (n=9) had at least three informative alleles; 9% (n=8) had more than three informative alleles and 18% (n=16) showed no informative allele at all. Overall, the frequency of informative alleles for these SNPs in the Brazilian population was very low. Consequently, the amount of information attained reached 9% of those expected, being able to discriminate only eight pairs of donor/recipient samples with more than three informative alleles, making them useless for the quantification of chimerism in our routine.

The relationship between interleukin-10 gene polymorphism at position -1082 and susceptibility to gingivitis in children.

PubMed

Dashash, M; Blinkhorn, A S; Hutchinson, I V; Pravica, V; Drucker, D B

2005-09-01

Interleukin (IL)-10 is an anti-inflammatory cytokine. The protective role of this cytokine against different diseases has been demonstrated in several studies. However, no such study has been carried out on gingivitis. The objective of this study was to determine whether differences exist between Caucasian children with and without gingivitis in the distribution of IL-10 alleles at position -1082. A total of 260 Caucasian children (86 controls, 174 patients), aged 8 to 12 years, from the University Dental Hospital of Manchester, U.K., were examined. Plaque (PI), calculus (CI), gingival (GI), and bleeding on probing (BOP) indices were used to assess gingival health. DNA was obtained from buccal epithelial cells. Amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping IL-10 polymorphism. Chi square tests were carried out to test the association between allele and genotype frequencies and the severity of gingivitis. Multiple logistic regression was used to determine the role of IL-10 gene polymorphism at position -1082 while adjusting for potential confounders such as plaque, age, and gender. Gingivitis was present in 67% of the children examined. Frequencies of alleles -1082*A and -1082*G were 45% and 55%, respectively. An increased risk of having gingivitis was found in allele A positive children (G/A, A/A); 75% versus 25% in allele A negative children (G/G); (P = 0.01). The -1082*A allele was significantly more common in children with gingivitis; 49% versus 37% in controls (P = 0.01). Multivariate logistic regression analysis showed that allele A remained a risk factor for gingivitis in children (P = 0.03) regardless of plaque or age. Also, allele A positive children were at increased odds of having gingivitis of 1.8 (95% confidence interval [CI]: 1.05 to 3.06) compared to allele A negative children after adjusting for plaque, age, and gender. These data suggest that the -1082*A allele could be a risk factor for gingivitis.

Selection in a subdivided population with local extinction and recolonization.

PubMed Central

Cherry, Joshua L

2003-01-01

In a subdivided population, local extinction and subsequent recolonization affect the fate of alleles. Of particular interest is the interaction of this force with natural selection. The effect of selection can be weakened by this additional source of stochastic change in allele frequency. The behavior of a selected allele in such a population is shown to be equivalent to that of an allele with a different selection coefficient in an unstructured population with a different size. This equivalence allows use of established results for panmictic populations to predict such quantities as fixation probabilities and mean times to fixation. The magnitude of the quantity N(e)s(e), which determines fixation probability, is decreased by extinction and recolonization. Thus deleterious alleles are more likely to fix, and advantageous alleles less likely to do so, in the presence of extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations. PMID:12807797

Phenotypic and allelic distribution of the ABO and Rhesus (D) blood groups in the Cameroonian population.

PubMed

Ndoula, S T; Noubiap, J J N; Nansseu, J R N; Wonkam, A

2014-06-01

Data on blood group phenotypes are important for blood transfusion programs, for disease association and population genetics studies. This study aimed at reporting the phenotypic and allelic distribution of ABO and Rhesus (Rh) groups in various ethnolinguistic groups in the Cameroonians. We obtained ABO and Rhesus blood groups and self-identified ethnicity from 14,546 Cameroonian students. Ethnicity was classified in seven major ethnolinguistic groups: Afro-Asiatic, Nilo-Saharan, Niger-Kordofanian/West Atlantic, Niger-Kordofanian/Adamawa-Ubangui, Niger-Kordofanian/Benue-Congo/Bantu/Grassfield, Niger-Kordofanian/Benue-Congo/Bantu/Mbam and Niger-Kordofanian/Benue-Congo/Bantu/Equatorial. ABO allelic frequencies were determined using the Bernstein method. Differences in phenotypic distribution of blood groups were assessed using the chi-square test; a P value <0.05 being considered as statistically significant. The frequencies of the antigens of blood groups O, A, B and AB were 48.62%, 25.07%, 21.86% and 4.45%, respectively. Rhesus-positive was 96.32%. The allelic frequencies of O, A and B genes were 0.6978, 0.1605 and 0.1416, respectively. Phenotypic frequencies of the blood groups in the general study population and in the different ethnolinguistic groups were in agreement with Hardy-Weinberg equilibrium expectations (P > 0.05). The frequencies of O, A, and B blood phenotypes were significantly lower, respectively, in the Nilo-Saharan group (P = 0.009), the Niger-Kordofanian/Benue-Congo/Bantu groups (P = 0.021) and the Niger-Kordofanian/West-Atlantic group. AB blood group was most frequent in the Niger-Kordofanian/Adamawa-Ubangui group (P = 0.024). Our study provides the first data on ethnic distribution of ABO and Rhesus blood groups in the Cameroonian population and suggests that its general profile is similar to those of several sub-Saharan African populations. We found some significant differences in phenotypic distribution amongst major ethnolinguistic groups. These data may be important for blood donor recruitment policy and blood transfusion service in Cameroon. © 2014 John Wiley & Sons Ltd.

Human Leukocyte Antigens and Systemic Lupus Erythematosus: A Protective Role for the HLA-DR6 Alleles DRB1*13:02 and *14:03

PubMed Central

Furukawa, Hiroshi; Kawasaki, Aya; Oka, Shomi; Ito, Ikue; Shimada, Kota; Sugii, Shoji; Hashimoto, Atsushi; Komiya, Akiko; Fukui, Naoshi; Kondo, Yuya; Ito, Satoshi; Hayashi, Taichi; Matsumoto, Isao; Kusaoi, Makio; Amano, Hirofumi; Nagai, Tatsuo; Hirohata, Shunsei; Setoguchi, Keigo; Kono, Hajime; Okamoto, Akira; Chiba, Noriyuki; Suematsu, Eiichi; Katayama, Masao; Migita, Kiyoshi; Suda, Akiko; Ohno, Shigeru; Hashimoto, Hiroshi; Takasaki, Yoshinari; Sumida, Takayuki; Nagaoka, Shouhei

2014-01-01

Many studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic lupus erythematosus (SLE) have been performed. However, few protective associations with HLA-DRB1 alleles have been reported. Here, we sought protective, as well as predispositional, alleles of HLA-DRB1 in Japanese SLE patients. An association study was conducted for HLA-DRB1 in Japanese SLE patients. Relative predispositional effects were analyzed by sequential elimination of carriers of each allele with the strongest association. We also explored the association of DRB1 alleles with SLE phenotypes including the presence of autoantibody and clinical manifestations. Significantly different carrier frequencies of certain DRB1 alleles were found to be associated with SLE as follows: increased DRB1*15:01 (P = 5.48×10−10, corrected P (Pc) = 1.59×10−8, odds ratio [OR] 2.17, 95% confidence interval [CI] 1.69–2.79), decreased DRB1*13:02 (P = 7.17×10−5, Pc = 0.0020, OR 0.46, 95% CI 0.34–0.63) and decreased DRB1*14:03 (P = 0.0010, Pc = 0.0272, OR 0.34, 95% CI 0.18–0.63). Additionally, the “*15:01/*13:02 or *14:03” genotype tended to be negatively associated with SLE (P = 0.4209, OR 0.66), despite there being significant positive associations with *15:01 when present together with alleles other than *13:02 or *14:03 (P = 1.79×10−11, OR 2.39, 95% CI 1.84–3.10). This protective effect of *13:02 and *14:03 was also confirmed in SLE patients with different clinical phenotypes. To the best of our knowledge, this is the first report of a protective association between the carrier frequencies of HLA-DRB1*13:02 and *14:03 and SLE in the Japanese population. PMID:24498373

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB1*13:02 and *14:03.

PubMed

Furukawa, Hiroshi; Kawasaki, Aya; Oka, Shomi; Ito, Ikue; Shimada, Kota; Sugii, Shoji; Hashimoto, Atsushi; Komiya, Akiko; Fukui, Naoshi; Kondo, Yuya; Ito, Satoshi; Hayashi, Taichi; Matsumoto, Isao; Kusaoi, Makio; Amano, Hirofumi; Nagai, Tatsuo; Hirohata, Shunsei; Setoguchi, Keigo; Kono, Hajime; Okamoto, Akira; Chiba, Noriyuki; Suematsu, Eiichi; Katayama, Masao; Migita, Kiyoshi; Suda, Akiko; Ohno, Shigeru; Hashimoto, Hiroshi; Takasaki, Yoshinari; Sumida, Takayuki; Nagaoka, Shouhei; Tsuchiya, Naoyuki; Tohma, Shigeto

2014-01-01

Many studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic lupus erythematosus (SLE) have been performed. However, few protective associations with HLA-DRB1 alleles have been reported. Here, we sought protective, as well as predispositional, alleles of HLA-DRB1 in Japanese SLE patients. An association study was conducted for HLA-DRB1 in Japanese SLE patients. Relative predispositional effects were analyzed by sequential elimination of carriers of each allele with the strongest association. We also explored the association of DRB1 alleles with SLE phenotypes including the presence of autoantibody and clinical manifestations. Significantly different carrier frequencies of certain DRB1 alleles were found to be associated with SLE as follows: increased DRB1*15:01 (P = 5.48×10⁻¹⁰, corrected P (Pc) = 1.59×10⁻⁸, odds ratio [OR] 2.17, 95% confidence interval [CI] 1.69-2.79), decreased DRB1*13:02 (P = 7.17×10⁻⁵, Pc = 0.0020, OR 0.46, 95% CI 0.34-0.63) and decreased DRB1*14:03 (P = 0.0010, Pc = 0.0272, OR 0.34, 95% CI 0.18-0.63). Additionally, the "*15:01/*13:02 or *14:03" genotype tended to be negatively associated with SLE (P = 0.4209, OR 0.66), despite there being significant positive associations with *15:01 when present together with alleles other than *13:02 or *14:03 (P = 1.79×10⁻¹¹, OR 2.39, 95% CI 1.84-3.10). This protective effect of *13:02 and *14:03 was also confirmed in SLE patients with different clinical phenotypes. To the best of our knowledge, this is the first report of a protective association between the carrier frequencies of HLA-DRB1*13:02 and *14:03 and SLE in the Japanese population.

A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism.

PubMed

Bentz, Eva-Katrin; Hefler, Lukas A; Kaufmann, Ulrike; Huber, Johannes C; Kolbus, Andrea; Tempfer, Clemens B

2008-07-01

To assess the association between transsexualism and allele and genotype frequencies of the common cytochrome P450 (CYP) 17 -34 T>C single nucleotide polymorphism (SNP). Case-control study. Academic research institution. 102 male-to-female (MtF) and 49 female-to-male (FtM) transsexuals, 756 male controls, and 915 female controls. Buccal swabs and multiplex polymerase chain reaction on a microarray system. Analysis of the CYP17 -34 T>C SNP. CYP17 -34 T>C SNP allele frequencies were statistically significantly different between FtM transsexuals and female controls (CYP17 T: 55/98 [56%] and CYP17 C: 43/98 [44%] versus CYP17 T: 1253/1826 [69%] and CYP17 C: 573/1826 [31%], respectively). In accordance, genotype distributions were also different between FtM transsexuals and female controls using a recessive genotype model (CYP17 T/T+T/C: 39/49 [80%] and C/C 10/49 [20%] vs. CYP17 T/T+T/C: 821/913 [90%] and C/C 92/913 [10%], respectively). The CYP17 -34 T>C allele and genotype distributions were not statistically significantly different between MtF transsexuals and male controls. Of note, the CYP17 -34 T>C allele distribution was gender-specific among controls (CYP17 C: males; 604 of 1512 [40%] vs. females; 573 of 1826 [31%]). The MtF transsexuals had an allele distribution equivalent to male controls, whereas FtM transsexuals did not follow the gender-specific allele distribution of female controls but rather had an allele distribution equivalent to MtF transsexuals and male controls. These data support CYP17 as a candidate gene of FtM transsexualism and indicate that loss of a female-specific CYP17 T -34C allele distribution pattern is associated with FtM transsexualism.

MNS, Duffy, and Kell blood groups among the Uygur population of Xinjiang, China.

PubMed

Lin, G Y; Du, X L; Shan, J J; Zhang, Y N; Zhang, Y Q; Wang, Q H

2017-03-15

Human blood groups are a significant resource for patients, leading to a fierce international competition in the screening of rare blood groups. Some rare blood group screening programs have been implemented in western countries and Japan, but not particularly in China. Recently, the genetic background of ABO and Rh blood groups for different ethnic groups or regions in China has been focused on increasingly. However, rare blood groups such as MN, Duffy, Kidd, MNS, and Diego are largely unexplored. No systematic reports exist concerning the polymorphisms and allele frequencies of rare blood groups in China's ethnic minorities such as Uygur and Kazak populations of Xinjiang, unlike those on the Han population. Therefore, this study aimed to investigate the allele frequencies of rare blood groups, namely, MNS, Duffy, Kell, Dombrock, Diego, Kidd, Scianna, Colton, and Lutheran in the Uygur population of Xinjiang Single specific primer-polymerase chain reaction was performed for genotyping and statistical analysis of 9 rare blood groups in 158 Uygur individuals. Allele frequencies were compared with distribution among other ethnic groups. Observed and expected values of genotype frequencies were compared using the chi-square test. Genotype frequencies obeyed the Hardy-Weinberg equilibrium (P > 0.5) and allele frequencies were stable. Of all subjects detected, 4 cases carried the rare phenotype S - s - of MNS blood group (frequency of 0.0253), and 1 case carried the phenotype Jk a-b- (frequency of 0.0063). Frequencies of the four groups, MNS, Duffy, Dombrock, and Diego, in the Uygur population differed from those in other ethnic groups. Gene distribution of the Kell, Kidd, and Colton was similar to that in Tibetan and Han populations, though there were some discrepancies. Gene distribution of Scianna and Lutheran groups showed monomorphism similar to that in Tibetan and Han populations. These findings could contribute to the investigation of the origin, evolution, and hematology of Uygur population of Xinjiang and assist in screening of rare blood groups in ethnic minorities, meeting of clinical blood supply demands, and building of the national rare blood group library.

Measuring the Sensitivity of Single-locus “Neutrality Tests” Using a Direct Perturbation Approach

PubMed Central

Garrigan, Daniel; Lewontin, Richard; Wakeley, John

2010-01-01

A large number of statistical tests have been proposed to detect natural selection based on a sample of variation at a single genetic locus. These tests measure the deviation of the allelic frequency distribution observed within populations from the distribution expected under a set of assumptions that includes both neutral evolution and equilibrium population demography. The present study considers a new way to assess the statistical properties of these tests of selection, by their behavior in response to direct perturbations of the steady-state allelic frequency distribution, unconstrained by any particular nonequilibrium demographic scenario. Results from Monte Carlo computer simulations indicate that most tests of selection are more sensitive to perturbations of the allele frequency distribution that increase the variance in allele frequencies than to perturbations that decrease the variance. Simulations also demonstrate that it requires, on average, 4N generations (N is the diploid effective population size) for tests of selection to relax to their theoretical, steady-state distributions following different perturbations of the allele frequency distribution to its extremes. This relatively long relaxation time highlights the fact that these tests are not robust to violations of the other assumptions of the null model besides neutrality. Lastly, genetic variation arising under an example of a regularly cycling demographic scenario is simulated. Tests of selection performed on this last set of simulated data confirm the confounding nature of these tests for the inference of natural selection, under a demographic scenario that likely holds for many species. The utility of using empirical, genomic distributions of test statistics, instead of the theoretical steady-state distribution, is discussed as an alternative for improving the statistical inference of natural selection. PMID:19744997

LINGO1 rs9652490 and rs11856808 polymorphisms are not associated with risk for multiple sclerosis

PubMed Central

2013-01-01

Background Some recent experimental data suggest a possible role of LINGO-1 in the pathogenesis of multiple sclerosis (MS). In an attempt to identify genetic biomarkers related to MS susceptibility, we genotyped two common SNPs in the LINGO1 gene which have been associated to other neurological conditions, in patients with MS and in healthy subjects. These SNPs are linked to several SNPs within the LINGO1 gene, especially in individuals of Oriental or Caucasian descent. Methods We analyzed the allelic and genotype frequency of two LINGO1 variants (rs9652490 and rs11856808) in 293 patients with MS and 318 healthy controls, using KASPar assays. Results LINGO1 rs9652490 and rs11856808 allelic and genotype frequencies did not differ significantly between MS patients and controls. The minor allele frequencies for rs9652490 were 0.171 (95% CI = 0.140-0.201) and 0.167 (95% CI = 0.138-0.196 for cases and controls respectively (p = 0.853). For rs11856808 the minor allele frequencies were 0.317 (95% CI = 0.280-0.355) and 0.310 (95% CI = 0.274-0.346) for cases and controls, respectively (p = 0.773). Allele and genotype frequencies were unrelated with the age of onset of MS, gender, and clinical course of MS. In addition, haplotype analyses did not reveal any putative risk related to haplotypes. Conclusions These results suggest that LINGO1 rs9652490 and rs11856808 polymorphisms are not related with risk for MS. This study adds to other published evidence indicating that, to date, the LINGO1 SNPs studied here could be useful risk biomarkers of developing essential tremor, but not other movement disorders. PMID:23574883

Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico

PubMed Central

Contreras-Cubas, Cecilia; Sánchez-Hernández, Beatríz E.; García-Ortiz, Humberto; Martínez-Hernández, Angélica; Barajas-Olmos, Francisco; Cid, Miguel; Mendoza-Caamal, Elvia C.; Centeno-Cruz, Federico; Ortiz-Cruz, Gabriela; Jiménez-López, José Concepción; Córdova, Emilio J.; Salas-Bautista, Eva Gabriela; Saldaña-Alvarez, Yolanda; Fernández-López, Juan Carlos; Mutchinick, Osvaldo M.

2016-01-01

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Folate deficiency has been related to several conditions, including neural tube defects (NTDs) and cardiovascular diseases. Hence, MTHFR genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C MTHFR polymorphisms in Mexican Amerindians (MAs), from the largest sample included in a genetic study (n = 2026, from 62 ethnic groups), and in a geographically-matched Mexican Mestizo population (MEZ, n = 638). The 677T allele was most frequent in Mexican individuals, particularly in MAs. The frequency of this allele in both MAs and MEZs was clearly enriched in the South region of the country, followed by the Central East and South East regions. In contrast, the frequency of the 1298C risk allele in Mexicans was one of the lowest in the world. Both in MAs and MEZs the variants 677T and 1298C displayed opposite allele frequency gradients from southern to northern Mexico. Our findings suggest that in Mestizos the 677T allele was derived from Amerindians while the 1298C allele was a European contribution. Some subgroups showed an allele frequency distribution that highlighted their genetic diversity. Notably, the distribution of the frequency of the 677T allele was consistent with that of the high incidence of NTDs reported in MEZ. PMID:27649570

Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity.

PubMed

Way, Baldwin M; Lieberman, Matthew D

2010-06-01

Genes and culture are often thought of as opposite ends of the nature-nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism-collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism-collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences.

Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity

PubMed Central

Lieberman, Matthew D.

2010-01-01

Genes and culture are often thought of as opposite ends of the nature–nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism–collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism–collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences. PMID:20592043

The G allele in IL-10-1082 G/A may have a role in lowering the susceptibility to panic disorder in female patients.

PubMed

Kim, Han-Joon; Kim, Yong-Ku

2016-12-01

Immune system activation is involved in the pathophysiology of panic disorder (PD). We investigated INF-γ+874 A/T, TNF-α-308 G/A, and IL-10-1082 G/A single nucleotide polymorphisms (SNPs) to determine their association with PD. This study enroled 135 PD patients and 135 healthy controls. INF-γ+874 A/T (rs2430561), TNF-α-308 G/A (rs1800629), and IL-10-1082 G/A (rs1800896) were genotyped. There were no differences in genotypes or allele frequencies between the patient and control groups, regardless of accompanying agoraphobia. However, for female patients, the G allele frequency in IL-10 SNP was higher in the control group than in the patient group. Additionally, the female control group had a higher frequency of the A/G and G/G genotype in the IL-10 SNP than the female patient group. We suggest that the G allele in IL-10-1082 G/A might have a role in reducing the manifestations of PD in female patients. Further studies are needed to extend and confirm our findings.

[Association between polymorphism in DVWA and IL-1beta and Kashin-Beck disease].

PubMed

Y U, Min; Guo, Xiong; Gao, Xiao-Yun; Lai, Jiang-Hua; Tu, Qian-Qian

2010-07-01

To investigate the association between IL-1beta and DVWA gene and Kashin-Beck disease (KBD). Peripheral genomic DNA were extracted from 105 patients with KBD and 98 healthy controls. PCR-RFLP were performed to detect SNP loci of IL-1beta gene and DVWA gene. The patients with KBD had significantly higher frequency of rs16944 (IL-1beta) locus (chi2 = 24.28, P < 0.001) and single allele frequency of rs16944 (chi2 = 5.683, P = 0.0171) than the healthy controls. There were no significant differences in genotype frequencies,single allele frequencies and haplotypes in rs4685241 and rs1143627 between the patients with KBD and the healthy controls. rs16944 (IL-1beta) is associated with KBD.

Interleukin-1beta gene polymorphisms in Taiwanese patients with gout.

PubMed

Chen, Man-Ling; Huang, Chung-Ming; Tsai, Chang-Hai; Tsai, Fuu-Jen

2005-04-01

The purpose of this study was to examine whether interleukin-1 beta (IL-1beta) promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical manifestations in Taiwanese patients with gout. The study included 196 patients in addition to 103 unrelated healthy control subjects living in central Taiwan. From genomic DNA, polymorphisms of the gene for IL-1beta promoter and IL-1beta exon 5 were typed. Allelic frequencies were compared between the two groups, and the relationship between allelic frequencies and clinical manifestations of gout was evaluated. No significant differences were observed in the allelic frequencies of the IL-1beta promoter between patients with gout and healthy control subjects. Additionally, we did not detect any association of the IL-1beta promoter genotype with the clinical and laboratory profiles of gout patients. However, there was a significant difference between the two groups in terms of hypertriglyceridemia (P=0.0004, chi(2)=12.52, OR 7.14, 95%CI 0.012-0.22). There was also a significant difference in the genotype of IL-1beta exon 5 polymorphism between patients with and without hypertriglyceridemia. Results of the present study suggest that polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are not related to gout patients in central Taiwan.

Frequencies of Null Alleles at Enzyme Loci in Natural Populations of Ponderosa and Red Pine

PubMed Central

Allendorf, Fred W.; Knudsen, Kathy L.; Blake, George M.

1982-01-01

Pinus ponderosa and P. resinosa population samples have mean frequencies of enzymatically inactive alleles of 0.0031 and 0.0028 at 29 and 27 enzyme loci, respectively. Such alleles are rare and are apparently maintained by selection-mutation balance. Ponderosa pine have much higher amounts of allozymic and polygenic phenotypic variation than red pine, yet both species have similar frequencies of null alleles. Thus, null alleles apparently do not contribute to polygenic variation, as has been suggested. The concordance between allozymic and polygenic variation adds support to the view that allozyme studies may be valuable in predicting the relative amount of polygenic variation in populations. PMID:17246067

Apolipoprotein E polymorphism in the Greek population.

PubMed

Sklavounou, E; Economou-Petersen, E; Karadima, G; Panas, M; Avramopoulos, D; Varsou, A; Vassilopoulos, D; Petersen, M B

1997-10-01

The APOE gene is located on chromosome 19, and the three common alleles are designated epsilon2, epsilon3, and epsilon4. The epsilon4 allele is associated with increased plasma cholesterol, atherosclerosis and cardiovascular disease, Alzheimer's disease, and decreased longevity. The objective of the present study was to estimate the distribution of APOE alleles in the Greek population by DNA analysis. The material consisted of 216 voluntary, healthy Greek blood donors (146 males/70 females). The APOE allele frequencies were epsilon2: 5.3%, epsilon3: 88.2%, epsilon4: 6.5%. The epsilon4 allele frequency of 6.5% in the Greek population is, together with the frequency in the Chinese population, among the lowest in the world.

Analyses of Genetic Variations of Glutathione S-Transferase Mu1 and Theta1 Genes in Bangladeshi Tannery Workers and Healthy Controls

PubMed Central

Akther, Jobaida; Ebihara, Akio; Nakagawa, Tsutomu; Islam, Laila N.; Suzuki, Fumiaki; Hosen, Md. Ismail; Hossain, Mahmud; Nabi, A. H. M. Nurun

2016-01-01

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/−), 31.4% had GSTT1 (−/+) alleles, and 6.4% had null genotypes (−/−) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/−, 30.5% were −/+, and 8.4% were −/−. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes. PMID:27294127

Serotonin transporter gene-linked polymorphic region: allele distributions in relationship to body weight and in anorexia nervosa.

PubMed

Hinney, A; Barth, N; Ziegler, A; von Prittwitz, S; Hamann, A; Hennighausen, K; Pirke, K M; Heils, A; Rosenkranz, K; Roth, H; Coners, H; Mayer, H; Herzog, W; Siegfried, A; Lehmkuhl, G; Poustka, F; Schmidt, M H; Schäfer, H; Grzeschik, K H; Lesch, K P; Lentes, K U; Remschmidt, H; Hebebrand, J

1997-01-01

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.

-383 A/C tumor necrosis factor receptor 1 polymorphism and ankylosing spondylitis in Mexicans: a preliminary study.

PubMed

Corona-Sanchez, Esther Guadalupe; Muñoz-Valle, José Francisco; Gonzalez-Lopez, Laura; Sanchez-Hernandez, Julia Dolores; Vazquez-Del Mercado, Monica; Ontiveros-Mercado, Heriberto; Huerta, Miguel; Trujillo, Xochitl; Rocha-Muñoz, Alberto Daniel; Celis, Alfredo; Ortega-Flores, Ricardo; Gamez-Nava, Jorge Ivan

2012-08-01

The objective of this study was to evaluate the differences in allele and genotype frequencies of -383 tumor necrosis factor receptor 1 (TNFR1) polymorphism between ankylosing spondylitis (AS) and controls. Mexican Mestizos with AS were matched by gender, age, and ethnicity with healthy controls and compared in allele and genotype frequencies of the -383 TNFR1 polymorphism. Polymorphisms were genotyped using PCR-RFLP. The AA genotype occurred at a higher frequency in the AS group (92%) compared with controls (79%, P = 0.03). A allele was increased in AS (96% vs. 88%, P = 0.015) and was associated with genetic susceptibility for AS (odds ratio = 3.48, 95% CI = 1.23-10.61). This preliminary study is the first assessing the association of the -383 A/C TNFR1 polymorphism with AS, although it has the limitation of a small sample size. These data are of interest for the genetic epidemiology of AS in the Mexican population, requiring further investigation in other countries.

Distribution of a length polymorphism 5{prime} to exon 1 of the antithrombin III (ATIII) gene in the Chinese

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

Low, P.S.; Liu, Y.; Saha, N.

A length polymorphism at the 5{prime} untranslated region of the ATIII gene has been described as having been detected by polymerase chain reaction (PCR) with a frequency of 0.75 for the short allele (S) in the Caucasian population. This length polymorphism of the ATIII gene has been studied in 251 Chinese healthy subjects. Genomic DNA was amplified by PCR with primers of published sequences. Fragments of the amplified DNA were separated by agarose gel electrophoresis (3% NuSieve and 1% Seakem GTG) and photographed on a UV transilluminator. The frequency of the short allele (S) was found to be significantly lowermore » (0.37) than that in the Caucasians (0.75). The distribution of genotypes of this polymorphism of the ATIII gene was at Hardy-Weinberg equilibrium. The large difference of allelic frequencies in the Mongoloid and Caucasian populations makes it a useful marker for population studies.« less

APOE, MTHFR, LDLR and ACE polymorphisms among Angami and Lotha Naga populations of Nagaland, India.

PubMed

Murry, Benrithung; Vakha, Neikethono; Achoubi, Nongthombam; Sachdeva, M P; Saraswathy, K N

2011-12-01

Several common polymorphisms in the ApoE, ACE, MTHFR and LDLR genes have been implicated in the pathogenesis of common complex diseases across world populations. This study investigates the prevalence of five known and clinically important common polymorphisms in Angami and Lotha Naga populations. A total of 112 unrelated healthy volunteers (52 Lotha Nagas and 60 Angami Nagas) participated in the study. All the five genes were found to be polymorphic in the studied populations. The Lotha Nagas displayed higher mutant allele frequencies than the Angami Nagas except for the T allele frequency of the AvaII polymorphism of the LDLR gene, though chi square did not reveal any significant population differences by genotypes. In view of the relatively high mutant allele frequencies in both the populations, they are likely to be at a high risk of developing various complex diseases as they shift from an active and rigorous lifestyle to a more sedentary one.

Differences in MCT1 A1470T polymorphism prevalence between runners and swimmers.

PubMed

Ben-Zaken, S; Eliakim, A; Nemet, D; Rabinovich, M; Kassem, E; Meckel, Y

2015-06-01

Skeletal muscle is the major producer and user of lactate in the body. Therefore, transport of lactate across cells' membrane is of considerable importance. Lactate transport is mediated by proton-linked monocarboxylate transporter (MCT1). The A1470T polymorphism (rs1049434) in MCT1 gene influences lactate transport, with T allele associated with reduction of lactate transport rate and elevation in blood lactate levels. The aim of the current study was to compare allelic and genotype frequencies of MCT1 A1470T polymorphism among Israeli track-and-field athletes, swimmers, and non-athletes. Genomic DNA was extracted from 173 track-and-field athletes (age 17-50), 80 swimmers (age 16-49), and 128 non-athletes (age 19-29). Track-and-field athletes were assigned to three subgroups: long-distance runners, middle-distance runners, and power event athletes. Swimmers were assigned to two subgroups: long-distance swimmers and short-distance swimmers. Genotyping was performed using polymerase chain reaction. T-allele frequency was significantly higher among long-distance swimmers (45%) compared with long- and middle-distance runners (27% and 30%, respectively; P < 0.01). In addition, T-allele frequency was significantly higher among short-distance swimmers (40%) compared with power event athletes (25%, P < 0.01). Overall, T-allele frequency was significantly higher among swimmers (42%) compared with runners (27%, P < 0.001). More research is needed to clarify whether this polymorphism displays advantage for swimming performance. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Power to Detect Linkage Disequilibrium with Quantitative Traits in Selected Samples

PubMed Central

Abecasis, Gonçalo R.; Cookson, William O. C.; Cardon, Lon R.

2001-01-01

Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL–marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis. PMID:11349228

Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population.

PubMed

Méndez, Claudia; Rey, Mauricio

2015-12-30

Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism. ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells. Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant. This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2 * 2, CYP2E1 * 1 combined with genotype homozygous ALDH2 * 1 found in this study could be leading to the population to a potential risk to alcoholism.

Genetic distribution of 15 autosomal STR markers in the Punjabi population of Pakistan.

PubMed

Shan, Muhammad Adnan; Hussain, Manzoor; Shafique, Muhammad; Shahzad, Muhammad; Perveen, Rukhsana; Idrees, Muhammad

2016-11-01

Genetic diversity of 15 autosomal short tandem repeat (STR) loci was evaluated in 713 unrelated individual samples of a Punjabi population of Pakistan. These loci were scrutinized to establish allelic frequencies and statistical parameters of forensic and paternity interests. A total of 165 alleles were observed with the corresponding allele frequencies ranging from 0.001 to 0.446. D2S1338 was found as the most informative locus while TPOX (0.611) was the least discriminating locus. The combined power of discrimination (CPD), the combined probability of exclusion (CPE), and cumulative probability of matching (CPM) were found equaled to 0.999999999999999998606227424808, 0.999995777557989, and 1.37543 × 10-18, respectively. All the loci followed the Hardy-Weinberg equilibrium after the Bonferroni correction (p < 0.0033) except one locus D3S1358. The study revealed that these STR loci are highly polymorphic, suitable for forensic and parentage analyses. In comparison to different populations (Asians and non-Asians), significant differences were recorded for these loci.

Highly Prevalent LIPH Founder Mutations Causing Autosomal Recessive Woolly Hair/Hypotrichosis in Japan and the Genotype/Phenotype Correlations

PubMed Central

Kono, Michihiro; Takama, Hiromichi; Hamajima, Nobuyuki; Akiyama, Masashi

2014-01-01

Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH), and the 2 missense mutations c.736T>A (p.Cys246Ser) and c.742C>A (p.His248Asn) are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016), and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024). In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH. PMID:24586639

Genetically-determined polymorphism of nonspecific esterases and phosphoglucomutase in eight introduced breeds of the silkworm, Bombyx mori, raised in Bulgaria.

PubMed

Staykova, Teodora

2008-01-01

Isoenzymes are very suitable markers for the study of the inter-breed diversity of the silkworm Bombyx mon L. (Lepidoptera: Bombycidae). More than 250 breeds are raised in Bulgaria, which are not very well studied with regard to their isoenzymic polymorphism. Polymorphism of nonspecific esterases from pupal haemolymph was analyzed, as well as of phosphoglucomutase from different organs of larvae, pupae and imago, from eight introduced breeds. Electrophoresis in polyacrylamide gels was used. A polylocus control of nonspecific esterases, and possible monolocus control of phosphoglucomutase was ascertained. Biallele and triallele polymorphism of phosphoglucomutase locus and in three of the esterase loci was determined. The allelic frequencies of the polymorphic loci in each breed were analyzed. Inter-breed differences were found in different allelic frequencies, different heterozygosity and polymorphism.

Genome-wide meta-analysis of common variant differences between men and women

PubMed Central

Boraska, Vesna; Jerončić, Ana; Colonna, Vincenza; Southam, Lorraine; Nyholt, Dale R.; William Rayner, Nigel; Perry, John R.B.; Toniolo, Daniela; Albrecht, Eva; Ang, Wei; Bandinelli, Stefania; Barbalic, Maja; Barroso, Inês; Beckmann, Jacques S.; Biffar, Reiner; Boomsma, Dorret; Campbell, Harry; Corre, Tanguy; Erdmann, Jeanette; Esko, Tõnu; Fischer, Krista; Franceschini, Nora; Frayling, Timothy M.; Girotto, Giorgia; Gonzalez, Juan R.; Harris, Tamara B.; Heath, Andrew C.; Heid, Iris M.; Hoffmann, Wolfgang; Hofman, Albert; Horikoshi, Momoko; Hua Zhao, Jing; Jackson, Anne U.; Hottenga, Jouke-Jan; Jula, Antti; Kähönen, Mika; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Klopp, Norman; Kutalik, Zoltán; Lagou, Vasiliki; Launer, Lenore J.; Lehtimäki, Terho; Lemire, Mathieu; Lokki, Marja-Liisa; Loley, Christina; Luan, Jian'an; Mangino, Massimo; Mateo Leach, Irene; Medland, Sarah E.; Mihailov, Evelin; Montgomery, Grant W.; Navis, Gerjan; Newnham, John; Nieminen, Markku S.; Palotie, Aarno; Panoutsopoulou, Kalliope; Peters, Annette; Pirastu, Nicola; Polašek, Ozren; Rehnström, Karola; Ripatti, Samuli; Ritchie, Graham R.S.; Rivadeneira, Fernando; Robino, Antonietta; Samani, Nilesh J.; Shin, So-Youn; Sinisalo, Juha; Smit, Johannes H.; Soranzo, Nicole; Stolk, Lisette; Swinkels, Dorine W.; Tanaka, Toshiko; Teumer, Alexander; Tönjes, Anke; Traglia, Michela; Tuomilehto, Jaakko; Valsesia, Armand; van Gilst, Wiek H.; van Meurs, Joyce B.J.; Smith, Albert Vernon; Viikari, Jorma; Vink, Jacqueline M.; Waeber, Gerard; Warrington, Nicole M.; Widen, Elisabeth; Willemsen, Gonneke; Wright, Alan F.; Zanke, Brent W.; Zgaga, Lina; Boehnke, Michael; d'Adamo, Adamo Pio; de Geus, Eco; Demerath, Ellen W.; den Heijer, Martin; Eriksson, Johan G.; Ferrucci, Luigi; Gieger, Christian; Gudnason, Vilmundur; Hayward, Caroline; Hengstenberg, Christian; Hudson, Thomas J.; Järvelin, Marjo-Riitta; Kogevinas, Manolis; Loos, Ruth J.F.; Martin, Nicholas G.; Metspalu, Andres; Pennell, Craig E.; Penninx, Brenda W.; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Schreiber, Stefan; Schunkert, Heribert; Spector, Tim D.; Stumvoll, Michael; Uitterlinden, André G.; Ulivi, Sheila; van der Harst, Pim; Vollenweider, Peter; Völzke, Henry; Wareham, Nicholas J.; Wichmann, H.-Erich; Wilson, James F.; Rudan, Igor; Xue, Yali; Zeggini, Eleftheria

2012-01-01

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10−8) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ∼115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits. PMID:22843499

Analysis of RANKL gene polymorphism (rs9533156 and rs2277438) in Iranian patients with chronic periodontitis and periimplantitis.

PubMed

Kadkhodazadeh, Mahdi; Ebadian, Ahmad Reza; Gholami, Gholam Ali; Khosravi, Alireza; Tabari, Zahra Alizadeh

2013-05-01

RANK/OPG/RANKL pathway plays a significant role in osteoclastogenesis, osteoclast activation, and regulation of bone resorption. The aim of this study was to investigate the association of RANKL gene polymorphisms (rs9533156 and rs2277438) with chronic periodontitis and peri-implantitis in an Iranian population. 77 patients with chronic periodontitis, 40 patients with peri-implantitis and 89 periodontally healthy patients were enrolled in this study. 5cc of blood was obtained from the cephalic vein of subjects arms and transferred into tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP) technique. Differences in the frequencies of genotypes and alleles in the disease and control groups were analyzed using Chi-square and Fisher's exact statistical tests. Comparison of frequency of alleles in SNP rs9533156 of RANKL gene between the chronic periodontitis group with the control and peri-implantitis groups revealed statistically significant differences (P=0.024 and P=0.027, respectively). Comparison of genotype expression of SNP rs9533156 on RANKL gene between the peri-implantitis group with chronic periodontitis and control groups revealed statistically significant differences (P=0.001); the prevalence of CT genotype was significantly higher amongst the chronic periodontitis group. Regarding SNP rs2277438 of RANKL gene, comparison of prevalence of genotypes and frequency of alleles did not reveal any significant differences (P=0.641/P=0.537, respectively). The results of this study indicate that CT genotype of rs9533156 RANKL gene polymorphism was significantly associated with peri-implantitis, and may be considered as a genetic determinant for peri-implantitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

GONe: Software for estimating effective population size in species with generational overlap

USGS Publications Warehouse

Coombs, J.A.; Letcher, B.H.; Nislow, K.H.

2012-01-01

GONe is a user-friendly, Windows-based program for estimating effective size (N e) in populations with overlapping generations. It uses the Jorde-Ryman modification to the temporal method to account for age structure in populations. This method requires estimates of age-specific survival and birth rate and allele frequencies measured in two or more consecutive cohorts. Allele frequencies are acquired by reading in genotypic data from files formatted for either GENEPOP or TEMPOFS. For each interval between consecutive cohorts, N e is estimated at each locus and over all loci. Furthermore, N e estimates are output for three different genetic drift estimators (F s, F c and F k). Confidence intervals are derived from a chi-square distribution with degrees of freedom equal to the number of independent alleles. GONe has been validated over a wide range of N e values, and for scenarios where survival and birth rates differ between sexes, sex ratios are unequal and reproductive variances differ. GONe is freely available for download at. ?? 2011 Blackwell Publishing Ltd.

Uterine leiomyoma is associated with a polymorphism in the interleukin 1-beta gene.

PubMed

Pietrowski, Detlef; Thewes, Roberta; Sator, Michael; Denschlag, Dominik; Keck, Christoph; Tempfer, Clemens

2009-08-01

To investigate whether polymorphisms in the interleukin-1beta (IL-1beta) gene are associated with uterine leiomyoma. Case-control study in a collective of 131 patients and 280 controls. Genotyping of the IL-1beta-511 and IL-1beta-3954 polymorphism was performed by PCR amplification and subsequent RFLP analysis. A significant difference in the allele frequencies of the IL-1beta-511 C

Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine.

PubMed

Samandary, Sarah; Kridane-Miledi, Hédia; Sandoval, Jacqueline S; Choudhury, Zareen; Langa-Vives, Francina; Spencer, Doran; Chentoufi, Aziz A; Lemonnier, François A; BenMohamed, Lbachir

2014-08-01

A significant portion of the world's population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) over a half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A(∗)24, HLA-B(∗)27, HLA-B(∗)53 and HLA-B(∗)58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B(∗)44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Associations of HLA-A, HLA-B and HLA-C Alleles Frequency with Prevalence of Herpes Simplex Virus Infections and Diseases Across Global Populations: Implication for the Development of an Universal CD8+ T-Cell Epitope-Based Vaccine

PubMed Central

Samandary, Sarah; Kridane-Miledi, Hédia; Sandoval, Jacqueline S.; Choudhury, Zareen; Langa-Vives, Francina; Spencer, Doran; Chentoufi, Aziz A.; Lemonnier, François A.; BenMohamed, Lbachir

2014-01-01

A significant portion of the world’s population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) Over half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A*24, HLA-B*27, HLA-B*53 and HLA-B*58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B*44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy. PMID:24798939

Genetic characteristic of swamp buffalo (Bubalus bubalis) from Pampangan, South Sumatra based on blood protein profile

NASA Astrophysics Data System (ADS)

Windusari, Yuanita; Hanum, Laila; Wahyudi, Rizki

2017-11-01

Swamp buffalo (Bubalus bubalis) is an endemic species and one of the genetic wealth of South Sumatra with a distribution area in the district of Pampangan (OganIlir and OganOganIlir). Suspected inbreeding causes decreased phenotypic properties. Inbreeding among various swamp buffalo is certainly not only lower the qualities but also genotypes and phenotypes. It is of interest to determine kinship variants swamp buffaloes from Pampangan through the analysis of a blood protein profile. Blood protein profile of four variants swamps buffalo was studied by using five electrophoresis system i.e. pre-albumin (Palb), albumin (Alb), ceruloplasmin (Cp), transferrin (Tf) and transferrin post (Ptf). In this paper, it is obtained that there was no significant differences among the four variants of the buffaloes were used as a sample. Prealbumin has two alleles (Palb1 and Palb2), albumin has three alleles (Alba, AlbB, AlbC), ceruloplasmin has one allele (BPA), post-transferrin has one allele (PTFA) with an allele frequency 1.0000 at any time transferrin has two alleles (TFA and TFB) with the allele frequency of 0.7500 and 1.0000. Characteristics prealbumin (Palb), albumin (Alb), ceruloplasmin (Cp), and post-transferrin (P-tf) is monomorphic, while transferrin is polymorphic average heterozygosity values all loci (H) 0.1286. Based on average heterozygosity, the swamp buffalo (Bubalusbubalis) from Pampangan has low genetic variation and closest genetic relationship.

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

PubMed

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

2011-06-01

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

Population data of five genetic markers in the Turkish population: comparison with four American population groups.

PubMed

Kurtuluş-Ulküer, M; Ulküer, U; Kesici, T; Menevşe, S

2002-09-01

In this study, the phenotype and allele frequencies of five enzyme systems were determined in a total of 611 unrelated Turkish individuals and analyzed by using the exact and the chi 2 test. The following five red cell enzymes were identified by cellulose acetate electrophoresis: phosphoglucomutase (PGM), adenosine deaminase (ADA), phosphoglucose isomerase (PGI), adenylate kinase (AK), and 6-phosphogluconate dehydrogenase (6-PGD). The ADA, PGM and AK enzymes were found to be polymorphic in the Turkish population. The results of the statistical analysis showed, that the phenotype frequencies of the five enzyme under study are in Hardy-Weinberg equilibrium. Statistical analysis was performed in order to examine whether there are significant differences in the phenotype frequencies between the Turkish population and four American population groups. This analysis showed, that there are some statistically significant differences between the Turkish and the other groups. Moreover, the observed phenotype and allele frequencies were compared with those obtained in other population groups of Turkey.

STR data for the AmpFlSTR Identifiler loci from Swedish population in comparison to European, as well as with non-European population.

