Hardy-Weinberg Equilibrium Proportions Research Articles

HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies for a Hong Kong Chinese population of 1064 individuals

HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies have been calculated from 1064 southern Chinese unrelated donors in a Hong Kong Bone Marrow Donor Registry. This is the first paper to report the distribution of DQB1-DQA1 and DPB1-DPA1 alleles in Hong Kong Chinese. Due to the Hardy-Weinberg equilibrium proportions (HWEP) deviation in DPB1 loci, this information may be of limited use for phylogenetic, comparative studies but will be useful for the permissible matching in HLA-DPB1 for Chinese patients awaiting haematopoietic stem cell transplantation in the near future due to the new recommendation of NMDP matching guidelines. The allele and haplotype data are available in the Allele Frequencies Net Database under the population name ‘‘Hong Kong Chinese HKBMDR, DQ and DP’’ and the identifier (AFND3667).

The novel mutations in the MEF2C gene associate with growth of Nanjiang Yellow goats

The myocyte enhancer factor 2 (MEF2) factors act as lynchpins in cell differentiation and organogenesis through transcriptional circuits and thus potentiate development of vertebrate. Nevertheless, the association between mutations in Myocyte enhancer factor 2 (MEF2s) especially MEF2C (Myocyte enhancer factor 2C) and livestock growth remains largely unknown. Here, in Nanjiang Yellow goat population (female, n = 219), we identified 10 single nucleotide variations (SNVs) in MEF2C using direct Sanger sequencing PCR product from DNA and cDNA. Among which eight were located in exons while two (g.143180 T>G and g.143666 C>T) were in introns, and the only one mutation embedded in coding region (g. 143515 C>T) led to a Pro 148 Ser exchange. In this goat population, all these ten SNVs presented lower to moderate polymorphism (0.28 < PIC < 0.48), and complied with Hardy-Weinberg Equilibrium proportions (P > 0.05). Notably, four SNVs including g.76303 A>G, g.143180 T>G, g.176090 A>G, and g.176845 T>C significantly associated with goat growth (p < 0.07), and the striking body mass connecting to g.143180 T>G variation even exceeded those H3H4 animals by over ~20% from birth to 12-mon old (p < 0.05). Furthermore, g.143180 T>G variation exhibited no connection with exon α splicing of MEF2C, but in silicon analysis revealed that T to G mutation potentially increased DNA accessibility of g.143180 T>G per se and the following 14-bp region by 2 to 22 fold, which directly relates the binding of dlx5 (Distal-Less Homeobox 5). These results confirm the close relationship between MEF2C and animal development, and also provide an important option guiding study in elucidating the substantial mechanisms that MEF2C exerts in promoting mammal growth.

Urdu speaking population from South India: Six extended haplotypes in linkage disequilibrium in Urdu Speaking Population.

B:C:DRB1:DQB1 allele and haplotype frequencies were determined among Urdu speaking population from South India by Sanger and Next Generation Sequencing. Seventy bone marrow registry donors and 327 cord blood units from the Jeevan Stem Cell Foundation (part of Be The Cure Registry), Chennai, Tamilnadu were included in the study. No overall deviations from expected Hardy-Weinberg equilibrium proportions were observed at all the five loci studied. The most frequent HLA class I alleles observed in this population were A*11:01:01, B*40:06:01, and C*06:02:01, showing a frequency of 15.87%, 12.72%, and 13.22%, respectively. The most frequent class II alleles observed in this population were DRB1*07:01:01 (15.62%) and DQB1*06:01:01 (21.41%). The top ranked haplotype A*01:01:01~B*57:01:01~C*06:02:01~DRB1*07:01:01~DQB1*03:03:02 (2.77%) reported in the present study, was the highly frequent haplotype found in Telugu speaking population who lived in the same region.

