Complex patterns of linkage disequilibrium in the Huntington disease region.

The genetic defect causing Huntington disease (HD) has been mapped to 4p16.3 by linkage analysis using DNA markers. Two apparently contradictory classes of recombination events in HD kindreds preclude precise targeting of efforts to clone the disease gene. Here, we report a new recombination event t...

Disgrifiad llawn

Wedi'i Gadw mewn:
Manylion Llyfryddiaeth
Prif Awduron: MacDonald, M E, Lin, C, Srinidhi, L, Bates, G, Altherr, M, Whaley, W L, Lehrach, H, Wasmuth, J, Gusella, J F
Fformat: Erthygl
Iaith:English
Cyhoeddwyd: 1991
Pynciau:
Research Article
Mynediad Ar-lein:https://ncbi.nlm.nih.gov/pmc/articles/PMC1683155/
https://ncbi.nlm.nih.gov/pubmed/1680285
Tagiau: Ychwanegu Tag
Dim Tagiau, Byddwch y cyntaf i dagio'r cofnod hwn!
id pubmed-1683155
record_format dspace
spelling pubmed-16831552006-12-06 Complex patterns of linkage disequilibrium in the Huntington disease region. MacDonald, M E Lin, C Srinidhi, L Bates, G Altherr, M Whaley, W L Lehrach, H Wasmuth, J Gusella, J F Am J Hum Genet Research Article The genetic defect causing Huntington disease (HD) has been mapped to 4p16.3 by linkage analysis using DNA markers. Two apparently contradictory classes of recombination events in HD kindreds preclude precise targeting of efforts to clone the disease gene. Here, we report a new recombination event that increases support for an internal candidate region of 2.5 Mb between D4S10 and D4S168. Analysis of 23 DNA polymorphisms in 4p16.3 revealed a complex pattern of association with the disease gene that failed to narrow the size of the candidate region. The degree of linkage disequilibrium did not show a continuous increase across the physical map, nor was a region of extreme disequilibrium identified. Markers displaying no association with the disorder were interspersed with and, in many cases, close to markers displaying significant disequilibrium. Comparison of closely spaced marker pairs on normal and HD chromosomes, as well as analysis of haplotypes across the HD region, suggest that simple recombination subsequent to a single original HD mutation cannot easily explain the pool of HD chromosomes seen today. A number of different mechanisms could contribute to the diversity of haplotypes observed on HD chromosomes, but it is likely that there has been more than one and possibly several independent origins of the HD mutation. 1991-10 /pmc/articles/PMC1683155/ /pubmed/1680285 Text en
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Research Article
spellingShingle Research Article
MacDonald, M E
Lin, C
Srinidhi, L
Bates, G
Altherr, M
Whaley, W L
Lehrach, H
Wasmuth, J
Gusella, J F
Complex patterns of linkage disequilibrium in the Huntington disease region.
description The genetic defect causing Huntington disease (HD) has been mapped to 4p16.3 by linkage analysis using DNA markers. Two apparently contradictory classes of recombination events in HD kindreds preclude precise targeting of efforts to clone the disease gene. Here, we report a new recombination event that increases support for an internal candidate region of 2.5 Mb between D4S10 and D4S168. Analysis of 23 DNA polymorphisms in 4p16.3 revealed a complex pattern of association with the disease gene that failed to narrow the size of the candidate region. The degree of linkage disequilibrium did not show a continuous increase across the physical map, nor was a region of extreme disequilibrium identified. Markers displaying no association with the disorder were interspersed with and, in many cases, close to markers displaying significant disequilibrium. Comparison of closely spaced marker pairs on normal and HD chromosomes, as well as analysis of haplotypes across the HD region, suggest that simple recombination subsequent to a single original HD mutation cannot easily explain the pool of HD chromosomes seen today. A number of different mechanisms could contribute to the diversity of haplotypes observed on HD chromosomes, but it is likely that there has been more than one and possibly several independent origins of the HD mutation.
author MacDonald, M E
Lin, C
Srinidhi, L
Bates, G
Altherr, M
Whaley, W L
Lehrach, H
Wasmuth, J
Gusella, J F
author_facet MacDonald, M E
Lin, C
Srinidhi, L
Bates, G
Altherr, M
Whaley, W L
Lehrach, H
Wasmuth, J
Gusella, J F
author_sort MacDonald, M E
title Complex patterns of linkage disequilibrium in the Huntington disease region.
title_short Complex patterns of linkage disequilibrium in the Huntington disease region.
title_full Complex patterns of linkage disequilibrium in the Huntington disease region.
title_fullStr Complex patterns of linkage disequilibrium in the Huntington disease region.
title_full_unstemmed Complex patterns of linkage disequilibrium in the Huntington disease region.
title_sort complex patterns of linkage disequilibrium in the huntington disease region.
publishDate 1991
url https://ncbi.nlm.nih.gov/pmc/articles/PMC1683155/
https://ncbi.nlm.nih.gov/pubmed/1680285
_version_ 1760340900602445824

Eitemau Tebyg