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Haplotype Frequencies (haplotype + frequency)
Terms modified by Haplotype Frequencies Selected AbstractsHaplotype Frequencies of Eight Y-Chromosome Short Tandem Repeats Loci in Four Amerindian Populations (State of Hidalgo, Mexico)JOURNAL OF FORENSIC SCIENCES, Issue 2 2007Carme Barrot Ph.D. POPULATION: Amerindian populations: Huastecos (n=97), Otomies de la Sierra (n=41), Otomies del Valle (n=40), and Tepehuas (n=13). [source] Peroxisome proliferator-activated receptor-, co-activator-1, (PGC-1,) gene polymorphisms and their relationship to Type 2 diabetes in Asian IndiansDIABETIC MEDICINE, Issue 11 2005K. S. Vimaleswaran Abstract Aims The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor-, co-activator-1 alpha (PGC-1,) gene with Type 2 diabetes in Asian Indians. Methods The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction,restriction fragment length polymorphism (PCR,RFLP). Haplotype frequencies were estimated using an expectation,maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) (P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) (P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264,2.241, P = 0.0004). Age adjusted glycated haemoglobin (P = 0.003), serum cholesterol (P = 0.001) and low-density lipoprotein (LDL) cholesterol (P = 0.001) levels and systolic blood pressure (P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. Conclusions The A allele of Thr394Thr (G , A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population. [source] Geographical segregation in Dunlin Calidris alpina populations wintering along the East Atlantic migratory flyway , evidence from mitochondrial DNA analysisDIVERSITY AND DISTRIBUTIONS, Issue 5 2008Ricardo J. Lopes ABSTRACT Dunlin Calidris alpina is one of the most abundant shorebirds using coastal habitats in the East Atlantic migratory flyway, that links arctic breeding locations (Greenland to Siberia) with wintering grounds (West Europe to West Africa). Differential migration and winter segregation between populations have been indicated by morphometrics and ringing recoveries. Here, we analyse the potential of genetic markers (mitochondrial DNA , mtDNA) to validate and enhance such findings. We compared mtDNA haplotypes frequencies at different wintering sites (from north-west Europe to West Africa). All birds from West Africa had western (European) haplotypes, while the eastern (Siberian) haplotypes were only present in European winter samples, reaching higher frequencies further north in Europe. Compilation of published results from migrating birds also confirmed these differences, with the sole presence of European haplotypes in Iberia and West Africa and increasingly higher frequencies of Siberian haplotypes from south-west to north-west Europe. Comparison with published haplotype frequencies of breeding populations shows that birds from Greenland, Iceland, and North Europe were predominant in wintering grounds in West Africa, while populations wintering in West Europe originated from more eastern breeding grounds (e.g. North Russia). These results show that genetic markers can be used to enhance the integrative monitoring of wintering and breeding populations, by providing biogeographical evidence that validate the winter segregation of breeding populations. [source] The association between endothelin-1 gene polymorphisms and susceptibility to vitiligo in a Korean populationEXPERIMENTAL DERMATOLOGY, Issue 7 2007Hyun-Jin Kim Abstract:, Background:, Vitiligo is a skin disorder affected by genetic, environmental, local and endocrine factors. Endothelin-1, which is expressed by keratinocytes, has paracrine effects on melanocytes, influencing their homeostasis, proliferation and pigmentation. It is thought to play a role in the skin response to 311-nm, narrow-band ultraviolet irradiation. Objective:, To investigate the association of endothelin-1 gene (EDN1) polymorphisms with vitiligo in a Korean population. Methods:, To evaluate the expression of endothelin-1 in cultured human keratinocytes after irradiation with narrow-band ultraviolet B (NBUVB), we performed RT-PCR and ELISA. In addition, we genotyped 312 vitiligo patients and 313 matched-healthy controls, and compared the genotype, allele and haplotype frequencies of EDN1 polymorphisms (intron 4 G/A, rs2071942 and exon 5 G/T, rs5370) between the two groups, using PCR-restriction fragment length polymorphism. The effects of sex, onset age, the presence of autoimmune diseases, family history and clinical type were analysed statistically. Results:, NBUVB induced the expression of endothelin-1 in cultured human keratinocytes. The genotype distributions and allele frequencies of EDN1 polymorphisms did not differ significantly between vitiligo patients and healthy controls. Moreover, the results were not related to sex, onset age, the presence of autoimmune diseases or family history. Interestingly, the haplotype frequencies of EDN1 polymorphisms differed significantly between vitiligo patients and healthy controls. When analysed according to clinical type, the haplotype frequencies in the focal and segmental clinical types differed significantly from healthy controls. Conclusion:, This study suggests that EDN1 is related to the development of vitiligo in the Korean population. [source] Determination of ABCB1 polymorphisms and haplotypes frequencies in a French populationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2007Elise Jeannesson Abstract The ATP-binding cassette (ABC) transporter ABCB1, or P-glycoprotein, is a transmembrane efflux pump well known for its implication in drug transport and chemoresistance. ABCB1 substrates include either drugs, such as antiretrovirals and immunomodulators, or physiological molecules like phospholipids. Pharmacogenetic analysis of ABCB1 polymorphisms, in addition to other xenobiotic metabolizing enzymes, might help to personalize and optimize drug therapy. Indeed, some polymorphisms of ABCB1 have been implicated in susceptibility to diseases, changes in drug pharmacokinetics, and in variation of the biological response to drug treatment. In addition, variant and haplotype distributions differ depending on ethnicity. Thus, some ethnies may be at higher risk for adverse events, inefficacy of treatment or prevalence of pathologies. This study aimed to determine frequencies of ABCB1 polymorphisms and haplotypes in a sample of French healthy individuals. DNA was isolated from blood-EDTA. Polymerase chain reaction-restriction fragment length polymorphism and TaqMan single nucleotide polymorphism genotyping assays were used to genotype 227 individuals for T-129C, G-1A, A61G, G1199A, C1236T, T-76A, G2677T/A and C3435T polymorphisms. The observed frequencies of the variant allele for these eight polymorphisms are 0.04, 0.08, 0.09, 0.06, 0.42, 0.46, 0.45 and 0.46 respectively. These polymorphisms are in linkage disequilibrium and haplotype frequencies were determined, the most frequent haplotype being the one with variants at position 1236, 2677 and 3435 and wild-type alleles at the other positions. Finally, the frequencies of these eight ABCB1 polymorphisms in our French individuals supposed to be healthy population are quite similar to those described in other Caucasian populations except for the C3435T polymorphism. [source] Quantifying bias due to allele misclassification in case-control studies of haplotypesGENETIC EPIDEMIOLOGY, Issue 7 2006Usha S. Govindarajulu Abstract Objectives Genotyping errors can induce biases in frequency estimates for haplotypes of single nucleotide polymorphisms (SNPs). Here, we considered the impact of SNP allele misclassification on haplotype odds ratio estimates from case-control studies of unrelated individuals. Methods We calculated bias analytically, using the haplotype counts expected in cases and controls under genotype misclassification. We evaluated the bias due to allele misclassification across a range of haplotype distributions using empirical haplotype frequencies within blocks of limited haplotype diversity. We also considered simple two- and three-locus haplotype distributions to understand the impact of haplotype frequency and number of SNPs on misclassification bias. Results We found that for common haplotypes (>5% frequency), realistic genotyping error rates (0.1,1% chance of miscalling an allele), and moderate relative risks (2,4), the bias was always towards the null and increases in magnitude with increasing error rate, increasing odds ratio. For common haplotypes, bias generally increased with increasing haplotype frequency, while for rare haplotypes, bias generally increased with decreasing frequency. When the chance of miscalling an allele is 0.5%, the median bias in haplotype-specific odds ratios for common haplotypes was generally small (<4% on the log odds ratio scale), but the bias for some individual haplotypes was larger (10,20%). Bias towards the null leads to a loss in power; the relative efficiency using a test statistic based upon misclassified haplotype data compared to a test based on the unobserved true haplotypes ranged from roughly 60% to 80%, and worsened with increasing haplotype frequency. Conclusions The cumulative effect of small allele-calling errors across multiple loci can induce noticeable bias and reduce power in realistic scenarios. This has implications for the design of candidate gene association studies that utilize multi-marker haplotypes. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Simple estimates of haplotype relative risks in case-control dataGENETIC EPIDEMIOLOGY, Issue 6 2006Benjamin French Abstract Methods of varying complexity have been proposed to efficiently estimate haplotype relative risks in case-control data. Our goal was to compare methods that estimate associations between disease conditions and common haplotypes in large case-control studies such that haplotype imputation is done once as a simple data-processing step. We performed a simulation study based on haplotype frequencies for two renin-angiotensin system genes. The iterative and noniterative methods we compared involved fitting a weighted logistic regression, but differed in how the probability weights were specified. We also quantified the amount of ambiguity in the simulated genes. For one gene, there was essentially no uncertainty in the imputed diplotypes and every method performed well. For the other, ,60% of individuals had an unambiguous diplotype, and ,90% had a highest posterior probability greater than 0.75. For this gene, all methods performed well under no genetic effects, moderate effects, and strong effects tagged by a single nucleotide polymorphism (SNP). Noniterative methods produced biased estimates under strong effects not tagged by an SNP. For the most likely diplotype, median bias of the log-relative risks ranged between ,0.49 and 0.22 over all haplotypes. For all possible diplotypes, median bias ranged between ,0.73 and 0.08. Results were similar under interaction with a binary covariate. Noniterative weighted logistic regression provides valid tests for genetic associations and reliable estimates of modest effects of common haplotypes, and can be implemented in standard software. The potential for phase ambiguity does not necessarily imply uncertainty in imputed diplotypes, especially in large studies of common haplotypes. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Haplotype analysis in the presence of informatively missing genotype dataGENETIC EPIDEMIOLOGY, Issue 4 2006Nianjun Liu Abstract It is common to have missing genotypes in practical genetic studies, but the exact underlying missing data mechanism is generally unknown to the investigators. Although some statistical methods can handle missing data, they usually assume that genotypes are missing at random, that is, at a given marker, different genotypes and different alleles are missing with the same probability. These include those methods on haplotype frequency estimation and haplotype association analysis. However, it is likely that this simple assumption does not hold in practice, yet few studies to date have examined the magnitude of the effects when this simplifying assumption is violated. In this study, we demonstrate that the violation of this assumption may lead to serious bias in haplotype frequency estimates, and haplotype association analysis based on this assumption can induce both false-positive and false-negative evidence of association. To address this limitation in the current methods, we propose a general missing data model to characterize missing data patterns across a set of two or more markers simultaneously. We prove that haplotype frequencies and missing data probabilities are identifiable if and only if there is linkage disequilibrium between these markers under our general missing data model. Simulation studies on the analysis of haplotypes consisting of two single nucleotide polymorphisms illustrate that our proposed model can reduce the bias both for haplotype frequency estimates and association analysis due to incorrect assumption on the missing data mechanism. Finally, we illustrate the utilities of our method through its application to a real data set. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Haplotype association analysis for late onset diseases using nuclear family dataGENETIC EPIDEMIOLOGY, Issue 3 2006Chun Li Abstract In haplotype-based association studies for late onset diseases, one attractive design is to use available unaffected spouses as controls (Valle et al. [1998] Diab. Care 21:949,958). Given cases and spouses only, the standard expectation-maximization (EM) algorithm (Dempster et al. [1977] J. R. Stat. Soc. B 39:1,38) for case-control data can be used to estimate haplotype frequencies. But often we will have offspring for at least some of the spouse pairs, and offspring genotypes provide additional information about the haplotypes of the parents. Existing methods may either ignore the offspring information, or reconstruct haplotypes for the subjects using offspring information and discard data from those whose haplotypes cannot be reconstructed with high confidence. Neither of these approaches is efficient, and the latter approach may also be biased. For case-control data with some subjects forming spouse pairs and offspring genotypes available for some spouse pairs or individuals, we propose a unified, likelihood-based method of haplotype inference. The method makes use of available offspring genotype information to apportion ambiguous haplotypes for the subjects. For subjects without offspring genotype information, haplotypes are apportioned as in the standard EM algorithm for case-control data. Our method enables efficient haplotype frequency estimation using an EM algorithm and supports probabilistic haplotype reconstruction with the probability calculated based on the whole sample. We describe likelihood ratio and permutation tests to test for disease-haplotype association, and describe three test statistics that are potentially useful for detecting such an association. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Maximum-likelihood estimation of haplotype frequencies in nuclear familiesGENETIC EPIDEMIOLOGY, Issue 1 2004Tim Becker Abstract The importance of haplotype analysis in the context of association fine mapping of disease genes has grown steadily over the last years. Since experimental methods to determine haplotypes on a large scale are not available, phase has to be inferred statistically. For individual genotype data, several reconstruction techniques and many implementations of the expectation-maximization (EM) algorithm for haplotype frequency estimation exist. Recent research work has shown that incorporating available genotype information of related individuals largely increases the precision of haplotype frequency estimates. We, therefore, implemented a highly flexible program written in C, called FAMHAP, which calculates maximum likelihood estimates (MLEs) of haplotype frequencies from general nuclear families with an arbitrary number of children via the EM-algorithm for up to 20 SNPs. For more loci, we have implemented a locus-iterative mode of the EM-algorithm, which gives reliable approximations of the MLEs for up to 63 SNP loci, or less when multi-allelic markers are incorporated into the analysis. Missing genotypes can be handled as well. The program is able to distinguish cases (haplotypes transmitted to the first affected child of a family) from pseudo-controls (non-transmitted haplotypes with respect to the child). We tested the performance of FAMHAP and the accuracy of the obtained haplotype frequencies on a variety of simulated data sets. The implementation proved to work well when many markers were considered and no significant differences between the estimates obtained with the usual EM-algorithm and those obtained in its locus-iterative mode were observed. We conclude from the simulations that the accuracy of haplotype frequency estimation and reconstruction in nuclear families is very reliable in general and robust against missing genotypes. © 2004 Wiley-Liss, Inc. [source] Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese populationINFLAMMATORY BOWEL DISEASES, Issue 12 2005T Takagawa MD Abstract Background: Interleukin-18 (IL-18) is a pleiotropic cytokine that induces the production of interferon (IFN)-, and also to regulate Th2 cytokines. Recently, association studies between IL-18 gene promoter polymorphisms and several Th1- or Th2-mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL-18 is involved in the pathogenesis. Methods: Using DNA direct sequencing, we investigated IL-18 gene promoter polymorphisms at ,607C/A and ,137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls. Results: In UC, the ,137C allele frequency was significantly higher in the proctitis-type patients than in controls (Pc = 0.0068). The ,137 genotype frequency was also significantly different in the proctitis-type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (,607A, ,137C), which had a lower promoter activity and IFN-, mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis-type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences. Conclusions: IL-18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC. [source] Analysis of DEFB1 regulatory SNPs in cystic fibrosis patients from North-Eastern ItalyINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2010L. Segat Summary Cystic fibrosis (CF) transmembrane regulator protein (CFTR) gene is undoubtedly the main