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Haplotype Association (haplotype + association)

Distribution by Scientific Domains
Medical Sciences71%
Life Sciences21%

Terms modified by Haplotype Association

  • haplotype association analysis
    		•

    Selected Abstracts

    A region on equine chromosome 13 is linked to recurrent airway obstruction in horses

    EQUINE VETERINARY JOURNAL, Issue 3 2007
    U. JOST
    Summary Reasons for study: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor , chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required. Methods: The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood halfsib families. Based on a history of clinical signs (coughing, nasal discharge, abnormal breathing and poor performance), horses were classified in a horse owner assessed respiratory signs index (HOARSI 1,4: from healthy, mild, moderate to severe signs). Four microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2,4) and Sire 2 (35 HOARSI 1 vs. 50 HOARSI 2,4), age ,7 years. Results: For both sires haplotypes could be established in the order AHT133-LEX047-VHL47-ASB37. The distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans, respectively. Haplotype association with mild to severe clinical signs of chronic lower airway disease (HOARSI 2,4) was significant in the offspring of Sire 1 (P = 0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage analysis showed the ECA13q13 region containing IL4RA to be linked to equine chronic lower airway disease in one family (P<0.01), but not in the second family. Conclusions: This supports a genetic background for equine RAO and indicates that IL4RA is a candidate gene with possible locus heterogeneity for this disease. Potential relevance: Identification of major genes for RAO may provide a basis for breeding and individual prevention for this important disease. [source]

    Contribution of a haplotype in the HLA region to anti,cyclic citrullinated peptide antibody positivity in rheumatoid arthritis, independently of HLA,DRB1

    ARTHRITIS & RHEUMATISM, Issue 12 2009
    Yukinori Okada
    Objective To examine the risk of anti,cyclic citrullinated peptide (anti-CCP) antibody positivity in rheumatoid arthritis (RA) patients carrying certain haplotypes in the HLA region. Methods A total of 1,389 Japanese patients with RA were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the HLA region using commercial oligonucleotide arrays (from Perlegen or Affymetrix) as well as for HLA,DRB1 alleles using a sequence-specific polymerase chain reaction method. Stepwise logistic regression was used to select from among the 30 SNPs the ones that represented a risk of anti-CCP antibody positivity. Haplotypes of the selected SNPs were inferred using an expectation-maximization algorithm. Associations of individual SNPs were evaluated with the Cochran-Armitage test for trend. DRB1 alleles and haplotypes were evaluated with the chi-square test. Heterogeneities of risks among the shared epitope (SE) and non-SE HLA,DRB1 alleles were examined using the exact test. Haplotype associations that were independent of individual HLA,DRB1 alleles were evaluated using the likelihood ratio test. Results Significant associations were found for 9 SNPs (smallest P value being 2.4 × 10,8) and in 4 HLA,DRB1 alleles (smallest P value being 2.0 × 10,10 in DRB1*0405). Stepwise logistic regression selected 4 SNPs (rs9262638, rs7775228, rs4713580, and rs9277359). Among the 16 inferred haplotypes of these 4 SNPs, 6 indicated significant associations (smallest P value being 1.9 × 10,11). Risks among SE and non-SE alleles were significantly heterogeneous (P = 0.0095 and P = 9.8 × 10,9, respectively), indicating the importance of stratification with individual DRB1 alleles rather than SE alleles. Conditional analysis of the risk associated with individual DRB1 alleles identified a risk haplotype that was independent of DRB1 (odds ratio 2.00 [95% confidence interval 1.44,2.79], P = 2.6 × 10,5). Conclusion Heterogeneous risks of anti-CCP antibody positivity were confirmed among SE and non-SE alleles in our patient population. A risk haplotype in the HLA region that is independent of HLA,DRB1 was confirmed. [source]

    Increased numbers of mononuclear cells from blood and CSF expressing interferon-gamma mRNA in multiple sclerosis are from both the CD4+ and the CD8+ subsets

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2000
    E. Wallström
    Activated, cytokine-producing lymphocytes may regulate central nervous system (CNS) inflammation in multiple sclerosis (MS). We utilize a novel combination of in situ hybridization (ISH) and immunocytochemical staining of peripheral blood lymphocytes (PBLs) to identify spontaneously interferon-gamma (IFN,) mRNA expressing cells as CD4+ or CD8+. A major proportion of the IFN, mRNA expressing lymphocytes belonged to the CD4+ lineage, which concords with the cellular composition of MS brain lesions, findings in experimental models and the HLA class II haplotype association in MS. There were also significantly more CD8+ IFN, mRNA expressing lymphocytes in the MS patients compared with healthy controls, further suggesting the contribution of activated cells from this lineage in the inflammatory response in MS. Both CD4+ and CD8+ IFN, mRNA expressing cells were enriched in the cerebrospinal fluid (CSF) as compared with the peripheral blood of the MS patients. Combined with emerging genetic data on HLA class I influences, our data argues for a joint role of activated CD8+ and CD4+ cells in the pathogenesis of MS. [source]

    Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcome

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2008
    Ann L. Truelove
    Summary Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case,control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005,0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy,Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01,0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis. [source]

    Ribosomal DNA sequences indicate isolated populations of Ichthyophonus hoferi in geographic sympatry in the north-eastern Pacific Ocean

    JOURNAL OF FISH DISEASES, Issue 10 2002
    C D Criscione
    Abstract Infections of Ichthyophonus hoferi, a cosmopolitan parasite of marine fish, have recently been reported in rockfish, Sebastes spp., from the north-eastern Pacific. Because I. hoferi also infects Pacific herring, Clupea pallasi Valenciennes, and salmonids in this region, we wanted to determine if Ichthyophonus parasites from rockfishes, Pacific herring and chinook salmon, Oncorhynchus tshawytscha (Walbaum), were the same. Small subunit ribosomal deoxyribonucleic acid sequence data revealed two haplotypes that were fixed among host species in geographic sympatry, one from rockfish and the other from both Pacific herring and salmon. These isolated populations of Ichthyophonus could be part of the same species that are ecologically separated because of host behaviours, or they could be distinct species that are host specific. Dietary patterns of the hosts indicate that ecological separation among hosts is possible, but the presence of distinct species may better explain the observed Ichthyophonus haplotype association with host species. [source]

    Sequence Variations of the Human MPDZ Gene and Association With Alcoholism in Subjects With European Ancestry

    ALCOHOLISM, Issue 4 2009
    Victor 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]

    An Analysis Paradigm for Investigating Multi-locus Effects in Complex Disease: Examination of Three GABAA Receptor Subunit Genes on 15q11-q13 as Risk Factors for Autistic Disorder.

    ANNALS OF HUMAN GENETICS, Issue 3 2006
    A. E. Ashley-Koch
    Summary Gene-gene interactions are likely involved in many complex genetic disorders and new statistical approaches for detecting such interactions are needed. We propose a multi-analytic paradigm, relying on convergence of evidence across multiple analysis tools. Our paradigm tests for main and interactive effects, through allele, genotype and haplotype association. We applied our paradigm to genotype data from three GABAA receptor subunit genes (GABRB3, GABRA5, and GABRG3) on chromosome 15 in 470 Caucasian autism families. Previously implicated in autism, we hypothesized these genes interact to contribute to risk. We detected no evidence of main effects by allelic (PDT, FBAT) or genotypic (genotype-PDT) association at individual markers. However, three two-marker haplotypes in GABRG3 were significant (HBAT). We detected no significant multi-locus associations using genotype-PDT analysis or the EMDR data reduction program. However, consistent with the haplotype findings, the best single locus EMDR model selected a GABRG3 marker. Further, the best pairwise genotype-PDT result involved GABRB3 and GABRG3, and all multi-locus EMDR models also selected GABRB3 and GABRG3 markers. GABA receptor subunit genes do not significantly interact to contribute to autism risk in our overall data set. However, the consistency of results across analyses suggests that we have defined a useful framework for evaluating gene-gene interactions. [source]

    Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand M,ori, Pacific Island, and Caucasian case,control sample sets

    ARTHRITIS & RHEUMATISM, Issue 11 2009
    Jade E. Hollis-Moffatt
    Objective To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of M,ori, Pacific Island, and Caucasian ancestry and to determine if the M,ori and Pacific Island samples could be useful for fine-mapping. Methods Patients (n= 56 M,ori, 69 Pacific Island, and 131 Caucasian) were recruited from rheumatology outpatient clinics and satisfied the American College of Rheumatology criteria for gout. The control samples comprised 125 M,ori subjects, 41 Pacific Island subjects, and 568 Caucasian subjects without arthritis. SLC2A9 single-nucleotide polymorphisms rs16890979 (V253I), rs5028843, rs11942223, and rs12510549 were genotyped (possible etiologic variants in Caucasians). Results Association of the major allele of rs16890979, rs11942223, and rs5028843 with gout was observed in all sample sets (P = 3.7 × 10,7, 1.6 × 10,6, and 7.6 × 10,5 for rs11942223 in the M,ori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the M,ori and Pacific Island control samples) was not observed in a single gout case. Conclusion Our data confirm a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set, with the effect on risk (odds ratio >2.0) greater than previous estimates. We also demonstrate association of SLC2A9 with gout in samples of M,ori and Pacific Island ancestry and a consistent pattern of haplotype association. The presence of both alleles of rs16890979 on susceptibility and protective haplotypes in the M,ori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in M,ori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping. [source]

    Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women

    GENES, BRAIN AND BEHAVIOR, Issue 6 2004
    H. S. Sun
    Depression and anxiety disorders often coexist clinically and both are known to have a genetic basis, but the mode of inheritance is too complicated to be determined so far. Serotonin is the biogenic amine neurotransmitter most commonly associated with depression and anxiety. Since tryptophan hydroxylase (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, its role in the pathophysiology of these psychiatric diseases has been intensively studied. In this study, we examined whether polymorphism of the TPH1 gene is related to the etiology of major depression, anxiety and comorbid depression and anxiety. Five single nucleoside polymorphisms of the TPH1 gene were studied in a population-based sample of postpartum Taiwanese women consisting of 120 subjects with depression or/and anxiety and 86 matched normal controls. A significant difference (P = 0.0107) in genotype frequency for the T27224C polymorphism was found between the comorbid and normal groups, and risk analysis showed that the C allele conferred a strong protective effect (odds ratio = 0.27; 95% confident interval = 0.11,0.7). Three-allele haplotypes involving T27224C polymorphism were constructed and haplotype associations between particular haplotype combinations and various diseases identified. However, the associations were weak and the overall haplotype frequency profiles in all groups were similar. The results suggest that depression, anxiety, and comorbid depression and anxiety disorders may have related etiologies. In addition, this study suggests that the TPH1 gene might play a role in the pathogenesis of these closely related disorders. [source]

    Interleukin 10 (IL-10) gene variants and susceptibility for paediatric onset Crohn's disease

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009
    D. K. AMRE
    Summary Background, A recent genome-wide association study in adult patients with ulcerative colitis (UC) has implicated the interleukin 10 (IL-10) gene as an important candidate gene. Moreover, a UC-associated single nucleotide polymorphism (SNP) rs3024405 was also significantly associated with adult Crohn's disease (CD). Aims, To examine whether IL-10 -CD associations extended to paediatric-onset CD. Methods, We implemented the case-control design at three paediatric gastroenterology clinics in Canada. CD patients (,20 years) were recruited along with healthy controls. DNA samples were genotyped for tag-single nucleotide polymorphisms (tag-SNPs) in the IL-10 gene. Allelic, genotype and haplotype associations with CD were studied. Results, A total of 270 patients and 336 controls were studied. The mean age (±s.d.) at diagnosis was 12.1 (±3.5). There were a slightly higher proportion of male patients (56.3%). Of the five IL-10 tag-SNPs, rs2222202 (C/T) (P = 0.03) and rs1800871 (C/T) (P = 0.05) showed significant allelic associations with CD. Specific IL-10 SNPs were associated with CD disease location and/or disease behaviour. Conclusions, Our gene-wide analysis replicates recent findings of associations between IL-10 and adult CD, and suggests that these associations extend to paediatric-onset CD as well. [source]

    Sequence diversity and haplotype associations with phenotypic responses to crowding: GIGANTEA affects fruit set in Arabidopsis thaliana

    MOLECULAR ECOLOGY, Issue 14 2007
    MARCUS T. BROCK
    Abstract Identifying the molecular genetic basis of intraspecific variation in quantitative traits promises to provide novel insight into their evolutionary history as well as genetic mechanisms of adaptation. In an attempt to identify genes responsible for natural variation in competitive responses in Arabidopsis thaliana, we examined DNA sequence diversity at seven loci previously identified as members of the phytochrome B signalling network. For one gene, GIGANTEA (GI), we detected significant haplotype structure. To test for GI haplogroup,phenotype associations, we genotyped 161 A. thaliana accessions at GI and censused the same accessions for total fruit set and the expression of three phenotypic traits (days to flowering, petiole length, and inflorescence height) in a greenhouse experiment where plants were grown in crowded and uncrowded environments. We detected a significant association between GI and total fruit set that resulted in a 14% difference in average fruit set among GI haplogroups. Given that fruit set is an important component of fitness in this species and given the magnitude of the effect, the question arises as to how variation at this locus is maintained. Our observation of frequent and significant epistasis between GI and background single nucleotide polymorphisms (SNP), where the fitness ranking of the GI allele either reverses or does not differ depending on the allele at the interacting SNP, suggests that epistatic selection may actively maintain or at least slow the loss of variation at GI. This result is particularly noteworthy in the light of the ongoing debate regarding the genetic underpinnings of phenotypic evolution and recent observations that epistasis for phenotypic traits and components of fitness is common in A. thaliana. [source]

    Y chromosome haplogroups: A correlation with testicular dysgenesis syndrome?