PubMed

Montelius, Kerstin; Karlsson, Andreas O; Holmlund, Gunilla

2008-06-01

The modern Swedish population is a mixture of people that originate from different parts of the world. This is also the truth for the clients participating in the paternity cases investigated at the department. Calculations based on a Swedish frequency database only, could give us overestimated figures of probability and power of exclusion in cases including clients with a genetic background other than Swedish. Here, we describe allele frequencies regarding the markers in the Identifiler-kit. We have compared three sets of population samples; Swedish, European and non-European to investigate how these three groups of population samples differ. Also, all three population sets were compared to data reported from other European and non-European populations. Swedish allele frequencies for the 15 autosomal STRs included in the Identifiler kit were obtained from unrelated blood donors with Swedish names. The European and non-European frequencies were based on DNA-profiles of alleged fathers from our paternity cases in 2005 and 2006.

The Correlation between the CLEC16A Gene and Genetic Susceptibility to Type 1 Diabetes in Chinese Children.

PubMed

Sang, Yanmei; Zong, Wei; Yan, Jie; Liu, Min

2012-01-01

Objective. The CLEC16A gene is related to the genetic susceptibility to T1DM with racial variability. This study investigated the association between CLEC16A gene polymorphisms and T1DM in Chinese children. Methods. 131 Chinese children with T1DM were selected for study, and 121 healthy adult blood donors were selected as normal controls. PCR and mass spectrometry was used to study the distributions of 17 CLEC16A alleles in patients and controls. The relationship between CLEC16A gene polymorphisms and T1DM was studied. Results. The distributions of two polymorphisms (rs12921922, rs12931878) of CLEC16A in T1DM and healthy controls were significantly different, while the distributions of other CLEC16A polymorphisms show no significant differences. The alleles of rs12921922 are C and T. The frequency of the T allele was significantly increased in patients versus healthy controls. The alleles of rs12931878 are A and C. The frequencies of the A allele are significantly increased in T1DM patients versus healthy controls. Conclusion. Two polymorphisms in the CLEC16A gene correlate with increased susceptibility to T1DM in Chinese children, revealing that it was another new gene that correlates with susceptibility to T1DM in multiple populations.

Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies.

PubMed

Solberg, Owen D; Mack, Steven J; Lancaster, Alex K; Single, Richard M; Tsai, Yingssu; Sanchez-Mazas, Alicia; Thomson, Glenys

2008-07-01

This paper presents a meta-analysis of high-resolution human leukocyte antigen (HLA) allele frequency data describing 497 population samples. Most of the datasets were compiled from studies published in eight journals from 1990 to 2007; additional datasets came from the International Histocompatibility Workshops and from the AlleleFrequencies.net database. In all, these data represent approximately 66,800 individuals from throughout the world, providing an opportunity to observe trends that may not have been evident at the time the data were originally analyzed, especially with regard to the relative importance of balancing selection among the HLA loci. Population genetic measures of allele frequency distributions were summarized across populations by locus and geographic region. A role for balancing selection maintaining much of HLA variation was confirmed. Further, the breadth of this meta-analysis allowed the ranking of the HLA loci, with DQA1 and HLA-C showing the strongest balancing selection and DPB1 being compatible with neutrality. Comparisons of the allelic spectra reported by studies since 1990 indicate that most of the HLA alleles identified since 2000 are very-low-frequency alleles. The literature-based allele-count data, as well as maps summarizing the geographic distributions for each allele, are available online.

Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies

PubMed Central

Solberg, Owen D.; Mack, Steven J.; Lancaster, Alex K.; Single, Richard M.; Tsai, Yingssu; Sanchez-Mazas, Alicia; Thomson, Glenys

2008-01-01

This paper presents a meta-analysis of high-resolution human leukocyte antigen (HLA) allele frequency data describing 497 population samples. Most of the datasets were compiled from studies published in eight journals from 1990 to 2007; additional datasets came from the International Histocompatibility Workshops and from the AlleleFrequencies.net database. In all, these data represent approximately 66,800 individuals from throughout the world, providing an opportunity to observe trends that may not have been evident at the time the data were originally analyzed, especially with regard to the relative importance of balancing selection among the HLA loci. Population genetic measures of allele frequency distributions were summarized across populations by locus and geographic region. A role for balancing selection maintaining much of HLA variation was confirmed. Further, the breadth of this meta-analysis allowed the ranking of the HLA loci, with DQA1 and HLA-C showing strongest balancing selection and DPB1 being compatible with neutrality. Comparisons of the allelic spectra reported by studies since 1990 suggest that most of the HLA alleles identified since 2000 are very-low-frequency alleles. The literature-based allele-count data, as well as maps summarizing the geographic distributions for each allele, are available online. PMID:18638659

Comparison of Prion Allele Frequency found in Suffolk and Targhee Sheep

USDA-ARS?s Scientific Manuscript database

Scrapie is a class of Transmissible Spongiform Encephalopathy that affects sheep and goats. The objective of this study was to compare genotypic and allelic frequencies among USSES Targhee and Suffolk sheep. A total of 122 sheep were genotyped for codon 171 with allele specific primers in 2 separate...

Association of aplastic anemia and FoxP3 gene polymorphisms in Koreans.

PubMed

In, Ji Won; Lee, Nuri; Roh, Eun Youn; Shin, Sue; Park, Kyoung Un; Song, Eun Young

2017-04-01

Aplastic anemia (AA) is characterized by pancytopenia and bone marrow failure, and most acquired AA is an immune-mediated disorder. Regulatory T cells (T regs ) suppressing autoreactive T cells were decreased in AA patients. FoxP3 is a major regulator for the development and function of T regs . Polymorphism in FoxP3 was shown to be associated with various autoimmune diseases, however, has not yet been studied in AA. In this study, we examined the association between FoxP3 polymorphisms and AA in Korean patients. The study population consisted of 94 patients diagnosed by bone marrow examination in Seoul National University Hospital (SNUH) during 1997-2012 and 195 healthy controls. FoxP3 polymorphisms (rs5902434 del/ATT, rs3761548 C/A, rs3761549 C/T, rs2232365 A/G) were analyzed by PCR-sequencing method. We analyzed differences of genotype and allele frequencies between patients and controls. We also compared differences of genotype and allele frequencies between responder and non-responder in patients treated with immunosuppressive therapy (IST). For the statistical analysis, the chi-square test and Fisher's exact test were used and P < 0.05 was regarded as statistically significant. There was no significant difference in the genotype frequencies of FoxP3 polymorphisms between patients and controls. With regards to the allele frequencies, rs3761548 C allele was significantly higher in AA patients than in controls (87.4% vs. 79.7%, P = 0.047). In patients treated with IST, rs3761549 C allele was significantly higher in non-responder patients than in responders (89.6% vs. 66.7%, P = 0.036) and female rs3761549 C/C genotype carriers were associated with greater risk for non-response to IST (84.2% vs. 16.7%, P = 0.006). Polymorphisms in rs3761548 and rs3761549 of FoxP3 in our population were associated with disease susceptibility and response for IST, respectively. This study suggests an association between FoxP3 polymorphisms and AA in Korean patients and will be useful in further understanding the genetic basis of disease susceptibility and response to IST in AA patients.

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

PubMed Central

2010-01-01

Background Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies. Methods Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients. Results We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). CYP3A4*1B, CYP3A5*3 and CYP3A5*6 alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. CYP3A5*1/CYP3A5*1 and CYP3A5*1/CYP3A5*3 genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin. Conclusion A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders. PMID:20630055

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

PubMed

Kudzi, William; Dodoo, Alexander N O; Mills, Jeremy J

2010-07-14

Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies. Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients. We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). CYP3A4*1B, CYP3A5*3 and CYP3A5*6 alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. CYP3A5*1/CYP3A5*1 and CYP3A5*1/CYP3A5*3 genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin. A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.

HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides.

PubMed

Kidnapillai, S; Sirisena, N D; Dissanayake, V H

2016-06-01

This preliminary study aims to describe the HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides (SA). An anonymised database of 373 Sri Lankan patients with SA referred for HLA-B27 testing was retrospectively analysed. Eighty five (22.8%) patients were positive for the HLA-B27 allele. A male preponderance was observed among the positives. The HLA-B27 allele frequency in this sample of patients with SA was relatively low compared to published studies in other populations. Further research is needed to identify the predominant subtypes of the allele to determine which subtypes are the most prevalent in a larger sample of Sri Lankan patients with SA, and to define their association with the specific types of SA.

Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

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

Poduslo, S.E.; Schwankhaus, J.D.

1994-09-01

A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal,more » and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.« less

Genetic polymorphism of the beta-2 adrenergic receptor in atopic and non-atopic subjects.

PubMed

Potter, P C; Van Wyk, L; Martin, M; Lentes, K U; Dowdle, E B

1993-10-01

To investigate a possible genetic basis for reported differences in beta-2 receptor expression in atopic subjects, DNA from 42 atopic children (22 asthmatics and 22 with allergic rhinitis) and 30 non-atopic subjects was Southern blotted and Ban-1 restriction fragment polymorphisms (RFLPS) were studied using a 2.6 kb probe of the human beta-2 receptor gene. Two alleles 3.1 kb and 2.9 kb were identified. Homozygotes and heterozygotes for the two alleles were found with equal frequency in the atopic patients who had asthma and in those who had allergic rhinitis only. The gene frequencies for the upper and lower alleles were 0.45 and 0.55 respectively. Our studies do not provide evidence for an association between a particular polymorphic form of the human beta-2 receptor gene and atopy.

TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil.

PubMed

dos Santos, B P; Valverde, J V; Rohr, P; Monticielo, O A; Brenol, J C T; Xavier, R M; Chies, J A B

2012-03-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and can affect several organs and systems. It is characterized by high production of autoantibodies against nuclear compounds. TLR7/8/9 are responsible for nucleic acid recognition and they trigger proinflammatory responses through activation of NK-kappaB and Type I IFN production, making a bridge between the innate and the adaptative immune systems. We analyzed the frequency of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and rs352140 in 370 patients with SLE and 415 healthy controls from southern Brazil. All analyses were conducted with regard to gender and ethnicity. Genotypic and allelic frequencies were different for TLR7 rs179008 (0.253 vs. 0.163, p = 0.020 and p = 0.003, OR for T allele: 1.74 CI 95% 1.12-2.70) and TLR9 rs5743836 (0.174 vs. 0.112, p = 0.045 and p = 0.017, OR for C allele: 1.59, CI 95% 0.99-2.57) between European-derived female groups. A higher frequency was observed for the presence of Anti-SSa/Ro for TRL9 rs5743836 C allele carriers (0.228 vs 0.126, Bonferroni corrected p = 0.06). No statistical differences were found for TLR9 haplotypic analyses. We suggest that TLR7 rs179008 and TLR9 rs5743836 can be considered SLE susceptibility factors for women of European descent in our population.

Association of LOC387715 A69S with vitreous hemorrhage in polypoidal choroidal vasculopathy.

PubMed

Sakurada, Yoichi; Kubota, Takeo; Mabuchi, Fumihiko; Imasawa, Mitsuhiro; Tanabe, Naohiko; Iijima, Hiroyuki

2008-06-01

To investigate whether the LOC387715 polymorphism is associated with polypoidal choroidal vasculopathy (PCV) and with vitreous hemorrhage (VH), one of the most severe clinical phenotypes, in the Japanese population. Cross-sectional case-control association study. One hundred and nine Japanese patients with PCV, composed of nine patients associated with VH (VH group) and 100 patients without VH (non-VH group), and 85 control subjects were analyzed for the LOC387715 polymorphism (rs = 10490924), using denaturing high-performance chromatography. There was a significant difference in the T allele frequency between PCV patients and control subjects (P < .0001). In comparison with wild-type homozygosity (GG), homozygosity for the at-risk allele genotype (TT) increased the likelihood for PCV 8.4-fold (3.6 to 19.5, 95% confidence interval [CI]) and heterozygosity for the at-risk allele genotype (TG) increased the likelihood for PCV 4.0-fold (1.9 to 8.4, 95% CI). There was a significant difference in the genotypic frequency at the LOC387715 site between the VH and non-VH groups (P = .0099, Chi-square test) with the TT genotype occurring in 88.9% in the VH group and 37.0% in the non-VH group. The frequency of the T allele in the VH group was significantly greater than that in the non-VH group (0.944 vs 0.610; P = .0039, Fisher exact test). The LOC387715 polymorphism is associated with PCV and clinical severity in the subgroups of PCV in the Japanese population.

Population cage experiments with a vertebrate: The temporal demography and cytonuclear genetics of hybridization on Gambusia fishes

USGS Publications Warehouse

Scribner, Kim T.; Avise, John C.

1994-01-01

The dynamics of mitochondrial and multilocus nuclear genotypic frequencies were monitored for 2 yr in experimental populations established with equal numbers of two poeciliid fishes (Gambusia affinis and Gambusia holbrooki) that hybridize naturally in the southeastern United States. In replicated "small-pool" populations (experiment I), 1018 sampled individuals at six time periods revealed an initial flush of hybridization, followed by a rapid decline in frequencies of G. affinis nuclear and mitochondrial alleles over 64 wk. Decay of gametic and cytonuclear disequilibria differed from expectations under random mating as well as under a model of assortative mating involving empirically estimated mating propensities. In two replicate "large-pond" populations (experiment II), 841 sampled individuals across four reproductive cohorts revealed lower initial frequencies of F1 hybrids than in experiment I, but again G. holbrooki alleles achieved high frequencies over four generations (72 wk). Thus, evolution within experimental Gambusia hybrid populations can be extremely rapid, resulting in consistent loss of G. affinis nuclear and cytoplasmic alleles. Concordance in results between experiments and across genetic markers suggests strong directional selection favoring G. holbrooki genotypes. Results are interpreted in light of previous reports of genotype-specific differences in life-history traits, reproductive ecology, patterns of recruitment, and size-specific mortality, and in the context of patterns of introgression previously studied indirectly from spatial observations on cytonuclear genotypes in natural Gambusia populations.

Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans

PubMed Central

Chandak, Giriraj R; Ward, Kirsten J; Yajnik, Chittaranjan S; Pandit, Anand N; Bavdekar, Ashish; Joglekar, Charu V; Fall, Caroline HD; Mohankrishna, P; Wilkin, Terence J; Metcalf, Bradley S; Weedon, Michael N; Frayling, Timothy M; Hattersley, Andrew T

2006-01-01

Background The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. Methods We genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. Results The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). Conclusion This is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels independent of ethnicity and that this association is similar in magnitude in Asian Indians and Caucasians. The -1131C allele is present in 36% of the Pune Indian population making it a powerful marker for looking at the role of elevated triglycerides in important conditions such as pancreatitis, diabetes and coronary heart disease. PMID:17032446

HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman, India

PubMed Central

Chaaithanya, Itta Krishna; Muruganandam, Nagarajan; Anwesh, Maile; Rajesh, Reesu; Ghosal, Sruti R; Kartick, Chinnaiah; Prasad, Kadiyala Nageswara; Muthumani, Karuppiah; Vijayachari, Paluru

2013-01-01

A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during July–August 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT-PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA-DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA-DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide-binding pockets of HLA-DQB1 molecules were investigated. The frequencies of HLA-DRB1 alleles were not significantly different, whereas lower frequency of HLA-DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0·001, corrected P = 0·024; odds ratio (OR) = 0, 95% confidence interval (95% CI) 0·0–0·331; Peto's OR = 0·1317, 95% CI 0·0428–0·405). Significantly lower frequency of glutamic acid at position 86 of peptide-binding pocket 1 coding HLA-DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0·004, OR = 0·307, 95% CI 0·125–0·707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA-DQ molecules are known to bind more CHIKV peptides than HLA-DRB1 molecules. The results suggest that HLA-DQB1 alleles and critical amino acid differences in the peptide-binding pockets of HLA-DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV. PMID:23710940

HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman, India.

PubMed

Chaaithanya, Itta Krishna; Muruganandam, Nagarajan; Anwesh, Maile; Rajesh, Reesu; Ghosal, Sruti R; Kartick, Chinnaiah; Prasad, Kadiyala Nageswara; Muthumani, Karuppiah; Vijayachari, Paluru

2013-10-01

A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during July-August 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT-PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA-DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA-DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide-binding pockets of HLA-DQB1 molecules were investigated. The frequencies of HLA-DRB1 alleles were not significantly different, whereas lower frequency of HLA-DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0·001, corrected P = 0·024; odds ratio (OR)  = 0, 95% confidence interval (95% CI) 0·0-0·331; Peto's OR = 0·1317, 95% CI 0·0428-0·405). Significantly lower frequency of glutamic acid at position 86 of peptide-binding pocket 1 coding HLA-DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0·004, OR = 0·307, 95% CI 0·125-0·707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA-DQ molecules are known to bind more CHIKV peptides than HLA-DRB1 molecules. The results suggest that HLA-DQB1 alleles and critical amino acid differences in the peptide-binding pockets of HLA-DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV. © 2013 John Wiley & Sons Ltd.

Comparison of HLA-A, -B and -DRB1 Loci Polymorphism between Kidney Transplants of Uremia Patients and Healthy Individuals in Central China

PubMed Central

Gao, Shilin; Feng, Guiwen; Feng, Yonghua; Wang, Zhigang; Zhang, Xiaobai

2016-01-01

Chronic kidney disease is becoming a global public health problem, which will usually cause uremia at the end stage of chronic kidney failure. So far, kidney transplant is the most effective and proper therapy for uremia, however, the short supply of matched donor kidney has been a persistent bottleneck for transplantation. HLA matching of HLA-A, -B and -DRB1 loci is very important for the allocation of kidney transplants. In this study, we investigated genotypes of HLA-A, -B and -DRB1 loci based on 1,464 uremia patients and 10,000 unrelated healthy individuals in Henan province of China, and compared the frequency distribution of these HLA alleles and corresponding haplotypes between patient and healthy groups. We detected 23 HLA-A, 49 HLA-B and 17 HLA-DRB1 alleles in total. The predominant alleles of HLA-A, -B and -DRB1 loci in patients are the same as those in healthy group. The seven most frequent alleles account for about 87%, 50%, and 77% at HLA-A, -B and -DRB1 loci, respectively. The haplotypes (combinations of HLA-A, -B, and -DRB1) with significantly different frequency between patients and controls mostly account for less than 1%. Overall, this suggests that HLA matching is not a potential difficulty for kidney transplant of uremia patients. However, three of the top seven frequent HLA-DRB1 alleles have a significantly different distribution in patients and controls, while only one alleles for HLA-B and zero for HLA-A loci. These HLA-DRB1 alleles may be closely associated with uremia. This study sheds new lights on the composition and difference of HLA genotypes in uremia patients and healthy populations in Central China that can serve as a guide to HLA matching for kidney transplants and a resource for HLA typing-related studies. PMID:27780235

BAT-25 polymorphism in Chinese from Jiangsu province and its implication for locus microsatellite instability screening.

PubMed

Zheng, Yan Ying; Xie, Ling; Liu, Li; Zhang, Shu Peng; Wu, Xiao Bin; Zhu, Chang Le; Lai, Ren Sheng

2012-10-08

Colorectal cancer is one of the most common tumors with high mortality in China. Microsatellite instability (MSI) analysis is important for the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) and for the prediction of 5-FU chemotherapy efficiency of colorectal tumors, especially in terms of therapeutic response and overall survival rates. Among the MSI markers recommended by the NIH/NCI, BAT-25 has been extensively studied for its major role in MSI. BAT-25 presents different polymorphisms in different ethnic populations and studies of its polymorphisms in the Chinese population are still very limited. To analyze the frequency of constitutive polymorphic variation at the BAT-25 locus in Chinese from Jiangsu Province and its implication for locus MSI screening. The frequency of allelic variation at the BAT-25 locus of cervical cells from 500 healthy women and blood from 16 healthy males was assessed by direct sequencing. Twenty samples were also analyzed by fragment analysis. DNA extracted from blood of 94 patients with gastrointestinal cancer or endometrial cancer was analyzed by fragment analysis. After comparison with the sequencing results, the more frequent allele lengths were 126-127 bp, 128-129 bp, 129-130 bp, respectively consistent with the 24 poly(T) (T24), T25 and T26 alleles. At the BAT-25 locus, 516 healthy individuals had respectively 1.36%, 97.28% and 1.36% of the T24, T25 and T26. Whereas for the 94 cancer patients allelic frequencies were 0.53%, 1.06%, 96.8%, 1.6% for T15, T24, T25 and T26 alleles respectively. Sixteen healthy males had only the T25 allele and heterozygous T15 was only found in 1 male patient with colon cancer. We established the relation between fragment length and thymine repeats in BAT-25. The results showed that the BAT-25 locus is quasimonomorphic in Chinese from Jiangsu province. Moreover we showed that variant alleles of BAT-25 were found more likely in blood from cancer patients than in healthy individuals, suggesting the need to perform comparative studies between tumor and blood, or normal tissue, as to obtain a correct MSI identification.

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

PubMed Central

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

2018-01-01

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

Confidence intervals for population allele frequencies: the general case of sampling from a finite diploid population of any size.

PubMed

Fung, Tak; Keenan, Kevin

2014-01-01

The estimation of population allele frequencies using sample data forms a central component of studies in population genetics. These estimates can be used to test hypotheses on the evolutionary processes governing changes in genetic variation among populations. However, existing studies frequently do not account for sampling uncertainty in these estimates, thus compromising their utility. Incorporation of this uncertainty has been hindered by the lack of a method for constructing confidence intervals containing the population allele frequencies, for the general case of sampling from a finite diploid population of any size. In this study, we address this important knowledge gap by presenting a rigorous mathematical method to construct such confidence intervals. For a range of scenarios, the method is used to demonstrate that for a particular allele, in order to obtain accurate estimates within 0.05 of the population allele frequency with high probability (> or = 95%), a sample size of > 30 is often required. This analysis is augmented by an application of the method to empirical sample allele frequency data for two populations of the checkerspot butterfly (Melitaea cinxia L.), occupying meadows in Finland. For each population, the method is used to derive > or = 98.3% confidence intervals for the population frequencies of three alleles. These intervals are then used to construct two joint > or = 95% confidence regions, one for the set of three frequencies for each population. These regions are then used to derive a > or = 95%% confidence interval for Jost's D, a measure of genetic differentiation between the two populations. Overall, the results demonstrate the practical utility of the method with respect to informing sampling design and accounting for sampling uncertainty in studies of population genetics, important for scientific hypothesis-testing and also for risk-based natural resource management.

Lack of Association Between Toll-like Receptor 2 Polymorphisms (R753Q and A-16934T) and Atopic Dermatitis in Children from Thrace Region of Turkey

PubMed Central

Can, Ceren; Yazıcıoğlu, Mehtap; Gürkan, Hakan; Tozkır, Hilmi; Görgülü, Adnan; Süt, Necdet Hilmi

2017-01-01

Background: Atopic dermatitis is the most common chronic inflammatory skin disease. A complex interaction of both genetic and environmental factors is thought to contribute to the disease. Aims: To evaluate whether single nucleotide polymorphisms in the TLR2 gene c.2258C>T (R753Q) (rs5743708) and TLR2 c.-148+1614T>A (A-16934T) (rs4696480) (NM_0032643) are associated with atopic dermatitis in Turkish children. Study Design: Case-control study. Methods: The study was conducted on 70 Turkish children with atopic dermatitis aged 0.5-18 years. The clinical severity of atopic dermatitis was evaluated by the severity scoring of atopic dermatitis index. Serum total IgE levels, specific IgE antibodies to inhalant and food allergens were measured in both atopic dermatitis patients and controls, skin prick tests were done on 70 children with atopic dermatitis. Genotyping for TLR2 (R753Q and A-16934T) single nucleotide polymorphisms was performed in both atopic dermatitis patients and controls. Results: Cytosine-cytosine and cytosin-thymine genotype frequencies of the TLR2 R753Q single nucleotide polymorphism in the atopic dermatitis group were determined as being 98.6% and 1.4%, cytosine allele frequency for TLR2 R753Q single nucleotide polymorphism was determined as 99.29% and the thymine allele frequency was 0.71%, thymine-thymine, thymine-adenine, and adenine-adenine genotype frequencies of the TLR2 A-16934T single nucleotide polymorphism were 24.3%, 44.3%, and 31.4%. The thymine allele frequency for the TLR2 A-16934T single nucleotide polymorphism in the atopic dermatitis group was 46.43%, and the adenine allele frequency was 53.57%, respectively. There was not statistically significant difference between the groups for all investigated polymorphisms (p>0.05). For all single nucleotide polymorphisms studied, allelic distribution was analogous among atopic dermatitis patients and controls, and no significant statistical difference was observed. No homozygous carriers of the TLR2 R753Q single nucleotide polymorphism were found in the atopic dermatitis and control groups. Conclusion: The TLR2 (R753Q and A-16934T) single nucleotide polymorphisms are not associated with atopic dermatitis in a group of Turkish patients. PMID:28443596

Lack of Association Between Toll-like Receptor 2 Polymorphisms (R753Q and A-16934T) and Atopic Dermatitis in Children from Thrace Region of Turkey.

PubMed

Can, Ceren; Yazıcıoğlu, Mehtap; Gürkan, Hakan; Tozkır, Hilmi; Görgülü, Adnan; Süt, Necdet Hilmi

2017-05-05

Atopic dermatitis is the most common chronic inflammatory skin disease. A complex interaction of both genetic and environmental factors is thought to contribute to the disease. To evaluate whether single nucleotide polymorphisms in the TLR2 gene c.2258C>T (R753Q) (rs5743708) and TLR2 c.-148+1614T>A (A-16934T) (rs4696480) (NM_0032643) are associated with atopic dermatitis in Turkish children. Case-control study. The study was conducted on 70 Turkish children with atopic dermatitis aged 0.5-18 years. The clinical severity of atopic dermatitis was evaluated by the severity scoring of atopic dermatitis index. Serum total IgE levels, specific IgE antibodies to inhalant and food allergens were measured in both atopic dermatitis patients and controls, skin prick tests were done on 70 children with atopic dermatitis. Genotyping for TLR2 (R753Q and A-16934T) single nucleotide polymorphisms was performed in both atopic dermatitis patients and controls. Cytosine-cytosine and cytosin-thymine genotype frequencies of the TLR2 R753Q single nucleotide polymorphism in the atopic dermatitis group were determined as being 98.6% and 1.4%, cytosine allele frequency for TLR2 R753Q single nucleotide polymorphism was determined as 99.29% and the thymine allele frequency was 0.71%, thymine-thymine, thymine-adenine, and adenine-adenine genotype frequencies of the TLR2 A-16934T single nucleotide polymorphism were 24.3%, 44.3%, and 31.4%. The thymine allele frequency for the TLR2 A-16934T single nucleotide polymorphism in the atopic dermatitis group was 46.43%, and the adenine allele frequency was 53.57%, respectively. There was not statistically significant difference between the groups for all investigated polymorphisms (p>0.05). For all single nucleotide polymorphisms studied, allelic distribution was analogous among atopic dermatitis patients and controls, and no significant statistical difference was observed. No homozygous carriers of the TLR2 R753Q single nucleotide polymorphism were found in the atopic dermatitis and control groups. The TLR2 (R753Q and A-16934T) single nucleotide polymorphisms are not associated with atopic dermatitis in a group of Turkish patients.

The genealogy of samples in models with selection.

PubMed

Neuhauser, C; Krone, S M

1997-02-01

We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models. DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case.

The Genealogy of Samples in Models with Selection

PubMed Central

Neuhauser, C.; Krone, S. M.

1997-01-01

We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models, DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case. PMID:9071604

Genetic differentiation among North Atlantic killer whale populations.

PubMed

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

2011-02-01

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

Haplotype frequency distribution for 7 microsatellites in chromosome 8 and 11 in relation to the metabolic syndrome in four ethnic groups: Tehran Lipid and Glucose Study.

PubMed

Daneshpour, Maryam Sadat; Hosseinzadeh, Nima; Zarkesh, Maryam; Azizi, Fereidoun

2012-03-01

Different variants of haplotype frequencies may lead to various frequencies of the same variants in individuals with drug resistance and disease susceptibility at the population level. In this study, the haplotype frequencies of 4 STR loci including the D8S1132, D8S1779, D8S514 and D8S1743, and 3 STR loci including D11S1304, D11S1998 and D11S934 were investigated in 563 individuals of four Iranian ethnic groups in the capital city of Iran, Tehran. One hundred thirty subjects had the metabolic syndrome. Haplotype frequencies of all markers were calculated. There were significant differences in the haplotype frequencies in short and long alleles between the metabolic affected subjects and controls. In addition, haplotype frequencies were significant in the four ethnic groups in both chromosomes 8 and 11. Our findings show a relation between the short allele of D8S1743 in all related haplotype frequencies of subjects with metabolic syndrome. These findings may require more studies of some candidate genes, including the lipoprotein lipase gene, in this chromosomal region. Copyright © 2011. Published by Elsevier B.V.

Frequencies of 23 Functionally Significant Variant Alleles Related with Metabolism of Antineoplastic Drugs in the Chilean Population: Comparison with Caucasian and Asian Populations

PubMed Central

Roco, Ángela; Quiñones, Luis; Agúndez, José A. G.; García-Martín, Elena; Squicciarini, Valentina; Miranda, Carla; Garay, Joselyn; Farfán, Nancy; Saavedra, Iván; Cáceres, Dante; Ibarra, Carol; Varela, Nelson

2012-01-01

Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06), CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12), CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range. PMID:23130019

HLA in North Colombia Chimila Amerindians.

PubMed

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

2018-04-01

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

Beta-fibrinogen allele frequencies in Peruvian Quechua, a high-altitude native population.

PubMed

Rupert, J L; Devine, D V; Monsalve, M V; Hochachka, P W

1999-06-01

Elevated hematocrits, which are found in many high-altitude populations, increase the oxygen-carrying capacity of blood and may represent an adaptation to hypoxic environments. However, as high hematocrit increases blood viscosity, which in turn is associated with hypertension and heart disease, it may be advantageous for high-altitude populations to limit other factors that contribute to increased blood viscosity. One such factor is the plasma concentration of the coagulation protein fibrinogen. Several common polymorphisms in the beta-fibrinogen gene have been identified that affect fibrinogen concentrations. We determined the allele frequencies of three of these polymorphisms (G/A-455(HaeIII), C/T-148(HindIII), and G/A+448(MnlI)) in sample groups drawn from three populations: Quechua-speaking natives living at over 3,200 m in the Peruvian Andes, North American natives (Na-Dene) from coastal British Columbia, and Caucasian North Americans. The frequencies of the alleles previously shown to be associated with increased fibrinogen levels were so low in the Quechuas that their presence could be accounted for solely by genetic admixture with Caucasians. Frequencies in the Na-Dene, a Native American group unrelated to the Quechua, were not significantly different from those in Caucasians.

Contribution of X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 3 (XRCC3) Genotype to Leiomyoma Risk.

PubMed

Chang, Wen-Shin; Tsai, Chia-Wen; Wang, Ju-Yu; Ying, Tsung-Ho; Hsiao, Tsan-Seng; Chuang, Chin-Liang; Yueh, Te-Cheng; Liao, Cheng-Hsi; Hsu, Chin-Mu; Liu, Shih-Ping; Gong, Chi-Li; Tsai, Chang-Hai; Bau, Da-Tian

2015-09-01

The present study aimed at investigating whether X-ray repair cross complementing protein 3 (XRCC3) genotype may serve as a useful marker for detecting leiomyoma and predicting risk. A total of 640 women (166 patients with leiomyoma and 474 healthy controls) were examined for their XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539, rs28903081 genotype. The distributions of genotypic and allelic frequencies between the two groups were compared. The results showed that the CT and TT genotypes of XRCC3 rs861539 were associated with increased leiomyoma risk (odds ratio=2.19, 95% confidence interval=1.23-3.90; odds ratio=3.72, 95% confidence interval=1.23-11.26, respectively). On allelic frequency analysis, we found a significant difference in the distribution of the T allelic frequency of the XRCC3 rs861539 (p=5.88 × 10(-5)). None of the other six single nucleotide polymorphisms were associated with altered leiomyoma susceptibility. The T allele (CT and TT genotypes) of XRCC3 rs861539 contributes to increased risk of leiomyoma among Taiwanese women and may serve as a early detection and predictive marker. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes

PubMed Central

Kubota, T; Yamaura, Y; Ohkawa, N; Hara, H; Chiba, K

2000-01-01

Aims To determine the frequencies of 11 CYP2D6 mutant alleles (CYP2D6*2,*3,*4,*5,*8,*10,*11,*12,*14,*17 and *18), and their relation to the metabolic capacity of CYP2D6 in Japanese subjects. Methods One hundred and sixty-two unrelated healthy Japanese subjects were genotyped with the polymerase chain reaction amplification method and 35 subjects were phenotyped with dextromethorphan. Results The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9, 6.2, 38.6 and 2.2% in our Japanese subjects, respectively. CYP2D6*3, *4, *8, *11, *12, *17 and *18 were not detected. The mean log metabolic ratio of dextromethorphan in subjects with genotypes predicting intermediate metabolizers was significantly greater than that of heterozygotes for functional and defective alleles. Conclusions CYP2D6*5 and CYP2D6*14 are the major defective alleles found in Japanese subjects. In addition, CYP2D6*10 may play a more important role than previously thought for the treatment of Japanese patients with drugs metabolized by CYP2D6. PMID:10886115

Allelic frequencies and association with carcass traits of six genes in local subpopulations of Japanese Black cattle.

PubMed

Nishimaki, Takahiro; Ibi, Takayuki; Siqintuya; Kobayashi, Naohiko; Matsuhashi, Tamako; Akiyama, Takayuki; Yoshida, Emi; Imai, Kazumi; Matsui, Mayu; Uemura, Keiichi; Eto, Hisayoshi; Watanabe, Naoto; Fujita, Tatsuo; Saito, Yosuke; Komatsu, Tomohiko; Hoshiba, Hiroshi; Mannen, Hideyuki; Sasazaki, Shinji; Kunieda, Tetsuo

2016-04-01

Marker-assisted selection (MAS) is expected to accelerate the genetic improvement of Japanese Black cattle. However, verification of the effects of the genes for MAS in different subpopulations is required prior to the application of MAS. In this study, we investigated the allelic frequencies and genotypic effects for carcass traits of six genes, which can be used in MAS, in eight local subpopulations. These genes are SCD, FASN and SREBP1, which are associated with the fatty acid composition of meat, and NCAPG, MC1R and F11, which are associated with carcass weight, coat color and blood coagulation abnormality, respectively. The frequencies of desirable alleles of SCD and FASN were relatively high and that of NCAPG was relatively low, and NCAPG was significantly associated with several carcass traits, including carcass weight. The proportions of genotypic variance explained by NCAPG to phenotypic variance were 4.83 for carcass weight. We thus confirmed that NCAPG is a useful marker for selection of carcass traits in these subpopulations. In addition, we found that the desirable alleles of six genes showed no negative effects on carcass traits. Therefore, selection using these genes to improve target traits should not have negative impacts on carcass traits. © 2015 Japanese Society of Animal Science.

Plasminogen Activator Inhibitor-1 (PAI-1) gene 4G/5G alleles frequency distribution in the Lebanese population.

PubMed

Shammaa, Dina M R; Sabbagh, Amira S; Taher, Ali T; Zaatari, Ghazi S; Mahfouz, Rami A R

2008-09-01

Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

Interleukin-1 alpha variation is associated with the risk of developing preeclampsia.

PubMed

Ghasemi, Masoumeh; Kashani, Elham; Fayyaz, Azadeh; Attar, Marzieh; Shahbazi, Majid

2015-10-01

Preeclampsia is a syndrome that affects 5% of all pregnancies, producing substantial maternal and prenatal morbidity and mortality. Several studies have reported that cytokine genes are associated with the persistence of preeclampsia or the severity of the disease. The aim of this study is to investigate the relationships between the polymorphisms of interleukin-1 alpha-889 (IL-1A) gene and preeclampsia. Genomic DNA was extracted from the peripheral blood of 305 patients with preeclampsia and 325 normal controls from Sayyad Shirazi Hospital of Golestan University. Then subjected to SSP-PCR amplification. STATA software and the chi square test were used for statistic calculations. The frequencies of IL-1A -889 genotypes C/C, T/T and C/T in preeclampsia cases were 34.8%, 8.2%, 57% and in controls were 20.9%, 7.6% and 71.3% respectively. There was a significant 1.5 fold excess frequency in genotype C/C in cases (CI=1.44-3.07, OR=2.1, P=0.0001). There was a significant difference in the frequencies of alleles or genotypes in IL-1A promoter regions between patients with preeclampsia and the control group. Turkomans showed the highest frequency of the C allele and Sistanies had the lowest frequency of the C allele in preeclampsia compared to control groups (CI=1.5-3.9, OR=2.48, P=0.0001). Our findings suggest that the IL-1A-899C/C genotype and C allele are associated with susceptibility to preeclampsia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Different Alleles of a Gene Encoding Leucoanthocyanidin Reductase (PaLAR3) Influence Resistance against the Fungus Heterobasidion parviporum in Picea abies1

PubMed Central

Ihrmark, Katarina

2016-01-01

Despite the fact that fungal diseases are a growing menace for conifers in modern silviculture, only a very limited number of molecular markers for pathogen resistance have been validated in conifer species. A previous genetic study indicated that the resistance of Norway spruce (Picea abies) to Heterobasidion annosum s.l., a pathogenic basidiomycete species complex, is linked to a quantitative trait loci that associates with differences in fungal growth in sapwood (FGS) that includes a gene, PaLAR3, which encodes a leucoanthocyanidin reductase. In this study, gene sequences showed the presence of two PaLAR3 allelic lineages in P. abies. Higher resistance was associated with the novel allele, which was found in low frequency in the four P. abies populations that we studied. Norway spruce plants carrying at least one copy of the novel allele showed a significant reduction in FGS after inoculation with Heterobasidion parviporum compared to their half-siblings carrying no copies, indicating dominance of this allele. The amount of (+) catechin, the enzymatic product of PaLAR3, was significantly higher in bark of trees homozygous for the novel allele. Although we observed that the in vitro activities of the enzymes encoded by the two alleles were similar, we could show that allele-specific transcript levels were significantly higher for the novel allele, indicating that regulation of gene expression is responsible for the observed effects in resistance, possibly caused by differences in cis-acting elements that we observe in the promoter region of the two alleles. PMID:27317690

[T(-786) --> C-polymorphism of the endothelial nitric oxide synthase promoter gene (eNOS) and exercise performance in sport].

PubMed

Drozdovs'ka, S B; Lysenko, O M; Dosenko, V Ie; Il'ïn, V M; Moĭbenko, O O

2013-01-01

Given the significant impact of the T(-786) --> C-polymorphism of the eNOS gene in the process of adaptation to physical stress, we aimed to investigate the effect of this polymorphism on physical performance in sportsmen and establish the possibility of its use as a marker of predisposition to the sport. DNA of 516 people, of which 195 qualified athletes and 321 people who had no experience of regular exercise was investigated. The frequency of genotypes and alleles of the T(-786) --> C-polymorphism of the eNOS gene in groups of athletes of different sports, the distribution of genotypes and alleles among athletes and those who are not involved in sports were studied. T allele frequency in a group of athletes on 6.4% (r(chi)2 = 0.03) than in control group. The association of the T allele of the T(-786) --> C-polymorphism of the eNOS gene with a predisposition for speed and power was established. In the group of athletes in speed and power sports, the T-allele frequency was higher than that in the control group by 12% (r(chi)2 = 0.002) and than in group endurance sports by 10% (r(chi)2 = 0.004). We found that the T(-786) --> C-polymorphism of the eNOS gene influence the power and efficiency ofthe functioning of the cardiorespiratory system of athletes during exercise.

The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

PubMed

Quek, S C; Low, P S; Saha, N; Heng, C K

2006-11-01

Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

Development of allele-specific primer PCR for a swine TLR2 SNP and comparison of the frequency among several pig breeds of Japan and the Czech Republic.

PubMed

Muneta, Yoshihiro; Minagawa, Yu; Kusumoto, Masahiro; Shinkai, Hiroki; Uenishi, Hirohide; Splichal, Igor

2012-05-01

In the present study, we have developed an allele-specific primer-polymerase chain reaction (ASP-PCR) for genotyping a single nucleotide polymorphism (SNP) of swine Toll-like receptor 2 (TLR2) (C406G), which is related to the prevalence of pneumonia caused by Mycoplasma hyopneumoniae. We also compared the allele frequency among several pig breeds of Japan and the Czech Republic. Allele-specific primers were constructed by introducing 1-base mismatch sequence before the SNP site. The swine TLR2 C406G mutation was successfully determined by the ASP-PCR using genomic DNA samples in Japan as previously genotyped by a sequencing method. Using the PCR condition determined, genomic DNA samples from pig blood obtained from 110 pigs from 7 different breeds in the Czech Republic were genotyped by the ASP-PCR. The genotyping results from the ASP-PCR were completely matched with the results from the sequencing method. The allele frequency of the swine TLR2 C406G mutation was 27.5% in the Czech Republic and 3.6% in Japan. The C406G mutation was only found in the Landrace breed in Japan, and was almost exclusively found in the Landrace breed in the Czech Republic as well. These results indicated the usefulness of ASP-PCR for detecting a specific SNP for swine TLR2.

Population prevalence of APOE, APOC3 and PPAR-alpha mutations associated to hypertriglyceridemia in French Canadians.

PubMed

Garenc, Christophe; Aubert, Samuel; Laroche, Jèrôme; Girouard, Joël; Vohl, Marie-Claude; Bergeron, Jean; Rousseau, François; Julien, Pierre

2004-01-01

Hypertriglyceridemia (HTG) is known as a common metabolic disorder associated with increased production, decrease catabolism and/or decreased hepatic uptake of triglyceride (TG)-rich particles. We assessed, in the Quebec City population, the allele frequency and haplotype distributions of mutations in genes related to HTG, such as the apolipoprotein E (APOE) (C112R and C158R), the apolipoprotein CIII (APOC3) (C-482T and C3238G) and the peroxisome proliferator-activated receptor alpha (PPARalpha) (L162V) genes. A total of 938 anonymous unlinked newborns from the metropolitan Quebec City area have been genotyped. Allele frequencies observed in the Quebec City population differed from known frequencies determined in other Caucasian populations. The co-transmitted allele distribution between the two-marker genotypes APOE/APOC3(C3238G) and APOC3(C-482T)/PPARalpha(L162V) presented a weak deviation from the assumption of genetic independence. Also, we observed a non-independent distribution of the T-482/G3238 allele combinations within the APOC3 gene, suggesting strong linkage disequilibrium between the C-482T and C3238G polymorphisms. Moreover, comparisons of allele frequencies observed in the population of Québec City to those obtained in other Caucasian populations suggested that the population of Québec City may be at a lower risk of developing HTG due to APOE, APOC3 and PPARalpha genetic variants. However, the strong linkage disequilibrium and the two-marker genotype distributions observed in the APOC3 gene suggest that these two variants may functionally interact in the Québec City population.

HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events

PubMed Central

Buhler, Stéphane; Sanchez-Mazas, Alicia

2011-01-01

Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies. Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the genetic history of human populations, and that their analysis allows a more thorough investigation of human MHC molecular evolution. PMID:21408106

Bias in effect size of systemic lupus erythematosus susceptibility loci across Europe: a case-control study

PubMed Central

2012-01-01

Introduction We aimed to investigate whether the effect size of the systemic lupus erythematosus (SLE) risk alleles varies across European subpopulations. Methods European SLE patients (n = 1,742) and ethnically matched healthy controls (n = 2,101) were recruited at 17 centres from 10 different countries. Only individuals with self-reported ancestry from the country of origin were included. In addition, participants were genotyped for top ancestry informative markers and for 25 SLE associated SNPs. The results were used to compare effect sizes between the Central Eureopan and Southern European subgroups. Results Twenty of the 25 SNPs showed independent association with SLE, These SNPs showed a significant bias to larger effect sizes in the Southern subgroup, with 15/20 showing this trend (P = 0.019) and a larger mean odds ratio of the 20 SNPs (1.46 vs. 1.34, P = 0.02) as well as a larger difference in the number of risk alleles (2.06 vs. 1.63, P = 0.027) between SLE patients and controls than for Central Europeans. This bias was reflected in a very significant difference in the cumulative genetic risk score (4.31 vs. 3.48, P = 1.8 × 10-32). Effect size bias was accompanied by a lower number of SLE risk alleles in the Southern subjects, both patients and controls, the difference being more marked between the controls (P = 1.1 × 10-8) than between the Southern and Central European patients (P = 0.016). Seven of these SNPs showed significant allele frequency clines. Conclusion Our findings showed a bias to larger effect sizes of SLE loci in the Southern Europeans relative to the Central Europeans together with clines of SLE risk allele frequencies. These results indicate the need to study risk allele clines and the implications of the polygenic model of inheritance in SLE. PMID:22541939

On the testing of Hardy-Weinberg proportions and equality of allele frequencies in males and females at biallelic genetic markers.

