| Linkage disequilibrium and extended haplotypes in the HLA-A to D6S105 region: implications for mapping the hemochromatosis gene (HFE). | |
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MedLine Citation:
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PMID: 8557248 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The hemochromatosis gene (HFE) maps to 6p21.3, in close linkage with the HLA Class I genes. Linkage disequilibrium (LD) studies were designed to narrow down the most likely candidate region for HFE, as an alternative to traditional linkage analysis. However, both the HLA-A and D6S105 subregions, which are situated 2-3 cM and approximately 3 Mb apart, have been suggested to contain HFE. The present report extends our previous study based upon the analysis of a large number of HFE and normal chromosomes from 66 families of Breton ancestry. In addition to the previously used RFLP markers spanning the 400-kb surrounding HLA-A, we examined three microsatellites: D6S510, HLA-F, and D6S105. Our combined data not only confirm a peak of LD at D6S105, but also reveal a complex pattern of LD over the i82 to D6S105 interval. Within our ethnically well-defined population of Brittany, the association of HFE with D6S105 is as great as that with HLA-A, while the internal markers display a lower LD. Fine haplotype analysis enabled us to identify two categories of haplotypes segregating with HFE. In contrast to the vast majority of normal haplotypes, 50% of HFE haplotypes are completely conserved over the HLA-A to D6S105 interval. These haplotypes could have been conserved through recombination suppression, selective forces and/or other evolutionary factors. This particular haplotypic configuration might account for the apparent inconsistencies between genetic linkage and LD data, and additionally greatly complicates positional cloning of HFE through disequilibrium mapping. |
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Authors:
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G Gandon; A M Jouanolle; B Chauvel; V Mauvieux; A le Treut; J Feingold; J Y Le Gall; V David; J Yaouanq |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human genetics Volume: 97 ISSN: 0340-6717 ISO Abbreviation: Hum. Genet. Publication Date: 1996 Jan |
Date Detail:
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Created Date: 1996-02-23 Completed Date: 1996-02-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: GERMANY |
Other Details:
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Languages: eng Pagination: 103-13 Citation Subset: IM |
Affiliation:
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UPR 41 CNRS Recombinnaisons Génétiques, Faculté de Médecine, Rennes, France. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/X17093 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Base Sequence Chromosome Mapping Chromosomes, Human, Pair 6* DNA Primers Family Female Genes, MHC Class I* Genetic Markers HLA-A Antigens / genetics* HLA-B Antigens / genetics Haplotypes / genetics* Hemochromatosis / genetics* Humans Linkage Disequilibrium* Male Molecular Sequence Data Pedigree Polymerase Chain Reaction Polymorphism, Genetic |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/Genetic Markers; 0/HLA-A Antigens; 0/HLA-B Antigens |
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