genetic factor involved in the modulation of CF phenotype. However, other factors such as human defensins and the genes encoding for these antimicrobial peptides have been hypothesized as possible modifiers influencing airways infection in CF patients, but their role in the pathogenesis of lung disease is still debated. Since DEFB1 gene encoding for human beta-defensin 1 displays features such as antimicrobial or chemotactic activity playing a role in inflammation, it has been considered as a possible candidate CF modifier gene. We analysed three single nucleotide polymorphisms (SNPs) in the 5,-untranslated region of the DEFB1 gene (namely g-52G>A, g-44C>G and g-20G>A) in a group of 62 CF patients from North Eastern Italy, and in 130 healthy controls, with the aim of verifying the possible association of these functional SNPs with the pulmonary phenotype of CF patients. DEFB1 SNPs have been genotyped by using Taqman allele-specific fluorescent probes and a real-time PCR platform. No significant differences were found for allele, genotype and haplotype frequencies of DEFB1 g-52G>A, g-44C>G and g-20G>A SNPs in CF patients stratified for Pseudomonas aeruginosa infection, as well as in patients with a severe and mild clinical phenotype or in patients stratified for CFTR genotypes. DEFB1 allele, genotype and haplotype frequencies of CF patients globally considered were similar to those of healthy controls. Our findings are discordant with respect to another recent study performed on CF patients coming from Southern Italy, probably due to different ethnicity of the patients. [source] HLA allele and haplotype frequencies in the Albanian population and their relationship with the other European populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2009G. Sulcebe Summary Human leucocyte antigen (HLA) alleles are very interesting markers in identifying population relationships. Moreover, their frequency distribution data are important in the implementation of donor,recipient registry programs for transplantation purposes and also in determining the genetic predisposition for many diseases. For these reasons, we studied the HLA class I and II allele and haplotype frequencies in 160 healthy, unrelated Albanian individuals originating from all regions of the country. The HLA genotyping was performed through a 2-digit resolution SSOP method. The data were analysed with Arlequin and Phylip programs. No deviation was found from the Hardy,Weinberg equilibrium. A total of 17 A*, 30 B*, 12 Cw*, 13 DRB1* and 5 DQB1* alleles were identified. The six most frequent HLA-A-B-DRB1 haplotypes were A*02,B*18,DRB1*11 (5.60%), A*02,B*51,DRB1*16 (4.74%), A*01,B*08,DRB1*03 (3.48%), A*24,B*35,DRB1*11 (2.77%), A*02,B*51,DRB1*13 (2.21%), A*24,B*35,DRB1*14 (1.89%). Interestingly, 12 HLA-A-B-Cw-DRB1-DQB1 haplotypes occurred at a frequency >1%. When compared with the other populations, a close relationship was found with North Greek, Bulgarian, Macedonian, Romanian, Turkish, Cretan, Serbian, Croatian and Italian populations. A higher differentiation in allele frequency level was found with Western Europe populations. These data are the first report of HLA allele and haplotype distribution in an Albanian population inside this country. When compared with other populations, their distribution frequencies show close similarities with neighbouring populations of the entire Balkan area. [source] Analysis of high-resolution HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles and haplotypes in 718 Chinese marrow donors based on donor,recipient confirmatory typingsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2009A.-L. Hei Summary High-resolution human leucocyte antigen (HLA)-A, -B, -Cw, -DRB1, and -DQB1 alleles and haplotype frequencies were analysed from 718 Chinese healthy donors selected from the Chinese Marrow Donor Program registry based on HLA donor,recipient confirmatory typings. A total of 28 HLA-A, 61 HLA-B, 30 HLA-Cw, 40 HLA-DRB1 and 18 HLA-DQB1 alleles were identified, and HLA-A*1101, A*2402, A*0201, B*4001, Cw*0702, Cw*0102, Cw*0304, DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0303 and DQB1*0601 were found with frequencies higher than 10% in this study population. Multiple-locus haplotype analysis by the maximum-likelihood method revealed 45 A,B, 38 Cw,B, 47 B,DRB1, 29 DRB1,DQB1, 24 A,B,DRB1, 38 A,Cw,B, 23 A,Cw,B,DRB1, 33 Cw,B,DRB1,DQB1 and 22 A,Cw,B,DRB1,DQB1 haplotypes with frequencies >0.5%. The most common two-, three-, four- and five-locus haplotypes in this population were: A*0207,B*4601 (7.34%), Cw*0102,B*4601 (8.71%), B*1302,DRB1*0701 (6.19%), DRB1*0901,DQB1*0303 (14.27%), A*3001,B*1302,DRB1*0701 (5.36%), A*0207,Cw*0102,B*4601 (7.06%), A*3001,Cw*0602,B*1302,DRB1*0701 (5.36%), Cw*0602,B*1302,DRB1*0701,DQB1*0202 (6.12%) and A*3001,Cw*0602,B*1302,DRB1*0701,DQB1*0202 (5.29%). Presentation of the high-resolution alleles and haplotypes data at HLA-A, -B, -Cw, -DRB1 and -DQB1 loci will be useful for HLA matching in transplantation as well as for other medical and anthropological applications in the Chinese population. [source] Promoter polymorphism of IL-18 gene in pulmonary tuberculosis in South Indian populationINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2007M. Harishankar Summary Interleukin-18 (IL-18) plays a vital role in both innate and acquired immunity. We analysed polymorphisms at ,607(C/A) and ,137(G/A) in the promoter region of IL-18 gene by allele-specific polymerase chain reaction in normal healthy subjects (n = 173) and patients with pulmonary tuberculosis (n = 165). Allele, genotype and haplotype frequencies did not differ significantly between normal healthy subjects and patients. The results suggest that the IL-18 gene promoter polymorphisms are not associated with susceptibility or resistance to pulmonary tuberculosis in south Indian population of Dravidian descent. [source] Polymorphism of LMP2, TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: implications for the evolution of allelic and haplotypic diversityINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2000F. Rueda Faucz In the class II region of the major histocompatibility complex (MHC), four genes implicated in