    APMIS, Issue 1 2003
    KEN McELREAVEY
    Testicular dysgenesis syndrome encompasses low sperm quality, hypospadias, cryptorchidism and testicular cancer. Epidemiological studies and genetic data from familial cases suggest that testicular dysgenesis syndrome has a common etiology. The Y chromosome is known to encode genes that are involved in germ cell development or maintenance. We have therefore investigated if different classes of Y chromosomes in the general population (Y chromosome haplogroups) are associated with aspects of the testicular dysgenesis syndrome. We defined the Y chromosome haplogroups in individuals from different European counties who presented with either (i) oligo- or azoospermia associated with a Y chromosome microdeletion, (ii) unexplained reduced sperm counts (<20×106/ml) or (iii) testicular cancer. We failed to find Y chromosome haplotype associations with either microdeletion formation or testicular cancer. However, in a study of the Danish population, we found that a specific Y chromosome haplogroup (hg26) is significantly overrepresented in men with unexplained reduced sperm counts compared with a Danish control population. The factors encoded by genes on this class of Y chromosome may be particularly susceptible to environmental influences that cause testicular dysgenesis syndrome. Our current data highlight the need for further analyses of clinically well-defined patient groups from a wide range of ethnic and geographic origins. [source]

    Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis

    ARTHRITIS & RHEUMATISM, Issue 6 2009
    H. Gunawardena
    Objective The identification of novel autoantibodies in juvenile dermatomyositis (DM) may have etiologic and clinical implications. The aim of this study was to describe autoantibodies to a 140-kd protein in children recruited to the Juvenile DM National Registry and Repository for UK and Ireland. Methods Clinical data and sera were collected from children with juvenile myositis. Sera that recognized a 140-kd protein by immunoprecipitation were identified. The identity of the p140 autoantigen was investigated by immunoprecipitation/immunodepletion, using commercial monoclonal antibodies to NXP-2, reference anti-p140, and anti-p155/140, the other autoantibody recently described in juvenile DM. DNA samples from 100 Caucasian children with myositis were genotyped for HLA class II haplotype associations and compared with those from 864 randomly selected UK Caucasian control subjects. Results Sera from 37 (23%) of 162 patients with juvenile myositis were positive for anti-p140 autoantibodies, which were detected exclusively in patients with juvenile DM and not in patients with juvenile DM,overlap syndrome or control subjects. No anti-p140 antibody,positive patients were positive for other recognized autoantibodies. Immunodepletion suggested that the identity of p140 was consistent with NXP-2 (the previously identified MJ autoantigen). In children with anti-p140 antibodies, the association with calcinosis was significant compared with the rest of the cohort (corrected P < 0.005, odds ratio 7.0, 95% confidence interval 3.0,16.1). The clinical features of patients with anti-p140 autoantibodies were different from those of children with anti-p155/140 autoantibodies. The presence of HLA,DRB1*08 was a possible risk factor for anti-p140 autoantibody positivity. Conclusion This study has established that anti-p140 autoantibodies represent a major autoantibody subset in juvenile DM. This specificity may identify a further immunogenetic and clinical phenotype within the juvenile myositis spectrum that includes an association with calcinosis. [source]

    Association of a specific ERAP1/ARTS1 haplotype with disease susceptibility in ankylosing spondylitis

    ARTHRITIS & RHEUMATISM, Issue 5 2009
    W. P. Maksymowych
    Objective Alterations in antigen processing have been proposed to play a significant role in the pathogenesis of ankylosing spondylitis (AS). A non,major histocompatibility complex gene encoding an endoplasmic reticulum aminopeptidase, ERAP1, has been implicated recently. This study assessed 13 coding single-nucleotide polymorphisms (SNPs) from 5 genes involved in antigen processing (ERAP1, TAP1, TAP2, LMP2, and LMP7) in 3 Canadian cohorts of patients with AS, to address the possibility of gene interactions in disease susceptibility. Methods The study involved 992 AS cases and 1,437 controls from 3 centers (472 cases and 451 controls from Alberta, 138 cases and 392 controls from Newfoundland, and 382 cases and 594 controls from Toronto). Most of the patients with AS and healthy, unrelated controls were Caucasians of northern European descent. Single-marker and haplotype associations were determined using an allelic likelihood ratio test in UNPHASED, version 3.0.12, and the WHAP program, respectively. P values for significance of haplotype associations were calculated using a permutation test. Results A specific ERAP1 haplotype, rs27044/10050860/30187-CCT, was strongly associated with increased risk of AS in all 3 case,control cohorts (pooled odds ratio [OR] 1.81, 95% confidence interval [95% CI] 1.46,2.24; P = 7 × 10,8), while a second specific ERAP1 haplotype, rs30187/26618/26653-CTG, reduced the disease risk (pooled OR 0.77, 95% CI 0.67,0.88; P = 9 × 10,5). Significant associations were also noted for 3 ERAP1 SNP variants (rs10050860, rs30187, and rs26653), although no significant haplotype interaction between ERAP1 and TAP/LMP loci was evident. Conclusion These data indicate that an AS disease locus may reside on a specific ERAP1 haplotype, and its effect is not multiplicative with contributions from TAP and LMP genes. [source]