Genetic diversity in Zimbabwean Sanga cattle breeds using microsatellite markers

Zimbabwe’s smallholder land-based livelihoods are dominated by the three local Sanga cattle breeds, namely Mashona, Tuli, and Nkone. A study was carried out to determine genetic diversity and differentiation among conservation populations of these breeds using 16 bovine-specific microsatellite markers. These markers included BM1818, BM1824, BM2113, CSRM60, CSSM66, ETH10, ETH225, ETH3, ILST006, INRA23, RM067, SPS115, TGLA122, TGLA126, TGLA227, and TGLA53. All marker loci contributed to breed differentiation based on the infinitesimal model (F ST ), with the most powerful markers being CSSM66 (25%), ETH225 (20.6%), and TGLA122 (13.8%) and the least powerful being RM067 (0.7%), BM1824 (1.0%), and ETH10 (1.1%). Three marker loci (BM1824, ETH225, and ETH3) revealed significant deviations from Hardy-Weinberg equilibrium (HWE) proportions. A total of 119 alleles were observed, ranging from 4 to 11 and averaging 7.4 alleles per locus. Thirty-four of these alleles were unique to specific breeds. Mean (Na) and effective (N e ) numbers of alleles were 5.167 ± 0.302 and 3.462 ± 0.163 alleles per locus, respectively, with no significant differences between breeds. Observed heterozygosity ( H O ) (0.73) was higher than expected heterozygosity ( H E ) (0.71), revealing that breeds were in HWE. Global F-statistics F IT , F ST , and F IS gave mean values of 0.059, 0.084 and -0.028, respectively. Overall breed genetic differentiation was moderate (F ST = 8.4%) and significant ( P < 0.001). Multivariate analyses separated the three breeds completely, and revealed that most of the genetic variation was within breed (92%). The analyses revealed that a significant amount of variation is maintained in these breeds and that they are distinct genetic entities that may be considered for utilization or conservation. Keywords: Breed relationships, cattle conservation, genetic variation, molecular markers, Zimbabwe

Introducing a new manuscript format: Enabling access to immunogenomic population data with short population reports

The capacity to replicate the findings of a study is key to the advancement of research, and access to the data on which a study is predicated is required for true replication. Population genetic studies have long been a focus of the immunogenetic research community, but access to the primary genotype data underlying these studies has historically been limited. With the notable exception of the International HLA and Immunogenetics Workshops, it is primarily allele and haplotype frequency data that are made available upon publication for most immunogenetic population studies. However, such frequency data are the products of a prior analysis, and may reflect unreported methodological biases. Access to the primary genotype data allows independent validation and true replication of the study, and knowledge of the ambiguities associated with those genotype data maximizes the utility of population data for replication and meta-analyses. With this issue of Human Immunology, we are introducing a new manuscript format. Structured descriptions of reference populations, populations of anthropological interest and control populations for disease studies, along with genetic data and minimal analyses, can now be submitted as Short Population Reports. Short Population Reports will be peer-reviewed, and will follow a standard format (described below), with the aim of fostering the availability and archiving of the genetic data underlying immunogenetic population studies. Human Immunology is partnering with the Allele Frequencies Net Database (AFND; http://www.allelefrequencies.net) to archive and make primary ambiguous genotype data, allele frequency data and haplotype frequency data for the HLA, KIR, cytokine and MIC genes publically accessible, along with demographic data for each population. Details of the AFND data-submission process can be found at http://www.allelefrequencies.net/submit. While public access to immunogenomic allele and haplotype frequency data has always been part of AFND’s mission, the availability of primary ambiguous genotype data is new. These data will be made available on AFND in one of three ways, as determined by the data submitter in accordance with their data-sharing permissions; the primary data will be (i) publically available for download, or (ii) maintained privately on AFND, and made available for analysis by anyone using software that will be provided by AFND or (iii) maintained privately on AFND and will only be analyzed by AFND for data validation purposes. We encourage all authors to seek data-sharing permissions that allow maximal sharing of their primary data. Genotype, allele and haplotype data deposited in the AFND can be referenced in the corresponding Short Population Report with a unique identifier provided by the AFND. As described below, Short Population Reports should include only three analyses – evaluation of Hardy–Weinberg equilibrium proportions, for validation of the genotyping data, calculation of allele frequencies, and estimation (or calculation) or haplotype frequencies. Population studies that include additional analyses should be submitted as Research Articles. However, authors are encouraged to cite specific Short Population Reports in Research Articles that present more detailed analyses; this approach fosters more in-depth presentation and discussion of methods and analyses in population studies published as Research Articles. An example Short Population Report authored by Williams and Middleton is included in this issue.