processing of MHC class I-presented antigens have been described. Two of these (TAP1 and TAP2) code for endoplasmic reticulum membrane transporter proteins and the other two (LMP2 and LMP7) for proteasome subunits. These genes are polymorphic, although much less so than classical MHC class I and II genes. There is controversy concerning the possible functional implications of this variation. Population genetics is one of the means of investigating the evolutionary and functional significance of genetic polymorphisms; however, few populations have been analysed with respect to TAP and LMP diversity. We present here the polymorphism of TAP1, TAP2, LMP2 and LMP7 genes in the Kaingang and Guarani Amerindian tribes, and in the Caucasoid population of the Brazilian State of Paraná. Allele frequencies found in the Caucasoids were close to those described for similar populations. Amerindians had a somewhat more restricted polymorphism, and allele and haplotype frequencies differed greatly between the two tribes. Overall linkage disequilibrium (LD) between the four genes was low in the Caucasoids, but high in the Amerindians, for which significant LD was seen for all informative pairs of loci. Comparing results of this and previous studies we observed that, whenever significant LD occurs in non-Amerindians, it tends to be similar in the different ethnic groups. While this might be interpreted as evidence of co-evolution of genes in the TAP-LMP region, the high haplotypic diversity in all populations and low LD in non-Amerindians indicate absence of co-evolution of the different genes. Distributions of allele and genotype frequencies are consistent with the hypothesis of selective neutrality. We conclude that genetic polymorphism of the human TAP and LMP genes and haplotypes is of little, if any, functional significance. [source] Genetic differentiation of Mediterranean horse mackerel (Trachurus mediterraneus) populations as revealed by mtDNA PCR-RFLP analysisJOURNAL OF APPLIED ICHTHYOLOGY, Issue 2 2009By C. Turan Summary The genetic population structure of Mediterranean horse mackerel, Trachurus mediterraneus, from seven locations throughout the Black, Marmara, Aegean and eastern Mediterranean seas was investigated using restriction fragment length polymorphism (RFLP) analysis of the mtDNA 16S rDNA region. An approximately 2000-bp segment was screened in 280 individuals using six restriction enzymes, resulting in 10 composite haplotypes. The most common haplotype was present in 56.42% individuals; the next most frequent haplotype was present in 22.85% individuals. Average haplotype diversity within samples was moderate (0.38), and nucleotide diversity was low (0.00435). Mean nucleotide divergence for the seven sampling sites was 0.0028. Nucleotide divergence among samples was moderate, with the highest value detected between the Aegean Sea (Izmir) and the eastern Black Sea (Trabzon) populations (0.007055), and the lowest (,0.000043) between the Marmara Sea (Adalar) and the western Black Sea (Sile) populations. In Monte Carlo pairwise comparisons of haplotype frequencies, the Sinop from the middle Black Sea, Trabzon from the eastern Black Sea, and Iskenderun Bay from the north-eastern Mediterranean Sea exhibited highly significant (P < 0.001) geographical differentiation from each other and from all other populations. Mantel's test indicated that the nucleotide divergence among populations of T. mediterraneus was not significantly associated with their geographical isolation (r = ,0.2963; P > 0.05). Consequently, the mtDNA 16S rDNA region provided evidence for the existence of three distinct T. mediterraneus populations (Sinop, Trabzon and Iskenderun Bay) in the Black and north-eastern Mediterranean seas. [source] Genetic and morphological differentiation in Tephritis bardanae (Diptera: Tephritidae): evidence for host-race formationJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2004T. Diegisser Abstract The fruit fly Tephritis bardanae infests flower heads of two burdock hosts, Arctium tomentosum and A. minus. Observations suggest host-associated mating and behavioural differences at oviposition indicating host-race status. Previously, flies from each host plant were found to differ slightly in allozyme allele frequencies, but these differences could as well be explained by geographical separation of host plants. In the present study, we explicitly test whether genetic and morphological variance among T. bardanae are explained best by host-plant association or by geographical location, and if this pattern is stable over a 10-year period. Populations of A. tomentosum flies differed significantly from those of A. minus flies in (i) allozyme allele frequencies at the loci Pep-A and Pgd, (ii) mtDNA haplotype frequencies and (iii) wing size. In contrast, geographical location had no significant influence on the variance estimates. While it remains uncertain whether morphometric differentiation reflects genotypic variability or phenotypic plasticity, allozyme and mtDNA differentiation is genetically determined. This provides strong evidence for host-race formation in T. bardanae. However, the levels of differentiation are relatively low indicating that the system is in an early stage of divergence. This might be due to a lack of time (i.e. the host shift occurred recently) or due to relatively high gene flow preventing much differentiation at loci not experiencing selection. [source] Molecular phylogeny of Turkish Trachurus species (Perciformes: Carangidae) inferred from mitochondrial DNA analysesJOURNAL OF FISH BIOLOGY, Issue 5 2008Y. Bektas Genetic variation among three species of Trachurus (T. trachurus, T. mediterraneus and T. picturatus) from Turkey was investigated by phylogenetic analysis of the entire mtDNA control region (CR) (862 bp, n = 182) and partial cytochrome (cyt) b (239 bp, n = 174) sequences. Individuals were collected at nine stations in four geographic locations: North-eastern Mediterranean Sea, Aegean Sea, Sea of Marmara and Black Sea. Polymerase chain reaction-direct sequencing of the CR and the partial cyt b genes produced 28 and 131 distinct haplotypes, respectively. Maximum likelihood, neighbour-joining