PubMed

Graffelman, Jan; Weir, Bruce S

2018-02-01

Standard statistical tests for equality of allele frequencies in males and females and tests for Hardy-Weinberg equilibrium are tightly linked by their assumptions. Tests for equality of allele frequencies assume Hardy-Weinberg equilibrium, whereas the usual chi-square or exact test for Hardy-Weinberg equilibrium assume equality of allele frequencies in the sexes. In this paper, we propose ways to break this interdependence in assumptions of the two tests by proposing an omnibus exact test that can test both hypotheses jointly, as well as a likelihood ratio approach that permits these phenomena to be tested both jointly and separately. The tests are illustrated with data from the 1000 Genomes project. © 2017 The Authors Genetic Epidemiology Published by Wiley Periodicals, Inc.

Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus.

PubMed

Liu, Q; Bu, D-F; Li, D; Zhu, X-J

2008-03-01

Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus.

HLA Class II Profile and Distribution of HLA-DRB1 and HLA-DQB1 Alleles and Haplotypes among Lebanese and Bahraini Arabs

PubMed Central

Almawi, Wassim Y.; Busson, Marc; Tamim, Hala; Al-Harbi, Einas M.; Finan, Ramzi R.; Wakim-Ghorayeb, Saria F.; Motala, Ayesha A.

2004-01-01

The gene frequencies of HLA class II alleles were studied in 95 healthy Lebanese Arab and 72 healthy Bahraini Arab subjects. Our aim was to establish the genetic relationship between Bahraini and Lebanese Arabs in terms of HLA class II gene and haplotype frequencies and to compare these results with frequencies for other countries with populations of Caucasian and non-Caucasian descent. Subjects were unrelated and of both sexes, and HLA-DRB1 and -DQB1 genotyping was done by the PCR sequence-specific primer technique. Comparative analysis of the HLA-DR and -DQ alleles revealed differences in the allelic distribution among Bahraini and Lebanese subjects. Analysis of the 25 HLA-DRB1 alleles that have been investigated showed that the DRB1*040101 and DRB1*110101 alleles were more frequent among Lebanese, whereas DRB1*030101 and DRB1*160101 alleles were more frequent among Bahrainis. Similarly, of the seven HLA-DQB1 alleles analyzed, the presence of DQB1*0201 was more frequent among Bahrainis, whereas DQB1*030101 was more frequent among Lebanese. The DRB1*160101-DQB1*050101 (0.1318 versus 0.0379%) and DRB1*030101-DQB1*0201 (0.1202 versus 0.0321%) haplotypes were more frequent among Bahrainis, while the DRB1*110101-DQB1*030101 (0.3142 versus 0.1198%) and DRB1*040101-DQB1*0302 (0.1416 versus 0.0278%) haplotypes were more frequent in Lebanese subjects. Furthermore, a high prevalence of the DRB1*040101-DRB1*110101-DQB1*0302-DQB1*030101 (12.63 versus 1.35%, P = 0.015) and the homozygous DRB1*110101-DRB1*110101-DQB1*030101-DQB1*030101 (7.37 versus 0.00%, P = 0.046) genotypes was seen among Lebanese, and DRB1*070101-DRB1*160101-DQB1*0201-DQB1*050101 (6.76 versus 0.00%, P = 0.034) was seen more frequently among Bahraini subjects. Our results underline significant differences between these two populations in HLA class II distribution, provide basic information for further studies of major histocompatibility complex heterogeneity among Arabic-speaking countries, and serve as a reference for further anthropological studies. PMID:15242955

Association of the LIPG 584C > T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

PubMed Central

2010-01-01

Background Endothelial lipase (EL) is a major determinant of high-density lipoprotein-cholesterol (HDL-C) metabolism, but the association of endothelial lipase gene (LIPG) polymorphism and serum HDL-C levels is scarce and conflicting in diverse populations. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association of LIPG 584C > T (rs2000813) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 645 subjects of Bai Ku Yao and 638 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LIPG 584C > T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.05 - 0.001). The frequency of C and T alleles was 73.5% and 26.5% in Bai Ku Yao, and 67.9% and 32.1% in Han (P < 0.01); respectively. The frequency of CC, CT and TT genotypes was 50.4%, 46.2% and 3.4% in Bai Ku Yao, and 41.4%, 53.1% and 5.5% in Han (P < 0.01); respectively. Serum HDL-C levels in both ethnic groups were different among the three genotypes (P < 0.05 for each). Serum TC levels in both ethnic groups were also different between the CC and CT/TT genotypes (P < 0.05 for each). The T allele carriers had higher serum HDL-C and TC levels than the T allele noncarriers. Multivariate logistic regression analysis showed that the levels of HDL-C and ApoB were correlated with genotypes in Bai Ku Yao (P < 0.05 for each), whereas the levels of TC and HDL-C were associated with genotypes in Han Chinese (P < 0.05 and P < 0.01). Serum lipid parameters were also correlated with several environmental factors in the both ethnic groups. Conclusions The frequency of LIPG 584T allele is lower in Bai Ku Yao than in Han Chinese. The LIPG 584T allele is associated with increased serum HDL-C, TC and ApoB levels. The differences in serum HDL-C, TC and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of LIPG 584C > T or different LIPG-enviromental interactions. PMID:20923576

Association of HLA-DRB1 alleles and neuropsychological function in autism.

PubMed

Chien, Yi-Ling; Wu, Yu-Yu; Chen, Chia-Hsiang; Gau, Susan Shur-Fen; Huang, Yu-Shu; Chien, Wei-Hsien; Hu, Fu-Chang; Chao, Yu-Lin

2012-02-01

Evidence suggests an association between autism and immune dysfunction. The associations between human lymphocyte antigen (HLA)-A2, B44, DRβ1*04 (DR4), C4B, and haplotype B44-SC30-DR4 and autism have been reported in western countries but there is a lack of such information in Asian population. This study aimed to assess the association between HLA-DRB1 allele frequencies and the clinical phenomenology of autism. The sample included 141 participants (male, 87.2%), who were diagnosed with autistic disorder based on clinical assessments and structured interviews using the Chinese version of the Autism Diagnostic Interview-Revised, and 156 healthy controls (male, 38.6%). The HLA-DRB1 alleles were determined by sequencing-based typing method. A subsample of patients (n=39) were assessed for intelligence and neuropsychological functions. The results showed that the pattern of DRB1 allele frequencies was significantly different between patients with autism and the controls (P=0.047). After adjusting for sex by haplotype regression, the frequencies of DR4, DR11, and DR14 were significantly different between patients with autism and healthy controls. In addition, patients with autism and DR4, DR11, or DR14 had different performance on intelligence and neuropsychology tests. Despite a relatively small sample size and a case-control association design, the findings suggest HLA-DRB1 gene might be associated with autism in Han Chinese. The true functional variants associated with autism in our samples remain to be further clarified. It warrants a replication study of a larger family sample and to validate the HLA genetic association with autism and its influence on neuropsychological function.

An Evaluation of Different Target Enrichment Methods in Pooled Sequencing Designs for Complex Disease Association Studies

PubMed Central

Day-Williams, Aaron G.; McLay, Kirsten; Drury, Eleanor; Edkins, Sarah; Coffey, Alison J.; Palotie, Aarno; Zeggini, Eleftheria

2011-01-01

Pooled sequencing can be a cost-effective approach to disease variant discovery, but its applicability in association studies remains unclear. We compare sequence enrichment methods coupled to next-generation sequencing in non-indexed pools of 1, 2, 10, 20 and 50 individuals and assess their ability to discover variants and to estimate their allele frequencies. We find that pooled resequencing is most usefully applied as a variant discovery tool due to limitations in estimating allele frequency with high enough accuracy for association studies, and that in-solution hybrid-capture performs best among the enrichment methods examined regardless of pool size. PMID:22069447

A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation?

PubMed

Lucotte, Gérard; Dieterlen, Florent

2003-01-01

The aim of this new meta-analysis (to the end of 2002) is to compile the Y allele frequencies of the C282Y mutation of hereditary hemochromatosis (HFE gene) for 63 European populations, representing a total of 10,708 unrelated people concerning control samples. A new allele map of C282Y frequencies in Europe was constructed. The highest European frequencies are observed in the Celtic populations in Ireland, in the United Kingdom, and in France, but elevated frequencies are also observed in Scandinavia.

Effects of apolipoprotein E genotype on cortical neuropathology in senile dementia of the Lewy body and Alzheimer's disease.

PubMed

Benjamin, R; Leake, A; Ince, P G; Perry, R H; McKeith, I G; Edwardson, J A; Morris, C M

1995-12-01

Apolipoprotein E (APO E) genotypes were determined in a UK population of neuropathologically confirmed control cases, and in cases of Lewy body dementia (SDLT) and late onset Alzheimer's disease (AD). APO E epsilon 4 allele frequency was significantly elevated in both SDLT and AD groups with a concomitant reduction in the APO E epsilon 3 allele frequency. The epsilon 2 allele frequency in the AD group was only 25% of the control population, though because of the relatively small sample size this reduction was not significant; the epsilon 2 allele frequency in the SDLT group was normal. No significant association was found between senile plaque density and neurofibrillary tangle density in the neocortex and APO E allele dose in either SDLT or AD. Although the possession of APO E epsilon 4 is associated with an increased risk of developing SDLT and AD, actual APO E genotype does not appear to affect the burden of pathology.

Molecular identification of rare FY*Null and FY*X alleles in Caucasian thalassemic family from Sardinia.

PubMed

Manfroi, Silvia; Scarcello, Antonio; Pagliaro, Pasqualepaolo

2015-10-01

Molecular genetic studies on Duffy blood group antigens have identified mutations underlying rare FY*Null and FY*X alleles. FY*Null has a high frequency in Blacks, especially from sub-Saharan Africa, while its frequency is not defined in Caucasians. FY*X allele, associated with Fy(a-b+w) phenotype, has a frequency of 2-3.5% in Caucasian people while it is absent in Blacks. During the project of extensive blood group genotyping in patients affected by hemoglobinopathies, we identified FY*X/FY*Null and FY*A/FY*Null genotypes in a Caucasian thalassemic family from Sardinia. We speculate on the frequency of FY*X and FY*Null alleles in Caucasian and Black people; further, we focused on the association of FY*X allele with weak Fyb antigen expression on red blood cells and its identification performing high sensitivity serological typing methods or genotyping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication.

PubMed

Carneiro, Miguel; Rubin, Carl-Johan; Di Palma, Federica; Albert, Frank W; Alföldi, Jessica; Martinez Barrio, Alvaro; Pielberg, Gerli; Rafati, Nima; Sayyab, Shumaila; Turner-Maier, Jason; Younis, Shady; Afonso, Sandra; Aken, Bronwen; Alves, Joel M; Barrell, Daniel; Bolet, Gerard; Boucher, Samuel; Burbano, Hernán A; Campos, Rita; Chang, Jean L; Duranthon, Veronique; Fontanesi, Luca; Garreau, Hervé; Heiman, David; Johnson, Jeremy; Mage, Rose G; Peng, Ze; Queney, Guillaume; Rogel-Gaillard, Claire; Ruffier, Magali; Searle, Steve; Villafuerte, Rafael; Xiong, Anqi; Young, Sarah; Forsberg-Nilsson, Karin; Good, Jeffrey M; Lander, Eric S; Ferrand, Nuno; Lindblad-Toh, Kerstin; Andersson, Leif

2014-08-29

The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci. Copyright © 2014, American Association for the Advancement of Science.

Polymorphisms and allele frequencies of the ABO blood group gene among the Jomon, Epi-Jomon and Okhotsk people in Hokkaido, northern Japan, revealed by ancient DNA analysis.

PubMed

Sato, Takehiro; Kazuta, Hisako; Amano, Tetsuya; Ono, Hiroko; Ishida, Hajime; Kodera, Haruto; Matsumura, Hirofumi; Yoneda, Minoru; Dodo, Yukio; Masuda, Ryuichi

2010-10-01

To investigate the genetic characteristics of the ancient populations of Hokkaido, northern Japan, polymorphisms of the ABO blood group gene were analyzed for 17 Jomon/Epi-Jomon specimens and 15 Okhotsk specimens using amplified product-length polymorphism and restriction fragment length polymorphism analyses. Five ABO alleles were identified from the Jomon/ Epi-Jomon and Okhotsk people. Allele frequencies of the Jomon/Epi-Jomon and Okhotsk people were compared with those of the modern Asian, European and Oceanic populations. The genetic relationships inferred from principal component analyses indicated that both Jomon/Epi-Jomon and Okhotsk people are included in the same group as modern Asian populations. However, the genetic characteristics of these ancient populations in Hokkaido were significantly different from each other, which is in agreement with the conclusions from mitochondrial DNA and ABCC11 gene analyses that were previously reported.

Is MYO9B the missing link between schizophrenia and celiac disease?

PubMed

Jungerius, Bart J; Bakker, Steven C; Monsuur, Alienke J; Sinke, Richard J; Kahn, Rene S; Wijmenga, Cisca

2008-04-05

There has long been discussion on the correlation between schizophrenia and autoimmune diseases (especially celiac disease), which makes the recently discovered celiac disease risk factor, MYO9B, an attractive functional and positional candidate gene for schizophrenia. To test this hypothesis we compared allele frequencies of three MYO9B tag SNPs in 315 schizophrenia cases and 1,624 healthy controls in a genetic association study. Highly significant differences in allele frequencies between schizophrenia cases and healthy controls were observed for SNP rs2305767 in intron 14 of MYO9B (P = 1.16 x 10(-4); OR 1.41, 95% CI 1.18-1.67). We demonstrate significant association of allelic variants in MYO9B with schizophrenia. To our knowledge, this is the first molecular genetic evidence for a correlation between autoimmune diseases and the risk of developing schizophrenia. Copyright 2007 Wiley-Liss, Inc.

The dynamics of maternal-effect selfish genetic elements.

PubMed

Smith, N G

1998-03-21

Maternal-effect selfish genes such as Medea or Scat act to kill progeny that do not bear a copy of the selfish gene present in the mother. Previous models of this system allowed for two types of allele, the selfish (killer) type and the sensitive (susceptible) wild-type. These models predict that the invasion conditions of the selfish allele are quite broad and that if invasion is possible a high frequency equilibrium is to be expected. The selfish element is therefore predicted to persist. Here a hypothetical third allele that neither kills nor is killed (i.e. insensitive) is considered. Such an allele could enter a population by recombination, mutation or migration. The incorporation of this third allele profoundly affects the dynamics of the system and, under some parameter values, it is possible for the spread of the insensitive allele to lead, eventually, to the fixation of the wild-type allele (reversible evolution). This is most likely if the death of progeny provides no direct benefit to the surviving sibs (i.e. in the absence of fitness compensation), as in insects without gregarious broods. Under these circumstances the selfish element cannot spread when infinitely rare, only after having risen to some finite frequency. A fitness cost to bearing the killer allele then causes its loss. However, if fitness compensation is found (e.g. in placental mammals) the invasion of the selfish element from an infinitely low level is possible for a wide range of costs and both stable coexistences of all three alleles and limit cycles of all three are then found. It is therefore to be expected that in mammals selfish maternal-effect genes are more likely both to spread and to persist than in insects, due to their different levels of fitness compensation.

Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population

PubMed Central

Rivas, Manuel A.; Avila, Brandon E.; Koskela, Jukka; Stevens, Christine; Pirinen, Matti; Neale, Benjamin M.; Ganna, Andrea; Graham, Daniel; Glaser, Benjamin; Peter, Inga; Atzmon, Gil; Barzilai, Nir; Levine, Adam P.; Schiff, Elena; Weisburd, Ben; Lek, Monkol; Bloom, Jonathan; Minikel, Eric V.; Petersen, Britt-Sabina; Beaugerie, Laurent; Seksik, Philippe; Cosnes, Jacques; Schreiber, Stefan; Bokemeyer, Bernd; Bethge, Johannes; Ahmad, Tariq; Plagnol, Vincent; Segal, Anthony W.; Targan, Stephan; Turner, Dan; Saavalainen, Paivi; Farkkila, Martti; Kontula, Kimmo; Palotie, Aarno; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Weersma, Rinse K.; Franke, Andre; Jostins, Luke; Barrett, Jeffrey C.; MacArthur, Daniel G.; Jalas, Chaim; Sokol, Harry; Xavier, Ramnik J.; Pulver, Ann; Cho, Judy H.; McGovern, Dermot P. B.; Daly, Mark J.

2018-01-01

As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10–100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel contributing alleles, show evidence of association to CD. Independently, we find that genomewide common variant risk defined by GWAS shows a strong difference between AJ and non-AJ European control population samples (0.97 s.d. higher, p<10−16). Taken together, the results suggest coordinated selection in AJ population for higher CD risk alleles in general. The results and approach illustrate the value of exome sequencing data in case-control studies along with reference data sets like ExAC (sites VCF available via FTP at ftp.broadinstitute.org/pub/ExAC_release/release0.3/) to pinpoint genetic variation that contributes to variable disease predisposition across populations. PMID:29795570

The C(-260)>T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.

PubMed

Longobardo, M T; Cefalù, A B; Pezzino, F; Noto, D; Emmanuele, G; Barbagallo, C M; Fiore, B; Monastero, R; Castello, A; Molini, V; Notarbartolo, A; Travali, S; Averna, M R

2003-11-01

CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients with and acute myocardial infarction 213 healthy controls were included in the study. Genotype frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by polimerase chain reaction and the amplified product was cleaved with HaeIII. The frequency of the T allele was not significantly different in patients compared with controls. In this study we were not able to detect differences of frequency of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of myocardial infarction and controls.

Profile of Rh, Kell, Duffy, Kidd, and Diego blood group systems among blood donors in the Southwest region of the Paraná state, Southern Brazil.

PubMed

Zacarias, Joana Maira Valentini; Langer, Ieda Bernadete Volkweis; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

2016-12-01

The aim of this study was to assess the distribution of alleles and genotypes of the blood group systems Rh, Kell, Duffy, Kidd, and Diego in 251 regular blood donors registered in the hemotherapy unit of the Southwestern region of Paraná, Southern Brazil. The frequencies were obtained by direct counting on a spreadsheet program and statistical analyses were conducted in order to compare them with other Brazilian populations using chi-squared with Yates correction on OpenEpi software. The frequencies of RHD* negative, RHCE*c/c and RHCE*e/e were higher than expected for the Caucasian population. A difference was also observed for FY alleles, FY*01/FY*01 genotype and FY*02N.01 -67T/C (GATA Box mutation). Two homozygous individuals were defined as a low frequency phenotype K + k- (KEL*01.01/KEL*01.01) and, for Diego blood group system the rare DI*01 allele was found in ten blood donors, of which one was DI*01/DI* 01 (0.4%). The allele and genotype frequencies of Kidd blood group system were similar to expected to Caucasians. The results showed the direction in which to choose donors, the importance of extended genotyping in adequate blood screening and the existence of rare genotypes in Brazilian regular blood donors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vitamin-D receptor (VDR) gene polymorphisms (Taq-I & Apa-I) in Syrian healthy population.

PubMed

Haddad, Shaden

2014-12-01

The vitamin D endocrine system regulates bone metabolism and calcium homeostasis as well as cellular proliferation and differentiation. Vitamin D receptor (VDR) mediates Vit-D activity, thus VDR gene polymorphisms may correlate with different diseases. This study aimed to determine the distribution of VDR gene (Taq-I and Apa-I) polymorphisms using a RFLP in unrelated normal healthy individuals of Syrian population. Allelic frequencies were 65% vs 35% and 66% vs 34% for T vs t and A vs a alleles, respectively. Genotype distribution was 36%, 58% and 6% for TT, Tt and tt and 42%, 47% and 10% for AA, Aa and aa, respectively. These results demonstrate that the frequency and distribution of the VDR polymorphisms in Syrian population are different from other populations worldwide.

[Association of aggressive behaviors of schizophrenia with short tandem repeats loci].

PubMed

Yang, Chun; Ba, Huajie; Tan, Xingqi; Zhao, Hanqing; Zhang, Shuyou; Yu, Haiying

2017-12-10

To assess the association of short tandem repeats (STRs) loci with aggressive behaviors of schizophrenia. Blood samples from 123 schizophrenic patients with aggressive behaviors and 489 schizophrenic patients without aggressive behaviors were collected. DNA from all samples was amplified with a PowerPlex 21 system and separated by electrophoresis to determine the genotypes and allelic frequencies of 20 STR loci including D3S1368, D1S1656, D6S1043, D13S317, Penta E, D16S639, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, and FGA. All of the 20 STR loci have reached Hardy-Weinberg equilibrium in both groups. A significant difference was found in allelic and genotypic frequencies of loci Penta D between the two groups (alleles: P=0.042; genotypes: P=0.014) but not for the remaining 19 loci (P> 0.05). Univariate analysis also showed a significant difference for allele 10 and genotypes 10-12 of Penta D between the two groups (P=0.0027, P=0.0001), with the OR being 1.81 (95%CI: 1.22-2.67) and 4.33 (95%CI: 1.95-9.59), respectively. Penta D may be associated with aggressive behaviors of schizophrenia. Allele 10 and genotypes 10-12 of Penta D may confer a risk for the disease.

A general model to explore complex dominance patterns in plant sporophytic self-incompatibility systems.

PubMed

Billiard, Sylvain; Castric, Vincent; Vekemans, Xavier

2007-03-01

We developed a general model of sporophytic self-incompatibility under negative frequency-dependent selection allowing complex patterns of dominance among alleles. We used this model deterministically to investigate the effects on equilibrium allelic frequencies of the number of dominance classes, the number of alleles per dominance class, the asymmetry in dominance expression between pollen and pistil, and whether selection acts on male fitness only or both on male and on female fitnesses. We show that the so-called "recessive effect" occurs under a wide variety of situations. We found emerging properties of finite population models with several alleles per dominance class such as that higher numbers of alleles are maintained in more dominant classes and that the number of dominance classes can evolve. We also investigated the occurrence of homozygous genotypes and found that substantial proportions of those can occur for the most recessive alleles. We used the model for two species with complex dominance patterns to test whether allelic frequencies in natural populations are in agreement with the distribution predicted by our model. We suggest that the model can be used to test explicitly for additional, allele-specific, selective forces.

Frequency of the CHEK2 1100delC mutation among women with breast cancer: an international study.

PubMed

Zhang, Shiyu; Phelan, Catherine M; Zhang, Phil; Rousseau, Francois; Ghadirian, Parviz; Robidoux, Andre; Foulkes, William; Hamel, Nancy; McCready, David; Trudeau, Maureen; Lynch, Henry; Horsman, Douglas; De Matsuda, Maria Lourdes Leon; Aziz, Zeba; Gomes, Magda; Costa, Mauricio Magalhaes; Liede, Alexander; Poll, Aletta; Sun, Ping; Narod, Steven A

2008-04-01

A founder allele in the CHEK2 gene (1100delC) has been associated with an elevated risk of breast cancer. This allele is responsible for the majority of CHEK2-associated breast cancers in women from northern European countries; however, within Europe, it seems to be rare in countries that are close to the Mediterranean. The frequency of the 1100delC allele has not been measured in non-White populations. We measured the frequency of the CHEK2 founder allele in 3,882 breast cancer patients and 8,609 controls from various countries. The allele was not seen among Asian patients (from Pakistan or the Philippines) and was present in 1 of 155 cases from Brazil. Among White women, the allele was present in 1.5% of 825 familial cases of breast cancer and in 0.7% of 1,106 patients with nonfamilial breast cancer. The allele was equally frequent in Jewish and non-Jewish patients. We estimate that the CHEK2 1100delC allele is associated with an odds ratio of 2.6 for breast cancer, which corresponds to a lifetime risk of approximately 24% in Ontario.

Genotyping of the Duffy Blood Group among Plasmodium knowlesi-Infected Patients in Malaysia

PubMed Central

De Silva, Jeremy Ryan; Lau, Yee Ling; Fong, Mun Yik

2014-01-01

The Duffy blood group is of major interest in clinical medicine as it plays an important role in Plasmodium knowlesi and Plasmodium vivax infection. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Peninsular Malaysia were determined. The blood group of 60 healthy blood donors and 51 P. knowlesi malaria patients were genotyped using allele specific polymerase chain reaction (ASP-PCR). The data was analyzed using Fisher's exact test in order to assess the significance of the variables. Our results show a high proportion of the FY*A/FY*A genotype (>85% for both groups) and a high frequency of the FY*A allele (>90% for both groups). The FY*A/FY*A genotype was the most predominant genotype in both infected and healthy blood samples. The genotype frequency did not differ significantly between the donor blood and the malaria patient groups. Also, there was no significant correlation between susceptibility to P. knowlesi infection with any Duffy blood genotype. PMID:25268233

Minor Allele Frequency Changes the Nature of Genotype by Environment Interactions.

PubMed

Verhulst, Brad; Neale, Michael C

2016-09-01

In the classical twin study, phenotypic variation is often partitioned into additive genetic (A), common (C) and specific environment (E) components. From genetical theory, the outcome of genotype by environment interaction is expected to inflate A when the interacting factor is shared (i.e., C) between the members of a twin pair. We show that estimates of both A and C can be inflated. When the shared interacting factor changes the size of the difference between homozygotes' means, the expected sibling or DZ twin correlation is .5 if and only if the minor allele frequency (MAF) is .5; otherwise the expected DZ correlation is greater than this value, consistent (and confounded) with some additional effect of C. This result is considered in the light of the distribution of minor allele frequencies for polygenic traits. Also discussed is whether such interactions take place at the locus level or affect an aggregated biological structure or system. Interactions with structures or endophenotypes that result from the aggregated effects of many loci will generally emerge as part of the A estimate.

More about the Viking hypothesis of origin of the delta32 mutation in the CCR5 gene conferring resistance to HIV-1 infection.

PubMed

Lucotte, Gérard; Dieterlen, Florent

2003-11-01

The chemokine receptor CCR5 constitutes the major coreceptor for the HIV-1, because a mutant allele of the CCR5 gene named delta32 was shown to provide to homozygotes a strong resistance against infection. In the present study the frequency of the delta32 allele was collected in 36 European populations and in Cyprus, and the highest allele frequencies were found in Nordic countries. We constructed an allele map of delta32 frequencies in Europe; the map is in accordance to the Vikings hypothesis of the origin of the mutation and his dissemination during the eighth to the tenth centuries.

Evolution of the Drosophila melanogaster-sigma virus system in natural populations from Languedoc (southern France).

PubMed

Fleuriet, A; Periquet, G

1993-01-01

An analysis of natural populations of Drosophila melanogaster in a southern French region (Languedoc) was started in 1983, concerning two non Mendelian systems: the P-M system of transposable elements and the sigma virus. This virus is not contagious, but only transmitted through gametes; it is usually present in a minority of individuals in natural populations. The first data collected revealed unexpectedly clear and fast-evolving phenomena; they also gave evidence of some interesting correlations between the two systems. This paper presents all the results gathered from 1983 to 1991 in the Drosophila-sigma system. Striking correlations were observed for three interconnected parameters: frequency of infected flies, frequency of an allele of the fly giving resistance to the virus, and adaptation of the virus to this allele. This adaptation consisted of a qualitative step (change of viral type) followed by quantitative variation (better adaptation to the allele). This analysis also showed, firstly, that the evolution of natural populations differs completely in Languedoc from the rest of France; secondly, that three geographical zones where selective forces worked differently persisted over time in Languedoc.

Population-genetic nature of copy number variations in the human genome.

PubMed

Kato, Mamoru; Kawaguchi, Takahisa; Ishikawa, Shumpei; Umeda, Takayoshi; Nakamichi, Reiichiro; Shapero, Michael H; Jones, Keith W; Nakamura, Yusuke; Aburatani, Hiroyuki; Tsunoda, Tatsuhiko

2010-03-01

Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000-4000 CNVs (4-6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV-SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV-SNP linkage disequilibrium (LD) for 500-900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP-SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs.

Prevalence of melanocortin receptor 4 (MC4R) V103I gene variant and its association with obesity among the Kampar Health Clinic cohort, Perak, Malaysia.

PubMed

Chua, H N; Fan, S H; Say, Y H

2012-04-01

This study investigated the prevalence of the Melanocortin receptor 4 (MC4R) V1031 gene variant and its association with obesity among a cohort of 254 patients (101 males; 118 obese) attending the Kampar Health Clinic. Genotyping revealed the mutated I allele frequency of 0.02, no homozygous mutated (II), and similar distribution of V and I alleles across BMI groups, genders and ethnic groups. No significant difference was found for the means of anthropometric measurements between alleles. Prevalence of this gene variant among the Malaysian cohort was similar with previous populations (2-4% of mutated allele carrier), but was not associated with obesity.

Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing technology.

PubMed

Koontz, Deborah A; Huckins, Jacqueline J; Spencer, Antonina; Gallagher, Margaret L

2009-08-24

Identification of CYP2A6 alleles associated with reduced enzyme activity is important in the study of inter-individual differences in drug metabolism. CYP2A6*12 is a hybrid allele that results from unequal crossover between CYP2A6 and CYP2A7 genes. The 5' regulatory region and exons 1-2 are derived from CYP2A7, and exons 3-9 are derived from CYP2A6. Conventional methods for detection of CYP2A6*12 consist of two-step PCR protocols that are laborious and unsuitable for high-throughput genotyping. We developed a rapid and accurate method to detect the CYP2A6*12 allele by Pyrosequencing technology. A single set of PCR primers was designed to specifically amplify both the CYP2A6*1 wild-type allele and the CYP2A6*12 hybrid allele. An internal Pyrosequencing primer was used to generate allele-specific sequence information, which detected homozygous wild-type, heterozygous hybrid, and homozygous hybrid alleles. We first validated the assay on 104 DNA samples that were also genotyped by conventional two-step PCR and by cycle sequencing. CYP2A6*12 allele frequencies were then determined using the Pyrosequencing assay on 181 multi-ethnic DNA samples from subjects of African American, European Caucasian, Pacific Rim, and Hispanic descent. Finally, we streamlined the Pyrosequencing assay by integrating liquid handling robotics into the workflow. Pyrosequencing results demonstrated 100% concordance with conventional two-step PCR and cycle sequencing methods. Allele frequency data showed slightly higher prevalence of the CYP2A6*12 allele in European Caucasians and Hispanics. This Pyrosequencing assay proved to be a simple, rapid, and accurate alternative to conventional methods, which can be easily adapted to the needs of higher-throughput studies.

The functional importance of sequence versus expression variability of MHC alleles in parasite resistance.

PubMed

Axtner, Jan; Sommer, Simone

2012-12-01

Understanding selection processes driving the pronounced allelic polymorphism of the major histocompatibility complex (MHC) genes and its functional associations to parasite load have been the focus of many recent wildlife studies. Two main selection scenarios are currently debated which explain the susceptibility or resistance to parasite infections either by the effects of (1) specific MHC alleles which are selected frequency-dependent in space and time or (2) a heterozygote or divergent allele advantage. So far, most studies have focused only on structural variance in co-evolutionary processes although this might not be the only trait subject to natural selection. In the present study, we analysed structural variance stretching from exon1 through exon3 of MHC class II DRB genes as well as genotypic expression variance in relation to the gastrointestinal helminth prevalence and infection intensity in wild yellow-necked mice (Apodemus flavicollis). We found support for the functional importance of specific alleles both on the sequence and expression level. By resampling a previously investigated study population we identified specific MHC alleles affected by temporal shifts in parasite pressure and recorded associated changes in allele frequencies. The allele Apfl-DRB*23 was associated with resistance to infections by the oxyurid nematode Syphacia stroma and at the same time with susceptibility to cestode infection intensity. In line with our expectation, MHC mRNA transcript levels tended to be higher in cestode-infected animals carrying the allele Apfl-DRB*23. However, no support for a heterozygote or divergent allele advantage on the sequence or expression level was detected. The individual amino acid distance of genotypes did not explain individual differences in parasite loads and the genetic distance had no effect on MHC genotype expression. For ongoing studies on the functional importance of expression variance in parasite resistance, allele-specific expression data would be preferable.

How-To-Do-It: Multiple Allelic Frequencies in Populations at Equilibrium: Algorithms and Applications.

ERIC Educational Resources Information Center

Nussbaum, Francis, Jr.

1988-01-01

Presents an algorithm for solving problems related to multiple allelic frequencies in populations at equilibrium. Considers sample problems and provides their solution using this tabular algorithm. (CW)

Allelic frequencies and statistical data obtained from 12 codis STR loci in an admixed population of the Brazilian Amazon

PubMed Central

da Costa Francez, Pablo Abdon; Rodrigues, Elzemar Martins Ribeiro; Frazão, Gleycianne Furtado; dos Reis Borges, Nathalia Danielly; dos Santos, Sidney Emanuel Batista

2011-01-01

The allelic frequencies of 12 short tandem repeat loci were obtained from a sample of 307 unrelated individuals living in Macapá, a city in the northern Amazon region, Brazil. These loci are the most commonly used in forensics and paternity testing. Based on the allele frequency obtained for the population of Macapá, we estimated an interethnic admixture for the three parental groups (European, Native American and African) of, respectively, 46%, 35% and 19%. Comparing these allele frequencies with those of other Brazilian populations and of the Iberian Peninsula population, no significant distances were observed. The interpopulation genetic distances (FST coefficients) to the present database ranged from FST = 0.0016 between Macapá and Belém to FST = 0.0036 between Macapá and the Iberian Peninsula. PMID:21637540

Allelic frequencies and statistical data obtained from 12 codis STR loci in an admixed population of the Brazilian Amazon.

PubMed

da Costa Francez, Pablo Abdon; Rodrigues, Elzemar Martins Ribeiro; Frazão, Gleycianne Furtado; Dos Reis Borges, Nathalia Danielly; Dos Santos, Sidney Emanuel Batista

2011-01-01

The allelic frequencies of 12 short tandem repeat loci were obtained from a sample of 307 unrelated individuals living in Macapá, a city in the northern Amazon region, Brazil. These loci are the most commonly used in forensics and paternity testing. Based on the allele frequency obtained for the population of Macapá, we estimated an interethnic admixture for the three parental groups (European, Native American and African) of, respectively, 46%, 35% and 19%. Comparing these allele frequencies with those of other Brazilian populations and of the Iberian Peninsula population, no significant distances were observed. The interpopulation genetic distances (F(ST) coefficients) to the present database ranged from F(ST) = 0.0016 between Macapá and Belém to F(ST) = 0.0036 between Macapá and the Iberian Peninsula.

Lipid regulatory genes polymorphism in children with and without obesity and cardiometabolic risk factors: The CASPIAN-III study

PubMed Central

Hovsepian, Silva; Javanmard, Shaghayegh Haghjooy; Mansourian, Marjan; Hashemipour, Mahin; Tajadini, Mohamadhasan; Kelishadi, Roya

2018-01-01

Background: Genetically, predisposed children are considered as at-risk individuals for cardiovascular disease. In this study, we aimed to compare the frequency of four-lipid regulatory polymorphism in obese and normal-weight children with and without cardiometabolic risk factors. Materials and Methods: In this nested case–control study, 600 samples of four groups of participants consisted of those with normal weight with and without cardiometabolic risk factors and obese with and without cardiometabolic risk factors. Allelic and genotypic frequencies of GCKR (rs780094), GCKR (rs1260333), MLXIPL (rs3812316), and FADS (rs174547) polymorphisms were compared in the four studied groups. Results: Data of 528 samples were complete and included in this study. The mean (standard deviation) age of participants was 15.01 (2.21) years. Frequency of tt allele (minor allele) of GCKR (rs1260333) polymorphism was significantly lower in normal weight metabolically healthy participants than metabolically unhealthy normal weight (MUHNW) and obese children with and without cardiometabolic risk factor (P = 0.01). Frequency of ga allele of GCKR (rs780094) polymorphism was significantly higher in normal weight children with cardiometabolic risk factor than in their obese counterparts with cardiometabolic risk factor (P = 0.04). Frequency of cg and gg alleles (minor type) of MLXIPL (rs3812316) polymorphism in normal weight metabolically healthy participants was significantly higher than MUHNW (P = 0.04) and metabolically healthy obese children (P = 0.04). Conclusion: The findings of our study indicated that the minor allele of GCKR (rs1260333) single nucleotide polymorphisms (SNPs) could have pathogenic effect for obesity and cardiometabolic risk factors. Ga allele of GCKR (rs780094) SNPs had a protective effect on obesity. Minor alleles of MLXIPL (rs3812316) could have a protective effect for obesity and cardiometabolic risk factors. PMID:29531563

Analysis for genotyping Duffy blood group in inhabitants of Sudan, the Fourth Cataract of the Nile

PubMed Central

2012-01-01

Background Genetic polymophisms of the Duffy antigen receptor for the chemokines (DARC) gene successfully protected against blood stage infection by Plasmodium vivax infection. The Fy (a-, b-) phenotype is predominant among African populations, particularly those originating from West Africa, and it is rare among non-African populations. The aim of this study was to analyse the frequency of four Duffy blood groups based on SNPs (T-33C, G125A, G298A and C5411T) in two local tribes of Sudanese Arabs, the Shagia and Manasir, which are both from the region of the Fourth Nile cataract in Sudan. Methods An analysis of polymorphisms was performed on 217 individuals (126 representatives of the Shagia tribe and 91 of the Manasir). Real-time PCR and TaqMan Genotyping Assays were used to study the prevalence of alleles and genotypes. Results The analysis of allelic and genotype frequency in the T-33C polymorphisms demonstrated a significant dominance of the C allele and CC genotype (OR = 0.53 [0.32-0.88]; p = 0.02) in both tribes. The G125A polymorphism is associated with phenotype Fy(a-, b-) and was identified in 83% of Shagia and 77% of Manasir. With regard to G298A polymorphisms, the genotype frequencies were different between the tribes (p = 0,002) and no single AA homozygote was found. Based on four SNPs examined, 20 combinations of genotypes for the Shagia and Manasir tribes were determined. The genotype CC/AA/GG/CT occurred most often in Shagia tribe (45.9%) but was rare in the Manasir tribe (6.6%) (p < 0.001 Shagia versus Manasir). The FY*AES allele was identified in both analysed tribes. The presence of individuals with the FY*A/FY*A genotype was demonstrated only in the Shagia tribe. Conclusion This is probably the first report showing genotypically Duffy-negative people who carry both FY*BES and FY*AES. The identification of the FY*AES allele in both tribes may be due to admixture of the non-African genetic background. Taken as a whole, allele and genotype frequencies between the Shagia and the Manasir were statistically different. However, the presence of individuals with the FY*A/FY*A genotype was demonstrated only in the Shagia tribe. PMID:22510366

Collagen Ialpha1 and vitamin D receptor gene polymorphisms in South African whites, blacks and Indians.

PubMed

Ojwang, P J; Pegoraro, R J; Rom, L; Lanning, P

2001-11-01

To determine whether polymorphic differences exist between black, white and Indian South Africans in genes associated with bone mineral density and osteoporosis. Genes selected were the vitamin D receptor (Apa I and Taq I polymorphisms) and collagen (Sp I transcription factor polymorphism) using standard molecular biology techniques. Department of Chemical Pathology, Nelson R Mandela School of Medicine, University of Natal, Durban, South Africa. Healthy male and female blood donors living in the Durban metropolitan region, South Africa. The group comprised black Africans (n=264), white Caucasians (n=247) and Asians of Indian origin (n=194). No significant differences in genotypes were seen between white and Indian subjects. Blacks had a significantly higher frequency of the TT Taq I genotype and a significantly lower frequency of the Ss Sp I genotype. No ss genotype was detected in blacks. The very low frequency of the collagen Sp I s allele and higher frequency of the VDR T allele in blacks may be associated with the lower incidence of osteoporosis in this ethnic group.

Novel microsatellite markers for the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae) and effects of null alleles on population genetics analyses.

PubMed

Song, W; Cao, L-J; Wang, Y-Z; Li, B-Y; Wei, S-J

2017-06-01

The oriental fruit moth (OFM) Grapholita molesta (Lepidoptera: Tortricidae) is an important economic pest of stone and pome fruits worldwide. We sequenced the OFM genome using next-generation sequencing and characterized the microsatellite distribution. In total, 56,674 microsatellites were identified, with 11,584 loci suitable for primer design. Twenty-seven polymorphic microsatellites, including 24 loci with trinucleotide repeat and three with pentanucleotide repeat, were validated in 95 individuals from four natural populations. The allele numbers ranged from 4 to 40, with an average value of 13.7 per locus. A high frequency of null alleles was observed in most loci developed for the OFM. Three marker panels, all of the loci, nine loci with the lowest null allele frequencies, and nine loci with the highest null allele frequencies, were established for population genetics analyses. The null allele influenced estimations of genetic diversity parameters but not the OFM's genetic structure. Both a STRUCTURE analysis and a discriminant analysis of principal components, using the three marker panels, divided the four natural populations into three groups. However, more individuals were incorrectly assigned by the STRUCTURE analysis when the marker panel with the highest null allele frequency was used compared with the other two panels. Our study provides empirical research on the effects of null alleles on population genetics analyses. The microsatellites developed will be valuable markers for genetic studies of the OFM.

The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes

PubMed Central

McGraw, K L; Zhang, L M; Rollison, D E; Basiorka, A A; Fulp, W; Rawal, B; Jerez, A; Billingsley, D L; Lin, H-Y; Kurtin, S E; Yoder, S; Zhang, Y; Guinta, K; Mallo, M; Solé, F; Calasanz, M J; Cervera, J; Such, E; González, T; Nevill, T J; Haferlach, T; Smith, A E; Kulasekararaj, A; Mufti, G; Karsan, A; Maciejewski, J P; Sokol, L; Epling-Burnette, P K; Wei, S; List, A F

2015-01-01

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progression-free survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise the largest MDS R72P SNP analysis. PMID:25768405

Association of apolipoprotein E polymorphism with myocardial infarction in Greek patients with coronary artery disease.

PubMed

Kolovou, Genovefa; Yiannakouris, Nikos; Hatzivassiliou, Marilena; Malakos, John; Daskalova, Deliana; Hatzigeorgiou, George; Cariolou, Marios A; Cokkinos, Dennis V

2002-01-01

Studies in several populations have indicated that genetic variation at the apolipoprotein E (apoE) structural locus influences the risk of coronary artery disease (CAD) and myocardial infarction (MI). This study aimed at investigating whether apoE polymorphism has an allelic and/or genotypic impact on the risk of MI in Greek patients with CAD. We compared apoE gene polymorphism in a group of patients with angiographically confirmed CAD but not MI [CAD/MI (-)-group, n = 143] and a group of age and sex-matched CAD patients who had experienced a non-fatal Ml [CAD/MI (+)-group, n = 124]. The patients were also compared with a group of healthy younger individuals (n = 240) with no family history of CAD. The apoE genotype distribution differed significantly between the two groups of CAD patients (p = 0.02). The epsilon2 allele was 5.3-fold less frequent in the CAD/ MI (+)-group compared with the CAD/MI (-)-group (1.2% vs. 6.3%, p = 0.01). The frequency of the epsilon2 allele in healthy subjects was 8.1%, which is 6.8-fold higher than in CAD/MI (+)-patients (p = 0.001) and twice as high compared with all CAD patients (p = 0.02). No differences in epsilon4 allele frequencies were observed between CAD/MI (+)- and CAD/MI (-)-patients (10.9% vs. 9.8%), or between patients with CAD and healthy subjects (10.3% vs. 10.2%). In summary, the epsilon4 allele was not found to be associated with an increased risk for CAD or MI. In contrast, a negative association of the epsilon2 allele with Ml was observed among Greek patients with CAD.

Polymorphic variations in IL-1β, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women.