Genetic characterisation of Tiruchy Black sheep of Tamil Nadu using microsatellite markers

A total of 203 alleles were observed in the sampled population for the 25 marker loci under investigation. The number of alleles observed at each locus varied from 4 (OarHH41) to 13 (OarHH35) with a mean of 8.12±0.45 across all loci. The effective number of alleles ranged from 1.59 (OarHH41) to 7.51 (OarHH35). The mean number of effective alleles was 4.48±0.27 across all loci. The polymorphic information content values ranged from 0.7029 (OarHH41) to 0.9164 (OarHH35) with a mean of 0.8441±0.012, which showed high level of genetic variability. The x2 test revealed that among the 25 microsatellites studied only ten were in Hardy-Weinberg Equilibrium proportions. The observed heterozygosity ranged from 0.2609 (OarHH41) to 0.9600 (OarCP49) with a mean of 0.6995 and the expected heterozygosity ranged from 0.3734 (OarHH41) to 0.8756 (OarHH35) with a mean of 0.7575. The within population inbreeding estimates or heterozygotes deficiency within population (FIS) was observed in 13 loci and the positive FIS value ranged from 0.0796 (CSSM31) to 0.5895 (OarJMP8). Only twelve loci revealed negative FIS values (FIS

P105 : ALLELE-, HAPLOTYPE- AND GENOTYPE-LEVEL ASSOCIATIONS WITH CROHN’S DISEASE IN JEWISH AND NON-JEWISH EUROPEAN AMERICANS

We studied the association between HLA-A,-B, -C, DRB1, DQA1, DQB1, DPA1 and DPB1 variation and Crohn’s Disease (CD), an inflammatory bowel disease, with a case-control study of Jewish and non-Jewish European American CD patients. 1352 Crohn’s Disease patients and healthy unrelated controls of European ancestry, determined with a panel of ∼300 AIMs, were HLA genotyped via reverse format SSO strip, Luminex rSSO and Roche 454 NGS genotyping. Patients and controls were matched for either self-reported Jewish or non-Jewish ethnicity. 474 Jewish CD patients and 89 Jewish controls, and 619 non-Jewish CD patients and 170 non-Jewish controls were genotyped. Typing ambiguity was reduced using the ImmPort Ambiguity Reduction Tool, and allele-names were analyzed at the two-field level. Adherence to expected Hardy–Weinberg equilibrium proportions (HWEP) at each locus was tested with PyPop, and the Bridging Immunogenomic Data-Analysis Workflow Gaps (BIGDAWG) R package was used to perform case-control analyses. Extended haplotypes were inferred from significantly associated two-locus haplotypes. HLA-B deviated from expected HWEP ( p = 0.0001) in non-Jewish CD patients, due to an excess of B ∗ 08:01 homozygotes (13 obs, 5.37 exp, p = 0.0010). Non-Jewish patients and controls differed significantly at the DRB1 locus ( p = 0.00013); DRB1 ∗ 01:03 is predisposing (OR 5.19 p = 0.0021), while ∗ 11:04 is protective (OR 0.3 p ∗ 07:01 ∼ DQA1 ∗ 02:01 ∼ DQB1 ∗ 02:02 is predisposing (OR 3.13 p = 0.0014) and A ∗ 11:01 ∼ DRB1 ∗ 11:04 is protective (OR 0.09 p = 0.0004). In the non-Jewish cohort, the inferred A ∗ 02:01 ∼ B ∗ 51:01 ∼ DRB1 ∗ 01:03 ∼ DQA1 ∗ 01: 01 ∼ DQB1 ∗ 05:01 ∼ DPA1 ∗ 01:03 ∼ DPB1 ∗ 04:01 and A ∗ 01:01 ∼ B ∗ 57:01 ∼ DRB1 ∗ 07:01 ∼ DPA1 ∗ 02:01 extended haplotypes predispose, and the C ∗ 07:01 ∼ DRB1 ∗ 11:04 ∼ DQA1 ∗ 05:01 ∼ DQB1 ∗ 03: 01 ∼ DPA1 ∗ 01:03 ∼ DPB1 ∗ 03:01 extended haplotype is protective. The associations with DRB1 ∗ 01:03 and DRB1 ∗ 07:01 are confirmatory, but the protective role of DRB1 ∗ 11:04 is novel; this allele differs from the neutral DRB1 ∗ 11:01 allele by a single amino-acid change (V86G). These associations extend to class I ∼ class II haplotypes. HWEP analysis suggests that the B ∗ 08:01+B ∗ 08:01 genotype is predisposing in non-Jewish patients, while there is no difference in B ∗ 08:01 frequency between patients and controls.