and maximum parsimony methods produced similar tree topologies. The results of both CR and cyt b sequence analyses revealed the existence of several species-specific nucleotide sites that can be used to discriminate between the three species. Genetic distances indicated that T. mediterraneus and T. picturatus are more closely related to each other than either is to T. trachurus. Inter-nucleotide and intra-nucleotide diversities of T. picturatus were larger than those of T. mediterraneus and T. trachurus. There was no evidence of a geographical difference in haplotype frequencies of these two mtDNA regions to be clustered. [source] MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic originJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2009Edward T. Mee Abstract Background, Mauritian cynomolgus macaques have greatly restricted genetic diversity in the MHC region compared to other non-human primates; however, the frequency of common MHC haplotypes among captive-bred populations has not been reported. Methods, Microsatellite PCR was used to determine MHC haplotype frequencies among captive macaques at a UK breeding facility. Allele-specific PCR and reference strand conformational analysis were used to determine the allele expression profile of a subset of animals. Results, Haplotypes H3 (21%) and H1 (19%) were most common in the captive population of Mauritian cynomolgus macaques. Predicted alleles were detected by allele-specific PCR-SSP in 98% of animals. Allele expression profiles were similar in animals with identical haplotypes. Conclusions, Mauritian cynomolgus macaques in the UK breeding facility have restricted MHC diversity comparable to a previously described population. Microsatellite-derived haplotypes are highly predictive of allele expression. A selective breeding program has been established to produce MHC-identical animals for biomedical research. [source] HLA typing in Taiwanese patients with oral submucous fibrosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2004Hsin-Ming Chen Background:, A significant association of certain human leukocyte antigens (HLA) and haplotypic pairs with oral submucous fibrosis (OSF) has been reported. However, controversial result of no HLA association with OSF has also been reported. In this study, the phenotype and haplotype frequencies of HLA-A, -B, -C, -DRB1, and -DQB1 in 135 Taiwanese OSF patients were calculated and compared with those in 540 healthy control Taiwanese. Methods:, The analysis of HLA-A, -B, and -C antigens, and of HLA-DRB1 and -DQB1 alleles in OSF patients and healthy control subjects, was performed by serologic typing and DNA typing using polymerase chain reaction with sequence-specific primers (PCR-SSP), respectively. Results:, We found that the phenotype frequency of HLA-B76 (3.0%) in OSF patients was significantly greater than that (0%) in healthy control subjects (corrected P (Pc) = 0.000). In addition, the haplotype frequencies of HLA-B48/Cw7 (3.0%), -B51/Cw7 (6.7%), and -B62/Cw7 (8.2%) in OSF patients were significantly greater than the corresponding haplotype frequencies (0, 0.7, and 1.9%, respectively) in healthy control subjects (Pc = 0.000). The relative risk (RR) values of haplotypes B51/Cw7 (9.57) and B62/Cw7 (4.7) were greater than the RR values of phenotypes B51 (1.81), B62 (2.31), and Cw7 (1.91) in OSF patients. In addition, the etiologic fraction (EF) value of haplotype B51/Cw7 (0.63) was higher than the EF values of phenotypes B51 (0.2) and Cw7 (0.59). Conclusions:, We conclude that some Taiwanese areca quid (AQ) chewers with particular HLA phenotypes and haplotypes are prone to have OSF. In addition, some particular HLA haplotypes may play more important roles than the individual HLA phenotypes for the genetic susceptibility to OSF. However, the significantly increased HLA phenotype B76 and three of the common HLA haplotypes detected are present in only about 20% of incident cases of OSF. [source] Sequence Variations of the Human MPDZ Gene and Association With Alcoholism in Subjects With European AncestryALCOHOLISM, Issue 4 2009Victor M. Karpyak Background:,Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice. Methods:, To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon,intron boundaries, and 2 kilobases in the 5, region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To explore potential associations of the human MPDZ gene with alcoholism and AWS, single SNP and haplotype analyses were performed using 13 common variants. Results:, Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019). Conclusions:, Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS. Further functional genomic analysis of MPDZ variants and investigation of their association with a broader array of alcoholism-related phenotypes could reveal additional genetic markers of alcoholism. [source] A Novel Single Nucleotide Polymorphism of the Neuropeptide Y (NPY) Gene Associated With Alcohol DependenceALCOHOLISM, Issue 5 2005Salim Mottagui-Tabar Background: Neuropeptide Y (NPY) is a major endogenous regulator of anxiety-related behaviors and emotionality. Transgenic work with NPY and null-mutant mice have implicated NPY in the control of alcohol consumption, suggesting that genetic variation of the prepro-NPY gene may also contribute to the heritability of alcoholism. The aim of this study was to examine whether polymorphic variants of the NPY gene are associated with the diagnosis of alcohol dependence. Methods: We compared allele frequencies of 5 NPY polymorphisms (,883-ins/del, ,602, ,399, ,84, and +1128) in a Nordic population of alcohol-dependent individuals (n= 428 males; n= 149 females) and ethnically matched controls (n= 84 males; n= 93 females) for whom alcohol dependence or any diagnosis of substance disorder was excluded. Patients were further subtyped into type I (late-onset) and type II (early-onset) alcoholics. Results: The ,602 marker showed a significant association with alcohol dependence (p= 0.0035; OR, 2.3; 95% CI, 1.3-4.0); a trend level association was further observed for the ,399 marker (p= 0.058; OR, 1.3; 95% CI, 0.99-1.7) and the +1128 marker (p= 0.053; OR, 1.8; 95% CI, 0.99-3.1). The association