PubMed

Pooja, Singh; Chaudhary, Preeti; Nayak, Lakshma V; Rajender, Singh; Saini, Karan Singh; Deol, Debashish; Kumar, Sandeep; Bid, Hemant Kumar; Konwar, Rituraj

2012-10-01

Cytokines are known as important regulators of the entire gamut of cancer from initiation, invasion and metastasis. This fact and plethora of gene polymorphism data prompted us to investigate cytokine gene polymorphisms in breast cancer (BC) patients. Selected polymorphisms in the IL-1β [-511 T>C (rs16944) and +3954 C>T (rs1143634)]; IL-6 [-174 G>C (rs1800795)]; IL-10 [-1082 A>G (rs1800896), -819 T>C (rs1800871) and -592 A>C (rs1800872)] genes were genotyped in 200 BC patients and 200 healthy volunteers in a case-control study using PCR-RFLP and direct DNA sequencing techniques. Peripheral cytokine levels were measured using ELISA. Allele and genotype data were analyzed for significance of differences between cases and controls using Chi-Square [χ(2)] test. Two sided P-values of less than 0.05 were considered to be statistically significant. Peripheral level of all three cytokines did not show any significant difference between cases and controls. Allele and genotype frequency of IL-1β [-511 T>C (rs16944)] did not show any difference between cases and controls. On the other hand mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] associated with increased risk of BC. This was also true for pre-menopausal cases and for mutant genotype in post-menopausal cases. Mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] appeared to be protective in nature such that controls had a higher frequency of both mutant alleles and genotypes. None of the three SNPs in IL-10 gene associated with risk of BC, except significant association of mutant allele and genotypes of -1082 A>G (rs1800896) polymorphism with postmenopausal BC. Mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] site associated with increased BC risk, while mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] polymorphism appeared to be protective. Also, there was significant association of mutant allele and genotypes of IL-10 [-1082 A>G (rs1800896)] with postmenopausal BC. None of the other polymorphisms investigated appear to affect BC risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

A whole genome SNP genotyping by DNA microarray and candidate gene association study for kidney stone disease

PubMed Central

2014-01-01

Background Kidney stone disease (KSD) is a complex disorder with unknown etiology in majority of the patients. Genetic and environmental factors may cause the disease. In the present study, we used DNA microarray to genotype single nucleotide polymorphisms (SNP) and performed candidate gene association analysis to determine genetic variations associated with the disease. Methods A whole genome SNP genotyping by DNA microarray was initially conducted in 101 patients and 105 control subjects. A set of 104 candidate genes reported to be involved in KSD, gathered from public databases and candidate gene association study databases, were evaluated for their variations associated with KSD. Results Altogether 82 SNPs distributed within 22 candidate gene regions showed significant differences in SNP allele frequencies between the patient and control groups (P < 0.05). Of these, 4 genes including BGLAP, AHSG, CD44, and HAO1, encoding osteocalcin, fetuin-A, CD44-molecule and glycolate oxidase 1, respectively, were further assessed for their associations with the disease because they carried high proportion of SNPs with statistical differences of allele frequencies between the patient and control groups within the gene. The total of 26 SNPs showed significant differences of allele frequencies between the patient and control groups and haplotypes associated with disease risk were identified. The SNP rs759330 located 144 bp downstream of BGLAP where it is a predicted microRNA binding site at 3′UTR of PAQR6 – a gene encoding progestin and adipoQ receptor family member VI, was genotyped in 216 patients and 216 control subjects and found to have significant differences in its genotype and allele frequencies (P = 0.0007, OR 2.02 and P = 0.0001, OR 2.02, respectively). Conclusions Our results suggest that these candidate genes are associated with KSD and PAQR6 comes into our view as the most potent candidate since associated SNP rs759330 is located in the miRNA binding site and may affect mRNA expression level. PMID:24886237

Genetic diversity of the msp-1, msp-2, and glurp genes of Plasmodium falciparum isolates along the Thai-Myanmar borders.

PubMed

Congpuong, Kanungnit; Sukaram, Rungniran; Prompan, Yuparat; Dornae, Aibteesam

2014-08-01

To study the genetic diversity at the msp-1, msp-2, and glurp genes of Plasmodium falciparum (P. falciparum) isolates from 3 endemic areas in Thailand: Tak, Kanchanaburi and Ranong provinces. A total of 144 P. falciparum isolates collected prior to treatment during January, 2012 to June, 2013 were genotyped. DNA was extracted; allele frequency and diversity of msp-1, msp-2, and glurp genes were investigated by nested polymerase chain reaction. P. falciparum isolates in this study had high rate of multiple genotypes infection (96.5%) with an overall mean multiplicity of infection of 3.21. The distribution of allelic families of msp-1 was significantly different among isolates from Tak, Kanchanaburi, and Ranong but not for the msp-2. K1 and MAD20 were the predominant allelic families at the msp-1 gene, whereas alleles belonging to 3D7 were more frequent at the msp-2 gene. The glurp gene had the least diverse alleles. Population structure of P. falciparum isolates from Tak and Ranong was quite similar as revealed by the presence of similar proportions of MAD20 and K1 alleles at msp-1 loci, 3D7 and FC27 alleles at msp-2 loci as well as comparable mean MOI. Isolates from Kanchanaburi had different structures; the most prevalent alleles were K1 and RO33. The present study shows that P. falciparum isolates from Tak and Ranong provinces had similar allelic pattern of msp-1 and msp-2 and diversity but different from Kanchanaburi isolates. These allelic variant profiles are valuable baseline data for future epidemiological study of malaria transmission and for continued monitoring of polymorphisms associated with antimalarial drug resistance in these areas.

Antagonistic versus non-antagonistic models of balancing selection: Characterizing the relative timescales and hitchhiking effects of partial selective sweeps

PubMed Central

Connallon, Tim; Clark, Andrew G.

2012-01-01

Antagonistically selected alleles -- those with opposing fitness effects between sexes, environments, or fitness components -- represent an important component of additive genetic variance in fitness-related traits, with stably balanced polymorphisms often hypothesized to contribute to observed quantitative genetic variation. Balancing selection hypotheses imply that intermediate-frequency alleles disproportionately contribute to genetic variance of life history traits and fitness. Such alleles may also associate with population genetic footprints of recent selection, including reduced genetic diversity and inflated linkage disequilibrium at linked, neutral sites. Here, we compare the evolutionary dynamics of different balancing selection models, and characterize the evolutionary timescale and hitchhiking effects of partial selective sweeps generated under antagonistic versus non-antagonistic (e.g., overdominant and frequency-dependent selection) processes. We show that that the evolutionary timescales of partial sweeps tend to be much longer, and hitchhiking effects are drastically weaker, under scenarios of antagonistic selection. These results predict an interesting mismatch between molecular population genetic and quantitative genetic patterns of variation. Balanced, antagonistically selected alleles are expected to contribute more to additive genetic variance for fitness than alleles maintained by classic, non-antagonistic mechanisms. Nevertheless, classical mechanisms of balancing selection are much more likely to generate strong population genetic signatures of recent balancing selection. PMID:23461340

Clarifying the association of genes within the major histocompatibility complex with narcolepsy

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

Acton, R.T.; Watson, B.; Rivers, C.

1994-09-01

HLA-DR2 and DQwl has been reported to be strongly associated with narcolepsy. The particular phenotype and strength of these associations varies between races. For example DQB*0601 has been reported associated with some African American (AA) narcoleptics while some Caucasian American (CA) narcoleptics do not possess DR2 or DQw1. We have sought to clarify the relationship of MHC genes with narcolepsy in the local CA and AA population. There was no significant difference in the frequency of DR phenotypes in CA or AA narcoleptics compared to race, age, sex and geographic region-matched controls. DR2 was increased in CA cataplexy positive (Cat+)more » narcoleptics compared to controls (p=0.028, odds ratio (OR)=2.4) and to Cat- narcoleptics (p=<0.001, OR=8.8). DR11 was increased in AA Cat+ narcoleptics compared to controls (p=0.004, OR=11.2) and to Cat- narcoleptics (p=0.002). DQB1*0601 was not significantly associated with narcolepsy in our AA population. We have assessed the frequency of the TNFa (13 alleles, 1.1Mb telomeric to DQ{alpha}), D6S105 (13 alleles, 1kb telomeric of HLA-A), and GLP-1R (19 alleles, 18.5 Mb centromeric of DQ{alpha}), dinucleotide repeats in narcoleptics compared to controls. The TNFa allele 117 was increased in CA Cat+ vs. controls (p=0.003). The GLP-1R allele 144 was increased in CA Cat- vs. controls (p=0.02). In AA narcoleptics, the TNFa allele 109 was significantly increased (p=0.04) along with the D6S105 allele 130 (p=0.02) compared to controls. The D6S105 allele 130 was increased in AA Cat- vs. controls (p=0.03). The GLP-1R allele 154 was significantly decreased in AA Cat+ vs. Cat- (p=0.04). These data suggest that DR and/or DQ genes are not responsible for narcolepsy and that cataplexy is associated with different regions around the MHC in various racial groups.« less

Frequencies of polymorphisms of the Rh, Kell, Kidd, Duffy and Diego systems of Santa Catarina, Southern Brazil.

PubMed

Costa, Daiane Cobianchi; Schinaider, Alessandra Arruda; Santos, Thais Mattos; Schörner, Everaldo José; Simon, Daniel; Maluf, Sharbel Weidner; de Moraes, Ana Carolina Rabello; Silva, Maria Claudia Silva

2016-01-01

Red blood cell genes are highly polymorphic with the distribution of alleles varying between different populations and ethnic groups. The objective of this study was to investigate gene polymorphisms of blood groups in the state of Santa Catarina, Southern Brazil. Three hundred and seventy-three unrelated blood donors and 31 transfusion-dependent patients were evaluated to investigate polymorphisms of the Rh, Kell, Duffy, Kidd, and Diego blood group systems in a population from the state of Santa Catarina. The subjects, from seven regions that comprise the blood-banking network of the state, were assessed between August 2011 and March 2014. The genotypes of the Rh, Kell, Duffy, Kidd, and Diego systems were determined using the restriction fragment length polymorphism-polymerase chain reaction and allele-specific polymerase chain reaction techniques. The genotype frequencies in this study were significantly different when populations from different regions of Santa Catarina were compared. Furthermore, there were also significant differences in the genetic frequencies compared to other Brazilian states. The genotype frequencies of the Kell and Kidd blood groups are similar to European populations from Naples, Italy and Zurich, Switzerland. This article reports for the first time the frequency of polymorphisms of blood group systems in blood donors from Santa Catarina, Southern Brazil. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Association of methylenetetrahydrofolate reductase C677T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

PubMed Central

2010-01-01

Background The association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and serum lipid profiles is still controversial in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. The aim of the present study was to eveluate the association of MTHFR C677T polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 780 subjects of Bai Ku Yao and 686 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the MTHFR C677T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.05-0.001). The frequency of C and T alleles was 77.4% and 22.6% in Bai Ku Yao, and 60.9% and 39.1% in Han (P < 0.001); respectively. The frequency of CC, CT and TT genotypes was 58.7%, 37.3% and 4.0% in Bai Ku Yao, and 32.6%, 56.4% and 11.0% in Han (P < 0.001); respectively. The levels of TC and LDL-C in both ethnic groups were significant differences among the three genotypes (P < 0.05-0.01). The T allele carriers had higher serum TC and LDL-C levels than the T allele noncarriers. The levels of ApoB in Han were significant differences among the three genotypes (P < 0.05). The T allele carriers had higher serum ApoB levels as compared with the T allele noncarriers. The levels of TC, TG and LDL-C in Bai Ku Yao were correlated with genotypes (P < 0.05-0.001), whereas the levels of LDL-C in Han were associated with genotypes (P < 0.001). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, cigarette smoking, and blood pressure in the both ethnic groups. Conclusions The differences in serum TC, TG, LDL-C and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of the MTHFR C677T or different MTHFR gene-enviromental interactions. PMID:20977771

Selection for genetic markers in beef cattle reveals complex associations of thyroglobulin and casein1-s1 with carcass and meat traits.

PubMed

Bennett, G L; Shackelford, S D; Wheeler, T L; King, D A; Casas, E; Smith, T P L

2013-02-01

Genetic markers in casein (CSN1S1) and thyroglobulin (TG) genes have previously been associated with fat distribution in cattle. Determining the nature of these genetic associations (additive, recessive, or dominant) has been difficult, because both markers have small minor allele frequencies in most beef cattle populations. This results in few animals homozygous for the minor alleles. selection to increase the frequencies of the minor alleles for 2 SNP markers in these genes was undertaken in a composite population. The objective was to obtain better estimates of genetic effects associated with these markers and determine if there were epistatic interactions. Selection increased the frequencies of minor alleles for both SNP from <0.30 to 0.45. Bulls (n = 24) heterozygous for both SNP were used in 3 yr to produce 204 steer progeny harvested at an average age of 474 d. The combined effect of the 9 CSN1S1 × TG genotypes was associated with carcass-adjusted fat thickness (P < 0.06) and meat tenderness predicted at the abattoir by visible and near-infrared reflectance spectroscopy (P < 0.04). Genotype did not affect BW from birth through harvest, ribeye area, marbling score, slice shear force, or image-based yield grade (P > 0.10). Additive, dominance, and epistatic SNP association effects were estimated from genotypic effects for adjusted fat thickness and predicted meat tenderness. Adjusted fat thickness showed a dominance association with TG SNP (P < 0.06) and an epistatic additive CSN1S1 × additive TG association (P < 0.03). For predicted meat tenderness, heterozygous TG meat was more tender than meat from either homozygote (P < 0.002). Dominance and epistatic associations can result in different SNP allele substitution effects in populations where SNP have the same linkage disequilibrium with causal mutations but have different frequencies. Although the complex associations estimated in this study would contribute little to within-population selection response, they could be important for marker-assisted management or reciprocal selection schemes.

Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever.

PubMed

Ozel, Emine Gulce; Duran, Gulay Gulbol; Celik, Muhammet Murat; Duran, Nizami; Gunesacar, Ramazan

2017-08-05

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a central role in the apoptosis signaling of various cell types including neutrophils. Neutrophils are the major cell population involved in acute inflammation in patients with FMF and the role of Fas and Fas ligand molecules in this cells of FMF patients may be crucial. Therefore, in the present study, we aimed to investigate whether the Fas cell surface receptor gene (FAS); NM_000043.5: c.-671A>G (rs1800682, MvaI) and Fas ligand gene (FASLG), NM_000639.2: c.-844C>T (rs763110, BsrD1) functional polymorphisms in patients with FMF and their relation to the main clinical features of the disease. The polymorphisms in the promoter regions of FAS c.-671A>G and FASLG c.-844C>T were investigated in 97 non-related FMF patients and 70 non-related healthy controls by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele were not significantly different between FMF patients and healthy subjects. The frequency of FASLG -844TC genotype was found significantly different between the patients with FMF and healthy controls whereas T or C allele frequency was not significantly different between the groups. Haplotype frequencies of the studied polymorphisms were also not significantly different between FMF patients and controls. There were no correlations between the studied FAS c.-671A>G and FASLG c.-844C>T polymorphisms and the main clinical features of FMF such as fever, arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our findings suggest that FAS c.-671AG genotype or G allele and FASLG c.-844 allele are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in the studied Turkish population. According to our results we may suggest that although not statistically significant, higher frequencies of FASLG c.-844CC genotype in FMF patients may be related to delayed apoptosis of neutrophils and ultimately cause neutrophilic inflammation by increasing FASLG expression. Copyright © 2017 Elsevier B.V. All rights reserved.

Human adaptation and population differentiation in the light of ancient genomes

PubMed Central

Key, Felix M.; Fu, Qiaomei; Romagné, Frédéric; Lachmann, Michael; Andrés, Aida M.

2016-01-01

The influence of positive selection sweeps in human evolution is increasingly debated, although our ability to detect them is hampered by inherent uncertainties in the timing of past events. Ancient genomes provide snapshots of allele frequencies in the past and can help address this question. We combine modern and ancient genomic data in a simple statistic (DAnc) to time allele frequency changes, and investigate the role of drift and adaptation in population differentiation. Only 30% of the most strongly differentiated alleles between Africans and Eurasians changed in frequency during the colonization of Eurasia, but in Europe these alleles are enriched in genic and putatively functional alleles to an extent only compatible with local adaptation. Adaptive alleles—especially those associated with pigmentation—are mostly of hunter-gatherer origin, although lactose persistence arose in a haplotype present in farmers. These results provide evidence for a role of local adaptation in human population differentiation. PMID:26988143

Human genetic selection on the MTHFR 677C>T polymorphism

PubMed Central

Mayor-Olea, Álvaro; Callejón, Gonzalo; Palomares, Arturo R; Jiménez, Ana J; Gaitán, María Jesús; Rodríguez, Alfonso; Ruiz, Maximiliano; Reyes-Engel, Armando

2008-01-01

Background The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA). Methods A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman® probes. A section of our population (n = 276) born in 1980–1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period. Results An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980–1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98. Conclusion Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations. PMID:19040733

Allele frequency distribution for 21 autosomal STR loci in Nepal.

PubMed

Kraaijenbrink, T; van Driem, G L; Opgenort, J R M L; Tuladhar, N M; de Knijff, P

2007-05-24

The allele frequency distributions of 21 autosomal loci contained in the AmpFlSTR Identifiler, the Powerplex 16 and the FFFL multiplex PCR kits, was studied in 953 unrelated individuals from Nepal. Several new alleles (i.e. not yet reported in the NIST Short Tandem Repeat DNA Internet DataBase [http://www.cstl.nist.gov/biotech/strbase/]) have been detected in the process.

TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression.

PubMed

Yoon, Ho-Kyoung; Kim, Yong-Ku

2009-04-30

Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior. One hundred and eighty one suicidal depressed patients and 143 non-suicidal depressed patients who met DSM-IV criteria for major depressive disorder were recruited from patients who were admitted to Korea University Ansan Hospital. One hundred seventy six normal controls were healthy volunteers who were recruited by local advertisement. Patients and normal controls were genotyped for HTR2A -1438A/G, TPH2 -703G/T and 5-HT1A C-1019G. The suicidal depressed patients were evaluated by the lethality of individual suicide attempts using Weisman and Worden's risk-rescue rating (RRR) and the Lethality Suicide Attempt Rating Scale-updated (LSARS-II). In order to assess the severity of depressive symptoms of patients, Hamilton's Depression Rating Scale (HDRS) was administered. Genotype and allele frequencies were compared between groups by chi(2) statistics. Association of genotype of the candidate genes with the lethality of suicidal behavior was examined with ANOVA by comparing the mean scores of LSARS and RRR according to the genotype. There were statistically significant differences in the genotype distributions and allele frequencies of TPH2 -703G/T between the suicidal depressive group and the normal control group. The homozygous allele G (G/G genotype) frequency was significantly higher in suicidal depressed patients than in controls. However, no differences in either genotype distribution or in allele frequencies of HTR2A -1438A/G and HTR1A C-1019G were observed between the suicidal depressed patients, the non-suicidal depressed patients, and the normal controls. There were no differences in the lethality of suicidal behavior in suicidal depressed patients according to the genotypes of three polymorphisms. Our results suggest that TPH2 -703G/T SNP may have an important effect on susceptibility to suicidal behavior. Furthermore, an increased frequency of G allele of TPH2 SNP may be associated with elevated suicidal behavior itself rather than with the diagnosis of major depression and may increase risk of suicidality, independent of diagnosis.

HLA class-I and class-II allele frequencies and two-locus haplotypes in Melanesians of Vanuatu and New Caledonia.

PubMed

Maitland, K; Bunce, M; Harding, R M; Barnardo, M C N M; Clegg, J B; Welsh, K; Bowden, D K; Williams, T N

2004-12-01

HLA class-I and class-II allele frequencies and two-locus haplotypes were examined in 367 unrelated Melanesians living on the islands of Vanuatu and New Caledonia. Diversity at all HLA class-I and class-II loci was relatively limited. In class-I loci, three HLA-A allelic groups (HLA-A*24, HLA-A*34 and HLA-A*11), seven HLA-B alleles or allelic groups (HLA-B*1506, HLA-B*5602, HLA-B*13, HLA-B*5601, HLA-B*4001, HLA-B*4002 and HLA-B*2704) and four HLA-C alleles or allelic groups (HLA-Cw*04, HLA-Cw*01, HLA-Cw*0702 and HLA-Cw*15) constituted more than 90% of the alleles observed. In the class-II loci, four HLA-DRB1 alleles (HLA-DRB1*15, HLA-DRB1*11, HLA-DRB1*04 and HLA-DRB1*16), three HLA-DRB3-5 alleles (HLA-DRB3*02, HLA-DRB4*01 and HLA-DRB5*01/02) and five HLA-DQB1 alleles (HLA-DQB1*0301, HLA-DQB1*04, HLA-DQB1*05, HLA-DQB1*0601 and HLA-DQB1*0602) constituted over 93, 97 and 98% of the alleles observed, respectively. Homozygosity showed significant departures from expected levels for neutrality based on allele frequency (i.e. excess diversity) at the HLA-B, HLA-Cw, HLA-DQB1 and HLA-DRB3/5 loci on some islands. The locus with the strongest departure from neutrality was HLA-DQB1, homozygosity being significantly lower than expected on all islands except New Caledonia. No consistent pattern was demonstrated for any HLA locus in relation to malaria endemicity.

First description and evaluation of SNPs in the ADH and ALDH genes in a population of alcoholics in Central-West Brazil.

PubMed

Teixeira, Thallita Monteiro; da Silva, Hugo Delleon; Goveia, Rebeca Mota; Ribolla, Paulo Eduardo Martins; Alonso, Diego Peres; Alves, Alessandro Arruda; Melo E Silva, Daniela; Collevatti, Rosane Garcia; Bicudo, Lucilene Arilho; Bérgamo, Nádia Aparecida; de Paula Silveira-Lacerda, Elisângela

2017-12-01

Worldwide, different studies have reported an association of alcohol-use disorder (AUD) with different types of Single Nucleotide Polymorphisms (SNPs) in the genes for aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH). In Brazil, there is little information about the occurrence of these SNPs in the AUD population and an absence of studies characterizing the population in the Central-West Region of Brazil. Actually, in Brazil, there are more than 4 million people with AUD. Despite the major health hazards of AUD, information on alcohol consumption and its consequences are not well understood. Therefore, it is extremely important to characterize these SNPs for the better understanding of AUD as a genetic disease in the Brazilian population. The present study, unlike other studies in other countries, is done with a subject population that shows a significant amount of racial homogenization. We evaluated the presence of SNPs in the ADH (ADH1B, ADH1C, and ADH4) and ALDH (ALDH2) genes in alcohol users of Goiânia, State of Goiás - Brazil, and then we established a possible relationship with AUD by allelic and genotypic study. This study was conducted with a population of people with AUD (n = 99) from Goiás Alcohol Dependence Recovery Center (GO CEREA) and Psychosocial Care Center for Alcohol and Drugs (CAPS AD), and with a population of people without AUD as controls (n = 100). DNA was extracted from whole-blood samples and the genotyping was performed using TaqMan ® SNP genotyping assays. For characterization and evaluation of SNPs in the population, genotype frequency, allele frequency, haplotype frequency, Hardy-Weinberg equilibrium, and linkage disequilibrium were analyzed. Statistical analyses were calculated by GENEPOP 4.5 and Haploview software. The allele 1 was considered as "wild" (or *1) and allele 2 as mutant (or *2). Significant differences were found for ADH1B*, ADH4*2, and ALDH2*2 SNPs when the genotype and allele frequencies were analyzed. In addition, four haplotypes were observed between ADH1B*2 and ADH1C*2 through linkage disequilibrium analysis. The genetic variants may be associated with protection against AUD in the population studied. Copyright © 2017 Elsevier Inc. All rights reserved.

Huntington disease reduced penetrance alleles occur at high frequency in the general population

PubMed Central

Kay, Chris; Collins, Jennifer A.; Miedzybrodzka, Zosia; Madore, Steven J.; Gordon, Erynn S.; Gerry, Norman; Davidson, Mark; Slama, Ramy A.

2016-01-01

Objective: To directly estimate the frequency and penetrance of CAG repeat alleles associated with Huntington disease (HD) in the general population. Methods: CAG repeat length was evaluated in 7,315 individuals from 3 population-based cohorts from British Columbia, the United States, and Scotland. The frequency of ≥36 CAG alleles was assessed out of a total of 14,630 alleles. The general population frequency of reduced penetrance alleles (36–39 CAG) was compared to the prevalence of patients with HD with genetically confirmed 36–39 CAG from a multisource clinical ascertainment in British Columbia, Canada. The penetrance of 36–38 CAG repeat alleles for HD was estimated for individuals ≥65 years of age and compared against previously reported clinical penetrance estimates. Results: A total of 18 of 7,315 individuals had ≥36 CAG, revealing that approximately 1 in 400 individuals from the general population have an expanded CAG repeat associated with HD (0.246%). Individuals with CAG 36–37 genotypes are the most common (36, 0.096%; 37, 0.082%; 38, 0.027%; 39, 0.000%; ≥40, 0.041%). General population CAG 36–38 penetrance rates are lower than penetrance rates extrapolated from clinical cohorts. Conclusion: HD alleles with a CAG repeat length of 36–38 occur at high frequency in the general population. The infrequent diagnosis of HD at this CAG length is likely due to low penetrance. Another important contributing factor may be reduced ascertainment of HD in those of older age. PMID:27335115

Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?

PubMed Central

Faure, Eric

2008-01-01

Background In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. Results Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. Conclusion We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of zoonoses in the actual CCR5-Δ32 distribution. PMID:18925940

Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African Buffalo: a plausible new mechanism for a high frequency anomaly.

PubMed

van Hooft, Pim; Greyling, Ben J; Getz, Wayne M; van Helden, Paul D; Zwaan, Bas J; Bastos, Armanda D S

2014-01-01

Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has important implications for our understanding not only of the evolutionary and ecological dynamics of sex-ratio distorters and suppressors, but also of the functioning of deleterious and sexually-antagonistic alleles, and their impact on population viability.

Range-Wide Sex-Chromosome Sequence Similarity Supports Occasional XY Recombination in European Tree Frogs (Hyla arborea)

PubMed Central

Brelsford, Alan; Perrin, Nicolas

2014-01-01

In contrast with mammals and birds, most poikilothermic vertebrates feature structurally undifferentiated sex chromosomes, which may result either from frequent turnovers, or from occasional events of XY recombination. The latter mechanism was recently suggested to be responsible for sex-chromosome homomorphy in European tree frogs (Hyla arborea). However, no single case of male recombination has been identified in large-scale laboratory crosses, and populations from NW Europe consistently display sex-specific allelic frequencies with male-diagnostic alleles, suggesting the absence of recombination in their recent history. To address this apparent paradox, we extended the phylogeographic scope of investigations, by analyzing the sequences of three sex-linked markers throughout the whole species distribution. Refugial populations (southern Balkans and Adriatic coast) show a mix of X and Y alleles in haplotypic networks, and no more within-individual pairwise nucleotide differences in males than in females, testifying to recurrent XY recombination. In contrast, populations of NW Europe, which originated from a recent postglacial expansion, show a clear pattern of XY differentiation; the X and Y gametologs of the sex-linked gene Med15 present different alleles, likely fixed by drift on the front wave of expansions, and kept differentiated since. Our results support the view that sex-chromosome homomorphy in H. arborea is maintained by occasional or historical events of recombination; whether the frequency of these events indeed differs between populations remains to be clarified. PMID:24892652

Using Pool-seq to Search for Genomic Regions Affected by Hybrid Inviability in the copepod T. californicus.

PubMed

Lima, Thiago G; Willett, Christopher S

2018-05-11

The formation of reproductive barriers between allopatric populations involves the accumulation of incompatibilities that lead to intrinsic postzygotic isolation. The evolution of these incompatibilities is usually explained by the Dobzhansky-Muller model, where epistatic interactions that arise within the diverging populations, lead to deleterious interactions when they come together in a hybrid genome. These incompatibilities can lead to hybrid inviability, killing individuals with certain genotypic combinations, and causing the population's allele frequency to deviate from Mendelian expectations. Traditionally, hybrid inviability loci have been detected by genotyping individuals at different loci across the genome. However, this method becomes time consuming and expensive as the number of markers or individuals increases. Here, we test if a Pool-seq method can be used to scan the genome of F2 hybrids to detect genomic regions that are affected by hybrid inviability. We survey the genome of hybrids between 2 populations of the copepod Tigriopus californicus, and show that this method has enough power to detect even small changes in allele frequency caused by hybrid inviability. We show that allele frequency estimates in Pool-seq can be affected by the sampling of alleles from the pool of DNA during the library preparation and sequencing steps and that special considerations must be taken when aligning hybrid reads to a reference when the populations/species are divergent.

Allele Frequencies for 15 Short Tandem Repeat Loci in Representative Sample of Croatian Population

PubMed Central

Projić, Petar; Škaro, Vedrana; Šamija, Ivana; Pojskić, Naris; Durmić-Pašić, Adaleta; Kovačević, Lejla; Bakal, Narcisa; Primorac, Dragan; Marjanović, Damir

2007-01-01

Aim To study the distribution of allele frequencies of 15 short tandem repeat (STR) loci in a representative sample of the Croatian population. Methods A total of 195 unrelated Caucasian individuals born in Croatia, from 14 counties and the City of Zagreb, were sampled for the analysis. All the tested individuals were voluntary donors. Buccal swab was used as the DNA source. AmpFlSTR® Identifiler® was applied to simultaneously amplify 15 STR loci. Total reaction volume was 12.5 μL. The polymerase chain reaction (PCR) amplification was carried out in PE Gene Amp PCR System Thermal Cycler. Electrophoresis of the amplification products was preformed on an ABI PRISM 3130 Genetic Analyzer. After PCR amplification and separation by electrophoresis, raw data were compiled, analyzed, and numerical allele designations of the profiles were obtained. Deviation from Hardy-Weinberg equilibrium, observed and expected heterozygosity, power of discrimination, and power of exclusion were calculated. Bonferroni’s correction was used before each comparative analysis. Results We compared Croatian data with those obtained from geographically neighboring European populations. The significant difference (at P<0.01) in allele frequencies was recorded only between the Croatian and Slovenian populations for vWA locus. There was no significant deviation from Hardy-Weinberg equilibrium for all the observed loci. Conclusion Obtained population data concurred with the expected “STR data frame” for this part of Europe. PMID:17696301

Allele Age Under Non-Classical Assumptions is Clarified by an Exact Computational Markov Chain Approach.

PubMed

De Sanctis, Bianca; Krukov, Ivan; de Koning, A P Jason

2017-09-19

Determination of the age of an allele based on its population frequency is a well-studied problem in population genetics, for which a variety of approximations have been proposed. We present a new result that, surprisingly, allows the expectation and variance of allele age to be computed exactly (within machine precision) for any finite absorbing Markov chain model in a matter of seconds. This approach makes none of the classical assumptions (e.g., weak selection, reversibility, infinite sites), exploits modern sparse linear algebra techniques, integrates over all sample paths, and is rapidly computable for Wright-Fisher populations up to N e  = 100,000. With this approach, we study the joint effect of recurrent mutation, dominance, and selection, and demonstrate new examples of "selective strolls" where the classical symmetry of allele age with respect to selection is violated by weakly selected alleles that are older than neutral alleles at the same frequency. We also show evidence for a strong age imbalance, where rare deleterious alleles are expected to be substantially older than advantageous alleles observed at the same frequency when population-scaled mutation rates are large. These results highlight the under-appreciated utility of computational methods for the direct analysis of Markov chain models in population genetics.

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

PubMed Central

Chesler, Elissa J.; Gatti, Daniel M.; Morgan, Andrew P.; Strobel, Marge; Trepanier, Laura; Oberbeck, Denesa; McWeeney, Shannon; Hitzemann, Robert; Ferris, Martin; McMullan, Rachel; Clayshultle, Amelia; Bell, Timothy A.; de Villena, Fernando Pardo-Manuel; Churchill, Gary A.

2016-01-01

Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility. PMID:27694113

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection.

PubMed

Chesler, Elissa J; Gatti, Daniel M; Morgan, Andrew P; Strobel, Marge; Trepanier, Laura; Oberbeck, Denesa; McWeeney, Shannon; Hitzemann, Robert; Ferris, Martin; McMullan, Rachel; Clayshultle, Amelia; Bell, Timothy A; Manuel de Villena, Fernando Pardo; Churchill, Gary A

2016-12-07

Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility. Copyright © 2016 by the Genetics Society of America.

The role of climate and out-of-Africa migration in the frequencies of risk alleles for 21 human diseases.

PubMed

Blair, Lily M; Feldman, Marcus W

2015-07-14

Demography and environmental adaptation can affect the global distribution of genetic variants and possibly the distribution of disease. Population heterozygosity of single nucleotide polymorphisms has been shown to decrease strongly with distance from Africa and this has been attributed to the effect of serial founding events during the migration of humans out of Africa. Additionally, population allele frequencies have been shown to change due to environmental adaptation. Here, we investigate the relationship of Out-of-Africa migration and climatic variables to the distribution of risk alleles for 21 diseases. For each disease, we computed the regression of average heterozygosity and average allele frequency of the risk alleles with distance from Africa and 9 environmental variables. We compared these regressions to a null distribution created by regressing statistics for SNPs not associated with disease on distance from Africa and these environmental variables. Additionally, we used Bayenv 2.0 to assess the signal of environmental adaptation associated with individual risk SNPs. For those SNPs in HGDP and HapMap that are risk alleles for type 2 diabetes, we cannot reject that their distribution is as expected from Out-of-Africa migration. However, the allelic statistics for many other diseases correlate more closely with environmental variables than would be expected from the serial founder effect and show signals of environmental adaptation. We report strong environmental interactions with several autoimmune diseases, and note a particularly strong interaction between asthma and summer humidity. Additionally, we identified several risk genes with strong environmental associations. For most diseases, migration does not explain the distribution of risk alleles and the worldwide pattern of allele frequencies for some diseases may be better explained by environmental associations, which suggests that some selection has acted on these diseases.

A Multiplex PCR assay to differentiate between dog and red fox.

PubMed

Weissenberger, M; Reichert, W; Mattern, R

2011-11-01

Foxes are frequently the cause of car accidents in Baden-Württemberg (BW, Germany). The domestic dog (Canis familiaris) is in close relation to the red fox (Vulpes vulpes) and the silver fox which is a coat colour variant of the red fox. As insurance claims that involve accidents with animals require authentication, we analyzed frequency distribution and allele sizes in two canine microsatellite loci in 26 dogs (different breeds) and 19 red foxes of the region of BW, Germany. Moreover, sequencing analysis was performed. Red foxes exhibited only 1 allele at each microsatellite locus, whereas in dog 7 alleles at the CPH4 locus and 6 alleles at the CPH12 locus were detected. Sequences of PCR products from the two species revealed several differences between dogs and foxes. We established a sequenced allelic ladder and give population data from dogs and red foxes from the region of BW, Germany. Using microsatellite polymorphisms is efficient in differentiating between dogs and foxes in forensic casework. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Stochastic sampling effects in STR typing: Implications for analysis and interpretation.

PubMed

Timken, Mark D; Klein, Sonja B; Buoncristiani, Martin R

2014-07-01

The analysis and interpretation of forensic STR typing results can become more complicated when reduced template amounts are used for PCR amplification due to increased stochastic effects. These effects are typically observed as reduced heterozygous peak-height balance and increased frequency of undetected alleles (allelic "dropout"). To investigate the origins of these effects, a study was performed using the AmpFlSTR(®) Identifiler Plus(®) and MiniFiler(®) kits to amplify replicates from a dilution series of NIST Human DNA Quantitation Standard (SRM(®) 2372A). The resulting amplicons were resolved and detected on two different genetic analyzer platforms, the Applied Biosystems 3130xL and 3500 analyzers. Results from our study show that the four different STR/genetic analyzer combinations exhibited very similar peak-height ratio statistics when normalized for the amount of template DNA in the PCR. Peak-height ratio statistics were successfully modeled using the Poisson distribution to simulate pre-PCR stochastic sampling of the alleles, confirming earlier explanations that sampling is the primary source for peak-height imbalance in reduced template dilutions. In addition, template-based pre-PCR sampling simulations also successfully predicted allelic dropout frequencies, as modeled by logistic regression methods, for the low-template DNA dilutions. We discuss the possibility that an accurately quantified DNA template might be used to characterize the linear signal response for data collected using different STR kits or genetic analyzer platforms, so as to provide a standardized approach for comparing results obtained from different STR/CE combinations and to aid in validation studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Apolipoprotein E genotyping in the Malay, Chinese and Indian ethnic groups in Malaysia-a study on the distribution of the different apoE alleles and genotypes.

PubMed

Seet, Wan Tai; Mary Anne, Tan Jin Ai; Yen, Tan Si

2004-02-01

Apolipoprotein E (apoE) is encoded by a polymorphic gene located on chromosome 19. The three common apoE alleles are epsilon2, epsilon3 and epsilon4. We studied the frequencies of the apoE alleles and genotypes in the three ethnic groups-Malay, Chinese and Indian-in Malaysia using DNA amplification followed by agarose gel electrophoresis. EDTA blood was collected and DNA was extracted using proteinase K-SDS digestion and purified by phenol-chloroform extraction. The apoE gene sequence was amplified using the PCR and apoE genotyping was performed by restriction enzyme digestion with HhaI. Genotyping of the apoE gene produces six genotypes-E2/E2, E2/E3, E3/E3, E2/E4, E3/E4 and E4/E4. The most common apoE genotype in the Malays, Chinese and Indians studied was E3/E3, thus the most common apoE allele was epsilon3. The three common apoE genotypes were E3/E3 followed by E3/E4 and E2/E3, except in the Indians where E2/E3 was not detected. The three apoE alleles were confirmed in the Malays, Chinese and Indians except for the epsilon2 allele which was absent in the Indians. The combined frequency of the apoE alleles in the Malays, Chinese and Indians was 0.058, 0.829 and 0.114 for epsilon2, epsilon3 and epsilon4, respectively.

Interleukin-10 gene polymorphisms are associated with Behcet's disease but not with Vogt-Koyanagi-Harada syndrome in the Chinese Han population.

PubMed

Hu, Jianmin; Hou, Shengping; Zhu, Xueping; Fang, Jing; Zhou, Yan; Liu, Yunjia; Bai, Lin; Kijlstra, Aize; Yang, Peizeng

2015-01-01

This study aimed to investigate the association of interleukin (IL)-10 gene polymorphisms with Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in the Chinese Han population. A two-stage association study was performed on 718 BD patients, 300 VKH patients, and 1,753 controls. Genotyping of the IL-10 gene was performed for six single nucleotide polymorphisms (SNPs), including rs1800871, rs1800872, rs1800896, rs3021094, rs3790622, and rs1554286 using PCR-restricted fragment length polymorphism or TaqMan SNP assays. Real-time PCR was performed to test the IL-10 mRNA expression of the associated polymorphisms. The first-stage result showed significantly increased frequencies of the rs1800871 T allele, rs1800872 A allele, and rs1554286 T allele in BD patients compared with controls (Pcorrected (Pcorr)=1.82×10(-5), OR=1.837; Pcorr=6.1×10(-5), OR=1.780; Pcorr=3.15×10(-5), OR=1.794, respectively). There was no association of the tested six SNPs with VKH syndrome. A second-stage study was therefore performed in BD patients to validate the result of the first stage, showing a significantly increased frequency of the rs1800871 T allele (Second stage, Pcorr=5.59×10(-5), OR=1.493; Combined data, Pcorr=3.65×10(-11), OR=1.632). Compared to the controls, an increased frequency of the rs1800871 T allele was observed in BD patients with extraocular findings, including genital ulcers, skin lesions, and a positive pathergy test. No difference was found among the mRNA expressions of IL-10 in the peripheral blood mononuclear cells (PBMCs) of controls with different genotypes of rs1800871 after stimulation of lipopolysaccharide (LPS) or anti-CD3/CD28 antibodies. The findings showed that IL-10 is a risk gene for BD but not for VKH syndrome.

DNA typing revealing high HLA-Cw polymorphism completes availability of major histocompatibility complex loci in forensic medicine.

PubMed

Keresztury, L; Rajczy, K; Tauszik, T; Gyódi, E; Petrányi, G G; Falus, A

2003-03-01

Studies of human population genetics in Hungary have revealed relevant heterogeneity in the major histocompatibility complex. In the present studies, two isolated ethnic groups were chosen: people living in the Káli Basin westward from the Danube River, and those living in Opusztaszer, a village eastward from Danube, who are known as native ancient Hungarians. Blood samples were collected from 70 people in the Káli Basin and from 45 people in Opusztaszer. The frequency of HLA-Cw alleles was determined by serology as well as by DNA typing in 46 and 32 samples of the two populations, respectively, and in 44 randomly selected subjects of Hungarian origin. Compared with a random population of cadaver donors (the deaths having resulted mostly from accidents or, in a smaller number, strokes or heart infarcts) and voluntary bone marrow donors (typed in the last 10 years) recruited from all parts of Hungary and representing the mixed Hungarian population, remarkable differences were found in haplotype and allele frequencies. HLA-A, -B, -Cw typing was performed by serology and, in the case of the HLA-Cw locus, by polymerase chain reaction (PCR)-SSP and/or PCR-SSOP techniques, as well. The PCR-SSO oligotyping procedure allowed the identification of 32 Cw alleles in contrast with the 9 serologically detectable types. Because of the combination of low antigen expression and the lack of specific serologic reagents of good quality, no HLA-Cw antigens were detectable in 41%, and only one was detected in 48%, of the investigated individuals by standard serologic typing. With PCR-SSO typing, however, 97% of the investigated individuals proved to be heterozygous for HLA-Cw alleles. The two isolated populations differed from each other, from mixed Hungarian and other Caucasian populations in HLA-Cw* allele frequencies, as well as in haplotype distribution. This newly recognized polymorphism at the HLA-Cw locus completes the availability of major histocompatibility complex typing in forensic science and practice.

Association of diamine oxidase and histamine N-methyltransferase polymorphisms with presence of migraine in a group of Mexican mothers of children with allergies.

PubMed

Meza-Velázquez, R; López-Márquez, F; Espinosa-Padilla, S; Rivera-Guillen, M; Ávila-Hernández, J; Rosales-González, M

2017-10-01

Low histamine metabolism has been suggested to play a role in the pathogenesis of allergy and migraine. We investigated the possible association between 2 single-nucleotide polymorphisms (SNP), C314T HNMT and C2029G DAO, and the presence and severity of migraine and migraine-related disability. We studied the frequency of C314T HNMT and C2029G DAO allelic variants in 162 mothers of children with allergies (80 with migraine and 82 without) using a TaqMan-based qPCR Assay and a case-control model. We conducted a logistic regression analysis to examine the association between migraine and the allelic and haplotype variants. Mutant C2029G DAO SNP was found significantly more frequently in the group of women with migraine than in controls (OR, 1.6; 95% CI, 1.1-2.1). No significant differences were found in frequencies of genotypes or alleles in the case of C314T HNMT SNP. Both mutated alleles were associated with migraine-related disability. Coexistence of alleles for both SNPs (haplotypes) showed a strong association with migraine. Haplotypes containing both mutated alleles (either heterozygous or homozygous) were very strongly associated with MIDAS grade iv migraine (OR, 45.0; 95% CI, 5.2-358). This suggests that mutant alleles of C314T for HNMT and C2029G for DAO polymorphisms may interact in a way that increases the risk and impact of migraine. We suggest a synergistic association between HNMT and DAO functional polymorphisms and migraine; this hypothesis must be further confirmed by larger studies. However, the characteristics and ethnic differences between analysed populations should be considered when interpreting the results. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Associations of the eNOS G894T gene polymorphism with target organ damage in children with newly diagnosed primary hypertension.

PubMed

Śladowska-Kozłowska, Joanna; Litwin, Mieczysław; Niemirska, Anna; Wierzbicka, Aldona; Roszczynko, Marta; Szperl, Małgorzata

2015-12-01

The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism is associated with the risk of primary hypertension (PH) and vascular complications in adults with PH. We explored the associations of the G894T polymorphism with 24-h ambulatory blood pressure, left ventricular mass (LVM), carotid intima media thickness (cIMT), urinary albumin excretion, oxidative stress and inflammatory parameters in 126 children with newly diagnosed PH and in 83 healthy children. Among the 126 children with PH 92 (73%) had ambulatory hypertension and 34 (27%) had severe ambulatory hypertension. Left ventricular hypertrophy (LVH) was detected in 39 (31%) patients, cIMT of >2 standard deviation scores in 21 (16.6%) patients, albuminuria of >30 mg/24 h in 18 (14.3%) patients and metabolic syndrome (MS) in 22 (17.5%) patients. The frequency of the T allele was 52.4% in the PH group and 54.2% in the control group (not significant), and in both groups the frequency of the T allele was consistent with the Hardy-Weinberg equilibrium. Compared with G allele carriers, hypertensive T allele carriers had increased cIMT (p < 0.05) and more severe albuminuria (not significant, p = 0.1); there was no difference between the groups in hypertension severity and LVM. T and G allele distribution did not differ between patients with and without metabolic syndrome. No significant correlations between the assessed parameters and the eNOS G894T gene polymorphism were found in the controls, although T allele carriers tended to have an increased cIMT (p = 0.09). The eNOS T allele is not more prevalent among hypertensive children than among healthy ones, but it is associated with early vascular damage in children with PH, independent of metabolic abnormalities. No associations between the eNOS G894T polymorphism and metabolic abnormalities were found.

A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer.