Isolation and characterization of novel microsatellite markers in the gray triggerfish, Balistes capriscus

Eight polymorphic microsatellites in the gray triggerfish, Balistes capriscus, are presented. For 24 genotyped individuals, the number of observed alleles per locus ranged from 10 to 21 (mean = 15), and observed heterozygosity varied between 0.708 and 1.000. Genotypic frequencies did not deviate significantly from Hardy–Weinberg equilibrium proportions, and there was no evidence of null alleles or linkage disequilibrium among loci. These microsatellite loci are additional markers for fisheries managers to utilize in population-level B. capriscus assessments.

Bulinus globosus (Planorbidae; Gastropoda) populations in the Lake Victoria basin and coastal Kenya show extreme nuclear genetic differentiation

Bulinus globosus, a key intermediate host for Schistosoma haematobium that causes urinary schistosomiasis, is a hermaphroditic freshwater Planorbid snail species that inhabits patchy and transient water bodies prone to large seasonal variations in water availability. Although capable of self-fertilizing, this species has been reported to be preferentially out crossing. In this study, we characterized the population genetic structure of 19 B. globosus populations sampled across the Lake Victoria basin and coastal Kenya using four polymorphic microsatellite loci. Population genetic structure was characterized and quantified using FST statistics and Bayesian clustering algorithms. The four loci used in this study contained sufficient statistical power to detect low levels of population genetic differentiation and were highly polymorphic with the number of alleles per locus across populations ranging from 16 to 22. Average observed and expected heterozygosities across loci in each population ranged from 0.13 to 0.69 and from 0.39 to 0.79, respectively. Twenty-five of the seventy-six possible population-locus comparisons significantly deviated from Hardy–Weinberg equilibrium proportions after Bonferroni corrections, mostly due to the deficiency of heterozygotes. Significant genetic differentiation was observed between populations and Bayesian inferences identified 15 genetic clusters. The excess homozygosity, significant inbreeding and population genetic differentiation observed in B. globosus populations are likely to be due to the habitat patchiness, mating system and the proneness to cyclic extinction and recolonization in transient habitats.

Discerning non-disjunction in Down syndrome patients by means of GluK1-(AGAT)(n) and D21S2055-(GATA)(n) microsatellites on chromosome 21.

