Extent and Distribution of Linkage Disequilibrium in Three Genomic Regions

Abecasis, Gonçalo R.; Noguchi, Emiko; Heinzmann, Andrea; Traherne, James A.; Bhattacharyya, Sumit; Leaves, N. I.; Anderson, Gavin; Zhang, Youming; Lench, Nicholas; Carey, Alisoun H.; Cardon, Lon R.; Moffatt, Miriam F.; Cookson, William

doi:10.1086/316944

Cited by 310 publications

(215 citation statements)

References 27 publications

(32 reference statements)

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…Highly irregular structures of linkage disequilibrium were also reported from other regions of the genome, when only 45% of the variation in linkage disequilibrium measures could be explained by physical distance. 20 Together with our results, this suggests caution in using single SNPs as markers and indicators for the role of a whole region or gene in linkage or association studies. Thus knowledge of all genetic variations in a gene is a prerequisite to determine which SNP (if any) could be used as a marker.…”

Section: Discussionsupporting

confidence: 66%

A complete screening of the IL4 gene

Kabesch¹,

Tzotcheva²,

Carr³

et al. 2003

Journal of Allergy and Clinical Immunology

106

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 66%

A complete screening of the IL4 gene

Kabesch¹,

Tzotcheva²,

Carr³

et al. 2003

Journal of Allergy and Clinical Immunology

106

View full text Add to dashboard Cite

“…15 A significant D 0 40.3 (P nc o0.05) was used as a cut-off criterion, as this has been estimated to be the minimal usable amount of LD in association studies, 22 resulting in a region of B0.8 Mb (between D6S306 and D6S1558). Single-point associations were obtained by the homozygous parent transmission disequilibrium test separately from DRB1*03-DQA1*0501-DQB1*0201 and DRB1*0401-DQA1*03-DQB1*0302 homozygous parents for the 50 SNPs successfully genotyped in the initial dataset of 205 families (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex

et al. 2009

View full text Add to dashboard Cite

The high-risk human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 alleles cannot explain the entire type 1 diabetes (T1D) association observed within the extended major histocompatibility complex. We have earlier identified an association with D6S2223, located 2.3 Mb telomeric of HLA-A, on the DRB1*03-DQA1*0501-DQB1*0201 haplotype, and this study aimed to fine-map the associated region also on the DRB1*0401-DQA1*03-DQB1*0302 haplotype, characterized by less extensive linkage disequilibrium. To exclude associations secondary to DRB1-DQA1-DQB1 haplotypes, 205 families with at least one parent homozygous for these loci, were genotyped for 137 polymorphisms. We found novel associations on the DRB1*0401-DQA1*03-DQB1*0302 haplotypic background with eight single nucleotide polymorphisms (SNPs) located within or near the PRSS16 gene. In addition, association at the butyrophilin (BTN)-gene cluster, particularly the BTN3A2 gene, was observed by multilocus analyses. We replicated the associations with SNPs in the PRSS16 region and, albeit weaker, to the BTN3A2 region, in an independent material of 725 families obtained from the Type 1 Diabetes Genetics Consortium. It is important to note that these associations were independent of the HLA-DRB1-DQA1-DQB1 genes, as well as of associations observed at HLA-A, -B and -C. Taken together, our results identify PRSS16 and BTN3A2, two genes thought to play important roles in regulating the immune response, as potentially novel susceptibility genes for T1D.

show abstract

“…Thus, the maintenance of its linkage disequilibrium with HLA-A29 needs a more elaborate explanation. In general, linkage disequilibrium is expected to diminish with recombination map distance (Abecasis et al 2001;Cargill et al 1999;Kruglyak 1999;Reich et al 2001). Strong linkage disequilibrium at a large physical distances could be explained by: (1) a low recombination rate in the chromosomal region; (2) a strong founder effect by a recent allele/mutation; or (3) selection.…”

Section: Discussionmentioning

confidence: 99%

Co-selection of the H63D mutation and the HLA-A29 allele: a new paradigm of linkage disequilibrium?

Cardoso¹,

Alves

Mascarenhas³

et al. 2002

Immunogenetics

View full text Add to dashboard Cite

The major histocompatibility complex (MHC) shows a remarkable conservation of particular HLA antigens and haplotypes in linkage disequilibrium in most human populations, suggesting the existence of a convergent evolution. A recent example of such conservation is the association of particular HLA haplotypes with the HFE mutations. With the objective of exploring the significance of that association, the present paper offers an analysis of the linkage disequilibrium between HLA alleles or haplotypes and the HFE mutations in a Portuguese population. Allele and haplotype associations between HLA and HFE mutations were first reviewed in a population of 43 hemochromatosis families. The results confirmed the linkage disequilibrium of the HLA haplotype HLA-A3-B7 and the HLA-A29 allele, respectively, with the HFE mutations C282Y and H63D. In order to extend the study of the linkage disequilibrium between H63D and the HLA-A29-containing haplotypes in a normal, random population, an additional sample of 398 haplotypes was analyzed. The results reveal significant linkage disequilibrium between the H63D mutation and all HLA-A29-containing haplotypes, favoring the hypothesis of a co-selection of H63D and the HLA-A29 allele itself. An insight into the biological significance of this association is given by the finding of significantly higher CD8 + T-lymphocyte counts in subjects simultaneously carrying the H63D mutation and the HLA-A29 allele.

show abstract

Extent and Distribution of Linkage Disequilibrium in Three Genomic Regions

Cited by 310 publications

References 27 publications

A complete screening of the IL4 gene

A complete screening of the IL4 gene

Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex

Co-selection of the H63D mutation and the HLA-A29 allele: a new paradigm of linkage disequilibrium?

Contact Info

Product

Resources

About