PubMed

Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

2005-04-29

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

PubMed Central

Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

2005-01-01

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. Methods We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. Results The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. Conclusion The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer. PMID:15860134

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

PubMed Central

2011-01-01

Background We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants. Methods From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels). We identified 292 SNPs in 270 genes associated with a disease or trait at P < 5 × 10-8. As part of the Human Genome-Diversity Project (HGDP), 158 (54.1%) of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, FST, was calculated to quantify differences in risk allele frequencies (RAFs) among populations and geographic areas. Results Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global FST (0.1042) for 158 SNPs among the populations was not significantly higher than the mean global FST of 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global FST (P < 0.05) was noted in eight SNPs, based on an empirical distribution of global FST of 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score. Conclusion Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease. PMID:21507254

Methylenetetrahydrofolate reductase gene polymorphisms: association with risk for pediatric acute lymphoblastic leukemia in north Indians.

PubMed

Sood, Swati; Das, Reena; Trehan, Amita; Ahluwalia, Jasmina; Sachdeva, Man Updesh; Varma, Neelam; Bansal, Deepak; Marwaha, Ram Kumar

2010-05-01

Genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. We conducted a case-control study in 95 north Indian children with acute lymphoblastic leukemia (ALL) and 255 controls, to investigate the role of MTHFR C677T and A1298C polymorphisms as risk factors in the development of ALL. PCR-RFLP on genomic DNA was carried out to determine C677T and A1298C genotypes. The frequency of MTHFR C677T for the T allele was found to be 23.2% among patients and 18.2% among controls. The frequency of the C allele in MTHFR A1298C was 44.2% among cases and 48.2% in controls. Patients showed a higher frequency of heterozygosity for the MTHFR C677T polymorphism as compared to controls (40% vs 27.8%; OR = 1.73, 95% CI 1.02-2.91, p = 0.02), and the A1298C polymorphism did not show any difference in genotype frequency between cases and controls. MTHFR 677CC/1298AC genotype frequencies showed a statistically significant difference between cases and controls (OR = 0.58, 95% CI 0.34-1.01, p = 0.04). In conclusion, our study in north Indian controls and patients with pediatric ALL showed increased frequency for MTHFR C677T in the heterozygous state and no significant difference in the frequency of A1298C genotype between the two groups.

Apolipoprotein E polymorphism and lipoprotein levels in a Gulf Arab population in Kuwait: a pilot study.

PubMed

Al-Shammari, S; Fatania, H; Al-Radwan, R; Akanji, A O

2004-01-01

APOE polymorphism is believed to confer susceptibility to coronary heart disease (CHD) and Alzheimer's disease. It is well known that patterns of APOE polymorphisms differ between populations and ethnic groups, although most of the data available so far have been in whites. We evaluated the frequencies of APOE genotypes and their relationships with serum levels of lipids, lipoproteins and apolipoproteins in two groups of Gulf Arab citizens: a control population of healthy voluntary blood donors (n=106), and a group of patients presenting to the lipid clinic for the first time with combined hyperlipidaemia (CH) (n=41). In both groups, fasting serum total cholesterol (TC), triglycerides (TG), HDL, LDL and apolipoprotein A1 and B levels were measured by routine autoanalyzer methods, and APOE genotyping was performed by validated PCR methods. The lipid and lipoprotein levels were related to the specific APOE allele frequencies. Allele frequencies were 5.7% for *E2, 85.4% for *E3, and 9.0% for *E4 in the healthy blood donor group. An essentially similar pattern was seen in the patients with CH. This APOE allelic distribution conforms to patterns described in Chinese, whites and South Asians. In both the blood donor and CH groups there were no consistent links between specific APOE pattern and serum lipoproteins, as would have been predicted from APO *E2 and APO *E4 frequencies. We conclude that APOE allelic patterns in healthy Kuwaiti blood donors and a smaller group of patients with CH do not satisfactorily predict circulating blood levels of lipids and lipoproteins.

The Frequency of CCR5del32 Mutation in Populations of Russians, Tatars and Bashkirs of Chelyabinsk Region, Russia.

PubMed

Govorovskaya, Irina; Khromova, Elena; Suslova, Tatiana; Alexeev, Leonid; Kofiadi, Ilya

2016-12-01

The distribution of genetic variants associated with natural resistance to viral infections can vary among human ethnic groups due to evolutionary factors, defining the different epidemiologic background of world populations. The polymorphisms, defining the natural resistance to HIV-infection and the rate of progression up to AIDS, are very important since epidemic is still on rise. We have studied the distribution of allele and genotype frequencies of CCR5delta32 mutation in major populations inhabiting Chelyabinsk region of the Russian Federation. Genetic survey included the population of 509 potential blood marrow donors: Russians (N = 300), Bashkirs (N = 118) and Tatars (N = 91). The genotyping assay was performed using real-time polymerase chain reaction (real-time PCR). The genotypes were defined by melting curve analysis. The CCR5delta32 allele and CCR5delta32/delta32 genotype are presented in population of Russians in Chelyabinsk region with the frequencies of F x  = 10.83% and P x  = 1.67, for the CCR5delta32 allele and its homozygosity, respectively. In populations of Bashkirs and Tatars CCR5delta32 allele and CCR5delta32/delta32 genotype are presented at lower frequencies of F x  = 6.36%/P x  = 0.85 and F x  = 7.14%/P x  = 1.10, respectively. These data are consistent with the theory of northern origin of the CCR5delta32 mutation.

High prevalence of hemoglobin disorders and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Republic of Guinea (West Africa).

PubMed

Millimono, Tamba S; Loua, Kovana M; Rath, Silvia L; Relvas, Luis; Bento, Celeste; Diakite, Mandiou; Jarvis, Martin; Daries, Nathalie; Ribeiro, Leticia M; Manco, Licínio; Kaeda, Jaspal S

2012-01-01

Reliable and accurate epidemiological data is a prerequisite for a cost effective screening program for inherited disorders, which however, is lacking in a number of developing countries. Here we report the first detailed population study in the Republic of Guinea, a sub-Saharan West African country, designed to assess the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies, including screening for thalassemia. Peripheral blood samples from 187 Guinean adults were screened for hemoglobin (Hb) variants by standard hematological methods. One hundred and ten samples from males were screened for G6PD deficiency by the fluorescent spot test. Molecular analysis was performed for the most common α-thalassemia (α-thal) deletions, β-globin gene mutations, G6PD variants B (376A), A (376G), A- (376G/202A) and Betica (376G/968C), using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) or sequencing. Of the 187 subjects screened, 36 were heterozygous for Hb S [β6(A3)Glu→Val, GAG>GTG] (allele frequency 9.62%). Sixty-four subjects were heterozygous and seven were homozygous for the -α(3.7) kb deletion (allele frequency 20.85%). β-Thalassemia alleles were detected in five subjects, four with the -29 (A>G) mutation (allele frequency 1.07%) and one with codon 15 (TGG>TAG) (allele frequency 0.96%). The G6PD A- and G6PD Betica deficient variants were highly prevalent with a frequency of 5.7 and 3.3%, respectively. While we did not test for ferritin levels or α(0)-thal, four females (5.2%) had red cell indices strongly suggestive of iron deficient anemia: Hb <9.7 g/dL; MCH <19.3 pg; MCV <68.2; MCHC <31.6 g/dl; RDW >19.8%. Our results are consistent with high frequency of alleles such as Hb S, α-thal and G6PD deficient alleles associated with malaria resistance. Finding a 9.6% Hb S allele frequency supports the notion for a proficient neonatal screening to identify the sickle cell patients, who might benefit from early prophylactic treatment for infections. The incidence of significant iron deficient anemia in women is lower than expected in an under developed country.

Association of NCOA3 polymorphisms with Dyslipidemia in the Chinese Han population.

PubMed

Yu, Mingxi; Gilbert, Siame; Li, Yong; Zhang, Huiping; Qiao, Yichun; Lu, Yuping; Tang, Yuan; Zhen, Qing; Cheng, Yi; Liu, Yawen

2015-10-09

Nuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes. Emerging evidence from previous studies using animal models suggests that the NCOA3 gene (NCOA3) plays a critical role in lipid metabolism as well as adipogenesis and obesity. The present study aims to investigate the association between NCOA3 SNPs and dyslipidemia in the Chinese Han population. Five hundred and twenty-nine (529) Chinese Han subjects were recruited. Four tag SNPs (rs2425955G > T, rs6066394T > C, rs10485463C > G, and rs6094753G > A) in NCOA3, selected from the HapMap website, were genotyped using MALDI-TOF mass spectrometry. Data analysis was performed using SPSS 16.0, SNPStats and haploview 4.2. Four SNPs (rs2425955, rs6066394, rs10485463, and rs6094753) were associated with triglyceride levels. Except for SNP rs10485463, genotype distributions and allele frequencies of the other three NCOA3 SNPs (rs2425955, rs6066394, and rs6094753) were significantly different between hypertriglyceridemia subjects and normal group. Significant differences were also observed in allele frequencies and genotype distributions of SNP rs10485463 between low-HDL cholesterolemia subjects and normal group. Carriers of rs2425955 T allele had a lower risk of hypertriglyceridemia compared to GG genotype. Similar results were observed from rs6094753. Subjects with rs6066394 CT genotype had a lower risk of hypertriglyceridemia than those with the TT genotype; however, CC and TT genotypes showed no significant difference in the risk of hypertriglyceridemia. Similar results were found in the association between rs6066394 and hypercholesterolemia. The variant alleles of rs2425955, rs6066394 and rs6094753 were associated with a lower risk of hypertriglyceridemia compared with the wild-type alleles. The G allele of rs10485463 was associated with an increased risk of low-HDL cholesterolemia. In the log-additive model the association between rs2425955 and hypertriglyceridemia remained significant after Bonferroni correction, and genotypes with variant alleles were associated with a lower risk of hypertriglyceridemia. In summary, this study demonstrated that variation in NCOA3 might influence the risk of dyslipidemia and serum lipid levels in Chinese Han population.

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

PubMed Central

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

2018-01-01

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

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.

Widespread Impact of HLA Restriction on Immune Control and Escape Pathways of HIV-1

PubMed Central

Listgarten, Jennifer; Pfeifer, Nico; Tan, Vincent; Kadie, Carl; Walker, Bruce D.; Ndung'u, Thumbi; Shapiro, Roger; Frater, John; Brumme, Zabrina L.; Goulder, Philip J. R.; Heckerman, David

2012-01-01

The promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 instances of differential escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine. PMID:22379086

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

PubMed

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

2015-11-01

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

The effect of rare alleles on estimated genomic relationships from whole genome sequence data.

PubMed

Eynard, Sonia E; Windig, Jack J; Leroy, Grégoire; van Binsbergen, Rianne; Calus, Mario P L

2015-03-12

Relationships between individuals and inbreeding coefficients are commonly used for breeding decisions, but may be affected by the type of data used for their estimation. The proportion of variants with low Minor Allele Frequency (MAF) is larger in whole genome sequence (WGS) data compared to Single Nucleotide Polymorphism (SNP) chips. Therefore, WGS data provide true relationships between individuals and may influence breeding decisions and prioritisation for conservation of genetic diversity in livestock. This study identifies differences between relationships and inbreeding coefficients estimated using pedigree, SNP or WGS data for 118 Holstein bulls from the 1000 Bull genomes project. To determine the impact of rare alleles on the estimates we compared three scenarios of MAF restrictions: variants with a MAF higher than 5%, variants with a MAF higher than 1% and variants with a MAF between 1% and 5%. We observed significant differences between estimated relationships and, although less significantly, inbreeding coefficients from pedigree, SNP or WGS data, and between MAF restriction scenarios. Computed correlations between pedigree and genomic relationships, within groups with similar relationships, ranged from negative to moderate for both estimated relationships and inbreeding coefficients, but were high between estimates from SNP and WGS (0.49 to 0.99). Estimated relationships from genomic information exhibited higher variation than from pedigree. Inbreeding coefficients analysis showed that more complete pedigree records lead to higher correlation between inbreeding coefficients from pedigree and genomic data. Finally, estimates and correlations between additive genetic (A) and genomic (G) relationship matrices were lower, and variances of the relationships were larger when accounting for allele frequencies than without accounting for allele frequencies. Using pedigree data or genomic information, and including or excluding variants with a MAF below 5% showed significant differences in relationship and inbreeding coefficient estimates. Estimated relationships and inbreeding coefficients are the basis for selection decisions. Therefore, it can be expected that using WGS instead of SNP can affect selection decision. Inclusion of rare variants will give access to the variation they carry, which is of interest for conservation of genetic diversity.

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

PubMed Central

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

2008-01-01

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

Pathogen Populations Evolve to Greater Race Complexity in Agricultural Systems – Evidence from Analysis of Rhynchosporium secalis Virulence Data

PubMed Central

Zhan, Jiasui; Yang, Lina; Zhu, Wen; Shang, Liping; Newton, Adrian C.

2012-01-01

Fitness cost associated with pathogens carrying unnecessary virulence alleles is the fundamental assumption for preventing the emergence of complex races in plant pathogen populations but this hypothesis has rarely been tested empirically on a temporal and spatial scale which is sufficient to distinguish evolutionary signals from experimental error. We analyzed virulence characteristics of ∼1000 isolates of the barley pathogen Rhynchosporium secalis collected from different parts of the United Kingdom between 1984 and 2005. We found a gradual increase in race complexity over time with a significant correlation between sampling date and race complexity of the pathogen (r20 = 0.71, p = 0.0002) and an average loss of 0.1 avirulence alleles (corresponding to an average gain of 0.1 virulence alleles) each year. We also found a positive and significant correlation between barley cultivar diversity and R. secalis virulence variation. The conditions assumed to favour complex races were not present in the United Kingdom and we hypothesize that the increase in race complexity is attributable to the combination of natural selection and genetic drift. Host resistance selects for corresponding virulence alleles to fixation or dominant frequency. Because of the weak fitness penalty of carrying the unnecessary virulence alleles, genetic drift associated with other evolutionary forces such as hitch-hiking maintains the frequency of the dominant virulence alleles even after the corresponding resistance factors cease to be used. PMID:22723870

Association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma gene and strength athlete status.

PubMed

Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Cieszczyk, Pawel; Zarebska, Aleksandra; Sawczyn, Stanislaw

2013-01-01

The 12Ala allele of the Peroxisome Proliferator-Activated Receptor gamma gene (PPARG) Pro12Ala polymorphism produces a decreased binding affinity of the PPARγ2 protein, resulting in low activation of the target genes. The 12Ala allele carriers display a significantly improved insulin sensitivity that may result in better glucose utilisation in working skeletal muscles. We hypothesise that the PPARG 12Ala allele could be associated with strength athlete status in Polish athletes. The genotype distribution of PPARG Pro12Ala was examined in 660 Polish athletes. The athletes were stratified into four subgroups: endurance, strength-endurance, sprint-strength and strength. Control samples were prepared from 684 unrelated sedentary volunteers. A χ(2) test was used to compare the PPARG Pro12Ala allele and genotype frequencies between the different groups of athletes and control subjects. Bonferroni's correction for multiple testing was applied. A statistically significant higher frequency of PPARG 12Ala alleles was observed in the subgroup of strength athletes performing short-term and very intense exertion characterised by predominant anaerobic energy production (13.2% vs. 7.5% in controls; P = 0.0007). The PPARG 12Ala allele may be a relevant genetic factor favouring strength abilities in professional athletes, especially in terms of insulin-dependent metabolism, a shift of the energy balance towards glucose utilisation and the development of a favourable weight-to-strength ratio.

Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa.

PubMed

Hinney, A; Lentes, K U; Rosenkranz, K; Barth, N; Roth, H; Ziegler, A; Hennighausen, K; Coners, H; Wurmser, H; Jacob, K; Römer, G; Winnikes, U; Mayer, H; Herzog, W; Lehmkuhl, G; Poustka, F; Schmidt, M H; Blum, W F; Pirke, K M; Schäfer, H; Grzeschik, K H; Remschmidt, H; Hebebrand, J

1997-03-01

The missense mutation (64Trp to 64Arg) in the beta 3-adrenergic-receptor has previously been described to confer a genetic predisposition to the development of obesity. To test the hypothesis we evaluated allele frequencies in children, adolescents and young adults who belonged to different weight groups that were delineated with percentiles for the body mass index (BMI; kg/m2). 99 underweight probands (BMI < or = 15th percentile). 80 normal weight probands (BMI: 5th-85th percentile). 238 obese children and adolescents (BMI > or = 97th percentile). 84 patients with anorexia nervosa (AN). The cohorts were screened by polymerase chain reaction with subsequent restriction fragment length polymorphism (PCR-RFLP) analysis. Data were statistically analysed for association. In addition to these case control studies, the transmission disequilibrium test (TDT) was applied to 80 families of obese probands and to 52 families of patients with AN. Both the tests for association and linkage were negative. The Trp64Arg allele frequencies in the three weight groups (obesity: 0.071; normal weight: 0.081; underweight: 0.056) and the AN patients (0.054) were similar. Extremely obese individuals showed no excess of the Trp64Arg allele. No homozygotes for the Trp64Arg allele were detected. Heterozygosity for the Trp64Arg allele is not of major importance in regulation of body weight in individuals younger than 35 y. Additionally, the extreme obese subgroup is not enriched for the polymorphism.

Association of polymorphisms in nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4), mu-opioid receptor gene (OPRM1), and ethanol-metabolizing enzyme genes with alcoholism in Korean patients.

PubMed

Kim, Soon Ae; Kim, Jong-Woo; Song, Ji-Young; Park, Sunny; Lee, Hee Jae; Chung, Joo-Ho

2004-01-01

Findings obtained from several studies indicate that ethanol enhances the activity of alpha4beta2 neuronal nicotinic acetylcholine receptor and support the possibility that a polymorphism of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) modulates enhancement of nicotinic receptor function by ethanol. To identify the association between the CfoI polymorphism of the CHRNA4 and alcoholism, we examined distribution of genotypes and allele frequencies in Korean patients diagnosed with alcoholism (n = 127) and Korean control subjects without alcoholism (n = 185) with polymerase chain reaction-restriction fragment length polymorphism methods. We were able to detect the association between the CfoI polymorphism of the CHRNA4 and alcoholism in Korean patients (genotype P = .023; allele frequency P = .047). The genotypes and allele frequencies of known polymorphisms in other alcoholism candidate genes, such as alcohol metabolism-related genes [alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 3 (ADH3), and cytochrome P450 2E1 (CYP2E1)] and mu-opioid receptor gene (OPRM1), were studied. The polymorphisms of ADH2, ALDH2, and CYP2E1 were significantly different in Korean patients with alcoholism and Korean control subjects without alcoholism, but ADH3 and OPRM1 did not differ between the two groups.

TNFalpha -308 C-->t and -863 C-->a polymorphisms and spermiogram characteristics.

PubMed

Kurz, Christine; Bentz, Eva-Katrin; Denschlag, Dominik; Berner, Isabel; Keck, Christoph; Tempfer, Clemens B; Pietrowski, Detlef

2008-01-01

Genetic factors may play a role in male infertility. In a prospective case-control study, we assessed the allele and genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms, detected by PCR of sperm DNA, of 577 Caucasian men recruited in an infertility clinic. Semen sampling was performed and spermiogram results were correlated to genetic data. The allele frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were not significantly different between non-normozoospermic (n = 447) and normozoospermic (n = 130) men [758/894 (85%) and 134/894 (15%) vs. 213/269 (82%) and 43/260 (18%), p = 0.5, odds ratio (OR) 1.1, 95% confidence interval (CI) 0.74-1.76, and 749/894 (84%) and 145/894 (16%) vs. 212/260 (82%) and 48/260 (18%), p = 0.4, OR 1.2, 95% CI 0.78-1.76, respectively]. The genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were also not significantly different between non-normozoospermic and normozoospermic men. In addition, mutant alleles were not overrepresented in subgroups of men with the oligoasthenoteratozoospermia syndrome and asthenozoospermia. The TNFalpha -308 C-->T and -863 C-->A polymorphisms are not associated with spermiogram characteristics and do not represent molecular markers for genetic susceptibility to male infertility. Copyright 2008 S. Karger AG, Basel.

CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity.

PubMed

Sata, F; Sapone, A; Elizondo, G; Stocker, P; Miller, V P; Zheng, W; Raunio, H; Crespi, C L; Gonzalez, F J

2000-01-01

To determine the existence of mutant and variant CgammaP3A4 alleles in three racial groups and to assess functions of the variant alleles by complementary deoxyribonucleic acid (cDNA) expression. A bacterial artificial chromosome that contains the complete CgammaP3A4 gene was isolated and the exons and surrounding introns were directly sequenced to develop primers to polymerase chain reaction (PCR) amplify and sequence the gene from lymphocyte DNA. DNA samples from Chinese, black, and white subjects were screened. Mutating the affected amino acid in the wild-type cDNA and expressing the variant enzyme with use of the baculovirus system was used to functionally evaluate the variant allele having a missense mutation. To investigate the existence of mutant and variant CgammaP3A4 alleles in humans, all 13 exons and the 5'-flanking region of the human CgammaP3A4 gene in three racial groups were sequenced and four alleles were identified. An A-->G point mutation in the 5'-flanking region of the human CgammaP3A4 gene, designated CgammaP3A4*1B, was found in the three different racial groups. The frequency of this allele in a white population was 4.2%, whereas it was 66.7% in black subjects. The CgammaP3A4*1B allele was not found in Chinese subjects. A second variant allele, designated CgammaP3A4*2, having a Ser222Pro change, was found at a frequency of 2.7% in the white population and was absent in the black subjects and Chinese subjects analyzed. Baculovirus-directed cDNA expression revealed that the CYP3A4*2 P450 had a lower intrinsic clearance for the CYP3A4 substrate nifedipine compared with the wild-type enzyme but was not significantly different from the wild-type enzyme for testosterone 6beta-hydroxylation. Another rare allele, designated CgammaP3A4*3, was found in a single Chinese subject who had a Met445Thr change in the conserved heme-binding region of the P450. These are the first examples of potential function polymorphisms resulting from missense mutations in the CgammaP3A4 gene. The CgammaP3A4*2 allele was found to encode a P450 with substrate-dependent altered kinetics compared with the wild-type P450.

High prevalence of dengue antibodies and the arginine variant of the FcγRIIa polymorphism in asymptomatic individuals in a population of Minas Gerais State, Southeast Brazil.

PubMed

Pereira, Anna Carolina Toledo da Cunha; de Siqueira, Tatiane Ribeiro; de Oliveira Prado, Andressa Anunciação; da Silva, Camila Almeida Veiga; de Fátima Silva Moraes, Thaís; Aleixo, Alan Alex; de Magalhaes, José Carlos; de Souza, Gabriel Augusto Pires; Drumond, Betânia Paiva; Ferreira, Gustavo Portela; de Mello Silva, Breno; de Brito Magalhães, Cintia Lopes; Santos, Luciana Lara; Ferreira, Jaqueline Maria Siqueira; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

2018-06-01

Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p = 0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.

Error correction and statistical analyses for intra-host comparisons of feline immunodeficiency virus diversity from high-throughput sequencing data.

PubMed

Liu, Yang; Chiaromonte, Francesca; Ross, Howard; Malhotra, Raunaq; Elleder, Daniel; Poss, Mary

2015-06-30

Infection with feline immunodeficiency virus (FIV) causes an immunosuppressive disease whose consequences are less severe if cats are co-infected with an attenuated FIV strain (PLV). We use virus diversity measurements, which reflect replication ability and the virus response to various conditions, to test whether diversity of virulent FIV in lymphoid tissues is altered in the presence of PLV. Our data consisted of the 3' half of the FIV genome from three tissues of animals infected with FIV alone, or with FIV and PLV, sequenced by 454 technology. Since rare variants dominate virus populations, we had to carefully distinguish sequence variation from errors due to experimental protocols and sequencing. We considered an exponential-normal convolution model used for background correction of microarray data, and modified it to formulate an error correction approach for minor allele frequencies derived from high-throughput sequencing. Similar to accounting for over-dispersion in counts, this accounts for error-inflated variability in frequencies - and quite effectively reproduces empirically observed distributions. After obtaining error-corrected minor allele frequencies, we applied ANalysis Of VAriance (ANOVA) based on a linear mixed model and found that conserved sites and transition frequencies in FIV genes differ among tissues of dual and single infected cats. Furthermore, analysis of minor allele frequencies at individual FIV genome sites revealed 242 sites significantly affected by infection status (dual vs. single) or infection status by tissue interaction. All together, our results demonstrated a decrease in FIV diversity in bone marrow in the presence of PLV. Importantly, these effects were weakened or undetectable when error correction was performed with other approaches (thresholding of minor allele frequencies; probabilistic clustering of reads). We also queried the data for cytidine deaminase activity on the viral genome, which causes an asymmetric increase in G to A substitutions, but found no evidence for this host defense strategy. Our error correction approach for minor allele frequencies (more sensitive and computationally efficient than other algorithms) and our statistical treatment of variation (ANOVA) were critical for effective use of high-throughput sequencing data in understanding viral diversity. We found that co-infection with PLV shifts FIV diversity from bone marrow to lymph node and spleen.

Accounting for genotype uncertainty in the estimation of allele frequencies in autopolyploids.

PubMed

Blischak, Paul D; Kubatko, Laura S; Wolfe, Andrea D

2016-05-01

Despite the increasing opportunity to collect large-scale data sets for population genomic analyses, the use of high-throughput sequencing to study populations of polyploids has seen little application. This is due in large part to problems associated with determining allele copy number in the genotypes of polyploid individuals (allelic dosage uncertainty-ADU), which complicates the calculation of important quantities such as allele frequencies. Here, we describe a statistical model to estimate biallelic SNP frequencies in a population of autopolyploids using high-throughput sequencing data in the form of read counts. We bridge the gap from data collection (using restriction enzyme based techniques [e.g. GBS, RADseq]) to allele frequency estimation in a unified inferential framework using a hierarchical Bayesian model to sum over genotype uncertainty. Simulated data sets were generated under various conditions for tetraploid, hexaploid and octoploid populations to evaluate the model's performance and to help guide the collection of empirical data. We also provide an implementation of our model in the R package polyfreqs and demonstrate its use with two example analyses that investigate (i) levels of expected and observed heterozygosity and (ii) model adequacy. Our simulations show that the number of individuals sampled from a population has a greater impact on estimation error than sequencing coverage. The example analyses also show that our model and software can be used to make inferences beyond the estimation of allele frequencies for autopolyploids by providing assessments of model adequacy and estimates of heterozygosity. © 2015 John Wiley & Sons Ltd.

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

PubMed

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

2017-01-01

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

Global analysis of genetic variation in human arsenic (+ 3 oxidation state) methyltransferase (AS3MT)

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

Fujihara, Junko; Soejima, Mikiko; Yasuda, Toshihiro

2010-03-15

Human arsenic (+ 3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. The objective of this study was to investigate the diversity of the AS3MT gene at the global level. The distribution of 18 single nucleotide polymorphisms (SNPs) in AS3MT was performed in 827 individuals from 10 populations (Japanese, Korean, Chinese, Mongolian, Tibetans, Sri Lankan Tamils, Sri Lankan Sinhalese, Nepal Tamangs, Ovambo, and Ghanaian). In the African populations, the A allele in A6144T was not observed; the allele frequencies of C35587 were much lower than those in other populations; the allele frequencies of A37616 and C37950more » were relatively higher than those in other populations. Among Asian populations, Mongolians showed a different genotype distribution pattern. A lower C3963 and T6144 frequencies were observed, and, in the C37616A and T37950C polymorphism, the Mongolian population showed higher A37616 and C37950 allele frequencies than other Asian populations, similarly to the African populations. A total of 66 haplotypes were observed in the Ovambo, 48, in the Ghanaian, 99, in the Japanese, 103, in the Korean, 103, in the South Chinese, 20, in the Sri Lankan Tamil, 12, in the Sri Lankan Sinhalese, 21, in the Nepal Tamang, 50, in the Tibetan, and 45, in the Mongolian populations. The D' values between the SNP pairs were extremely high in the Sri Lankan Sinhalese population. Relatively higher D' values were observed in Mongolian and Sri Lankan Tamil populations. Network analysis showed two clusters that may have different origins, African and Asians (Chinese and/or Japanese). The present study is the first to demonstrate the existence of genetic heterogeneity in a world wide distribution of 18 SNPs in AS3MT.« less

Association of dopamine receptor D2 gene (DRD2) Taq1 polymorphisms with eating behaviors and obesity among Chinese and Indian Malaysian university students.

PubMed

Lek, Fang-Ying; Ong, Hing-Huat; Say, Yee-How

2018-01-01

This study investigated the association of DRD2 Taq1A, Taq1B and Taq1D gene polymorphisms with eating behavior, the preference/intake frequency/craving of high-fat foods and obesity in 394 Malaysian adults (161 males, 233 females; 308 Chinese, 86 Indians; 67 obese, 327 non-obese). Eating behaviors namely Cognitive Restraint, Uncontrolled Eating and Emotional Eating scores were assessed by the Three Factor Eating Questionnaire-R18. The preference/intake frequency/craving of 26 common high-fat Malaysian foods was assessed using a 7-point hedonic scale. Anthropometric measurements were taken and Taq1 gene polymorphisms were genotyped by PCR-Restriction Fragment Length Polymorphism using DNA extracted from mouthwash samples. The overall minor allele frequencies of Taq1A, Taq1B and Taq1D according to ethnicities (Chinese/Indian) were 0.37/0.29, 0.39/0.28, 0.06/0.30, respectively; genotype and allele distributions of Taq1B and Taq1D were significantly different between ethnicities. Eating behaviorscores were not significantly different between gender and ethnicities. Those with A1 or B1 allele had lower Cognitive Restraint score and higher Uncontrolled Eating score, while those with A1/A1 or B1/B1 genotype had higher fast food preference. D1 allele was associated with increased starchy food craving and mamak (Malaysian Indian-Muslim) food preference, but not eating behavior scores. All three gene variants were not associated with obesity and adiposity. Taken together, we posit that three DRD2 Taq1 gene polymorphisms influence the eating behavior and preference/intake frequency/craving of certain high-fat foods in Malaysian adults, but their role in obesity and adiposity is still inconclusive and needs further investigation.

Association of the apolipoprotein E {epsilon}4 allele with clinical subtypes of autopsy-confirmed Alzheimer`s Disease

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

Zubenko, G.S.; Stiffler, S.; Kopp, U.

1994-09-15

Consistent with previous reports, we observed a significant association of the APOE {epsilon}4 allele with Alzheimer`s Disease (AD) in a series of 91 autopsy-confirmed cases. The {epsilon}4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 {+-} 0.07), although the {epsilon}4 allele frequency in the AD cases with a negative family history (0.38 {+-} 0.05) remained significantly greater than that for the non-AD control group (0.13 {+-} 0.03). A similar increase in {epsilon}4 allele frequency (0.54 {+-} 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloidmore » angiopathy (0.35 {+-} 0.04). Contrary to previous reports, no effect of the dosage of the {epsilon}4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of {epsilon}4 and atherosclerosis, the {epsilon}4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of {epsilon}4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the {epsilon}4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an {epsilon}4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the {epsilon}4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE {epsilon}4 allele. 22 refs., 2 figs., 5 tabs.« less

Characterization of casein gene complex and genetic diversity analysis in Indian goats.

PubMed

Rout, P K; Kumar, A; Mandal, A; Laloe, D; Singh, S K; Roy, R

2010-04-01

Milk protein polymorphism plays an important role in genetic diversity analysis, phylogenetic studies, establishing geographical diversity, conservation decision, and improving breeding goals. Milk protein polymorphism in Indian goat breeds has not been well studied; therefore, an investigation was carried out to analyze the genetic structure of the casein gene and milk protein diversity at six milk protein loci in nine Indian goat breeds/genetic groups from varied agro-climatic zones. Milk protein genotyping was carried out in 1098 individual milk samples by SDS-PAGE at alphaS1-CN (CSN1S1), beta-CN (CSN2), alphaS2-CN (CSN1S2), kappa-CN (CSN3), beta-LG, and alpha-LA loci. Indian goats exhibited alphaS1-casein A allele in higher frequency in the majority of breeds except Ganjam and local goats. The alphaS1-casein A allele frequencies varied from 0.45 to 0.77. A total of 16 casein haplotypes were observed in seven breeds and breed specific haplotypes were observed with respect to geographic region. The average number of alleles was lowest in Ganjam (1.66 +/- 0.81) and highest in Sirohi goats (2.50 +/- 1.05). Expected heterozygosity at six different loci demonstrated genetic diversity and breed fragmentation. Neighbor-Joining tree was built basing on Nei's distance. There was about 16.95% variability due to differences between breeds, indicating a strong subdivision. Principal component analysis was carried out to highlight the relationship among breeds. The variability among goat breeds was contributed by alphaS2-CN, beta-LG and alphaS1-CN. The Indian goats exhibited alphaS1-CN (CSN1S1) A allele in higher frequency in all the breeds indicating the higher casein yield in their milk.

Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure

PubMed Central

Duque, Gustavo Salgado; da Silva, Dayse Aparecida; de Albuquerque, Felipe Neves; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; de Albuquerque, Denilson Campos

2016-01-01

Background Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. Objectives To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Methods Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. Results The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. Conclusions More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. PMID:27812677

Association of two Common Single Nucleotide Polymorphisms (+45T/G and +276G/T) of ADIPOQ Gene with Coronary Artery Disease in Type 2 Diabetic Patients

PubMed Central

Mohammadzadeh, Ghorban; Ghaffari, Mohammad-Ali; Heibar, Habib; Bazyar, Mohammad

2016-01-01

Background: Adiponectin, an adipocyte-secreted hormone, is known to have anti-atherogenic, anti-inflammatory, and anti-diabetic properties. In the present study, the association between two common single nucleotide polymorphisms (SNPs) (+45T/G and +276G/T) of ADIOPQ gene and coronary artery disease (CAD) was assessed in the subjects with type 2 diabetes (T2DM). Methods: Genotypes of two SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism in 200 subjects with T2DM (100 subjects with CAD and 100 without CAD). Results: The frequency of TT genotype of +276G/T was significantly elevated in CAD compared to controls (χ2=7.967, P=0.019). A similar difference was found in the allele frequency of +276G/T between two groups (χ2=3.895, P=0.048). The increased risk of CAD was associated with +276 TT genotype when compared to reference GG genotype (OR=5.158; 95% CI=1.016-26.182, P=0.048). However, no similar difference was found in genotype and allele frequencies of SNP +45T/G between two groups. There was a CAD protective haplotype combination of +276 wild-type and +45 mutant-type allele (276G-45G) (OR=0.37, 95% CI=0.16-0.86, P=0.022) in the subject population. Conclusion: Our findings indicated that T allele of SNP +276G/T is more associated with the increased risk of CAD in subjects with T2DM. Also, a haplotype combination of +45G/+276G of these two SNPs has a protective effect on the risk of CAD. PMID:26781170

A study of the possible association of plasminogen activator inhibitor type 1 4G/5G insertion/deletion polymorphism with susceptibility to schizophrenia and in its subtypes.

PubMed

Yenilmez, C; Ozdemir Koroglu, Z; Kurt, H; Yanas, M; Colak, E; Degirmenci, I; Gunes, H V

2017-02-01

Inhibition of the fibrinolytic system may occur at the level of plasminogen activation, mainly by PAI-1. Mental and physical stress caused to alterations of platelet function, and also decreased to fibrinolytic activity. Furthermore, stress-induced thrombosis regulation was proposed to be by PAI-1 in schizophrenia patients. In this study, the distribution of genotypes and frequency of alleles of the plasminogen activator inhibitor type 1 (PAI-1) gene 4G/5G polymorphism in different Turkish clinical schizophrenia subtypes was investigated for its role in schizophrenia development. The clinical schizophrenia subtypes include paranoid, catatonic, disorganized, undifferentiated and residual, as diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition IV (DSM-IV). Samples of genomic DNA (250 total, including 150 schizophrenia patients and 100 healthy subjects) were analysed. PAI-1 4G/5G genotyping was performed by polymerase chain reaction-allele-specific amplification. PCR products were separated by 2% agarose gel electrophoresis and then visualized. The genotype distributions (P = 0·136) and allele frequencies (P = 0·721 for 4G, P = 0. 097 for 5G) were not significantly different between patients with schizophrenia and control subjects for the 4G/5G polymorphism. Similar results were also found for the genotype distributions (P = 0·640) and allele frequencies (P = 0·763 for 4G, P = 0·448 for 5G) in the clinical schizophrenia subtypes compared to the each other. We conclude that PAI-1 4G/5G polymorphism was not significantly associated with schizophrenia or its subtypes in the Turkish population. However, we recognize that with our sample sizes, we cannot exclude weak associations. © 2016 John Wiley & Sons Ltd.

Haplotypic Background of a Private Allele at High Frequency in the Americas

PubMed Central

Schroeder, Kari B.; Jakobsson, Mattias; Crawford, Michael H.; Schurr, Theodore G.; Boca, Simina M.; Conrad, Donald F.; Tito, Raul Y.; Osipova, Ludmilla P.; Tarskaia, Larissa A.; Zhadanov, Sergey I.; Wall, Jeffrey D.; Pritchard, Jonathan K.; Malhi, Ripan S.; Smith, David G.; Rosenberg, Noah A.

2009-01-01

Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the “American Modal Haplotype” (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all modern Native Americans and Western Beringians trace a large portion of their ancestry to a single founding population that may have been isolated from other Asian populations prior to expanding into the Americas. PMID:19221006

A study of the association of childhood asthma with HLA alleles in the population of Siliguri, West Bengal, India.

PubMed

Lama, M; Chatterjee, M; Chaudhuri, T K

2014-09-01

Asthma is a heterogeneous disease for which a strong genetic basis is firmly established. It is a complex disorder influenced by gene-environment interaction. Human leukocyte antigen (HLA) genes have been shown to be consistently associated with asthma and its related phenotypes in various populations. The aim of this study was to determine the frequency of the selected HLA classes I and II allelic groups in asthmatic and control groups. HLA typing was performed using polymerase chain reaction-sequence-specific typing (PCR-SSP) method. The allele frequency was estimated by direct counting. Frequency of each HLA allelic group was compared between asthmatic group and control group using χ(2) test. P-value was corrected by multiplying with the number of the allelic groups studied. Odds ratio (OR) and its corresponding 95% confidence interval (CI) for each allelic group were calculated using graphpad instat 3.10. The results of this study showed a significantly higher frequency of HLA-DRB1*03 in asthmatics than in controls (11.43% vs 3.64%, OR = 3.78, 95% CI = 1.61-8.85, P = 0.0025, Pcorr  < 0.05). Analysis of HLA alleles in low and high total serum immunoglobulin E (IgE) level in asthmatics revealed no significant association. HLA-DRB1*03 may be implicated in the susceptibility to asthma in the pediatric population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.

PubMed Central

Stine, O C; Smith, K D

1990-01-01

The effects of mutation, migration, random drift, and selection on the change in frequency of the alleles associated with Huntington disease, porphyria variegata, and lipoid proteinosis have been assessed in the Afrikaner population of South Africa. Although admixture cannot be completely discounted, it was possible to exclude migration and new mutation as major sources of changes in the frequency of these alleles by limiting analyses to pedigrees descendant from founding families. Calculations which overestimated the possible effect of random drift demonstrated that drift did not account for the observed changes in gene frequencies. Therefore these changes must have been caused by natural selection, and a coefficient of selection was estimated for each trait. For the rare, dominant, deleterious allele associated with Huntington disease, the coefficient of selection was estimated to be .34, indicating that this allele has a selective disadvantage, contrary to some recent studies. For the presumed dominant and probably deleterious allele associated with porphyria variegata, the coefficient of selection lies between .07 and .02. The coefficient of selection for the rare, clinically recessive allele associated with lipoid proteinosis was estimated to be .07. Calculations based on a model system indicate that the observed decrease in allele frequency cannot be explained solely on the basis of selection against the homozygote. Thus, this may be an example of a pleiotropic gene which has a dominant effect in terms of selection even though its known clinical effect is recessive. PMID:2137963

The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.

PubMed

Stine, O C; Smith, K D

1990-03-01

The effects of mutation, migration, random drift, and selection on the change in frequency of the alleles associated with Huntington disease, porphyria variegata, and lipoid proteinosis have been assessed in the Afrikaner population of South Africa. Although admixture cannot be completely discounted, it was possible to exclude migration and new mutation as major sources of changes in the frequency of these alleles by limiting analyses to pedigrees descendant from founding families. Calculations which overestimated the possible effect of random drift demonstrated that drift did not account for the observed changes in gene frequencies. Therefore these changes must have been caused by natural selection, and a coefficient of selection was estimated for each trait. For the rare, dominant, deleterious allele associated with Huntington disease, the coefficient of selection was estimated to be .34, indicating that this allele has a selective disadvantage, contrary to some recent studies. For the presumed dominant and probably deleterious allele associated with porphyria variegata, the coefficient of selection lies between .07 and .02. The coefficient of selection for the rare, clinically recessive allele associated with lipoid proteinosis was estimated to be .07. Calculations based on a model system indicate that the observed decrease in allele frequency cannot be explained solely on the basis of selection against the homozygote. Thus, this may be an example of a pleiotropic gene which has a dominant effect in terms of selection even though its known clinical effect is recessive.

Trait-specific long-term consequences of genomic selection in beef cattle.

PubMed

de Rezende Neves, Haroldo Henrique; Carvalheiro, Roberto; de Queiroz, Sandra Aidar

2018-02-01

Simulation studies allow addressing consequences of selection schemes, helping to identify effective strategies to enable genetic gain and maintain genetic diversity. The aim of this study was to evaluate the long-term impact of genomic selection (GS) in genetic progress and genetic diversity of beef cattle. Forward-in-time simulation generated a population with pattern of linkage disequilibrium close to that previously reported for real beef cattle populations. Different scenarios of GS and traditional pedigree-based BLUP (PBLUP) selection were simulated for 15 generations, mimicking selection for female reproduction and meat quality. For GS scenarios, an alternative selection criterion was simulated (wGBLUP), intended to enhance long-term gains by attributing more weight to favorable alleles with low frequency. GS allowed genetic progress up to 40% greater than PBLUP, for female reproduction and meat quality. The alternative criterion wGBLUP did not increase long-term response, although allowed reducing inbreeding rates and loss of favorable alleles. The results suggest that GS outperforms PBLUP when the selected trait is under less polygenic background and that attributing more weight to low-frequency favorable alleles can reduce inbreeding rates and loss of favorable alleles in GS.

The correlation between growth hormone receptor (GHR) polymorphism and obstructive sleep apnea syndrome among the Han and Hani population in China.

PubMed

Ji, Juanjuan; Yang, Yunwei; Lin, Yan; Li, Xudong; Wu, Xiaoguang; Yang, Xi; Zhong, Ling; Tang, Ying; Huang, Zhiyong; He, Xiaoguang

2018-04-13

Obstructive sleep apnea syndrome (OSAS) is a common health problem that is associated with abnormality in craniofacial morphology. The growth hormone receptor (GHR) belongs to the cytokine receptor superfamily and mediates the majority of growth hormone signaling, which, among other functions, determines mandibular growth and development. The aim of this study was to determine if correlations exist between single nucleotide polymorphisms (SNPs) in the GHR gene and OSAS in the Han or Hani ethnic groups in China. A total of 274 Han subjects (106 with OSAS and 168 without OSAS) and a total of 270 Hani subjects (64 with OSAS and 206 without OSAS) were enrolled in our study. Genomic DNA was extracted from peripheral blood obtained from all subjects. Genotyping was undertaken for eight SNPs in the GHR gene (rs3756416, rs7727047, rs2910875, rs12153009, rs2972781, rs12518414, rs4410646, and rs6451620) using PCR amplification and Sanger sequencing. The genotype frequency of rs12518414 was associated with OSAS in both the Han and Hani groups, and the A allele frequency was remarkably lower in Hani OSAS patients compared with Hani controls (16.7 vs 29.9%). In addition, the G allele frequency of the rs3756416 SNP was significantly lower in OSAS patients compared with normal controls in the Hani ethnic group (12.5 vs 24.6%). In a comparison between ethnic groups, genotype frequencies of four SNPs (rs2972781, rs6451620, rs12518414, and rs7727047) differed between Han and Hani OSAS patients, with the A allele frequency of the rs12518414 and G allele frequency of the rs7727047 were significantly higher in the Han OSAS patients. In conclusion, significant associations were detected between some SNPs in the GHR gene and OSAS occurrence while others appeared to be ethnicity-dependent.