INTRODUCTION:Down syndrome (DS), the leading genetic cause of mental retardation, stems from non-disjunction of chromosome 21.AIM:Our aim was to discern non-disjunction in DS patients by genotyping GluK1-(AGAT)n and D21S2055-(GATA)n microsatellites on chromosome 21 using a family-based study design.MATERIALS AND METHODS:We have used a PCR and automated DNA sequencing followed by appropriate statistical analysis of genotype data for the present studyRESULTS AND DISCUSSION:We show that a high power of discrimination and a low probability of matching indicate that both markers may be used to distinguish between two unrelated individuals. That the D21S2055-(GATA)n allele distribution is evenly balanced, is indicated by a high power of exclusion [PE=0.280]. The estimated values of observed heterozygosity and polymorphism information content reveal that relative to GluK1-(AGAT)n[Hobs=0.286], the D21S2055- (GATA)n[Hobs=0.791] marker, is more informative. Though allele frequencies for both polymorphisms do not conform to Hardy-Weinberg equilibrium proportions, we were able to discern the parental origin of non-disjunction and also garnered evidence for triallelic (1:1:1) inheritance. The estimated proportion of meiosis-I to meiosis-II errors is 2:1 in maternal and 4:1 in paternal cases for GluK1-(AGAT)n, whereas for D21S2055-(GATA)n, the ratio is 2:1 in both maternal and paternal cases. Results underscore a need to systematically evaluate additional chromosome 21-specific markers in the context of non-disjunction DS.

Isolation and Characterization of Microsatellite Loci in Pistacia weinmannifolia (Anacardiaceae)

Fourteen polymorphic microsatellite loci were isolated from the genomic DNA of Pistacia weinmannifolia, using the Fast Isolation by AFLP of Sequences Containing repeats (FIASCO) method, and screened on 12 individuals from each of two wild populations. The 14 polymorphic loci had an average of 4.1 alleles per locus varying from 1 to 9. The observed (Ho) and expected (He) heterozygosities across the two populations ranged from 0.000 to 0.933 and from 0.000 to 0.906, respectively. Tests for departure from Hardy-Weinberg equilibrium (HWE) and genotypic linkage disequilibrium (LD) were conducted for each of the two populations separately. It was found that no locus significantly deviated from HWE proportions and no significant LD was detected between loci (p < 0.001). In the test of cross-species utility, we successfully amplified nine (64.2%) of 14 loci in P. chinensis and four (28.6%) in P. mexicana. The relatively high level of polymorphism for these markers will facilitate further studies of gene flow, population structure and evolutionary history of P. weinmannifolia and its congeners.

Numerical algorithms for estimation and calculation of parameters in modeling pest population dynamics and evolution of resistance

Computational simulation models can provide a way of understanding and predicting insect population dynamics and evolution of resistance, but the usefulness of such models depends on generating or estimating the values of key parameters. In this paper, we describe four numerical algorithms generating or estimating key parameters for simulating four different processes within such models. First, we describe a novel method to generate an offspring genotype table for one- or two-locus genetic models for simulating evolution of resistance, and how this method can be extended to create offspring genotype tables for models with more than two loci. Second, we describe how we use a generalized inverse matrix to find a least-squares solution to an over-determined linear system for estimation of parameters in probit models of kill rates. This algorithm can also be used for the estimation of parameters of Freundlich adsorption isotherms. Third, we describe a simple algorithm to randomly select initial frequencies of genotypes either without any special constraints or with some pre-selected frequencies. Also we give a simple method to calculate the “stable” Hardy–Weinberg equilibrium proportions that would result from these initial frequencies. Fourth we describe how the problem of estimating the intrinsic rate of natural increase of a population can be converted to a root-finding problem and how the bisection algorithm can then be used to find the rate. We implemented all these algorithms using MATLAB and Python code; the key statements in both codes consist of only a few commands and are given in the appendices. The results of numerical experiments are also provided to demonstrate that our algorithms are valid and efficient.

Microsatellite markers for the Common ringtail possum (Pseudocheirus peregrinus) and their amplification in other Pseudocheirids

Eleven microsatellite markers were developed for the Common ringtail possum, an arboreal marsupial abundant in fragmented forests of south-eastern Australia. Loci were highly polymorphic (4-32 alleles per locus) and heterozygosity ranged from 0.66 to 1. Two loci deviated significantly from Hardy-Weinberg equilibrium proportions, possibly because of low-frequency null alleles. These markers will be informative for examining patterns of gene flow, relatedness and mating systems within fragmented populations of the Common ringtail possum and have potential for use in other Pseudocheirids.

