Document Detail

Ancestral differences in the distribution of the delta 2642 glutamic acid polymorphism is associated with varying CAG repeat lengths on normal chromosomes: insights into the genetic evolution of Huntington disease.
MedLine Citation:
PMID:  7757069     Owner:  NLM     Status:  MEDLINE    
This study addresses genetic factors associated with normal variation of the CAG repeat in the Huntington disease (HD) gene. To achieve this, we have studied patterns of variation of three trinucleotide repeats in the HD gene including the CAG and adjacent CCG repeats as well as a GAG polymorphism at residue 2642 (delta 2642). We have previously demonstrated that variation in the CCG repeat is associated with variation of the CAG repeat length on normal chromosomes. Here we show that differences in the GAG trinucleotide polymorphism at residue 2642 is also significantly correlated with CAG size on normal chromosomes. The B allele which is associated with higher CAG repeat lengths on normal chromosomes is markedly enriched on affected chromosomes. Furthermore, this glutamic acid polymorphism shows significant variation in different ancestries and is absent in chromosomes of Japanese, Black and Chinese descent. Haplotype analysis of both the CCG and delta 2642 polymorphisms have indicated that both are independently associated with differences in CAG length on normal chromosomes. These findings lead to a model for the genetic evolution of new mutations for HD preferentially occurring on normal chromosomes with higher CAG repeat lengths and a CCG repeat length of seven and/or a deletion of the glutamic acid residue at delta 2642. This study also provides additional evidence for genetic contributions to demographic differences in prevalence rates for HD.
E Almqvist; N Spence; K Nichol; S E Andrew; J Vesa; L Peltonen; M Anvret; J Goto; I Kanazawa; Y P Goldberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human molecular genetics     Volume:  4     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-06-29     Completed Date:  1995-06-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  207-14     Citation Subset:  IM    
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
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MeSH Terms
African Continental Ancestry Group / genetics
Asian Continental Ancestry Group / genetics
China / epidemiology
Chromosomes, Human*
Europe / epidemiology
European Continental Ancestry Group / genetics
Gene Frequency
Glutamic Acid / genetics*
Huntington Disease / epidemiology,  genetics*
Japan / epidemiology
Polymorphism, Restriction Fragment Length*
Repetitive Sequences, Nucleic Acid / genetics*
Reg. No./Substance:
56-86-0/Glutamic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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