APJ receptor A445C gene polymorphism in Turkish patients with coronary artery disease

PubMed Central

Akcılar, Raziye; Yümün, Gündüz; Bayat, Zeynep; Donbaloğlu, Okan; Erselcan, Kubilay; Ece, Ezgi; Kökdaşgil, Hülya; Genç, Osman

2015-01-01

Coronary artery disease (CAD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. Apelin is a novel endogenous peptide with inotropic and vasodilatory properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor. We aimed to determine genotype and allele frequencies of APJ receptor A445C gene polymorphism in Turkish patients with CAD and healthy controls by RFLP-PCR. This study was performed on 159 unrelated CAD patients and 62 healthy controls. We obtained AA, AC and CC genotype frequencies in CAD patients as 41.5%, 49.1% and 9.4%, respectively. In the control group, frequencies of genotypes were found as 35.5% for AA, 48.4% for AC and 16.1% for CC. We did not observe difference in APJ receptor A445C polymorphism between CAD patients and healthy controls (χ2 = 2.178; df = 2; P = 0.336). The A allele was encountered in 66% (210) of the CAD and 59.7% (74) of the controls. The C allele was seen in 34% (108) of the CAD and 40.3% (50) of the controls. Allele frequencies of interested genes were not significantly different between groups (χ2 = 1.57; df = 1; p = 0.225). The frequencies of APJ receptor A445C genotype were not significantly different between control and patients. None of the three APJ receptor A445C genotypes, AA, AC and CC displayed significant difference in CAD patients. We did not find any difference in the clinical parameters except for weight and diastolic blood pressure levels in the AA, AC and CC genotypes of patients. Individuals with CC genotypes had significantly higher weight, systolic and diastolic blood pressure levels and systolic blood pressure than other genotypes, P ≤ 0.05. In addition, HDL-C level was found decreased, but this reduction was not statistically significant. Contrarily, the low levels of weight, SBP, DBP and TC were statistically significant in the subjects with AA genotype in CAD. In conclusion, CC genotype carriers may have more risk than other genotypes in the development of hypertension in CAD, but not AAgenotype carriers. We suggest that this polymorphism may not be a marker of CAD, but it may cause useful in function of the apelin/APJ system and may be a genetic predisposing factor for diagnostic processes and can be helpfull in finding new treatment strategies. We think that it is required to further comprehensive studies in order to make clear this situation in CAD. PMID:26770497

[Allelic variants of apolipoproteins B and CII genes in patients with ischemic heart disease and in healthy persons from the Moscow population].

PubMed

Pogoda, T V; Nikonova, A L; Kolosova, T V; Liudvikova, E K; Perova, N V; Limborskaia, S A

1995-07-01

Allelic frequencies of a microsatellite of the apolipoprotein CII gene (APOCII) and a minisatellite of the apolipoprotein B gene (APOB) were studied using polymerase chain reaction (PCR). The study was conducted on a random sample of male Moscow inhabitants and a sample of patients with coronary heart disease (CHD) from the same population. Fourteen variants of the APOB minisatellite (the 82% heterozygosity level) and 13 alleles of the APOCII microsatellite (the 85% heterozygosity level) were found. CHD patients significantly differed from the control group in the distributions of alleles in these loci: APOB 32, APOB 46, APOB 48, and APOB 50 as well as APOCII 17 and APOCII 29 were found more frequently. A relationship was found between the distributions of APOB and APOCII in the CHD patients. The CHD patients with alleles APOCII 21 and APOCII 30 very often had the allele APOB 32; and patients with the genotype APOB 34, 36 had the allele APOCII 29 even more often than affected individuals in general. Individuals of the control group with the allele APOCII 30 exhibited hypertriglyceridemia without increased levels of total cholesterol and apolipoprotein B in plasma.

Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian Tamil Rheumatoid Arthritis patients.

PubMed

Muralidharan, Niveditha; Gulati, Reena; Misra, Durga Prasanna; Negi, Vir S

2018-02-01

The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.

DD genotype of ace gene I/D polymorphism is associated in a Turkish study population with osteoarthritis.

PubMed

Bayram, Banu; Sayın, Emrah; Güneş, Hasan Veysi; Değirmenci, Irfan; Türkoğlu, Züleyha; Doganer, Fulya; Coşan, Didem Turgut

2011-03-01

This study was conducted in Turkish osteoarthritis patients to determine the frequency of I/D polymorphism genotypes of angiotensin converting enzyme gene, and to examine the role of this polymorphism in osteoarthritis development. Genomic DNA obtained from 200 persons (135 patients with osteoarthritis and 65 healthy controls) was used in the study. DNA was multiplied by polymerase chain reaction using I and D allele-specific primers. Polymerase chain reaction products were assessed with CCD camera by being exposed to 2% agarose gel electrophoresis. There was statistically significant difference between the groups with respect to genotype distribution (P < 0.001). The D allele frequency was indicated as 69% and I allele was as 31% in the patients, whereas it was 55-45% in the control group. Consequently, in this study, we may assert that ACE gene I/D polymorphism DD genotype determination is significant criteria for identifying patients who are likely to develop osteoarthritis in east population of Turkey.

The great diversity of major histocompatibility complex class II genes in Philippine native cattle

PubMed Central

Takeshima, S.N.; Miyasaka, T.; Polat, M.; Kikuya, M.; Matsumoto, Y.; Mingala, C.N.; Villanueva, M.A.; Salces, A.J.; Onuma, M.; Aida, Y.

2014-01-01

Bovine leukocyte antigens (BoLA) are extensively used as markers for bovine disease and immunological traits. However, none of the BoLA genes in Southeast Asian breeds have been characterized by polymerase chain reaction (PCR)-sequence-based typing (SBT). Therefore, we sequenced exon 2 of the BoLA class II DRB3 gene from 1120 individual cows belonging to the Holstein, Sahiwal, Simbrah, Jersey, Brahman, and Philippine native breeds using PCR-SBT. Several cross-breeds were also examined. BoLA-DRB3 PCR-SBT identified 78 previously reported alleles and five novel alleles. The number of BoLA-DRB3 alleles identified in each breed from the Philippines was higher (71 in Philippine native cattle, 58 in Brahman, 46 in Holstein × Sahiwal, and 57 in Philippine native × Brahman) than that identified in breeds from other countries (e.g., 23 alleles in Japanese Black and 35 in Bolivian Yacumeño cattle). A phylogenetic tree based on the DA distance calculated from the BoLA-DRB3 allele frequency showed that Philippine native cattle from different Philippine islands are closely related, and all of them are closely similar to Philippine Brahman cattle but not to native Japanese and Latin American breeds. Furthermore, the BoLA-DRB3 allele frequency in Philippine native cattle from Luzon Island, located in the Northern Philippines was different from that in cattle from Iloilo, Bohol, and Leyte Islands, which are located in the Southern Philippines. Therefore, we conclude that Philippine native cattle can be divided into two populations, North and South areas. Moreover, a neutrality test revealed that Philippine native cattle from Leyte showed significantly greater genetic diversity, which may be maintained by balancing selection. This study shows that Asian breeds have high levels of BoLA-DRB3 polymorphism. This finding, especially the identification of five novel BoLA-DRB3 alleles, will be helpful for future SBT studies of BoLA-DRB3 alleles in East Asian cattle. PMID:25606401

Genetic differences in human circadian clock genes among worldwide populations.

PubMed

Ciarleglio, Christopher M; Ryckman, Kelli K; Servick, Stein V; Hida, Akiko; Robbins, Sam; Wells, Nancy; Hicks, Jennifer; Larson, Sydney A; Wiedermann, Joshua P; Carver, Krista; Hamilton, Nalo; Kidd, Kenneth K; Kidd, Judith R; Smith, Jeffrey R; Friedlaender, Jonathan; McMahon, Douglas G; Williams, Scott M; Summar, Marshall L; Johnson, Carl Hirschie

2008-08-01

The daily biological clock regulates the timing of sleep and physiological processes that are of fundamental importance to human health, performance, and well-being. Environmental parameters of relevance to biological clocks include (1) daily fluctuations in light intensity and temperature, and (2) seasonal changes in photoperiod (day length) and temperature; these parameters vary dramatically as a function of latitude and locale. In wide-ranging species other than humans, natural selection has genetically optimized adaptiveness along latitudinal clines. Is there evidence for selection of clock gene alleles along latitudinal/photoperiod clines in humans? A number of polymorphisms in the human clock genes Per2, Per3, Clock, and AANAT have been reported as alleles that could be subject to selection. In addition, this investigation discovered several novel polymorphisms in the human Arntl and Arntl2 genes that may have functional impact upon the expression of these clock transcriptional factors. The frequency distribution of these clock gene polymorphisms is reported for diverse populations of African Americans, European Americans, Ghanaians, Han Chinese, and Papua New Guineans (including 5 subpopulations within Papua New Guinea). There are significant differences in the frequency distribution of clock gene alleles among these populations. Population genetic analyses indicate that these differences are likely to arise from genetic drift rather than from natural selection.

[A cross-racial analysis on the susceptible gene polymorphisms of salt-sensitive hypertension].

PubMed

Lu, Jia-peng; Zhang, Ling; Wang, Wei

2010-10-01

To compare the genetic distributions of salt-sensitivity of four ethnic populations in Hapmap database. The frequencies data (395 subjects) of salt-sensitivity polymorphisms (AGT/M235T, ACE/ID, CYP11B2/C-344T, ADDI/Gly460Trp, GNB3/C825 and CYP3A5/A6986G)of Utah residents with ancestry from northern and western Europe (CEU), Han Chinese in Beijing (CHB), Japanese in Tokyo (JPT) and Yoruba mother-father-child trios in Ibadan, Nigeria (YRI) were obtained from International HapMap Project. The good-fit χ(2) test was performed to test whether the frequencies of each genotype reached Hardy-Weinberg equilibrium. The differences of the genotype and allele distribution and trend analysis were detected via χ(2) test. Furthermore, multiple comparisons between two populations were analyzed by Lancaster's partition of chi-squares. There were significant differences of each genotype distribution among four ethnic populations (P < 0.05). The distribution of genotype frequencies and susceptible allele frequencies of salt sensitive candidate genes were similar between CHB and JPT. Excepted for GNB3/825T allele (38.8% vs.34.4%, P = 0.521), susceptible allele frequencies in AGT/235T (79.2% vs. 41.2%, P < 0.001), ACE/I (56.5% vs. 43.5%, P < 0.001), CYP11B2/-344T (74.1% vs. 56.7%, P = 0.001), ADDI/460Trp (51.8% vs. 20.4%, P < 0.001) and CYP3A5/A6986 (30.1% vs. 3.6%, P < 0.001) were significantly higher in CHB than in CEU. There distribution of ADDI/460Trp allele was significant lower in YRI (4%) than in CHB (51.8%, P < 0.001). However frequencies of AGT/235T, CYP11B2/-334T, GNB3/825T and CYP3A5/6986A in CHB were significantly lower than those in YRI (P < 0.05). Trend analyses showed significantly increased trend in AGT/235T (41.2% < 79.2% < 92.0%, P < 0.001), CYP11B2/-334T (56.7% < 74.1% < 84.8%, P < 0.001) and CYP3A5/6986A (3.6% < 30.1% < 84.5%, P < 0.001) in CEU, CHB and YRI. There are significant discrepancy of salt-sensitivity variant distributions among four ethnic populations in Hapmap database. The frequencies of the susceptible polymorphisms related to salt-sensitivity in Beijing Han population was similar with JPT, higher than in CEU but lower than in YRI, suggesting high salt-sensitive and risk for hypertension in Beijing Han population. Prevention and individual therapy for high-risk population will help to reduce the prevalence of salt-sensitive hypertension and cardiovascular diseases.

HLA-DRB1*08 allele may help to distinguish between type 1 diabetes mellitus and type 2 diabetes mellitus in Mexican children.

PubMed

Rodríguez-Ventura, Ana L; Yamamoto-Furusho, Jesus K; Coyote, Ninel; Dorantes, Luis M; Ruiz-Morales, Jorge A; Vargas-Alarcón, Gilberto; Granados, Julio

2007-02-01

It may be difficult to distinguish type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) in the pediatric population. Autoantibodies may help to differentiate both types of diabetes, but sometimes these are positive in patients with T2DM and negative in patients with T1DM. The human leukocyte antigen (HLA)-DR genotype has been associated with T1DM and with T2DM only in adults and in determined cases. To determine the differences in HLA class II allele frequencies in Mexican children with T1DM and T2DM. We included 72 children with T1DM, 28 children with T2DM, and 99 healthy controls. All were Mexican, and diabetes was diagnosed according to the clinical and laboratory criteria established by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. The HLA-DRB1 typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe and polymerase chain reaction sequence-specific primers. We found an increased frequency of HLA-DRB1*08 and a decreased frequency of HLA-DRB1*04 in the group with T2DM vs. T1DM [p = 0.0001, odds ratio (OR) = 10.58, 95% confidence interval (CI) = 3-40.8 and p = 0.0006, OR = 0.24, 95% CI = 0.11-0.53, respectively]. No significant differences were found between HLA-DRB1 alleles in T2DM vs. controls. In the group with T1DM, there was a significantly increased frequency of the HLA-DR4 and HLA-DR3 alleles relative to controls (p = 0.0000001, OR = 3.59, 95% CI = 2.2-5.8 and p = 0.00009, OR = 4.66, 95% CI = 2.1-10.3, respectively). There are significant differences in the HLA profile in Mexican children with T1DM and T2DM. HLA typing could play a role in the differentiation between both types of diabetes in this population.

Gene polymorphisms of TNF-alpha-308 (G/A), IL-10(-1082) (G/A), IL-6(-174) (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus.

PubMed

Settin, Ahmad; Ismail, Azza; El-Magd, Megahed Abo; El-Baz, Rizk; Kazamel, Amira

2009-01-01

Type 1 diabetes (T1D) is a genetically conditioned autoimmune disease in which cytokines play an important role. Objectives. To check for the association of polymorphisms of cytokine genes with type 1 diabetes. Subjects. This work included 50 cases with T1D and 98 healthy individuals from the Nile Delta region of Egypt. Cases included 20 males and 30 females with a median age of 25 and range of 15-50 years. DNA was amplified using PCR with sequence-specific primers for detection of polymorphisms related to tumor necrosis factor (TNF)-alpha(- 308) (G/A), interleukin (IL)-10(- 1082) (G/A), IL-6(- 174) (G/C), and IL-1Ra (VNTR). Cases with T1D showed significant higher frequency of genotypes of TNF-alpha(- 308) AA (p < 0.001, odds ratio (OR) = 7.91), IL-6-17CC (p < 0.05, OR = 3.36) and IL-1Ra A1A1 (p < 0.05, OR = 3.68) with significant lower frequencies of TNF-alpha(- 308) GA, and IL-1Ra A1A2 genotypes (p < 0.001 and < 0.05, respectively). They also showed significant higher frequency of TNF-alpha(- 308) allele A (p < 0.05, OR = 2.0), IL-1Ra allele A1 (p < 0.05, OR = 2.98) with a significant lower frequency of TNF-alpha(- 308) G allele and IL-1Ra A2 allele (p < 0.05). No significant difference was detected among cases in relation to IL-10(- 1082) (G/A) genotypes or alleles nor in relation to age, sex, consanguinity or family history of the disease. Polymorphisms related to TNF-alpha and IL-1Ra genes may be considered genetic markers for T1D among Egyptians with a potential impact on family counseling and management.

The population genetics of sporophytic self-incompatibility in Senecio squalidus L. (Asteraceae): the number, frequency, and dominance interactions of S alleles across its British range.

PubMed

Brennan, Adrian C; Harris, Stephen A; Hiscock, Simon J

2006-02-01

Sporophytic self-incompatibility (SSI) was studied in 11 British Senecio squalidus populations to quantify mating system variation and determine how its recent colonization of the United Kingdom has influenced its mating behavior. S allele number, frequency, and dominance interactions in populations were assessed using full diallels of controlled pollinations. A mean of 5.1 S alleles per population was observed, and no population contained more than six S alleles. Numbers of S alleles within populations of S. squalidus declined with increasing distance from the center of its introduction (Oxford). Cross-classification of S alleles allowed an estimate of approximately seven and no more than 11 S alleles for the entire British S. squalidus population. The low number of S alleles observed in British S. squalidus compared to other SI species is consistent with the population bottleneck associated with S. squalidus' introduction to the Oxford Botanic Garden and subsequent colonization of Britain. Extensive S allele dominance interactions were observed to be a feature of the S. squalidus SSI system and may represent an adaptive response to improve limited mate availability imposed by the presence of so few S alleles. Multilocus allozyme genotypes were also identified for individuals in all populations and geographic patterns of S locus and allozyme loci variation investigated. Less interpopulation structure was observed for the S locus than for allozyme diversity--a finding indicative of the effects of negative frequency-dependent selection at the S locus maintaining equal S phenotypes within populations and enhancing effective migration between populations.

Evaluation of whether the ACE gene I/D polymorphism constitutes a risk factor for chronic obstructive pulmonary disease in the Turkish population.

PubMed

Ayada, C; Toru, U; Genç, O; Yerlikaya, A; Sahin, S; Turgut, S; Turgut, G

2014-12-12

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction that occurs as a result of the normal inflammatory process to protect against harmful irritants and chemicals. Another physiological regulatory process, the renin angiotensin system (RAS), plays an important role in the pathology of many diseases. Angiotensin converting enzyme (ACE) is a key enzyme of RAS. We investigated the frequency of the ACE gene I/D polymorphism in patients with COPD in Turkey. This study was performed on 47 unrelated patients with COPD and 64 healthy subjects. DNA samples were isolated from peripheral blood, and ACE DNA was amplified by polymerase chain reaction. The frequencies of ACE genotypes were 27.7, 55.3, and 17% for DD, ID, and II in the COPD group, respectively, and 43.8, 43.8, and 12.4% in the control group. There was no statistically significant difference between groups (X(2) = 3.078; df = 2; P = 0.220). The distributions of ACE gene D alleles were 38.2% (N = 52) in the COPD group and 61.8% (N = 84) in the control group; and those of I alleles were 48.8% (N = 42) in the COPD group and 51.2% (N = 44) in the control group. There was no statistically significant difference between groups for allele frequency (X(2) = 2.419; df = 2; P = 0.120). We believe these results can be useful for large-scale population genetic research considering the frequency of the ACE gene variation in COPD patients in the Turkish population.

A note on Hardy-Weinberg equilibrium of VNTR data by using the Federal Bureau of Investigation's fixed-bin method

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

Devlin, B.; Risch, N.

1992-09-01

To fully utilize the information of VNTR data for forensic inference, the probability of observing the matching suspect and evidentiary profile in a reference population is estimated, usually by assuming independence of alleles within and between loci. This assumption has been challenged on the basis of the observation that there is frequently an excess of single-band phenotypes (SBP) in forensic data bases, which could indicate lack of independence. Nevertheless, another explanation is that the excess SBP are artifacts of laboratory methods. In this report the authors examine the excess of SBP for three VNTR loci studied by the FBI (D17S79more » and D2S44, for blacks, and D14S13, for Caucasians). The FBI claims that the excess is due to the effect of null alleles; the null alleles are suspected to be small to be detected. The authors estimate the frequency of null alleles for two loci (D17S79 and D14A13) by comparing, for these loci, the data from the FBI data base and the data from the Lifecodes data base. These comparisons yield information on small fragments because Lifecodes uses the restriction enzyme PstI, which yields larger fragments than does HaeIII, which the FBI uses. For D17S19 in blacks, the authors estimate a null allele frequency of 4.4%, and, for D14S13 in Caucasians, they estimate a frequency of 3.0%. The null-allele frequency for D2S44 in blacks is derived similarly, again being based on analysis of DNA cut with HaeIII and PstI; the estimate of the null-allele frequency for this locus is 1.5%. Using these null-allele frequency estimates and a goodness-of-fit test, the authors show that there is no evidence for deviations from Hardy-Weinberg expectations of genotype probabilities at these loci. 20 refs., 1 fig.« less

Prion protein genotype survey confirms low frequency of scrapie-resistant K222 allele in British goat herds.

PubMed

Goldmann, W; Marier, E; Stewart, P; Konold, T; Street, S; Langeveld, J; Windl, O; Ortiz-Pelaez, A

2016-02-13

Scrapie in goats is a transmissible, fatal prion disease, which is endemic in the British goat population. The recent success in defining caprine PRNP gene variants that provide resistance to experimental and natural classical scrapie has prompted the authors to conduct a survey of PRNP genotypes in 10 goat breeds and 52 herds to find goats with the resistant K222 allele. They report here the frequencies in 1236 tested animals of the resistance-associated K222 and several other alleles by breed and herd. Eight animals were found to be heterozygous QK222 goats (0.64 per cent genotype frequency, 95 per cent CI 0.28 to 1.27 per cent) but no homozygous KK222 goats were detected. The K222 allele was found in Saanen, Toggenburg and Anglo-Nubian goats. The fact that only a few goats with the K222 allele have been identified does not preclude the possibility to design and implement successful breeding programmes at national level. British Veterinary Association.

Alpha1-Antitrypsin Deficiency–Related Alleles Z and S and the Risk of Wegener’s Granulomatosis

PubMed Central

Mahr, Alfred D.; Edberg, Jeffrey C.; Stone, John H.; Hoffman, Gary S.; St. Clair, E. William; Specks, Ulrich; Dellaripa, Paul F.; Seo, Philip; Spiera, Robert F.; Rouhani, Farshid N.; Brantly, Mark L.; Merkel, Peter A.

2011-01-01

Objective Deficiency of α1-antitrypsin (α1AT) may be a determinant of susceptibility to Wegener’s granulomatosis (WG). Several previous, mainly small, case–control studies have shown that 5–27% of patients with WG carried the α1AT deficiency Z allele. It is not clear whether the S allele, the other major α1AT deficiency variant, is associated with WG. This study investigated the relationship of the α1AT deficiency Z and S alleles with the risk of developing WG in a large cohort. Methods We studied the distribution of the α1AT deficiency alleles Z and S in 433 unrelated Caucasian patients with WG and 421 ethnically matched controls. Genotyping was performed using an allele discrimination assay. Results were compared between cases and controls using exact statistical methods. Results Among the patients with WG, the allele carriage frequencies of Z and S were 7.4% and 11.5%, respectively. The frequencies of the 6 possible genotypes differed in a statistically significant manner between cases and controls (P = 0.01). The general genetic 2-parameter codominant model provided the best fit to the data. Compared with the normal MM genotype, the odds ratio (OR) for MZ or MS genotypes was 1.47 (95% confidence interval [95% CI] 0.98–2.22), and the OR for ZZ, SS, or SZ genotypes was 14.58 (95% CI 2.33–∞). ORs of similar direction and magnitude were observed within the restricted cohorts that excluded cases and controls carrying ≥1 Z or ≥1 S allele. Conclusion Both Z and S alleles display associations with risk of WG in a codominant genetic pattern. These findings strengthen the evidence of a causal link between α1AT deficiency and susceptibility to WG. PMID:20827781

Developing STR databases on structured populations: the native South Siberian population versus the Russian population.

PubMed

Zhivotovsky, Lev A; Malyarchuk, Boris A; Derenko, Miroslava V; Wozniak, Marcin; Grzybowski, Tomasz

2009-09-01

Developing a forensic DNA database on a population that consists of local ethnic groups separated by physical and cultural barriers is questionable as it can be genetically subdivided. On the other side, small sizes of ethnic groups, especially in alpine regions where they are sub-structured further into small villages, prevent collecting a large sample from each ethnic group. For such situations, we suggest to obtain both a total population database on allele frequencies across ethnic groups and a list of theta-values between the groups and the total data. We have genotyped 558 individuals from the native population of South Siberia, consisting of nine ethnic groups, at 17 autosomal STR loci of the kit packages AmpFlSTR SGM Plus i, Cyrillic AmpFlSTR Profiler Plus. The groups differentiate from each other with average theta-values of around 1.1%, and some reach up to three to four percent at certain loci. There exists between-village differentiation as well. Therefore, a database for the population of South Siberia is composed of data on allele frequencies in the pool of ethnic groups and data on theta-values that indicate variation in allele frequencies across the groups. Comparison to additional data on northeastern Asia (the Chukchi and Koryak) shows that differentiation in allele frequencies among small groups that are separated by large geographic distance can be even greater. In contrast, populations of Russians that live in large cities of the European part of Russia are homogeneous in allele frequencies, despite large geographic distance between them, and thus can be described by a database on allele frequencies alone, without any specific information on theta-values.

Polymorphism in exon 6 of the human NT5E gene is associated with aortic valve calcification.

PubMed

Kochan, Zdzislaw; Karbowska, Joanna; Gogga, Patrycja; Kutryb-Zajac, Barbara; Slominska, Ewa M; Smolenski, Ryszard T

2016-12-01

NT5E encodes ecto-5'-nucleotidase (e5NT, CD73) which hydrolyses extracellular AMP to adenosine. Adenosine has been shown to play a protective role against aortic valve calcification (AVC). We identified two nonsynonymous missense single nucleotide polymorphisms (c.1126A > G, p.T376A and c.1136T > C, p.M379T) in exon 6 of the human NT5E gene. Since both substitutions might affect e5NT activity and consequently alter extracellular adenosine levels, we evaluated the association between NT5E alleles and calcific aortic valve disease in 119 patients (95 patients with AVC and 24 controls). In AVC patients, the frequency of the G allele at c.1126 and the frequency of the GG genotype as well as the frequency of the C allele at c.1136, and the frequencies of CC and TC genotypes tended to be higher as compared to controls. The allele and genotype frequencies in AVC patients and controls were also compared to those calculated from the 1000 Genomes Project data for control individuals of European ancestry (n = 503). We found that the frequency of the C allele at c.1136 is significantly higher in patients with AVC than in the European controls (0.111 vs. 0.054, P = 0.0052). Moreover, e5NT activity in aortic valves showed a trend toward lower levels in AVC patients with CC and TC genotypes than in those with the TT genotype. Our findings indicate that the genetic polymorphism of NT5E may contribute to the pathogenesis of calcific aortic valve disease and that the C allele of SNP c.1136 is associated with an increased risk of AVC.

Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

PubMed

Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

2015-01-01

The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

PubMed Central

Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

2016-01-01

Background: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Methods: Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. Results: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10−3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10−7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Conclusions: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID:27364786

Schizophrenia and neurotrophin-3 alleles.

PubMed

Jŏnsson, E; Brené, S; Zhang, X R; Nimgaonkar, V L; Tylec, A; Schalling, M; Sedvall, G

1997-05-01

Studies of brain anatomy and premorbid functioning indicate that schizophrenia may be of neurodevelopmental origin. In the neurotrophic factor neurotrophin-3 (NT-3) gene, the A3/147-bp allele in a dinucleotide repeat polymorphism located in the promoter region was found to be associated with schizophrenia in a Japanese study. Another NT-3 polymorphism (Glu63Gly) indicated an association with schizophrenic patients with a putative neurodevelopmental form of the disease. We examined Swedish schizophrenic patients (n = 109) and control subjects (n = 78) for the same two NT-3 polymorphisms, as well as a third silent exonic polymorphism (at Pro55). No significant difference was found between the two groups. However, in a meta-analysis including the present and previous studies of Caucasian subjects, the A3/147-bp allele frequency was found to be significantly higher in the schizophrenic patients. In the present study, carriers of the A3/147 bp allele tended to have an earlier age of onset and to display more extrapyramidal symptoms. In the silent exonic polymorphism (at Pro55), female schizophrenic patients had higher adenine and lower guanine allele frequencies than control female subjects. Together with previous studies, the results provide some support for an association between the NT-3 gene and certain forms of schizophrenia. This warrants further investigation of NT-3 and other neurotrophic factors with additional polymorphisms and larger patient samples.

Ferrochelatase gene mutation in Singapore and a novel frame-shift mutation in an Asian boy with erythropoietic protoporphyria.

PubMed

Alagappan, Uma; Pramono, Zacharias A D; Chong, Wei-Sheng

2017-03-01

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused by decreased activity of the enzyme ferrochelatase (FECH ). The frequency of the hypomorphic c.333-48C allele in a population directly contributes to the prevalence of EPP in the same population. This study sought to identify the molecular basis of EPP in a Chinese patient from Singapore and the c.333-48C allele frequency among the Chinese population in Singapore. FECH gene was screened for mutation in the patient's DNA sample by polymerase chain reaction amplification and DNA sequencing. To validate the identified mutation, the FECH region harboring the mutation was screened in DNA samples from all healthy controls. One patient and 46 ethnically matched healthy controls were included in the study. A novel c.474dupC which leads to a frameshift and premature stop codon was identified in one allele, while the other allele showed to carry c.333-48C and c.337C>T variants in the patient's FECH. The frequency of the c.333-48C hypomorphic allele is 27% among Chinese population in Singapore. c.474dupC in one allele trans to hypomorphic c.333-48C and c.337C>T allele in FECH gene may be the underlying cause of the clinical EPP of the studied patient. The FECH hypomorphic c.333-48C allele frequency in Singapore is lower than the Han Chinese (41.3%) and Japanese (43%) populations but nearly the same as the Southeast Asian (31%) population and higher than the European (2.7-11%) population. © 2016 The International Society of Dermatology.

Association of gene polymorphisms in ABO blood group chromosomal regions and menstrual disorders

PubMed Central

SU, YONG; KONG, GUI-LIAN; SU, YA-LI; ZHOU, YAN; LV, LI-FANG; WANG, QIONG; HUANG, BAO-PING; ZHENG, RUI-ZHI; LI, QUAN-ZHONG; YUAN, HUI-JUAN; ZHAO, ZHI-GANG

2015-01-01

This study aimed to investigate whether single nucleotide polymorphisms (SNPs) located near the gene of the ABO blood group play an important role in the genetic aetiology of menstrual disorders (MDs). Polymerase chain reaction-ligase detection reaction technology was used to detect eight SNPs near the ABO gene location on the chromosomes in 250 cases of MD and 250 cases of normal menstruation. The differences in the distribution of each genotype, as well as the allele frequency in the normal and control groups, were analysed using Pearson's χ2 test to search for disease-associated loci. SHEsis software was used to analyse the linkage disequilibrium and haplotype frequencies and to inspect the correlation between haplotypes and the disease. Compared with the control group, the experimental group exhibited statistically significant differences in the genotype distribution frequencies of the rs657152 locus of the ABO blood group gene and the rs17250673 locus of the tumour necrosis factor cofactor 2 (TRAF2) gene, which is located downstream of the ABO gene. The allele distribution frequencies of rs657152 and rs495828 loci in the ABO blood group gene exhibited significant differences between the groups. Dominant and recessive genetic model analysis of each locus revealed that the experimental group exhibited statistically significant differences from the control group in the genotype distribution frequencies of rs657152 and rs495828 loci, respectively. These results indicate that the ABO blood group gene and TRAF2 gene may be a cause of MDs. PMID:26136981

No association between the TaqI A1 RFLP of the D2 receptor gene and alcoholism in a Mexican population

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

Cruz-Fuentes, C.; Carmarena, B.; Eroza, V.

1994-09-01

The suggested association of the A1 allele of the D2 dopamine receptor (DRD2) human gene with alcoholism was studied by comparing the DRD2/TaqI genotypes of 36 healthy controls and 38 individuals who met the DSM-III-R diagnostic criteria for alcohol dependence. All subjects were unrelated, with parents and grandparents of Mexican origin. The alcoholics in our sample suffered one of the following conditions: delirium tremens (16.6%), alcohol hallucinosis (56.6%) or uncomplicated alcohol withdrawal (26.4%). Eight-eight percent of the controls carried the A1 allele. The frequency of the DRD2 A1 allele in the Mexican urban sample (pA1 = 0.61) was 2 tomore » 3-fold higher than reported in Caucasian populations from the USA and Europe, but similar to the allele frequencies found in defined Amerindian populations. There were not significant differences in the prevalence or allele frequency between alcoholics (pA1 = 0.64) and controls, regardless if the alcoholics were subtyped accordingly to severity, age of onset or positive family history. Alcoholics had higher scores than controls in the neuroticism (N) and psychoticism (P) subscales on the Eysenck personality test: alcoholics P = 6.2 {+-} 2.9, N = 16.0 {+-} 4.2 vs. controls P = 2.5 {+-} 2.3, N = 5.7 {+-} 5.1; p<0.001 and p<0.001, respectively. However, no relationship between personality traits and genotypes was found. Our results do not support a consistent association between the TaqI A1 RFLP for the DRD2 gene and alcoholism.« less

Allele-specific primer polymerase chain reaction for a single nucleotide polymorphism (C1205T) of swine toll-like receptor 5 and comparison of the allelic frequency among several pig breeds in Japan and the Czech Republic.

PubMed

Muneta, Yoshihiro; Minagawa, Yu; Kusumoto, Masahiro; Shinkai, Hiroki; Uenishi, Hirohide; Splichal, Igor

2012-06-01

In the present study, an allele-specific primer-polymerase chain reaction (ASP-PCR) for genotyping a single nucleotide polymorphism (SNP) of swine Toll-like receptor 5 (TLR5) (C1205T; P402L) that is related to the impaired recognition of Salmonella enterica serovar Choleraesuis (SC) was developed. The allele frequencies in several pig breeds in Japan and the Czech Republic were also compared. The swine TLR5 C1205T mutation was successfully determined by ASP-PCR using genomic DNA samples in Japan that had previously been genotyped by a sequencing method. Using the PCR condition determined, genomic DNA samples from blood obtained from 110 pigs from seven different breeds in the Czech Republic were genotyped by the ASP-PCR. The genotyping results from the ASP-PCR completely matched the results from the sequencing method. The allele frequency of the swine TLR5 C1205T mutation was 27.5% in the Landrace breed of the Czech Republic compared with 50.0% in Japanese Landrace. In Japan, the C1205T mutation was found only in the Landrace breed, whereas in the Czech Republic it was found in both the Landrace and Piétrain breeds. These results indicate the usefulness of ASP-PCR for detecting a specific SNP for swine TLR5 affecting ligand recognition. They also suggest the possibility of genetically improving pigs to enhance their resistance against SC infection by eliminating or selecting this specific SNP of swine TLR5. © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

Hla-B genotype in Japanese patients with Crohn's disease.

PubMed

Kinouchi, Yoshitaka; Matsumoto, Keisuke; Negoro, Kenichi; Takagi, Sho; Takahashi, Seiichi; Hiwatashi, Nobuo; Shimosegawa, Tooru

2003-10-01

The HLA-B gene is one of the susceptibility genes for inflammatory bowel disease. Previous association studies of HLA-B showed several associated alleles and haplotypes of HLA-B in patients with ulcerative colitis, and among the associated alleles HLA-B*52 is well known to be strongly associated with ulcerative colitis in Japanese patients. However, there are no convincing reports about HLA-B including the B*52 allele in patients with Crohn's disease. The purpose of this study was to determine if HLA-B, especially the B*52 allele, confers susceptibility to Crohn's disease or determines the disease phenotype of Crohn's disease. A total of 195 patients with Crohn's disease (49 ileitis, 106 ileocolitis, 34 colitis, 6 uncertain) and 185 healthy controls were studied in this case-controlled study. All patients and healthy controls were Japanese. Genotyping of the HLA-B gene was performed by a polymerase chain reaction, sequence-specific primer that can classify the gene into 23 allele groups. Allele frequencies were compared between patients with Crohn's disease and healthy controls with chi-squared test using a 2 x 2 contingency table. P value was corrected by the number of allele groups (n = 23) observed in the Japanese population or the number of clinical subgroups. Corrected P values of <0.05 were considered to be statistically significant. Before the correction for multiple testing, B*4001 and B*44 were associated with patients with Crohn's disease, positively and negatively, respectively. However, after the correction there were no significant differences in any HLA-B alleles between patients with Crohn's disease and healthy controls. In the subgroup analysis according to clinical phenotypes (disease location, anal lesion, age at diagnosis, need for surgery), none of the HLA-B alleles except B*52 showed any disease phenotype-genotype associations. The allele frequency of B*52 in the colitis type (16.2 percent; corrected P = 0.011) was significantly higher than that in the combined group of the ileitis (7.1 percent) and ileocolitis (5.2 percent) types. These results demonstrated that HLA-B did not confer overall susceptibility to Crohn's disease in Japan, but the B*52 allele may affect the location of the disease.

Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

PubMed

Leonenko, Ganna; Richards, Alexander L; Walters, James T; Pocklington, Andrew; Chambert, Kimberly; Al Eissa, Mariam M; Sharp, Sally I; O'Brien, Niamh L; Curtis, David; Bass, Nicholas J; McQuillin, Andrew; Hultman, Christina; Moran, Jennifer L; McCarroll, Steven A; Sklar, Pamela; Neale, Benjamin M; Holmans, Peter A; Owen, Michael J; Sullivan, Patrick F; O'Donovan, Michael C

2017-10-01

Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] < 0.001) in genes intolerant of loss-of-function (LoF) variation and in genes whose messenger RNAs bind to fragile X mental retardation protein (FMRP). We further delineate the genetic architecture of schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies. © 2017 Wiley Periodicals, Inc.

Genetic structure of Columbia River redband trout populations in the Kootenai River drainage, Montana, revealed by microsatellite and allozyme loci

USGS Publications Warehouse

Knudsen, K.-L.; Muhlfeld, C.C.; Sage, G.K.; Leary, R.F.

2002-01-01

We describe the genetic divergence among 10 populations of redband trout Oncorhynchus mykiss gairdneri from the upper Columbia River drainage. Resident redband trout from two watersheds in the Kootenai River drainage and hatchery stocks of migratory Kamloops redband trout from Kootenay Lake, British Columbia, were analyzed using allele frequency data from microsatellite and allozyme loci. The Kamloops populations have significantly different allele frequencies from those of the Kootenai River drainage. Of the total genetic variation detected in the resident redband trout, 40.7% (microsatellites) and 15.5% (allozymes) were due to differences between populations from the two Kootenai River watersheds. The divergence among populations within each watershed, however, was less than 3.5% with both techniques. Our data indicate that watershed-specific broodstocks of redband trout are needed by fisheries managers for reintroduction or the supplementation of populations at risk of extinction.

H1-MAPT and the Risk for Familial Essential Tremor

PubMed Central

García-Martín, Elena; Martínez, Carmen; Alonso-Navarro, Hortensia; Benito-León, Julián; Lorenzo-Betancor, Oswaldo; Pastor, Pau; López-Alburquerque, Tomás; Samaranch, Lluis; Lorenzo, Elena; Agúndez, José A. G.; Jiménez-Jiménez, Félix Javier

2012-01-01

The most frequent MAPT H1 haplotype is associated with the risk for developing progressive supranuclear palsy and other neurodegenerative diseases such as Parkinson’s disease. A recent report suggests that the MAPT H1 is associated with the risk for developing essential tremor. We wanted to confirm this association in a different population. We analyzed the distribution of allelic and genotype frequencies of rs1052553, which is an H1/H2 SNP, in 200 subjects with familial ET and 291 healthy controls. rs1052553 genotype and allelic frequencies did not differ significantly between subjects with ET and controls and were unrelated with the age at onset of tremor or gender, and with the presence of head, voice, chin, and tongue tremor. Our study suggests that the MAPT H1 rs1052553 is not associated with the risk for developing familial ET in the Spanish population. PMID:22911817

Genetic structure characterization of Chileans reflects historical immigration patterns.

PubMed

Eyheramendy, Susana; Martinez, Felipe I; Manevy, Federico; Vial, Cecilia; Repetto, Gabriela M

2015-03-17

Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography.

Genetic structure characterization of Chileans reflects historical immigration patterns

PubMed Central

Eyheramendy, Susana; Martinez, Felipe I.; Manevy, Federico; Vial, Cecilia; Repetto, Gabriela M.

2015-01-01

Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography. PMID:25778948

Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a meta-analysis.

PubMed

Huang, Xiao-Lei; Wu, Guo-Cui; Wang, Yu-Jie; Yang, Xiao-Ke; Yang, Guo-Jun; Tao, Jin-Hui; Duan, Yu; Yan, Jun-Wei; Li, Xiang-Pei; Ye, Dong-Qing; Wang, Jing

2016-08-01

The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

Distribution of FcgammaRIIa and FcgammaRIIIb genotypes in patients with generalized aggressive periodontitis.

PubMed

de Souza, Rodrigo C; Colombo, Ana Paula V

2006-07-01

Polymorphisms in FcgammaR have been associated with different forms of periodontitis. This study determined the frequency of FcgammaRIIa and FcgammaRIIIb alleles/genotypes in patients with generalized aggressive periodontitis (GAgP). Thirty-one GAgP and 49 periodontally healthy Brazilian subjects participated in the study. Full-mouth periodontal examinations were carried out, and mouthwash samples were collected for human DNA isolation. FcgammaR genotyping was performed by polymerase chain reaction and hybridization with allele-specific oligonucleotide probes. Significant differences between groups were sought by Mann-Whitney, chi2, and Fisher exact tests and configural frequency analysis. FcgammaRIIa-H131 (53.8%) and FcgammaRIIIb-NA1 (75%) were the most prevalent alleles in this sample population. A significant overrepresentation of FcgammaRIIIb-NA2 was observed in the GAgP group, whereas FcgammaRIIIb-NA1 was detected more often in healthy individuals (odds ratio, 32.5; 95% confidence interval [CI], 10.6 to 99.8; P<0.001). No significant differences in the distribution of the FcgammaRIIa genotypes were observed between the groups. The prevalence of FcgammaRIIIb-NA2/NA2 was higher in GAgP patients, whereas FcgammaRIIIb-NA1/NA1 was predominant in the healthy group (chi2=45.1; P<0.001). The combination of the genotypes FcgammaRIIIb-NA2/NA2 plus FcgammaRIIa-H/H131 was observed more frequently in GAgP subjects than expected from marginal frequencies (chi2=12.5; P<0.001). The data suggest that the FcgammaRIIIb-NA2 allele and/or FcgammaRIIIb-NA2/NA2 genotype and the composite genotype FcgammaRIIIb-NA2/NA2 plus FcgammaRIIa-H/H131 may be associated with GAgP, whereas FcgammaRIIIb-NA1 and/or FcgammaRIIIb-NA1/NA1 may be related to periodontal health in this sample of the Brazilian population.

Cytokine polymorphisms in patients with pemphigus.

PubMed

Eberhard, Yanina; Burgos, Elisa; Gagliardi, Julio; Vullo, Carlos Maria; Borosky, Alicia; Pesoa, Susana; Serra, Horacio Marcelo

2005-01-01

The aim of this study was to assess whether tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1) and interleukin-10 (IL-10) polymorphisms are among the factors influencing the development of pemphigus. Whole blood from 20 patients with pemphigus and 24 control subjects was taken. Genomic DNA was obtained and cytokine genotyping for IL-10 (-1082 G/A; -819 C/T), TGFB1 (codon 10 C/T, codon 25 G/C) and TNFA (-308 G/A) was performed using the ARMS-PCR method. The distribution of IL-10 (-819) alleles was significantly different between the pemphigus and control groups (P=0.009). In particular, allele T was associated with the disease (OR 3.291, 95% CI 1.350-8.020). Similar results were observed when only pemphigus vulgaris (PV) patients were analyzed (P=0.012, OR 3.410, 95% CI 1.346-8.639). An increased frequency of the low producer IL-10 haplotype (-1082/-819 A/T) in patients with pemphigus compared with controls was observed (OR 2.714, 95% CI 1.102-6.685) and this association was also significant when only PV patients were considered (OR 2.667, 95% CI 1.043-6.816). There were no differences between patients and controls in the frequency of any other gene polymorphism analyzed. The increased frequency of the low producer IL-10 haplotype (-1082 /-819 A/T) suggest that the carriage of this haplotype might predispose to pemphigus or the high and intermediate producer haplotypes may be protective factors. The prevalence of the allele IL-10 (-819 T) in pemphigus patients cannot be explained by the current hypothesis, according to which a particular allele of the gene is associated with a different level of cytokine production and therefore affects the predisposition to a particular disease. However, this cytokine polymorphism might be linked to an unknown susceptibility factor.

Structure of allelic variants of subtype 5 of histone H1 in pea Pisum sativum L.

PubMed

Bogdanova, V S; Lester, D R; Berdnikov, V A; Andersson, I

2005-06-01

The pea genome contains seven histone H1 genes encoding different subtypes. Previously, the DNA sequence of only one gene, His1, coding for the subtype H1-1, had been identified. We isolated a histone H1 allele from a pea genomic DNA library. Data from the electrophoretic mobility of the pea H1 subtypes and their N-bromosuccinimide cleavage products indicated that the newly isolated gene corresponded to the H1-5 subtype encoded by His5. We confirmed this result by sequencing the gene from three pea lines with H1-5 allelic variants of altered electrophoretic mobility. The allele of the slow H1-5 variant differed from the standard allele by a nucleotide substitution that caused the replacement of the positively charged lysine with asparagine in the DNA-interacting domain of the histone molecule. A temperature-related occurrence had previously been demonstrated for this H1-5 variant in a study on a worldwide collection of pea germplasm. The variant tended to occur at higher frequencies in geographic regions with a cold climate. The fast allelic variant of H1-5 displayed a deletion resulting in the loss of a duplicated pentapeptide in the C-terminal domain.