Characterization of 12 polymorphic microsatellite markers for a facultatively eusocial sweat bee (Megalopta genalis)

We developed a library of twelve polymorphic di- and tri-nucleotide microsatellite markers for Megalopta genalis, a facultatively eusocial sweat bee. We tested each locus in a panel of 23 unrelated females and found 7-20 alleles per locus. Observed and expected heterozygosities ranged from 0.65 to 0.96 and from 0.69 to 0.95 respectively. None of the loci deviated from Hardy-Weinberg equilibrium proportions or was found to be in gametic disequilibrium.

Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis

Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP). Case control study. Buccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression. The frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-alpha (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86; confidence interval, 1.4-3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups. TNF-alpha-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-alpha is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases.

Characterisation of polymorphic microsatellite markers for skates (Elasmobranchii: Rajidae) from expressed sequence tags

Simple sequence repeat markers (SSRs, microsatellites) were characterised for skates (Elasmobranchii: Rajidae) from published expressed sequence tags (ESTs) of Leucoraja erinacea. These were tested in four European species (Raja clavata, Raja montagui, Dipturus batis, and Leucoraja naevus). Thirteen of the fourteen amplified loci were polymorphic in at least one species. Polymorphic loci possessed on average 4.5–5.9 alleles per species, and expected heterozygosity ranged from 0.05 to 0.88. Possible null alleles were detected at three loci, while one locus showed significant deviation from Hardy–Weinberg Equilibrium proportions. Three locus-pairs exhibited significant linkage disequilibrium in one or more species. This marker set will be valuable for population genetic analyses of the focal taxa, and may prove useful for studies of other skate species.

Association between the -174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women

In worldwide studies, interleukin-6 (IL-6) is implicated in age-related disturbances. The aim of the present report was to determine the possible association of IL-6 -174 C/G promoter polymorphism with the cytokine profile as well as with the presence of selected cardiovascular risk features. This was a cross-sectional study on Brazilian women aged 60 years or older. A sample of 193 subjects was investigated for impaired glucose regulation, diabetes, hypertension, and dyslipidemia. Genotyping was done by direct sequencing of PCR products. IL-6 and C-reactive protein were quantified by high-sensitivity assays. General linear regression models or the Student t-test were used to compare continuous variables among genotypes, followed by adjustments for confounding variables. The chi-square test was used to compare categorical variables. The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In a recessive model, mean waist-to-hip ratio, serum glycated hemoglobin and serum glucose were markedly lower in C homozygotes (P = 0.001, 0.028, and 0.047, respectively). In a dominant hypothesis, G homozygotes displayed a trend towards higher levels of circulating IL-6 (P = 0.092). Non-parametric analysis revealed that impaired fasting glucose and hypertension were findings approximately 2-fold more frequent among G homozygous subjects (P = 0.042 and 0.043, respectively). Taken together, our results show that the IL-6 -174 G-allele is implicated in a greater cardiovascular risk. To our knowledge, this is the first investigation of IL-6 promoter variants and age-related disturbances in the Brazilian elderly population.

Molecular Characterisation of Nilagiri Sheep (Ovis aries) of South India Based on Microsatellites

Genetic variation in Nilagiri sheep, the only apparel wool breed in South India was studied using 25 FAO recommended ovine-specific microsatellite markers. The number of observed alleles ranged from 3 to 8 with a mean of 5 across all loci. The size of alleles ranged from 72 to 228 bp. The frequency of alleles ranged from 0.0104 to 0.5781. In total, 125 alleles were observed at the 25 loci studied. The effective number of alleles ranged from 2.18 to 6.49. The mean number of effective alleles was 3.84 across all loci. All the 25 loci were found to be highly polymorphic. The PIC values ranged from 0.4587 to 0.8277 with a mean of 0.6485. Of 25 microsatellites studied, 17 were in Hardy-Weinberg Equilibrium proportions. The observed heterozygosity ranged from 0.4222 to 1.000 with a mean value of 0.7610 whereas the expected heterozygosity ranged from 0.5415 to 0.8459 with a mean value of 0.7213. Except six loci, the other loci revealed negative within-population inbreeding estimates (F IS ) indicating excess of heterozygotes in the population ofNilagiri sheep.