for the ,602 marker remained and was strengthened when analyzed in type I subjects only, although this association was not seen in type II patients, and there also was a significant association in the female subjects but not in males. The ,602 single nucleotide polymorphism was in strong linkage dysequilibrium (r2= 0.7; p < 0.0001) with the +1128 single nucleotide polymorphism, which has previously been reported to be associated with a diagnosis of alcoholism. Haplotype-based association confirmed these results. Conclusions: We report a novel polymorphism at position ,602 in the 5, region of the NPY gene that is significantly associated with alcohol dependence. We also describe the haplotype frequencies and linkage dysequilibrium pattern of four variations in that region. [source] A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitisALLERGY, Issue 9 2009M. Benson Background:, Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway. Objective:, To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR. Methods:, CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls. Results:, Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T-cell tyrosine kinase (ITK) and CD3D. Significant chi-squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen-challenged CD4+ cells from patients, but not from controls. Conclusion:, Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR. [source] Dispersal, recruitment and migratory behaviour in a hawksbill sea turtle aggregationMOLECULAR ECOLOGY, Issue 3 2008XIMENA VELEZ-ZUAZO Abstract We investigated the dispersal, recruitment and migratory behaviour of the hawksbill sea turtle (Eretmochelys imbricata), among different life-history stages and demographic segments of the large hawksbill turtle aggregation at Mona Island, Puerto Rico. There were significant differences in both mitochondrial DNA (mtDNA) haplotype diversity and haplotype frequencies among the adult males, females and juveniles examined, but little evidence for temporal heterogeneity within these same groups sampled across years. Consistent with previous studies and the hypothesis of strong natal homing, there were striking mtDNA haplotype differences between nesting females on Mona Island and nesting females in other major Caribbean rookeries. Breeding males also showed strong, albeit weaker, genetic evidence of natal homing. Overall, Bayesian mixed-stock analysis suggests that Mona Island was the natal rookery for 79% (65,94%) of males in the aggregation. In contrast, the Mona Island rookery accounted for only a small subset of the new juvenile recruits to the foraging grounds or in the population of older juvenile hawksbills turtles on Mona. Instead, both new recruits and the older juvenile hawksbill turtles on Mona more likely recruited from other Caribbean rookeries, suggesting that a mechanism besides natal homing must be influencing recruitment to feeding habitats. The difference in the apparent degree of natal homing behaviour among the different life-history stages of hawksbill turtles at Mona Island underscores the complexity of the species' life-history dynamics and highlights the need for both local and regional conservation efforts. [source] Range-wide phylogeography and gene zones in Pinus pinaster Ait. revealed by chloroplast microsatellite markersMOLECULAR ECOLOGY, Issue 10 2007GABRIELE BUCCI Abstract Some 1339 trees from 48 Pinus pinaster stands were characterized by five chloroplast microsatellites, detecting a total of 103 distinct haplotypes. Frequencies for the 16 most abundant haplotypes (pk > 0.01) were spatially interpolated over a lattice made by 430 grid points. Fitting of spatially interpolated values on raw haplotype frequencies at the same geographical location was tested by regression analysis. A range-wide ,diversity map' based on interpolated haplotype frequencies allowed the identification of one ,hotspot' of diversity in central and southeastern Spain, and two areas of low haplotypic diversity located in the western Iberian peninsula and Morocco. Principal component analysis (PCA) carried out on haplotypes frequency surfaces allowed the construction of a colour-based ,synthetic' map of the first three PC components, enabling the detection of the main range-scale genetic trends and the identification of three main ,gene pools' for the species: (i) a ,southeastern' gene pool, including southeastern France, Italy, Corsica, Sardinia, Pantelleria and northern Africa; (ii) an ,Atlantic' gene pool, including all the western areas of the Iberian peninsula; and (iii) a ,central' gene pool, located in southeastern Spain. Multivariate and amova analyses carried out on interpolated grid point frequency values revealed the existence of eight major clusters (,gene zones'), whose genetic relationships were related with the history of the species. In addition, demographic models showed more ancient expansions in the eastern and southern ranges of maritime pine probably associated to early postglacial recolonization. The delineation of the gene zones provides a baseline for designing conservation areas in this key Mediterranean pine. [source] Population fragmentation leads to spatial and temporal genetic structure in the endangered Spanish imperial eagleMOLECULAR ECOLOGY, Issue 3 2007B. MARTÍNEZ-CRUZ Abstract The fragmentation of a population may have important consequences for population genetic diversity and structure due to the effects of genetic drift and reduced gene flow. We studied the genetic consequences of the fragmentation of the Spanish imperial eagle (Aquila adalberti) population into small patches through a temporal analysis. Thirty-four museum individuals representing the population predating the fragmentation were analysed for a 345-bp segment of the mitochondrial control region and a set of 10 nuclear microsatellite loci. Data from a previous study on the current population (N = 79) were re-analysed for this subset of 10 microsatellite markers and results compared to those obtained from the historical sample. Three shared mitochondrial haplotypes were found in both populations, although fluctuations in haplotype frequencies and the occurrence of a fourth haplotype in the