Polymorphism of Glucokinase Gene in Non-Insulin Dependent Diabetes Mellitus

PubMed Central

Kim, Deog-Yoon; Choi, Jung-Hee; Woo, Jeong-Taek; Paeng, Jeong-Ryung; Yang, In-Myung; Kim, Sung-Woon; Kim, Jin-Woo; Kim, Young-Seol; Kim, Kwang-Won; Choi, Young-Kil

1994-01-01

Several lines of evidence suggest a strong genetic component to NIDDM. To clarify the role of glucokinase gene in the development of NIDDM, restriction fragment length polymorphism (RFLP) of glucokinase gene and 3′ microsatellite polymorphism analyses by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) were performed in NIDDM and control subjects. Compared to NIDDM with 1.3 kb allele/Pvu I digestion of glucokinase, 10% of NIDDM did not demonstrate 1.3 kb allele and these patients were charcterized by increased insulin secretion. In 3′ microsatellite polymorphism analysis, autoradiography of PCR products revealed three different alleles, including Z, Z+2 and Z+4. Z was the most common allele in both NIDDM and nondiabetic controls. There was no significant allele associated with NIDDM. Frequency of the homozygote Z/Z genotype was significantly lower in NIDDM subjects (16.7%) compared to normal control (46.7%) (p<0.05). There was no difference in clinical findings according to 3′ microsatellite genotypes in NIDDM. These data suggest that there does not appear to be a significant glucokinase allele associated with NIDDM but Z/Z genotype may play a suppressive role in the pathogenesis of a certain type of NIDDM in Korea. Further studies may be required to identify the molecular basis of this association. PMID:7913622

HLA Association with Drug-Induced Adverse Reactions

PubMed Central

Fan, Wen-Lang; Shiao, Meng-Shin; Hui, Rosaline Chung-Yee; Wang, Chuang-Wei; Chang, Ya-Ching

2017-01-01

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs. PMID:29333460

Culture-gene coevolution of individualism-collectivism and the serotonin transporter gene.

PubMed

Chiao, Joan Y; Blizinsky, Katherine D

2010-02-22

Culture-gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism-collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture-gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism-collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture-gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism-collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture-gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed.

Genetic factors and multiple sclerosis in the Moroccan population: a role for HLA class II.

PubMed

Ouadghiri, S; El Alaoui Toussi, K; Brick, C; Ait Benhaddou, E H; Benseffaj, N; Benomar, A; El Yahyaoui, M; Essakalli, M

2013-12-01

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease. Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS. A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR=2.67, 95% CI=1.36-5.23, P=0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR=2.78, 95% CI=1.41-5.48, P=0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found. Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Analysis of Thiopurine S-Methyltransferase Deficient Alleles in Acute Lymphoblastic Leukemia Patients in Mexican Patients.

PubMed

Jiménez-Morales, Silvia; Ramírez-Florencio, Mireya; Mejía-Aranguré, Juan Manuel; Núñez-Enríquez, Juan Carlos; Bekker-Mendez, Carolina; Torres-Escalante, José Luis; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Del Carmen Rodríguez-Zepeda, María; Leal, Yelda A; González-Montalvo, Pablo Miguel; Pantoja-Guillen, Francisco; Peñaloza-Gonzalez, José Gabriel; Gutiérrez-Juárez, Erick Israel; Núñez-Villegas, Nora Nancy; Pérez-Saldivar, Maria Luisa; Guerra-Castillo, Francisco Xavier; Flores-Villegas, Luz Victoria; Ramos-Cervantes, María Teresa; Fragoso, José Manuel; García-Escalante, María Guadalupe; Del Carmen Pinto-Escalante, Doris; Ramírez-Bello, Julián; Hidalgo-Miranda, Alfredo

2016-11-01

It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico. We included 849 unrelated subjects, of which 368 ALL children and 342 non-ALL subjects were from Mexico City, and 60 ALL cases and 79 non-ALL individuals were from Yucatan. Genotyping of the rs1800462, rs1800460 and rs1142345 SNPs was performed by 5'exonuclease technique using TaqMan probes (Life Technologies Foster City, CA). The mutant TPMT alleles were present in 4.8% (81/1698 chromosomes) and only 0.2% were homozygote TPMT*3A/TPMT*3A. We did not find statistically significant differences in the distribution of the mutant alleles between patients from Mexico City and Yucatan in either ALL cases or non-ALL. Nonetheless, the TPMT*3C frequency in ALL patients was higher than non-ALL subjects (p = 0.03). To note, the null homozygous TPMT*3A/TPMT*3A genotype was found in 2.5% of the non-ALL subjects. TPMT mutant alleles did not exhibit differential distribution between both evaluated populations; however, TPMT*3C is overrepresented in ALL cases in comparison with non-ALL group. Assessing the TPMT mutant alleles could benefit the ALL children and those undergoing 6-MP and MX treatment. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Evidence for pleiotropism and recent selection in the PLAG1 region in Australian Beef cattle.

PubMed

Fortes, M R S; Kemper, K; Sasazaki, S; Reverter, A; Pryce, J E; Barendse, W; Bunch, R; McCulloch, R; Harrison, B; Bolormaa, S; Zhang, Y D; Hawken, R J; Goddard, M E; Lehnert, S A

2013-12-01

A putative functional mutation (rs109231213) near PLAG1 (BTA14) associated with stature was studied in beef cattle. Data from 8199 Bos taurus, Bos indicus and Tropical Composite cattle were used to test the associations between rs109231213 and various phenotypes. Further, 23 496 SNPs located on BTA14 were tested for association with these phenotypes, both independently and fitted together with rs109231213. The C allele of rs109231213 significantly increased hip height, weight, net food intake, age at puberty in males and females and decreased IGF-I concentration in blood and fat depth. When rs109231213 was fitted as a fixed effect in the model, there was an overall reduction in associations between other SNPs and these traits but some SNPs remained associated (P < 10(-4) ). Frequency of the mutant C allele of rs109231213 differed among B. indicus (0.52), B. taurus (0.96) and Tropical Composite (0.68). Most chromosomes carrying the C allele had the same surrounding 10 SNP haplotype, probably because the C allele was introgressed into Brahman from B. taurus cattle. A region of reduced heterozygosity surrounds the C allele; this is small in B. taurus but 20 Mb long in Brahmans, indicating recent and strong selection for the mutant allele. Thus, the C allele appears to mark a mutation that has been selected almost to fixation in the B. taurus breeds studied here and introduced into Brahman cattle during grading up and selected to a frequency of 0.52 despite its negative effects on fertility. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Apolipoprotein E: Risk factor for Alzheimer disease

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

Tsai, M.S.; Thibodeau, S.N.; Tangalos, E.G.

1994-04-01

The apolipoprotein E gene (APOE) has three common alleles (E2, E3, and E4) that determine six genotypes in the general population. In this study, the authors examined 77 patients with late-onset Alzheimer disease (AD), along with an equal number of age- and sex-matched controls, for an association with the APOE-E4 allele. They show that the frequency of this allele among AD patients was significantly higher than that among the control population (.351 vs. .130, P = .000006). The genotype frequencies also differed between the two groups (P = .0002), with the APOE-E4/E3 genotype being the most common in the ADmore » group and the APOE-E3/E3 being the most common in the control group. In the AD group, homozygosity for E4 was found in nine individuals, whereas none was found in the control group. The odds ratio for AD, when associated with one or two E4 alleles, was 4.6 (95% confidence interval [CI] 1.9-12.3), while the odds ratio for AD, when associated with heterozygosity for APOE-E4, was 3.6 (05% CI 1.5-9.8). Finally, the median age at onset among the AD patients decreased from 83 to 78 to 74 years as the number of APOE-E4 alleles increased from 0 to 1 to 2, respectively (test for trend, P = .001). The data, which are in agreement with recent reports, suggest that the APOE-E4 allele is associated with AD and that this allelic variant may be an important risk factor for susceptibility to AD in the general population. 30 refs., 5 tabs.« less

Ethnic differentiation at VNTR loci, with special reference to forensic applications

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

Devlin, B.; Risch, N.

1992-09-01

Allele-rich VNTR loci provide valuable information for forensic inference. Interpretation of this information is complicated by measurement error, which renders discrete alleles difficult to distinguish. Two methods have been used to circumvent this difficulty-i.e, binning methods and direct evaluation of allele frequencies, the latter achieved by modeling the data as a mixture distribution. The authors use this modeling approach to estimate the allele frequency distributions for two loci-D17S79 and D2S44-for black, Caucasian, and Hispanic samples from the Lifecodes and FBI data bases. The databases are differentiated by the restriction enzyme used: PstI (Lifecodes) and HaeIII (FBI). The results show thatmore » alleles common in one ethnic group are almost always common in all ethnic groups, and likewise for rare alleles; this pattern holds for both loci. Gene diversity, or heterozygosity, measured as one minus the sum of the squared allele frequencies, is greater for D2S44 than for D17S79, in both data bases. The average gene diversity across ethnic groups when PstI (HaeIII) is used is .918 (.918) for D17S79 and is .985 (.983) for D2S44. The variance in gene diversity among ethnic groups is greater for D17S79 than for D2S44. The number of alleles, like the gene diversity, is greater for D2S44 than for D17S79. The mean numbers of alleles across ethnic groups, estimated from the PstI (HaeIII) data, are 40.25 (41.5) for D 17S79 and 104 (103) for D2S44. The number of alleles is correlated with sample size. The authors use the estimated allele frequency distributions for each ethnic group to explore the effects of unwittingly mixing populations and thereby violating independence assumptions. They show that, even in extreme cases of mixture, the estimated genotype probabilities are good estimates of the true probabilities, contradicting recent claims. 35 refs., 9 figs., 3 tabs.« less

Detection of susceptibility genes as modifiers due to subgroup differences in complex disease.

PubMed

Bergen, Sarah E; Maher, Brion S; Fanous, Ayman H; Kendler, Kenneth S

2010-08-01

Complex diseases invariably involve multiple genes and often exhibit variable symptom profiles. The extent to which disease symptoms, course, and severity differ between affected individuals may result from underlying genetic heterogeneity. Genes with modifier effects may or may not also influence disease susceptibility. In this study, we have simulated data in which a subset of cases differ by some effect size (ES) on a quantitative trait and are also enriched for a risk allele. Power to detect this 'pseudo-modifier' gene in case-only and case-control designs was explored blind to case substructure. Simulations involved 1000 iterations and calculations for 80% power at P<0.01 while varying the risk allele frequency (RAF), sample size (SS), ES, odds ratio (OR), and proportions of the case subgroups. With realistic values for the RAF (0.20), SS (3000) and ES (1), an OR of 1.7 is necessary to detect a pseudo-modifier gene. Unequal numbers of subjects in the case groups result in little decrement in power until the group enriched for the risk allele is <30% or >70% of the total case population. In practice, greater numbers of subjects and selection of a quantitative trait with a large range will provide researchers with greater power to detect a pseudo-modifier gene. However, even under ideal conditions, studies involving alleles with low frequencies or low ORs are usually underpowered for detection of a modifier or susceptibility gene. This may explain some of the inconsistent association results for many candidate gene studies of complex diseases.

Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts.

PubMed

Bouwman, Aniek C; Hayes, Ben J; Calus, Mario P L

2017-10-30

Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of allele counts results in less shrinkage towards the mean for low minor allele frequency (MAF) variants. Scaling may become relevant for estimating ASE as more low MAF variants will be used in genomic evaluations. We show the impact of scaling on estimates of ASE using real data and a theoretical framework, and in terms of power, model fit and predictive performance. In a dairy cattle dataset with 630 K SNP genotypes, the correlation between DGV for stature from a random regression model using centered allele counts (RRc) and centered and scaled allele counts (RRcs) was 0.9988, whereas the overall correlation between ASE using RRc and RRcs was 0.27. The main difference in ASE between both methods was found for SNPs with a MAF lower than 0.01. Both the ratio (ASE from RRcs/ASE from RRc) and the regression coefficient (regression of ASE from RRcs on ASE from RRc) were much higher than 1 for low MAF SNPs. Derived equations showed that scenarios with a high heritability, a large number of individuals and a small number of variants have lower ratios between ASE from RRc and RRcs. We also investigated the optimal scaling parameter [from - 1 (RRcs) to 0 (RRc) in steps of 0.1] in the bovine stature dataset. We found that the log-likelihood was maximized with a scaling parameter of - 0.8, while the mean squared error of prediction was minimized with a scaling parameter of - 1, i.e., RRcs. Large differences in estimated ASE were observed for low MAF SNPs when allele counts were scaled or not scaled because there is less shrinkage towards the mean for scaled allele counts. We derived a theoretical framework that shows that the difference in ASE due to shrinkage is heavily influenced by the power of the data. Increasing the power results in smaller differences in ASE whether allele counts are scaled or not.

Effects of allelic variations in starch synthesis-related genes on grain quality traits of Korean nonglutinous rice varieties under different temperature conditions

PubMed Central

Mo, Young-Jun; Jeung, Ji-Ung; Shin, Woon-Chul; Kim, Ki-Young; Ye, Changrong; Redoña, Edilberto D.; Kim, Bo-Kyeong

2014-01-01

Influences of allelic variations in starch synthesis-related genes (SSRGs) on rice grain quality were examined. A total of 187 nonglutinous Korean rice varieties, consisting of 170 Japonica and 17 Tongil-type varieties, were grown in the field and in two greenhouse conditions. The percentages of head rice and chalky grains, amylose content, alkali digestion value, and rapid visco-analysis characteristics were evaluated in the three different environments. Among the 10 previously reported SSRG markers used in this study, seven were polymorphic, and four of those showed subspecies-specific allele distributions. Six out of the seven polymorphic SSRG markers were significantly associated with at least one grain quality trait (R2 > 0.1) across the three different environments. However, the association level and significance were markedly lower when the analysis was repeated using only the 170 Japonica varieties. Similarly, the significant associations between SSRG allelic variations and changes in grain quality traits under increased temperature were largely attributable to the biased allele frequency between the two subpopulations. Our results suggest that within Korean Japonica varieties, these 10 major SSRG loci have been highly fixed during breeding history and variations in grain quality traits might be influenced by other genetic factors. PMID:24987303

Race, common genetic variation, and therapeutic response disparities in heart failure.

PubMed

Taylor, Mathew R; Sun, Albert Y; Davis, Gordon; Fiuzat, Mona; Liggett, Stephen B; Bristow, Michael R

2014-12-01

Because of its comparatively recent evolution, Homo sapiens exhibit relatively little within-species genomic diversity. However, because of genome size, a proportionately small amount of variation creates ample opportunities for both rare mutations that may cause disease as well as more common genetic variations that may be important in disease modification or pharmacogenetics. Primarily because of the East African origin of modern humans, individuals of African ancestry (AA) exhibit greater degrees of genetic diversity than more recently established populations, such as those of European ancestry (EA) or Asian ancestry. Those population effects extend to differences in frequency of common gene variants that may be important in heart failure natural history or therapy. For cell-signaling mechanisms important in heart failure, we review and present new data for genetic variation between AA and EA populations. Data indicate that: 1) neurohormonal signaling mechanisms frequently (16 of the 19 investigated polymorphisms) exhibit racial differences in the allele frequencies of variants comprising key constituents; 2) some of these differences in allele frequency may differentially affect the natural history of heart failure in AA compared with EA individuals; and 3) in many cases, these differences likely play a role in observed racial differences in drug or device response. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Statistical and population genetics issues of two Hungarian datasets from the aspect of DNA evidence interpretation.

PubMed

Szabolcsi, Zoltán; Farkas, Zsuzsa; Borbély, Andrea; Bárány, Gusztáv; Varga, Dániel; Heinrich, Attila; Völgyi, Antónia; Pamjav, Horolma

2015-11-01

When the DNA profile from a crime-scene matches that of a suspect, the weight of DNA evidence depends on the unbiased estimation of the match probability of the profiles. For this reason, it is required to establish and expand the databases that reflect the actual allele frequencies in the population applied. 21,473 complete DNA profiles from Databank samples were used to establish the allele frequency database to represent the population of Hungarian suspects. We used fifteen STR loci (PowerPlex ESI16) including five, new ESS loci. The aim was to calculate the statistical, forensic efficiency parameters for the Databank samples and compare the newly detected data to the earlier report. The population substructure caused by relatedness may influence the frequency of profiles estimated. As our Databank profiles were considered non-random samples, possible relationships between the suspects can be assumed. Therefore, population inbreeding effect was estimated using the FIS calculation. The overall inbreeding parameter was found to be 0.0106. Furthermore, we tested the impact of the two allele frequency datasets on 101 randomly chosen STR profiles, including full and partial profiles. The 95% confidence interval estimates for the profile frequencies (pM) resulted in a tighter range when we used the new dataset compared to the previously published ones. We found that the FIS had less effect on frequency values in the 21,473 samples than the application of minimum allele frequency. No genetic substructure was detected by STRUCTURE analysis. Due to the low level of inbreeding effect and the high number of samples, the new dataset provides unbiased and precise estimates of LR for statistical interpretation of forensic casework and allows us to use lower allele frequencies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Correlation of HLA-A, B, DRB1 genes with leukemia].

PubMed

Du, Ying; Liang, Xiao-lan; Li, Qian; Wu, Wen-jie; Liu, Jian; Sun, Le-jing; Qiu, Lu-gui

2013-04-01

This study was aimed to investigate the correlation between HLA gene distribution and allele frequency of the patients with leukemia. PCR-SSP technique was used to detect the HLA genotype of 2994 umbilical cord blood units from healthy newborns (as control), the detecting result of which was compared with HLA genotypes of 1246 patients with leukemia searched in our cord blood bank. The differences between two groups were compared and analyzed. The results indicated that as compared with the control group, the allele frequencies of HLA-B*56 (0.56%), B*70 (0.24%) obviously increased (RR = 2.2546, 6.2598, χ(2) = 5, 5.98, P < 0.05), while the allele frequencies of HLA-A*03 (3.45%), A*30 (4.86%), B*13 (8.75%), B44* (3.25%), B61* (5.70%), DRB1*07 (8.23%), DRB1*15 (14.21%) obviously decreased in patients with leukemia (RR = 0.5889, 0.7187, 0.7359, 0.5713, 0.7127, 0.6242, 0.7976, χ(2) = 19.23, 9.82, 14.33, 20.48, 11.99, 33.21, 11.56, P < 0.01). It is concluded that HLA-B*56, B*70 alleles seem to be characterized by the genetic susceptibility to leukemia and may be served as risk markers for leukemia occurrence, while the HLA-A*03, A*30, B*13, B*44, B*61, DRB1*07, DRB1*15 can be considered as genetic indicators for resistance of leukemia.

Polymorphisms of glutathione S-transferase π 1 and toll-like receptors 2 and 9: Association with breast cancer susceptibility

PubMed Central

AL-HARRAS, MOHAMMAD F.; HOUSSEN, MAHA E.; SHAKER, MOHAMED E.; FARAG, KAMEL; FAROUK, OMAR; MONIR, REHAN; EL-MAHDY, RASHA; ABO-HASHEM, EKBAL M.

2016-01-01

Polymorphisms in antioxidant enzymes and innate immune receptors have been implicated in the development of various types of cancer. The present study aimed to investigate whether polymorphisms of glutathione S-transferase π 1 (GSTP1) and toll-like receptors (TLRs) 2 and 9 are associated with susceptibility to breast cancer among females. The study was conducted on 72 Egyptian female patients with breast cancer, along with 100 healthy volunteers. Polymorphisms of GSTP1 (codon 105 Ile/Val) and TLR9 rs187084 (1237T/C) genes were assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, while the −196 to −174 deletion/insertion (del/ins) polymorphism of TLR2 was detected by PCR. The results indicated a decrease in GSTP1 Val allele frequency in breast cancer patients compared with healthy controls, at rates of 22.9 vs. 32.5%, respectively. In addition, the breast cancer group demonstrated a decreased TLR9 C allele frequency compared with the control group, at rates of 36.1 vs. 51.5%, respectively (P=0.0047). A non-significant difference was detected in the frequency of the TLR2 −196 to −174 del allele in breast cancer patients when compared to normal controls. In conclusion, these results suggested that the GSTP1 Val and TLR9 1237C alleles, but not TLR2 −196 to −174 del, are likely to be associated with breast cancer development among females. PMID:26998146

Polymorphisms of glutathione S-transferase π 1 and toll-like receptors 2 and 9: Association with breast cancer susceptibility.

PubMed

Al-Harras, Mohammad F; Houssen, Maha E; Shaker, Mohamed E; Farag, Kamel; Farouk, Omar; Monir, Rehan; El-Mahdy, Rasha; Abo-Hashem, Ekbal M

2016-03-01

Polymorphisms in antioxidant enzymes and innate immune receptors have been implicated in the development of various types of cancer. The present study aimed to investigate whether polymorphisms of glutathione S-transferase π 1 (GSTP1) and toll-like receptors (TLRs) 2 and 9 are associated with susceptibility to breast cancer among females. The study was conducted on 72 Egyptian female patients with breast cancer, along with 100 healthy volunteers. Polymorphisms of GSTP1 (codon 105 Ile/Val) and TLR9 rs187084 (1237T/C) genes were assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, while the -196 to -174 deletion/insertion (del/ins) polymorphism of TLR2 was detected by PCR. The results indicated a decrease in GSTP1 Val allele frequency in breast cancer patients compared with healthy controls, at rates of 22.9 vs. 32.5%, respectively. In addition, the breast cancer group demonstrated a decreased TLR9 C allele frequency compared with the control group, at rates of 36.1 vs. 51.5%, respectively (P=0.0047). A non-significant difference was detected in the frequency of the TLR2 -196 to -174 del allele in breast cancer patients when compared to normal controls. In conclusion, these results suggested that the GSTP1 Val and TLR9 1237C alleles, but not TLR2 -196 to -174 del, are likely to be associated with breast cancer development among females.

Frequency of Cry1F resistance alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae) in Brazil.

PubMed

Farias, Juliano R; Andow, David A; Horikoshi, Renato J; Bernardi, Daniel; Ribeiro, Rebeca da S; Nascimento, Antonio Rb do; Santos, Antonio C Dos; Omoto, Celso

2016-12-01

The frequency of resistance alleles is a major factor influencing the rate of resistance evolution. Here, we adapted the F 2 screen procedure for Spodoptera frugiperda (J. E. Smith) with a discriminating concentration assay, and extended associated statistical methods to estimate the frequency of resistance to Cry1F protein in S. frugiperda in Brazil when resistance was not rare. We show that F 2 screen is efficient even when the resistance frequency is 0.250. It was possible to screen 517 isoparental lines from 12 populations sampled in five states of Brazil during the first half of 2012. Western Bahia had the highest allele frequency of Cry1F resistance, 0.192, with a 95% confidence interval (CI) between 0.163 and 0.220. All other states had a similar and lower frequency varying from 0.042 in Paraná to 0.080 in Mato Grosso do Sul. The high frequency in western Bahia may be related to year-round availability of maize, the high population density of S. frugiperda, the lack of refuges and the high adoption rate of Cry1F maize. Cry1F resistance alleles were not rare and occurred at frequencies that have already compromised the useful life of TC1507 maize in western Bahia. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

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

PubMed

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

2018-04-01

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

Stochastic modelling of shifts in allele frequencies reveals a strongly polygynous mating system in the re-introduced Asiatic wild ass.

PubMed

Renan, Sharon; Greenbaum, Gili; Shahar, Naama; Templeton, Alan R; Bouskila, Amos; Bar-David, Shirli

2015-04-01

Small populations are prone to loss of genetic variation and hence to a reduction in their evolutionary potential. Therefore, studying the mating system of small populations and its potential effects on genetic drift and genetic diversity is of high importance for their viability assessments. The traditional method for studying genetic mating systems is paternity analysis. Yet, as small populations are often rare and elusive, the genetic data required for paternity analysis are frequently unavailable. The endangered Asiatic wild ass (Equus hemionus), like all equids, displays a behaviourally polygynous mating system; however, the level of polygyny has never been measured genetically in wild equids. Combining noninvasive genetic data with stochastic modelling of shifts in allele frequencies, we developed an alternative approach to paternity analysis for studying the genetic mating system of the re-introduced Asiatic wild ass in the Negev Desert, Israel. We compared the shifts in allele frequencies (as a measure of genetic drift) that have occurred in the wild ass population since re-introduction onset to simulated scenarios under different proportions of mating males. We revealed a strongly polygynous mating system in which less than 25% of all males participate in the mating process each generation. This strongly polygynous mating system and its potential effect on the re-introduced population's genetic diversity could have significant consequences for the long-term persistence of the population in the Negev. The stochastic modelling approach and the use of allele-frequency shifts can be further applied to systems that are affected by genetic drift and for which genetic data are limited. © 2015 John Wiley & Sons Ltd.

GJB2 Mutations in Mongolia: Complex Alleles, Low Frequency, and Reduced Fitness of the Deaf

PubMed Central

Tekin, Mustafa; Xia, Xia-Juan; Erdenetungalag, Radnaabazar; Cengiz, F. Basak; White, Thomas W.; Radnaabazar, Janchiv; Dangaasuren, Begzsuren; Tastan, Hakki; Nance, Walter E.; Pandya, Arti

2016-01-01

Summary We screened the GJB2 gene for mutations in 534 (108 multiplex and 426 simplex) probands with non-syndromic sensorineural deafness, who were ascertained through the only residential school for deaf in Mongolia and in 217 hearing controls. Twenty different alleles, including four novel changes, were identified. Biallelic GJB2 mutations were found in 4.5% of the deaf probands (8.3% in multiplex, 3.5% in simplex). The most common mutations were c.IVS1+1G>A (c.-3201G>A) and c.235delC with allele frequencies of 3.5% and 1.5%, respectively. The c.IVS1+1G>A mutation appears to have diverse origins based on its association with multiple haplotypes constructed using nearby SNP markers. The p.V27I and p.E114G variants were frequently detected in both deaf probands and hearing controls. The p.E114G variant was always associated with p.V27I, and haplotype analysis confirmed that it was always in cis with the p.V27I variant. Although in vitro experiments using Xenopus oocytes have suggested that p.[V27I;E114G] disturb the gap junction function of Cx26, the equal distribution of this complex allele in both deaf probands and hearing controls makes it a less likely cause of profound congenital deafness. We found a lower frequency of assortative mating (37.5%) and decreased genetic fitness (62%) of the deaf in Mongolia as compared to the western populations, which provides an explanation for lower frequency of GJB2 deafness in Mongolia. PMID:20201936

Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.

PubMed

Jiménez-Jiménez, Félix Javier; Esguevillas, Gara; Alonso-Navarro, Hortensia; Zurdo, Martín; Turpín-Fenoll, Laura; Millán-Pascual, Jorge; Adeva-Bartolomé, Teresa; Cubo, Esther; Navacerrada, Francisco; Amo, Gemma; Rojo-Sebastián, Ana; Rubio, Lluisa; Díez-Fairén, Mónica; Pastor, Pau; Calleja, Marisol; Plaza-Nieto, José Francisco; Pilo-de-la-Fuente, Belén; Arroyo-Solera, Margarita; García-Albea, Esteban; Agúndez, José A G; García-Martín, Elena

2018-05-03

The possible role of gammaaminobutyric acid (GABA) in the pathophysiology of restless legs syndrome (RLS) is suggested by the symptomatic improvement achieved with GABAergic drugs. Thalamic GABA levels have shown positive correlation with periodic limb movements indices and with RLS severity. We tried to investigate the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS. We studied the genotype and allelic variant frequencies of the most common SNPs in the GABRR1(rs12200969, rs1186902), GABRR2(rs282129), GABRR3(rs832032), GABRA4(rs2229940), GABRE(rs1139916), and GABRQ(rs3810651) genes in 205 RLS patients and 230 age- and gender-matched healthy controls using specific TaqMan assays. The frequencies of the GABRR3 rs832032TT genotype and the allelic variant GABRR3 rs832032T were significantly higher in RLS patients than in controls (odds ratio [95% confidence intervals] 7.08[1.48-46.44] and 1.66[1.16-2.37], respectively), although only the higher frequency of the rs832032T allele remained as significant after multiple comparison analysis, both in the whole series and in the female gender. The frequencies of the other genotypes of allelic variants did not differ significantly between RLS patients and controls. RLS patients carrying the GABRA4 rs2229940TT genotype showed a significantly younger age at onset of RLS symptoms than those with the other two genotypes. These results suggest association between GABRR3rs832032 polymorphism and the risk for RLS, and a modifier effect of GABRA4 rs2229940 on the age of onset of RLS.

Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

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

Fong, I.; Lai, P.S.; Ouah, T.C.

1994-09-01

The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1more » = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.« less

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

USDA-ARS?s Scientific Manuscript database

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

Type 2 diabetes mellitus: distribution of genetic markers in Kazakh population.

PubMed

Sikhayeva, Nurgul; Talzhanov, Yerkebulan; Iskakova, Aisha; Dzharmukhanov, Jarkyn; Nugmanova, Raushan; Zholdybaeva, Elena; Ramanculov, Erlan

2018-01-01

Ethnic differences exist in the frequencies of genetic variations that contribute to the risk of common disease. This study aimed to analyse the distribution of several genes, previously associated with susceptibility to type 2 diabetes and obesity-related phenotypes, in a Kazakh population. A total of 966 individuals belonging to the Kazakh ethnicity were recruited from an outpatient clinic. We genotyped 41 common single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes in other ethnic groups and 31 of these were in Hardy-Weinberg equilibrium. The obtained allele frequencies were further compared to publicly available data from other ethnic populations. Allele frequencies for other (compared) populations were pooled from the haplotype map (HapMap) database. Principal component analysis (PCA), cluster analysis, and multidimensional scaling (MDS) were used for the analysis of genetic relationship between the populations. Comparative analysis of allele frequencies of the studied SNPs showed significant differentiation among the studied populations. The Kazakh population was grouped with Asian populations according to the cluster analysis and with the Caucasian populations according to PCA. According to MDS, results of the current study show that the Kazakh population holds an intermediate position between Caucasian and Asian populations. A high percentage of population differentiation was observed between Kazakh and world populations. The Kazakh population was clustered with Caucasian populations, and this result may indicate a significant Caucasian component in the Kazakh gene pool.

Worldwide Distribution of Four SNPs in X‐Ray and Repair and Cross‐Complementing Group 1 (XRCC1)

PubMed Central

Takeshita, Haruo; Yasuda, Toshihiro; Kimura‐Kataoka, Kaori

2014-01-01

Abstract Purpose X‐ray repair cross‐complementing group 1 (XRCC1) repairs single‐strand breaks in DNA. Several reports have shown the association of single nucleotide polymorphisms (SNPs) (Arg194Trp, Pro206Pro, Arg280His, Arg399Gln) in XRCC1 to diseases. Limited population data are available regarding SNPs in XRCC1, especially in African populations. In this study, genotype distributions of four SNPs in worldwide populations were examined and compared with those reported previously. Materials and Methods Four SNPs (Arg194Trp, Pro206Pro, Arg280His, Arg399Gln) in XRCC1 from genomic DNA samples of 10 populations were evaluated by using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results The frequency of the minor allele corresponding to the Trp allele of XRCC1Arg194Trp was higher in Asian populations than in African and Caucasian populations. As for XRCC1Pro206Pro, Africans showed higher minor allele frequencies than did Asian populations, except for Tamils and Sinhalese. XRCC1 Arg280His frequencies were similar among Africans and Caucasians but differed among Asian populations. Similarly, lower mutant XRCC1 Arg399Gln frequencies were observed in Africans. Conclusions This study is the first to show the existence of a certain genetic heterogeneity in the worldwide distribution of four SNPs in XRCC1. PMID:25387884

[Distribution of Apo E gene sequencing in patients with coronary heart disease of phlegm-stasis syndrome].

PubMed

Fang, Zhu-yuan; Jiang, Wei-min; Zhu, Chang-le

2011-09-01

To study the correlation between Apo E gene polymorphism and patients with coronary heart disease (CHD) of phlegm-stasis syndrome (PSS). 78 CHD patients were assigned to PSS (49 cases) and non-phlegm-stasis syndrome (NPSS). Polymorphisms of Apo E gene in 78 CHD patients and 100 healthy subjects were detected by complete DNA sequencing. Five gene types as E3/3, E4/4, E2/ 3, E2/4, and E3/4 were detected in the two groups. The frequencies of genotype E3/3 and epsilon 3 allele were significantly lower in CHD patients than in the healthy subjects (P<0.01). But the frequencies of genotype E3/4 and epsilon 4 allele were significantly higher in CHD patients than in the healthy subjects (P<0.01). In CHD patients, the frequencies of genotype E2/4 + E3/4 + E4/4 and epsilon 4 allele were higher in PSS than in NPSS. Apo E epsilon 4 allele was a susceptible allele to CHD, which was closely correlated to CHD PSS. It was inferred that it might be one of main susceptible alleles for CHD PSS.

Identification of human phosphoglucomutase 3 (PGM3) as N-acetylglucosamine-phosphate mutase (AGM1).

PubMed

Pang, H; Koda, Y; Soejima, M; Kimura, H

2002-03-01

We performed phenotyping of human phosphoglucomutase 3 (PGM(3)) and screening for mutations in the human N-acetylglucosamine-phosphate mutase gene (AGM(1)) to identify PGM(3) as AGM(1). By sequencing the coding region of AGM(1), two alleles containing a G or A base at nucleotide 1396, that can respectively encode aspartic acid or asparagine at codon 466, were identified. Cell extracts of COS7 cells after transfection with the pcDNA 3.1(+) plasmid containing an AGM(1) allele with 1396G or 1396A showed similar electrophoretic patterns to the PGM(3) 1 or PGM(3) 2 protein, respectively, with the isozyme detection method used for PGM(3) phenotyping. The genotypes determined by the two alleles of AGM(1) coincided exactly with the PGM(3) phenotypes in 20 individuals. We also investigated the allele frequency of the AGM(1) nucleotide polymorphism in a Japanese population by DNA sequencing and found that the frequencies of alleles 1396G and 1396A were similar to previously reported PGM(3) *1 and PGM(3) *2 frequencies. Overall, the facts that the AGM(1) gene product shows PGM activity, AGM(1) is polymorphic, the electrophoretic mobility is similar between AGM(1) allele-specific products and PGM(3) 1 and 2 proteins, PGM(3) phenotypes and AGM(1) genotypes completely coincide in 20 individuals, and AGM(1) allele frequencies are similar to those of PGM(3) *1 and PGM(3) *2 in Japanese populations, suggest that PGM(3) is identical to AGM(1).

Reconstruction of Haplotype-Blocks Selected during Experimental Evolution.

PubMed

Franssen, Susanne U; Barton, Nicholas H; Schlötterer, Christian

2017-01-01

The genetic analysis of experimentally evolving populations typically relies on short reads from pooled individuals (Pool-Seq). While this method provides reliable allele frequency estimates, the underlying haplotype structure remains poorly characterized. With small population sizes and adaptive variants that start from low frequencies, the interpretation of selection signatures in most Evolve and Resequencing studies remains challenging. To facilitate the characterization of selection targets, we propose a new approach that reconstructs selected haplotypes from replicated time series, using Pool-Seq data. We identify selected haplotypes through the correlated frequencies of alleles carried by them. Computer simulations indicate that selected haplotype-blocks of several Mb can be reconstructed with high confidence and low error rates, even when allele frequencies change only by 20% across three replicates. Applying this method to real data from D. melanogaster populations adapting to a hot environment, we identify a selected haplotype-block of 6.93 Mb. We confirm the presence of this haplotype-block in evolved populations by experimental haplotyping, demonstrating the power and accuracy of our haplotype reconstruction from Pool-Seq data. We propose that the combination of allele frequency estimates with haplotype information will provide the key to understanding the dynamics of adaptive alleles. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Phenotypic and genotypic expression of self-incompatibility haplotypes in Arabidopsis lyrata suggests unique origin of alleles in different dominance classes.

PubMed

Prigoda, Nadia L; Nassuth, Annette; Mable, Barbara K

2005-07-01

The highly divergent alleles of the SRK gene in outcrossing Arabidopsis lyrata have provided important insights into the evolutionary history of self-incompatibility (SI) alleles and serve as an ideal model for studies of the evolutionary and molecular interactions between alleles in cell-cell recognition systems in general. One tantalizing question is how new specificities arise in systems that require coordination between male and female components. Allelic recruitment via gene conversion has been proposed as one possibility, based on the division of DNA sequences at the SRK locus into two distinctive groups: (1) sequences whose relationships are not well resolved and display the long branch lengths expected for a gene under balancing selection (Class A); and (2) sequences falling into a well-supported group with shorter branch lengths (Class B) that are closely related to an unlinked paralogous locus. The purpose of this study was to determine if differences in phenotype (site of expression assayed using allele-specific reverse transcription-polymerase chain reaction) or function (dominance relationships assayed through controlled pollinations) accompany the sequence-based classification. Expression of Class A alleles was restricted to floral tissues, as predicted for genes involved in the SI response. In contrast, Class B alleles, despite being tightly linked to the SI phenotype, were unexpectedly expressed in both leaves and floral tissues; the same pattern found for a related unlinked paralogous sequence. Whereas Class A included haplotypes in three different dominance classes, all Class B haplotypes were found to be recessive to all except one Class A haplotype. In addition, mapping of expression and dominance patterns onto an S-domain-based genealogy suggested that allelic dominance may be determined more by evolutionary history than by frequency-dependent selection for lowered dominance as some theories suggest. The possibility that interlocus gene conversion might have contributed to allelic diversity is discussed.

Epidemiology of human leukocyte antigens among omani population.

PubMed

Al Salmi, Issa; Metry, Abdul Massiah; Al Ismaili, Faisal; Hola, Alan; Shaheen, Faissal; Fakhoury, Hana; Hannawi, Suad

2017-01-01

Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease.

PubMed

Campbell, Purdey; Brix, Thomas H; Wilson, Scott G; Ward, Lynley C; Hui, Jennie; Beilby, John P; Hegedüs, Laszlo; Walsh, John P

2015-02-14

Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10 -4 ) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10 -4 ) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10 -6 ); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease. © 2015 John Wiley & Sons Ltd.

Angiotensinogen gene M235T and angiotensin II-type 1 receptor gene A/C1166 polymorphisms in chronic obtructive pulmonary disease

PubMed Central

Ayada, Ceylan; Toru, Ümran; Genç, Osman; Şahin, Server; Turgut, Sebahat; Turgut, Günfer

2015-01-01

Chronic obstructive pulmonary disease (COPD) occurs irreversibly and is characterized by progressive airflow obstruction. Renin angiotensin system (RAS) has many different key enzymes and receptors that have a role for different systemic processes. We aimed to determine genotype and allele frequencies of angiotensinogen (AGT) M235T and angiotensin II-type 1 receptor (AT1-R) A/C1166 polymorphisms in patients with COPD. This study was performed on 56 unrelated COPD patients and 29 healthy subjects. DNA samples for each individual were isolated from peripheral blood by phenol/chloroform method, analyzed by polymerase chain reaction and enzymatic digestion methodologies. The distribution for each of AGT genotypes were 23.2% for MM (13), 75.0% for MT (42) and 1.8% for TT (1) in the COPD group; 37.9% for MM (11), 34.5% for MT (10) and 27.6% for TT (8) in the control group. The distribution of AGT genotypes was found significantly different between groups (X2 = 18.604; df = 2; P = 0.000). The frequencies for each of the AT1-R genotypes were found as 53.6% for AA (30), 42.9% for AC (24), 3.6% for CC (2) in the COPD group; 55.2% for AA (16), 41.4% for AC (12) and 3.4% for CC (1) in the control group. The distribution of AT1-R genotypes did not change significantly between groups. Allele frequencies of interested genes were not significantly different between groups. We suggest that AGT polymorphism may play a role for the development of COPD. We believe these data can be served for large scale population genetics research, considering the frequency of AGT and AT1-R genes and alleles in COPD patients in the Turkish population. PMID:26064378

Genetic implications of bottleneck effects of differing severities on genetic diversity in naturally recovering populations: An example from Hawaiian coot and Hawaiian gallinule

USGS Publications Warehouse

Sonsthagen, Sarah A.; Wilson, Robert E.; Underwood, Jared G.

2017-01-01

The evolutionary trajectory of populations through time is influenced by the interplay of forces (biological, evolutionary, and anthropogenic) acting on the standing genetic variation. We used microsatellite and mitochondrial loci to examine the influence of population declines, of varying severity, on genetic diversity within two Hawaiian endemic waterbirds, the Hawaiian coot and Hawaiian gallinule, by comparing historical (samples collected in the late 1800s and early 1900s) and modern (collected in 2012–2013) populations. Population declines simultaneously experienced by Hawaiian coots and Hawaiian gallinules differentially shaped the evolutionary trajectory of these two populations. Within Hawaiian coot, large reductions (between −38.4% and −51.4%) in mitochondrial diversity were observed, although minimal differences were observed in the distribution of allelic and haplotypic frequencies between sampled time periods. Conversely, for Hawaiian gallinule, allelic frequencies were strongly differentiated between time periods, signatures of a genetic bottleneck were detected, and biases in means of the effective population size were observed at microsatellite loci. The strength of the decline appears to have had a greater influence on genetic diversity within Hawaiian gallinule than Hawaiian coot, coincident with the reduction in census size. These species exhibit similar life history characteristics and generation times; therefore, we hypothesize that differences in behavior and colonization history are likely playing a large role in how allelic and haplotypic frequencies are being shaped through time. Furthermore, differences in patterns of genetic diversity within Hawaiian coot and Hawaiian gallinule highlight the influence of demographic and evolutionary processes in shaping how species respond genetically to ecological stressors.

Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in African but not American sickle cell disease.

PubMed

Noble, Jenelle A; Duru, Kimberley C; Guindo, Aldiouma; Yi, Li; Imumorin, Ikhide G; Diallo, Dapa A; Thomas, Bolaji N

2015-01-01

Elucidating the genomic diversity of CD209 gene promoter polymorphism could assist in clarifying disease pathophysiology as well as contribution to co-morbidities. CD209 gene promoter polymorphism has been shown to be associated with susceptibility to infection. We hypothesize that CD209 mutant variants occur at a higher frequency among Africans and in sickle cell disease. We analyzed the frequency of the CD209 gene (rs4804803) in healthy control and sickle cell disease (SCD) populations and determined association with disease. Genomic DNA was extracted from blood samples collected from 145 SCD and 231 control Africans (from Mali), 331 SCD and 379 control African Americans and 159 Caucasians. Comparative analysis among and between groups was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Per ethnic diversification, we found significant disparity in genotypic (23.4% versus 16.9% versus 3.2%) and allelic frequencies (48.7% versus 42.1% versus 19.8%) of the homozygote mutant variant of the CD209 (snp 309A/G) gene promoter between Africans, African Americans and Caucasians respectively. Comparative evaluation between disease and control groups reveal a significant difference in genotypic (10.4% versus 23.4%; p = 0.002) and allelic frequencies (39.7% versus 48.7%; p = 0.02) of the homozygote mutant variant in African SCD and healthy controls respectively, an observation that is completely absent among Americans. Comparing disease groups, we found no difference in the genotypic (p = 0.19) or allelic (p = 0.72) frequencies of CD209 homozygote mutant variant between Africans and Americans with sickle cell disease. The higher frequency of CD209 homozygote mutant variants in the African control group reveals a potential impairment of the capacity to mount an immune response to infectious diseases, and possibly delineate susceptibility to or severity of infectious co-morbidities within and between groups.

Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in African but not American sickle cell disease

PubMed Central

Noble, Jenelle A.; Duru, Kimberley C.; Guindo, Aldiouma; Yi, Li; Imumorin, Ikhide G.; Diallo, Dapa A.