Single Nucleotide Polymorphisms of the Alcohol Dehydrogenase Genes among the 28 Caste and Tribal Populations of India

KEYWORDS ADH2 & ADH3; Indian castes and tribes; social hierarchy; lifestyles; alcoholism ABSTRACT We report single nucleotide polymorphisms (SNPs) at the four sites in ADH2 and ADH3 genes among the 28 populations from southern parts of Andhra Pradesh, India. A total of 1048 individuals belonging to 28 endogamous populations distributed in the contiguous areas of the 6 southernmost districts of Andhra Pradesh were enrolled for the present study. Genotyping involved PCR and sequencing. We sequenced exon 3 and 9 of ADH2 and exon 8 of ADH3, besides the ADH2 3'UTR- rs17033 (72 bases down stream of ADH2 Arg369Cys). The two sites of ADH2 (Arg47His and Arg369Cys) are found to be completely monomorphic showing only Arg47 and 369Arg (ADH2*1 allele), the remaining two sites were polymorphic. None of the 28 populations of this study deviated significantly from Hardy Weinberg Equilibrium proportions. The allele frequencies do not show any clear trend across socioeconomic groups. The degree of heterogeneity in the genotype frequencies among the hierarchical groups is significant for Ile349Val (df = 12; χ2 = 22.050) and not for the 3'UTR rs17033 (df = 6; χ2 = 9.765). The haplotype distribution among the hierarchical groups is found to be highly homogeneous and statistically nonsignificant (χ 2 = 0.248, df = 18). Linkage disequilibrium does not exist between the two-polymorhic loci. The results were interpreted in the light of cultural patterns of the Indian hierarchical society.

A family‐based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron‐2 (STin2) polymorphism and attention‐deficit‐hyperactivity disorder (ADHD)

Serotonin transporter (SLC6A4) polymorphisms are variously implicated in mediating susceptibility to attention-deficit-hyperactivity disorder (ADHD), a highly heritable and heterogeneous disorder with onset in childhood. Since there has been no survey in this regard from India, a sample of 56 ADHD cases and 174 healthy individuals from Kolkata were genotyped for the SLC6A4 promoter (5-HTTLPR) and intron-2 (STin2) polymorphisms. We report that the observed distribution of allele frequencies is consonant with that expected as per Hardy-Weinberg equilibrium proportions. Pair-wise combination of alleles comprising the 5-HTTLPR and STin2 polymorphic systems exhibit significant (chi(2) = 14.74, df = 1; P = 0.0001) linkage disequilibrium of low magnitude (D' = 0.269). The estimates of haplotype-based haplotype relative risk (HHRR) (chi(2) = 4.92, P = 0.027; RR = 1.47; 95% CI = 1.01-2.13) and transmission disequilibrium test (TDT) statistics (chi(2) = 7.00, P = 0.008; OR = 3.00; 95% CI = 1.53-5.90) using a family-based study design, indicate significant preferential transmission of the STin2.12 (A12) allele to ADHD cases. Maternal inheritance of the A12 allele is significant in terms of the HHRR (chi(2) = 6.53, P = 0.011; RR = 2.00; 95% CI = 1.08-3.72) and TDT (chi(2) = 8.07, P = 0.005; OR = 6.50; 95% CI = 1.76-23.98) suggesting a novel role for epigenetic mechanisms in the etiology of ADHD. Similar analyses yielded no evidence of association between the 5-HTTLPR polymorphism and ADHD. Studies including additional polymorphic markers, ADHD subjects and other ethnic groups are warranted to further substantiate the present findings.