historical population resulted in lower current levels of haplotype and nucleotide diversity. However, microsatellite markers revealed undiminished levels of nuclear diversity. No evidence for genetic structure was observed for the historical Spanish imperial eagle population, suggesting that the current pattern of structure is the direct consequence of population fragmentation. Temporal fluctuations in mitochondrial and microsatellite allelic frequencies were found between the historical and the current population as well as for each pairwise comparison between historical and current Centro and historical and current Parque Nacional de Doñana nuclei. Our results indicate an ancestral panmictic situation for the species that management policies should aim to restore. A historical analysis like the one taken here provides the baseline upon which the relative role of recent drift in shaping current genetic patterns in endangered species can be evaluated and this knowledge is used to guide conservation actions. [source] Molecular ecology of zebra mussel invasionsMOLECULAR ECOLOGY, Issue 4 2006GEMMA E. MAY Abstract The invasion of the zebra mussel, Dreissena polymorpha, into North American waters has resulted in profound ecological disturbances and large monetary losses. This study examined the invasion history and patterns of genetic diversity among endemic and invading populations of zebra mussels using DNA sequences from the mitochondrial cytochrome oxidase I (COI) gene. Patterns of haplotype frequency indicate that all invasive populations of zebra mussels from North America and Europe originated from the Ponto-Caspian Sea region. The distribution of haplotypes was consistent with invasive populations arising from the Black Sea drainage, but could not exclude the possibility of an origin from the Caspian Sea drainage. Similar haplotype frequencies among North American populations of D. polymorpha suggest colonization by a single founding population. There was no evidence of invasive populations arising from tectonic lakes in Turkey, while lakes in Greece and Macedonia contained only Dreissena stankovici. Populations in Turkey might be members of a sibling species complex of D. polymorpha. Ponto-Caspian derived populations of D. polymorpha (, = 0.0011) and Dreissena bugensis (one haplotype) exhibited low levels of genetic diversity at the COI gene, perhaps as a result of repeated population bottlenecks. In contrast, geographically isolated tectonic lake populations exhibited relatively high levels of genetic diversity (, = 0.0032 to 0.0134). It is possible that the fluctuating environment of the Ponto-Caspian basin facilitated the colonizing habit of invasive populations of D. polymorpha and D. bugensis. Our findings were concordant with the general trend of destructive freshwater invaders in the Great Lakes arising from the Ponto-Caspian Sea basin. [source] A population genetic comparison of argali sheep (Ovis ammon) in Mongolia using the ND5 gene of mitochondrial DNA; implications for conservationMOLECULAR ECOLOGY, Issue 5 2004T. Tserenbataa Abstract We sequenced 556 bp of the mitochondrial ND5 gene to infer aspects of population structure and to test subspecific designations of argali sheep (Ovis ammon) in Mongolia. Analysis of molecular variance (amova) revealed greater variation within than among putative subspecies and populations, suggesting high levels female-mediated gene flow. Compared with bighorn sheep (O. canadensis) in North America, substantially less differentiation in mitochondrial DNA was found among argali populations over 1200 km than was found among bighorn populations over 250 km. This result is consistent with differences in argali and bighorn life history traits. Argali run for long distances across open terrain in the presence of a threat rather than running up into steep escape terrain like bighorn sheep do. Our results suggest recognizing only one Evolutionary Significant Unit (subspecies) of argali in Mongolia, but they may support recognizing two Management Units, because two regions do exhibit slightly different haplotype frequencies at the ND5 gene of mtDNA. [source] Phylogeography of the common ivy (Hedera sp.) in Europe: genetic differentiation through space and timeMOLECULAR ECOLOGY, Issue 8 2002D. Grivet Abstract We studied the phylogeography of ivy (Hedera sp.), a liana widespread in Europe, throughout its natural range. The populations sampled belong to four closely related species differing by ploidy levels and morphological characters. Chloroplast (cp) markers were used and 13 haplotypes were detected, usually shared across species, contrary to ribosomal internal transcribed spacer (ITS) variants. We demonstrated the existence of a strong overall cpDNA phylogeographical structure. Several methods of data analysis were conducted to describe how this structure and the genetic diversity change through space and time. Southern populations, especially those from Spain, are the most divergent. Pairwise estimates of differentiation point to isolation by distance, and the existence of a latitudinal gradient of divergence was demonstrated using a regression procedure. Similarly, latitudinal differences in haplotype richness and diversity exist, as shown by population permutations (,differentiation through space'). Finally, we measured differentiation by taking into account successive levels of divergence between haplotypes (,differentiation through time'). Genetic differentiation turns out to be much greater when differences between closely related haplotypes are not considered. Further, these results indicate that the phylogeographical structure is essentially due to the relative distribution of the most similar haplotypes. Diversity decreases from south to north, whereas haplotype frequencies change longitudinally. It appears that Hedera survived in Spanish and Balkan refugia during the last ice age. A third refugium must have been present in the Alps or in Italy. During the northward expansion, the decrease in overall diversity was attenuated by some mixing of lineages at intermediate latitudes, resulting in comparatively higher levels of differentiation in the south. [source] |