2015-01-01

Elucidating the genomic diversity of CD209 gene promoter polymorphism could assist in clarifying disease pathophysiology as well as contribution to co-morbidities. CD209 gene promoter polymorphism has been shown to be associated with susceptibility to infection. We hypothesize that CD209 mutant variants occur at a higher frequency among Africans and in sickle cell disease. We analyzed the frequency of the CD209 gene (rs4804803) in healthy control and sickle cell disease (SCD) populations and determined association with disease. Genomic DNA was extracted from blood samples collected from 145 SCD and 231 control Africans (from Mali), 331 SCD and 379 control African Americans and 159 Caucasians. Comparative analysis among and between groups was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Per ethnic diversification, we found significant disparity in genotypic (23.4% versus 16.9% versus 3.2%) and allelic frequencies (48.7% versus 42.1% versus 19.8%) of the homozygote mutant variant of the CD209 (snp 309A/G) gene promoter between Africans, African Americans and Caucasians respectively. Comparative evaluation between disease and control groups reveal a significant difference in genotypic (10.4% versus 23.4%; p = 0.002) and allelic frequencies (39.7% versus 48.7%; p = 0.02) of the homozygote mutant variant in African SCD and healthy controls respectively, an observation that is completely absent among Americans. Comparing disease groups, we found no difference in the genotypic (p = 0.19) or allelic (p = 0.72) frequencies of CD209 homozygote mutant variant between Africans and Americans with sickle cell disease. The higher frequency of CD209 homozygote mutant variants in the African control group reveals a potential impairment of the capacity to mount an immune response to infectious diseases, and possibly delineate susceptibility to or severity of infectious co-morbidities within and between groups. PMID:25755928

Stepwise positive association between APOA5 minor allele frequencies and increasing plasma triglyceride quartiles in random patients with hypertriglyceridemia of unclarified origin.

PubMed

Hadarits, Ferenc; Kisfali, Péter; Mohás, Márton; Maász, Anita; Sümegi, Katalin; Szabó, Melinda; Hetyésy, Katalin; Valasek, Andrea; Janicsek, Ingrid; Wittmann, István; Melegh, Béla

2011-03-01

Apolipoprotein A5 (ApoA5) gene and its protein product play a central role in the complex regulation of circulating triglyceride levels in humans. Naturally occurring variants of the apolipoprotein A5 gene have been associated with increased triglyceride levels and have been found to confer risk for cardiovascular diseases. In our study, four polymorphisms, the T-1131C, IVS3+G476A, T1259C, and C56G alleles of APOA5 were analyzed in a total of 436 patients by polymerase chain reaction-restriction fragment length polymorphism methods. The randomly selected patients were classified into four quartile (q) groups based on triglyceride levels (q1: TG<1.31 mmol/l; q2: 1.31-2.90 mmol/l; q3: 2.91-4.85 mmol/l; q4: TG>4.85 mmol/l). We observed significant stepwise increasing association between the four APOA5 minor allele carrier frequencies and plasma triglyceride quartiles: -1131C (q1: 4.44%; q2: 8.95%; q3: 12.9%; q4: 20.6%), IVS3 + 476A (q1: 4.44%; q2: 5.79%; q3: 11.1%; q4: 19.7%), 1259C (q1: 4.44%; q2: 6.84%; q3: 11.1%; q4: 20.6%) and 56G (q1: 5.64%; q2: 6.31%; q3: 11.16%; q4: 11.9%). The serum total cholesterol and high density lipoprotein-cholesterol levels also showed allele-dependent differences in the quartiles. The findings presented here revealed a special arrangement of APOA5 minor alleles in patients with different serum triglyceride ranges in Hungarians.

Association of a Polymorphism in the BIRC6 Gene with Pseudoexfoliative Glaucoma

PubMed Central

Ayub, Humaira; Micheal, Shazia; Akhtar, Farah; Khan, Muhammad Imran; Bashir, Shaheena; Waheed, Nadia K.; Ali, Mahmood; Schoenmaker-Koller, Frederieke E.; Shafique, Sobia; Qamar, Raheel; den Hollander, Anneke I.

2014-01-01

Recently an association was observed between alleles in genes of the unfolded protein response pathway and primary open angle glaucoma (POAG). The goal of the current study is to investigate the role of these two genes, protein disulphide isomerase A member 5 (PDIA5) and baculoviral IAP repeat containing 6 (BIRC6), in different forms of glaucoma. 278 patients with POAG, 132 patients with primary angle closure glaucoma (PACG) and 135 patients with pseudoexfoliative glaucoma (PEXG) were genotyped for single nucleotide polymorphisms (SNPs) rs11720822 in PDIA5 and 471 POAG, 184 PACG and 218 PEXG patients were genotyped for rs2754511 in BIRC6. Genotyping was done by allelic discrimination PCR, and genotype and allele frequencies were calculated. Logistic regression analyses were performed using R software to determine the association of these SNPs with glaucoma. The allele and genotype frequencies of rs11720822 in PDIA5 were not associated with POAG, PACG or PEXG. The TT genotype of rs2754511 in BIRC6 was found to be protective for PEXG (p = 0.05, OR 0.42 [0.22–0.81]) in the Pakistani population, but not for POAG or PACG. This study did not confirm a previously reported association of risk alleles in PDIA5 and BIRC6 with POAG, but did demonstrate a protective role of the T allele of rs2754511 in the BIRC6 gene in PEXG. This supports a role for the unfolded protein response pathway and regulation of apoptotic cell death in the pathogenesis of PEXG. PMID:25118708

Increased frequency of angiotensin-converting enzyme DD genotype in Saudi overweight and obese patients.

PubMed

El-Hazmi, Mohsen Af; Warsy, Arjumand S

2003-01-01

Several studies have been carried out to investigate the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) in obese and normal weight individuals, often with contradictory results in different populatios. In some studies, the DD genotype occurs at a high frequency in obesity, while in others no association has been demonstrated. Since obesity and overweight are of frequent occurrence in the Saudi population, we initiated this study to investigate the I/D polymorphism of ACE in obese, overweight and normal weight Saudis. The study group included 457 Saudi males and females. The height and weight were measured and body mass index (BMI) was calculated. Based on the BMI value, the total study population was classified as normal, overweight and obese. A total of 117 obese (BMI >30 (kg/m(2))), 185 overweight (BMI=25-29.9 (kg/m(2))) and 155 normal weight individuals (BMI< (kg/m (2)) were enrolled. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used to study the ACE polymorphism. For the deletion (D) form, a 190 bp and for the insertion (I) form, 490 bp DNA fragment were obtained on 2% agarose gel electrophoresis. The frequency of DD genotype was 76.9% in the obese, and 73.5% in the overweight individuals, compared to 19.66% and 24.86% of the ID genotype in the obese and overweight, respectively. Among the normal weight individuals, the frequency was significantly lower for DD and higher for the ID genotype, i.e., 58.7% for DD and 40% for ID. The allele frequencies in the obese were 0.867 and 0.133 for the D and I alleles, respectively. While in the overweight, the frequencies were 0.859 and 0.141 for these alleles, respectively, compared to 0.787 and 0.213 in the normal weight individuals. The DD genotype and D allele occur at a high frequency in Saudi overweight and obese individuals, and may have some role in fat accumulation by affecting metabolic pathways of fat, thus leading to the development of overweight and obesity.

Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes: HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese.

PubMed

Hamaguchi, K; Kimura, A; Seki, N; Higuchi, T; Yasunaga, S; Takahashi, M; Sasazuki, T; Kusuda, Y; Okeda, T; Itoh, K; Sakata, T

2000-01-01

Polymorphisms in the 5'-flanking region of the tumor necrosis factor (TNF)-alpha gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF-alpha-857T allele (designated as TNFP-D allele) or -863A/-1,031C allele (designated as TNFP-B allele) were significantly increased in the patients as compared with the controls. Since these TNF-alpha alleles are in linkage disequilibria with certain DRB1 and HLA-B alleles, two-locus analyses were carried out. The TNFP-D allele did not increase the risk in either the presence or absence of the DRB1*0405 or HLA-B54 allele, while the DRB1*0405 and HLA-B54 alleles per se could confer susceptibility in both the TNFP-D allele-positive and -negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1*0405 and HLA-B54. Similarly, the TNFP-B allele did not show significant association with the disease in either the HLA-B61-positive or -negative population, while the HLA-B61 allele could significantly increase the risk in the TNFP-B allele-positive population. These data suggest that the associations of TNFP-D and -B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA-B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese.

Description of a novel HLA-B35 (B*3514) allele found in a Mexican family of Nahua Aztec descent.

PubMed

Vargas-Alarcon, G; Martinez-Laso, J; Granados, J; Diaz-Campos, N; Alvarez, M; Gomez-Casado, E; Alcocer-Varela, J; Arnaiz-Villena, A

1996-02-01

A new allele, HLA-B*3514, has been found in a Mexican family from Nahua descent. Its exon 2 is identical to that of B*3501 allele, but exon 3 bears a 3-base difference at codons 152 and 156, which results in Val-->Glu and Leu-->Trp changes, respectively, in the corresponding HLA molecule at the peptide-binding site. These substitutions may have originated from a DNA stretch donation from an allele belonging to the B15 group, enabling HLA-B*3514 to cope with the presentation of a new set of antigenic peptides. The high frequency of serologic B35 in Amerindians, together with the variety of B35 alleles detected by DNA sequencing in these populations, suggest that a frequent B35 subtype was present in the founder population and that several B35 subtypes may have been recently generated, probably due to the abrupt arrival of new pathogens following European invasions.

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

PubMed

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

2006-01-01

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

Nature's inordinate fondness for metabolic enzymes: why metabolic enzyme loci are so frequently targets of selection.

PubMed

Marden, James H

2013-12-01

Metabolic enzyme loci were some of the first genes accessible for molecular evolution and ecology research. New technologies now make the whole genome, transcriptome or proteome readily accessible, allowing unbiased scans for loci exhibiting significant differences in allele frequency or expression level and associated with phenotypes and/or responses to natural selection. With surprising frequency and in many cases in proportions greater than chance relative to other genes, glycolysis and TCA cycle enzyme loci appear among the genes with significant associations in these studies. Hence, there is an ongoing need to understand the basis for fitness effects of metabolic enzyme polymorphisms. Allele-specific effects on the binding affinity and catalytic rate of individual enzymes are well known, but often of uncertain significance because metabolic control theory and in vivo studies indicate that many individual metabolic enzymes do not affect pathway flux rate. I review research, so far little used in evolutionary biology, showing that metabolic enzyme substrates affect signalling pathways that regulate cell and organismal biology, and that these enzymes have moonlighting functions. To date there is little knowledge of how alleles in natural populations affect these phenotypes. I discuss an example in which alleles of a TCA enzyme locus associate with differences in a signalling pathway and development, organismal performance, and ecological dynamics. Ultimately, understanding how metabolic enzyme polymorphisms map to phenotypes and fitness remains a compelling and ongoing need for gaining robust knowledge of ecological and evolutionary processes. © 2013 John Wiley & Sons Ltd.

MHC standing genetic variation and pathogen resistance in wild Atlantic salmon

PubMed Central

Dionne, Mélanie; Miller, Kristina M.; Dodson, Julian J.; Bernatchez, Louis

2009-01-01

Pathogens are increasingly emerging in human-altered environments as a serious threat to biodiversity. In this context of rapid environmental changes, improving our knowledge on the interaction between ecology and evolution is critical. The objective of this study was to evaluate the influence of an immunocompetence gene, the major histocompatibility complex (MHC) class IIβ, on the pathogen infection levels in wild Atlantic salmon populations, Salmo salar, and identify selective agents involved in contemporary coevolution. MHC variability and bacterial infection rate were determined throughout the summer in juvenile salmon from six rivers belonging to different genetic and ecological regions in Québec, Canada. A total of 13 different pathogens were identified in kidney by DNA sequence analysis, including a predominant myxozoa, most probably recently introduced in North America. Infection rates were the highest in southern rivers at the beginning of the summer (average 47.6±6.3% infected fish). One MHC allele conferred a 2.9 times greater chance of being resistant to myxozoa, while another allele increased susceptibility by 3.4 times. The decrease in frequency of the susceptibility allele but not other MHC or microsatellite alleles during summer was suggestive of a mortality event from myxozoa infection. These results supported the hypothesis of pathogen-driven selection in the wild by means of frequency-dependent selection or change in selection through time and space rather than heterozygous advantage, and underline the importance of MHC standing genetic variation for facing pathogens in a changing environment. PMID:19414470

Disruption of diphthamide synthesis genes and resulting toxin resistance as a robust technology for quantifying and optimizing CRISPR/Cas9-mediated gene editing.

PubMed

Killian, Tobias; Dickopf, Steffen; Haas, Alexander K; Kirstenpfad, Claudia; Mayer, Klaus; Brinkmann, Ulrich

2017-11-13

We have devised an effective and robust method for the characterization of gene-editing events. The efficacy of editing-mediated mono- and bi-allelic gene inactivation and integration events is quantified based on colony counts. The combination of diphtheria toxin (DT) and puromycin (PM) selection enables analyses of 10,000-100,000 individual cells, assessing hundreds of clones with inactivated genes per experiment. Mono- and bi-allelic gene inactivation is differentiated by DT resistance, which occurs only upon bi-allelic inactivation. PM resistance indicates integration. The robustness and generalizability of the method were demonstrated by quantifying the frequency of gene inactivation and cassette integration under different editing approaches: CRISPR/Cas9-mediated complete inactivation was ~30-50-fold more frequent than cassette integration. Mono-allelic inactivation without integration occurred >100-fold more frequently than integration. Assessment of gRNA length confirmed 20mers to be most effective length for inactivation, while 16-18mers provided the highest overall integration efficacy. The overall efficacy was ~2-fold higher for CRISPR/Cas9 than for zinc-finger nuclease and was significantly increased upon modulation of non-homologous end joining or homology-directed repair. The frequencies and ratios of editing events were similar for two different DPH genes (independent of the target sequence or chromosomal location), which indicates that the optimization parameters identified with this method can be generalized.

Genetic conservation in applied tree breeding programs.

Treesearch

R. Johnson; B. St. Clair; S. Lipow

2001-01-01

This paper reviews how population size and structure impacts the maintenance of genetic variation in breeding and gene resource populations. We discuss appropriate population sizes for low frequency alleles and point out some examples of low frequency alleles in the literature. Development of appropriate breeding populations and gene resource populations are discussed...

Human minisatellite alleles detectable only after PCR amplification.

PubMed

Armour, J A; Crosier, M; Jeffreys, A J

1992-01-01

We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

Interleukin-18 -607C/A gene polymorphism in Egyptian asthmatic children.

PubMed

Shaaban, Hala Hamdi; Mohy, Abeer Mohamed; Abdel-Razek, Abdel-Rahman Ahmed; Wahab, Amira Abdel

2014-08-01

Asthma is a multifactorial respiratory disease determined by interactions of multiple disease susceptibility genes and environmental factors. Interleukin (IL)-18 is an important cytokine for initiating and perpetuating the catabolic and inflammatory response in allergic asthma. A number of single nucleotide polymorphisms that influence IL-18 production are found in the gene promoter region. The aim of this study was to investigate the association of IL-18 -607C/A promoter polymorphism with asthma and whether this polymorphism influenced the severity of asthma in affected children. The influence of this promoter gene polymorphism on total serum IgE level in studied subjects was also investigated. This study was carried out at the Allergy Clinic of Abu El Reesh Children's Hospital at Cairo University, Egypt. This study included 40 asthmatic children, subdivided into four groups according to different degrees of asthma severity, and 20 apparently healthy subjects as the control group. All cases were subjected to history taking, clinical examination, and the following laboratory investigations: complete blood count, total serum IgE level assay by ELISA and genomic DNA extraction, and analysis for IL-18 -607C/A promoter gene polymorphism using the PCR-RFLP (restriction fragment length polymorphism) technique. In the present study the IL-18 -607AA genotype frequency was higher in cases (22.5 %) than in the control group (15 %); however, the difference was not statistically significant (p = 0.773). No statistically significant difference between the degree of asthma severity and IL-18 -607C/A polymorphism was found (p = 0.489). No significant association could be detected upon comparing the frequencies of C and A alleles among the two studied groups (p = 0.366). Also, no significant differences were demonstrated for the allele frequencies when the intermittent with mild [odds ratio (OR) = 2.72, 95 % CI 1.03-2.33, p = 0.067], intermittent with moderate, and severe (OR = 2.8, 95 % CI 1.01-8.5, p = 0.066) asthma groups were compared. The median value of the total serum IgE level in asthmatic cases with the mutant genotype (AA) was significantly higher [360 IU/L (96.6-1,340 IU/L)] than in the control group [119 IU/L (70.6-158.9 IU/L)] (p = 0.033). No significant statistical difference was encountered regarding the distribution of IL-18 -607C/A genotypes and allele frequencies in asthma patients and healthy controls. Also, there were no significant associations between asthma severity and different genotypes or alleles. The median value of the total serum IgE level in asthmatic cases with the mutant genotype (AA) was significantly higher than in the control group. Thus, IL-18 -607AA genotype frequency might be related to higher total serum IgE.

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.

Tumor necrosis factor-alpha and interleukin-4 gene polymorphisms in Chinese patients with gout.

PubMed

Chen, M-L; Tsai, F-J; Tsai, C-H; Huang, C-M

2007-01-01

The purpose of this study was to examine whether polymorphisms of interleukin-4 (IL-4) (promoter-590 and intron 3) and tumor necrosis factor-alpha (TNF-alpha) promoter-308 genes are markers of susceptibility to or clinical manifestations of gout in Taiwanese patients. The study included 196 Taiwanese patients with gout and 103 unrelated healthy control subjects living in central Taiwan. Polymorphisms of the IL-4 (promoter-590 and intron 3) and TNF-alpha (promoter-308) genes were typed from genomic DNA. Allelic frequencies and carriage rates were then compared between gout patients and control subjects. The correlation between allelic frequencies, carriage rates and clinical manifestations of gout were evaluated. No significant differences were observed in the allelic frequencies and carriage rates of the IL-4 (promoter-590 and intron 3) and TNF-alpha gene polymorphisms between patients with gout and healthy control subjects. Furthermore, the IL-4 (promoter-590 and intron 3) and TNF-alpha genotypes were not found to be associated with the clinical and laboratory profiles in gout patients. However, there was a significant difference in the TNF-alphapolymorphism genotype between patients with and without hypertriglyceridemia (P=0.001, xi2=11.47, OR=10.3, 95%CI=3.57-29.7). The results of our study suggest that polymorphisms of the IL-4 (promoter-590 and intron 3) and TNF-alpha promoter-308 genes are not related to gout in Chinese patients in Taiwan.

The Role of G22 A Adenosine Deaminase 1 Gene Polymorphism and the Activities of ADA Isoenzymes in Fertile and Infertile Men.

PubMed

Fattahi, Amir; Khodadadi, Iraj; Amiri, Iraj; Latifi, Zeinab; Ghorbani, Marzieh; Tavilani, Heidar

2015-10-01

To evaluate frequency distribution of adenosine deaminase 1 (ADA1) G22 A alleles and genotypes in fertile and infertile men. In this study we evaluate frequency distribution of ADA1 G22 A alleles and genotypes in 200 fertile and 200 infertile men. The polymerase chain reaction-restriction fragment length polymorphism technique was used for determining ADA1 G22 A variants. In addition, ADA isoenzymes activities (ADA1 and ADA2) were measured using colorimetric method. The frequency of GG genotype was significantly higher and GA genotype was lower in infertile males compared with fertile men (P = .048 and P = .045, respectively). However, there was not any noticeable difference in allele distribution between groups (P >.05). Based on logistic regression analysis, the GA genotype has a protective role and can decrease the risk of male infertility 1.7 times (P = .046). There were significantly higher activities of ADAT and its isoenzymes in infertile males compared with fertile men (P <.05). Also, the ADA1 activity with GG genotype was higher than GA carriers in all population (P = .001). Our results revealed that the activity of ADA isoenzymes and distribution of ADA1 G22 A genotypes were different among fertile and infertile men and more likely the GA genotype, which had lower ADA1 activity and was higher in fertile men is a protective factor against infertility. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects

PubMed Central

Martínez, Carmen; García-Martín, Elena; Blanco, Gerardo; Gamito, Francisco J G; Ladero, José M; Agúndez, José A G

2005-01-01

Aims To study the effect of CYP2C8*3, the most common CYP2C8 variant allele on the dis-position of (R)-ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles. Methods Three hundred and fifty-five randomly selected Spanish Caucasians were screened for the common CYP2C8 and CYP2C9 mutations. The pharmacokinetics of (R)-ibuprofen were studied in 25 individuals grouped into different CYP2C8 genotypes. Results The allele frequency of CYP2C8*3 (0.17) was found to be higher than that reported for other Caucasian populations (P = 0.0001). The frequencies of CYP2C9*2 and CYP2C9*3 were 0.19 (0.16–0.21) and 0.10 (0.08–0.12), respectively. An association between CYP2C8*3 and CYP2C9*2 alleles was observed, occurring together at a frequency 2.4-fold higher than expected for a random association of alleles (P = 0.0001). The presence of the CYP2C8*3 allele was found to influence the pharmacokinetics of (R)-ibuprofen in a gene–dose effect manner. Thus, after administration of 400 mg ibuprofen, the plasma half-life (95% confidence intervals) for individuals with genotypes CYP2C8*1/*1, CYP2C8*1/*3 and CYP2C8*3/*3, was 2.0 h (1.8–2.2), 4.2 h (1.9–6.5; P < 0.05) and 9.0 h (7.8–10.2; P < 0.002), respectively. A statistically significant trend with respect to the number of variant CYP2C8*3 alleles was also observed for the area under the concentration-time curve (P < 0.025), and drug clearance (P < 0.03). Conclusion Polymorphism of the CYP2C8 gene was found to be common, with nearly 30% of the population studied carrying the variant CYP2C8*3 allele. The presence of the latter caused a significant effect on the disposition of (R)-ibuprofen. This suggests that a substantial proportion of Caucasian subjects may show alterations in the disposition of drugs that are CYP2C8 substrates. PMID:15606441

A prevalence-based association test for case-control studies.

PubMed

Ryckman, Kelli K; Jiang, Lan; Li, Chun; Bartlett, Jacquelaine; Haines, Jonathan L; Williams, Scott M

2008-11-01

Genetic association is often determined in case-control studies by the differential distribution of alleles or genotypes. Recent work has demonstrated that association can also be assessed by deviations from the expected distributions of alleles or genotypes. Specifically, multiple methods motivated by the principles of Hardy-Weinberg equilibrium (HWE) have been developed. However, these methods do not take into account many of the assumptions of HWE. Therefore, we have developed a prevalence-based association test (PRAT) as an alternative method for detecting association in case-control studies. This method, also motivated by the principles of HWE, uses an estimated population allele frequency to generate expected genotype frequencies instead of using the case and control frequencies separately. Our method often has greater power, under a wide variety of genetic models, to detect association than genotypic, allelic or Cochran-Armitage trend association tests. Therefore, we propose PRAT as a powerful alternative method of testing for association.

The functional spectrum of low-frequency coding variation.

PubMed

Marth, Gabor T; Yu, Fuli; Indap, Amit R; Garimella, Kiran; Gravel, Simon; Leong, Wen Fung; Tyler-Smith, Chris; Bainbridge, Matthew; Blackwell, Tom; Zheng-Bradley, Xiangqun; Chen, Yuan; Challis, Danny; Clarke, Laura; Ball, Edward V; Cibulskis, Kristian; Cooper, David N; Fulton, Bob; Hartl, Chris; Koboldt, Dan; Muzny, Donna; Smith, Richard; Sougnez, Carrie; Stewart, Chip; Ward, Alistair; Yu, Jin; Xue, Yali; Altshuler, David; Bustamante, Carlos D; Clark, Andrew G; Daly, Mark; DePristo, Mark; Flicek, Paul; Gabriel, Stacey; Mardis, Elaine; Palotie, Aarno; Gibbs, Richard

2011-09-14

Rare coding variants constitute an important class of human genetic variation, but are underrepresented in current databases that are based on small population samples. Recent studies show that variants altering amino acid sequence and protein function are enriched at low variant allele frequency, 2 to 5%, but because of insufficient sample size it is not clear if the same trend holds for rare variants below 1% allele frequency. The 1000 Genomes Exon Pilot Project has collected deep-coverage exon-capture data in roughly 1,000 human genes, for nearly 700 samples. Although medical whole-exome projects are currently afoot, this is still the deepest reported sampling of a large number of human genes with next-generation technologies. According to the goals of the 1000 Genomes Project, we created effective informatics pipelines to process and analyze the data, and discovered 12,758 exonic SNPs, 70% of them novel, and 74% below 1% allele frequency in the seven population samples we examined. Our analysis confirms that coding variants below 1% allele frequency show increased population-specificity and are enriched for functional variants. This study represents a large step toward detecting and interpreting low frequency coding variation, clearly lays out technical steps for effective analysis of DNA capture data, and articulates functional and population properties of this important class of genetic variation.

Polymorphism of the beta 3-adrenergic receptor gene in morbid obesity.

PubMed

Oksanen, L; Mustajoki, P; Kaprio, J; Kainulainen, K; Jänne, O; Peltonen, L; Kontula, K

1996-12-01

The Trp64-->Arg allele of the beta 3-adrenergic receptor gene was recently proposed to be associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), features of insulin resistance and a tendency to gain weight. We investigated whether the Arg64 allele predisposes to severe obesity. A genetic association study of 254 subjects with morbid obesity [body-mass index (BMI) > or = 40; mean 42.8 +/- 7.0] and 151 lean healthy control subjects [BMI < or = 25; mean BMI 22.3 +/- 1.9]. beta 3-adrenergic receptor genotyping was carried out with a solid-phase minisequencing technique. Serum lipids, glucose and insulin levels in the obese subjects were also determined. The frequency of the Arg64 did not significantly differ in the morbidly obese patients (9.1%) and lean controls (8.9%), nor was there any statistically significant association between the mean BMI values and the beta 3-adrenergic receptor genotype. However, obese subjects carrying the Arg64 allele developed obesity more often before the age of 15 y than those without it (P < 0.05, adjusted for multiple comparisons). The frequency of the Arg64 allele was similar in nondiabetic and diabetic patients; the mean age at the onset of NIDDM did not differ according to the beta 3-adrenergic receptor genotype. There was no significant association between the receptor genotype and the level of the serum cholesterol, HDL-cholesterol, triglyceride, glucose or insulin, nor was this polymorphism associated with the behavioural or psychopathological characteristics of the morbidly obese subjects. Response to a 16 w treatment program including a very-low calorie diet (VLCD) regimen, dietary and exercise counseling, as well as behavioural modifications, did not differ according to the genotype. Our data do not support a significant role for the codon 64 polymorphism of the beta 3-adrenergic receptor as a genetic marker of morbid obesity. Although there was an association between the Arg64 allele and an earlier onset of obesity in individuals subsequently developing morbid obesity, this allele was not associated with the actual BMI gained or response to weight-loss therapy on a hypocaloric diet.

Gaucher disease: molecular heterogeneity and phenotype-genotype correlations.

PubMed

Theophilus, B; Latham, T; Grabowski, G A; Smith, F I

1989-08-01

Gaucher disease (GD) is the most prevalent lysosomal storage disease. This autosomal recessive trait results from the defective activity of acid beta-glucosidase (beta-Glc). Four different exonic point mutations have been identified as causal alleles for GD. To facilitate screening for these alleles, assays were developed using allele-specific oligonucleotide hybridization to amplified genomic DNA sequences. Specifically, intron bases flanking exons 5, 9, and 10 were determined, and conditions for PCR amplification of these exons were obtained. Two different procedures were developed to distinguish signals obtained from the structural beta-Glc gene exons and those from the pseudogene. These procedures were used to determine the distribution of all known GD alleles in a population of 44 affected patients of varying phenotypes and ethnicity. The high frequency of one of the exon 9 mutations in Ashkenazi Jewish GD type 1 patients was confirmed, and, in addition, this mutation was present in ethnically diverse non-Jewish type 1 GD patients. Homozygotes (N = 5) for this allele were midly affected older individuals, and this mutant allele was not found in any patient with neuronopathic disease. The exon 10 mutation was confirmed as the predominant allele in types 2 and 3 GD. However, several type 1 GD patients, including one of Ashkenazi-Jewish heritage, also were heterozygous for this allele. The presence of this allele in type 1 patients did not correlate with the severity of clinical symptoms. The second exon 9 mutation and the exon 5 mutation were rare, since they occurred only heterozygously either in one type 2 GD patient or in two related Ashkenazi-Jewish GD patients, respectively. Although most GD patients (38 of 44) had at least one of the known mutant alleles, 57% were heterozygotes for only one of these mutations. Fourteen percent of patients were negative for all mutations. A total of 73% of GD patients had at least one unknown allele. The varying clinical phenotypes and ethnic origins of these incompletely characterized patients suggest that multiple other GD alleles exist.

HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity

PubMed Central

Salvarani, C.; Boiardi, L.; Mantovani, V.; Ranzi, A.; Cantini, F.; Olivieri, I.; Bragliani, M.; Collina, E.; Macchioni, P.

1999-01-01

OBJECTIVE—To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.
METHODS—A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation.
RESULTS—No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7).
CONCLUSION—These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.

 PMID:10225816

A General Model of Negative Frequency Dependent Selection Explains Global Patterns of Human ABO Polymorphism

PubMed Central

Villanea, Fernando A.; Safi, Kristin N.; Busch, Jeremiah W.

2015-01-01

The ABO locus in humans is characterized by elevated heterozygosity and very similar allele frequencies among populations scattered across the globe. Using knowledge of ABO protein function, we generated a simple model of asymmetric negative frequency dependent selection and genetic drift to explain the maintenance of ABO polymorphism and its loss in human populations. In our models, regardless of the strength of selection, models with large effective population sizes result in ABO allele frequencies that closely match those observed in most continental populations. Populations must be moderately small to fall out of equilibrium and lose either the A or B allele (Ne ≤ 50) and much smaller (N e ≤ 25) for the complete loss of diversity, which nearly always involved the fixation of the O allele. A pattern of low heterozygosity at the ABO locus where loss of polymorphism occurs in our model is consistent with small populations, such as Native American populations. This study provides a general evolutionary model to explain the observed global patterns of polymorphism at the ABO locus and the pattern of allele loss in small populations. Moreover, these results inform the range of population sizes associated with the recent human colonization of the Americas. PMID:25946124

Culture–gene coevolution of individualism–collectivism and the serotonin transporter gene

PubMed Central

Chiao, Joan Y.; Blizinsky, Katherine D.

2010-01-01

Culture–gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism–collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture–gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism–collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture–gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism–collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture–gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed. PMID:19864286

Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate

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

Feng, Hongshu; Lee, A.; Gasser, D.L.

1994-11-01

The inheritance of alleles of the transforming growth factor alpha (TGFA) locus has been studied in families affected with cleft lip with or without cleft palate (CL/P), by using the transmission/disequilibrium test described by Spielman and colleagues. Only heterozygous parents with an affected child can be included in this test, but within such families a significantly greater frequency of C2 alleles were transmitted to affected children than would be expected by chance. There was no evidence that the total number of C2 alleles transmitted to affected and unaffected children differed significantly from random segregation. These data provide evidence from withinmore » families that a gene for susceptibility to CL/P is in significant linkage disequilibrium with the C2 allele of the TGFA locus. 30 refs., 1 fig., 2 tabs.« less

ACTN3 R577X genotype and performance of elite middle-long distance swimmers in China

PubMed Central

Li, YC; Wang, LQ; Yi, LY; Liu, JH; Lu, YF; Wang, M

2016-01-01

The ACTN3 gene is one of the genes that have a potential influence on physical performance. Studies have shown that the 577R genotype of ACTN3 is more prevalent in sprint athletes, while the 577X genotype is more prevalent in endurance athletes. In swimming, both power and endurance related phenotypes are equally needed for swimmers to excel at the elite level. Therefore, the ACTN3 R577X polymorphism may become a genetic marker for swimmers. The study aimed to examine the association of the ACTN3 R577X genotype with the performance of elite middle-long distance (MLD) swimmers. The distributions of the ACTN3 R577X (rs1815739) genotype and allele were examined in a general population (206) and a group of elite MLD swimmers (160) in China by using PCR-RFLP and TOF. Compared with the general population, the elite MLD swimmers, especially the females, had a higher frequency of the RR genotype. The swimmers had a higher frequency of the R allele than the general population. However, the difference was not statistically significant. After being stratified by performance, the difference of the R allele frequency between the international master athletes and the general population was statistically significant. The elite MLD swimmers had a higher frequency of the RR genotype than the RX+XX genotype compared with the general population. The ACTN3 R577X polymorphism was associated with the performance of elite MLD swimmers in China. The SNP R577X could be used as a biomarker for selecting elite MLD swimmers in China. PMID:28416896

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

PubMed Central

Zhang, Y.; Ling, Z.Y.; Deng, S.B.; Du, H.A.; Yin, Y.H.; Yuan, J.; She, Q.; Chen, Y.Q.

2014-01-01

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD. PMID:25118627

The insulin-sensitivity sulphonylurea receptor variant is associated with thyrotoxic paralysis.

PubMed

Rolim, Ana Luiza R; Lindsey, Susan C; Kunii, Ilda S; Crispim, Felipe; Moisés, Regina Célia M S; Maciel, Rui M B; Dias-da-Silva, Magnus R

2014-10-01

Thyrotoxicosis is the most common cause of the acquired flaccid muscle paralysis in adults called thyrotoxic periodic paralysis (TPP) and is characterised by transient hypokalaemia and hypophosphataemia under high thyroid hormone levels that is frequently precipitated by carbohydrate load. The sulphonylurea receptor 1 (SUR1 (ABCC8)) is an essential regulatory subunit of the β-cell ATP-sensitive K(+) channel that controls insulin secretion after feeding. Additionally, the SUR1 Ala1369Ser variant appears to be associated with insulin sensitivity. We examined the ABCC8 gene at the single nucleotide level using PCR-restriction fragment length polymorphism (RFLP) analysis to determine its allelic variant frequency and calculated the frequency of the Ala1369Ser C-allele variant in a cohort of 36 Brazilian TPP patients in comparison with 32 controls presenting with thyrotoxicosis without paralysis (TWP). We verified that the frequency of the alanine 1369 C-allele was significantly higher in TPP patients than in TWP patients (61.1 vs 34.4%, odds ratio (OR)=3.42, P=0.039) and was significantly more common than the minor allele frequency observed in the general population from the 1000 Genomes database (61.1 vs 29.0%, OR=4.87, P<0.005). Additionally, the C-allele frequency was similar between TWP patients and the general population (34.4 vs 29%, OR=1.42, P=0.325). We have demonstrated that SUR1 alanine 1369 variant is associated with allelic susceptibility to TPP. We suggest that the hyperinsulinaemia that is observed in TPP may be linked to the ATP-sensitive K(+)/SUR1 alanine variant and, therefore, contribute to the major feedforward precipitating factors in the pathophysiology of TPP. © 2014 Society for Endocrinology.

Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA).

PubMed

Abdollahi, Elham; Tavasolian, Fataneh; Ghasemi, Nasrin; Mirghanizadeh, Seyed Ali; Azizi, Mohammdareza; Ghoryani, Mohsen; Samadi, Morteza

2015-01-01

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive spontaneous abortions before the 20th week of gestation. The purpose of the present study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin (IL)-23 receptor gene (IL-23R; rs11209026, 1142 G wild type → A reduced function, Arg381Gln, R381Q) and RSA. For the study, 200 RSA patients (confirmed using established diagnostic criteria) and 200 normal individuals in fertility and infertility centers in the cities of Yazd and Isfahan were recruited during a period from 2012-2013. Using PCR-RFLP, the R381Q variant was screened for in the IL-23R gene of the patients and controls. The results indicated there were significant differences in the frequency of this genetic variant in the patients versus the healthy controls, i.e. 2% and 7.5%, respectively (p value = 0.01; odds ratio = 0.25; CI = 95%). No significant difference was found for the G allelic frequency in patients with RSA and in the control group (p = 0.60). The A allelic frequency was significantly different between the two groups (p = 0.01). Based on these findings, it is concluded that the frequency of single nucleotide polymorphism in the IL-23 receptor (R381Q) in patients with recurrent spontaneous abortion (RSA) is less than that found in normal control women.

Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand.

PubMed

Aberdein, D; Munday, J S; Dittmer, K E; Heathcott, R W; Lyons, L A

2017-11-01

AIMS To determine the frequency of the FAS-ligand gene (FASLG) variant associated with feline autoimmune lymphoproliferative syndrome (FALPS) and the proportion of carriers of the variant in three British shorthair (BSH) breeding catteries in New Zealand. METHODS Buccal swabs were collected from all cats in two BSH breeding catteries from the South Island and one from the North Island of New Zealand. DNA was extracted and was tested for the presence of the FASLG variant using PCR. Cats with the FASLG variant were identified and the frequency of the FASLG variant allele calculated. Pedigree analysis was performed and inbreeding coefficients were calculated for cats with the FASLG variant. RESULTS Of 32 BSH cats successfully tested for the presence of the FASLG variant, one kitten (3%) was homozygous (FALPS-affected), and seven (22%) cats were heterozygous (carriers) for the FASLG variant allele, and 24 (75%) cats were homozygous for the wild type allele. The overall frequency of the FASLG variant allele in these 32 cats was 0.14. Cats carrying the FASLG variant were from all three breeding catteries sampled, including two catteries that had not previously reported cases of FALPS. Pedigree analysis revealed common ancestry of FALPS-affected and carrier cats within six generations, as well as frequent inbreeding, with inbreeding coefficients >0.12 for five cats with the FASLG variant. CONCLUSIONS AND CLINICAL RELEVANCE There was a high frequency of the FASLG variant allele (0.14) in this small sample of BSH cats, with 22% of healthy cats identified as carriers of the FASLG variant. For an inherited disease, lethal at a young age, in a small population in which inbreeding is common, these results are significant. To prevent future cases of disease and stop further spread of the FASLG variant allele within the BSH population in New Zealand, it is recommended that all BSH and BSH-cross cats be tested for the presence of the FASLG variant before mating. Cats identified as carriers of the variant allele should be desexed and not used for breeding. Results support the need for further investigations of the true frequency of the FASLG variant allele and occurrence of FALPS in the wider population of BSH cats in New Zealand.

Population structure of the giant garter snake, Thamnophis gigas

USGS Publications Warehouse

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

2006-01-01

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

An entropy-based statistic for genomewide association studies.

PubMed

Zhao, Jinying; Boerwinkle, Eric; Xiong, Momiao

2005-07-01

Efficient genotyping methods and the availability of a large collection of single-nucleotide polymorphisms provide valuable tools for genetic studies of human disease. The standard chi2 statistic for case-control studies, which uses a linear function of allele frequencies, has limited power when the number of marker loci is large. We introduce a novel test statistic for genetic association studies that uses Shannon entropy and a nonlinear function of allele frequencies to amplify the differences in allele and haplotype frequencies to maintain statistical power with large numbers of marker loci. We investigate the relationship between the entropy-based test statistic and the standard chi2 statistic and show that, in most cases, the power of the entropy-based statistic is greater than that of the standard chi2 statistic. The distribution of the entropy-based statistic and the type I error rates are validated using simulation studies. Finally, we apply the new entropy-based test statistic to two real data sets, one for the COMT gene and schizophrenia and one for the MMP-2 gene and esophageal carcinoma, to evaluate the performance of the new method for genetic association studies. The results show that the entropy-based statistic obtained smaller P values than did the standard chi2 statistic.

Frequencies of genes for coat colour and horns in Nordic cattle breeds

PubMed Central

Kantanen, Juha; Olsaker, Ingrid; Brusgaard, Klaus; Eythorsdottir, Emma; Holm, Lars-Erik; Lien, Sigbjørn; Danell, Birgitta; Adalsteinsson, Stefan

2000-01-01

Gene frequencies of coat colour and horn types were assessed in 22 Nordic cattle breeds in a project aimed at establishing genetic profiles of the breeds under study. The coat colour loci yielding information on genetic variation were: extension, agouti, spotting, brindle, dun dilution and colour sided. The polled locus was assessed for two alleles. A profound variation between breeds was observed in the frequencies of both colour and horn alleles, with the older breeds generally showing greater variation in observed colour, horn types and segregating alleles than the modern breeds. The correspondence between the present genetic distance matrix and previous molecular marker distance matrices was low (r = 0.08 – 0.12). The branching pattern of a neighbour-joining tree disagreed to some extent with the molecular data structure. The current data indicates that 70% of the total genetic variation could be explained by differences between the breeds, suggesting a much greater breed differentiation than typically found at protein and microsatellite loci. The marked differentiation of the cattle breeds and observed disagreements with the results from the previous molecular data in the topology of the phylogenetic trees are most likely a result of selection on phenotypic characters analysed in this study. PMID:14736370

Spatial variation of insecticide resistance in the dengue vector Aedes aegypti presents unique vector control challenges.

PubMed

Deming, Regan; Manrique-Saide, Pablo; Medina Barreiro, Anuar; Cardeña, Edgar Ulises Koyoc; Che-Mendoza, Azael; Jones, Bryant; Liebman, Kelly; Vizcaino, Lucrecia; Vazquez-Prokopec, Gonzalo; Lenhart, Audrey

2016-02-04

Dengue is a major public health problem in Mexico, where the use of chemical insecticides to control the principal dengue vector, Aedes aegypti, is widespread. Resistance to insecticides has been reported in multiple sites, and the frequency of kdr mutations associated with pyrethroid resistance has increased rapidly in recent years. In the present study, we characterized patterns of insecticide resistance in Ae. aegypti populations in five small towns surrounding the city of Merida, Mexico. A cross-sectional, entomological survey was performed between June and August 2013 in 250 houses in each of the five towns. Indoor resting adult mosquitoes were collected in all houses and four ovitraps were placed in each study block. CDC bottle bioassays were conducted using F0-F2 individuals reared from the ovitraps and kdr allele (Ile1016 and Cys1534) frequencies were determined. High, but varying, levels of resistance to chorpyrifos-ethyl was detected in all study towns, complete susceptibility to bendiocarb in all except one town, and variations in resistance to deltamethrin between towns, ranging from 63-88% mortality. Significant associations were detected between deltamethrin resistance and the presence of both kdr alleles. Phenotypic resistance was highly predictive of the presence of both alleles, however, not all mosquitoes containing a mutant allele were phenotypically resistant. An analysis of genotypic differentiation (exact G test) between the five towns based on the adult female Ae. aegypti collected from inside houses showed highly significant differences (p < 0.0001) between genotypes for both loci. When this was further analyzed to look for fine scale differences at the block level within towns, genotypic differentiation was significant for both loci in San Lorenzo (Ile1016, p = 0.018 and Cys1534, p = 0.007) and for Ile1016 in Acanceh (p = 0.013) and Conkal (p = 0.031). The results from this study suggest that 3 years after switching chemical groups, deltamethrin resistance and a high frequency of kdr alleles persisted in Ae. aegypti populations. The spatial variation that was detected in both resistance phenotypes and genotypes has practical implications, both for vector control operations as well as insecticide resistance management strategies.

PEPA-1* genotype affects return rate for hatchery steelhead

USGS Publications Warehouse

Reisenbichler, R.R.; Hayes, M.C.; Rubin, S.P.; Wetzel, L.A.; Baker, B.M.

2006-01-01

Allozymes continue to be useful as genetic markers in a variety of studies; however, their utility often hinges on the selective neutrality of the allelic variation. Our study tested for neutrality between the two most common alleles (*100 and *110) at the cytosol nonspecific dipeptidase locus (PEPA-1*) in steelhead Oncorhynchus mykiss from Dworshak National Fish Hatchery in Idaho. We tested for differential growth and survival among fish with the * 100/100, *100/ 110, and *110/110 genotypes rearing in a hatchery or a natural stream. We repeated the study for two year-classes, using heterozygous (*100/110) adults to make the experimental crosses. This design avoided differences in family contribution among genotypes because each cross produced all three genotypes. We divided the progeny from each family into two groups. One group was reared in a hatchery for 1 year and then released for migration to the sea and subsequent return to the hatchery as adults. The other group was released into a natural stream and monitored for 3 years. We found no significant differences in size or survival among PEPA-1* genotypes for either the naturally reared fish or the hatchery-reared fish immediately prior to release as smolts. For females, survival to returning adult also was similar among genotypes; however, hatchery-reared males with the *110/110 genotype returned at a higher rate than did males with the *100/ 100 genotype; heterozygous males were intermediate. These results indicate that selection occurs at the PEPA-1* locus or at one or more loci tightly linked to it. The finding of nearly equal frequencies for these two alleles in the source population suggests that selection differentials among genotypes reverse or vary from year to year; otherwise, steady directional selection would drive the *100 allele to low frequencies or extinction. Locus PEPA-1* seems inappropriate for genetic marks in studies of steelhead that span the full life cycle and probably should be avoided for any portion of the life cycle. Inferences about gene flow and population structure from studies that are substantially influenced by PEPA-1* allele frequencies might be misleading. ?? Copyright by the American Fisheries Society 2006.

Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms

PubMed Central

Ojeda-Granados, Claudia; Panduro, Arturo; Gonzalez-Aldaco, Karina; Sepulveda-Villegas, Maricruz; Rivera-Iñiguez, Ingrid

2017-01-01

Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern. PMID:29125573