Document Detail


Factors associated with HD CAG repeat instability in Huntington disease.
MedLine Citation:
PMID:  17660463     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The Huntington disease (HD) CAG repeat exhibits dramatic instability when transmitted to subsequent generations. The instability of the HD disease allele in male intergenerational transmissions is reflected in the variability of the CAG repeat in DNA from the sperm of male carriers of the HD gene.
RESULTS: In this study, we used a collection of 112 sperm DNAs from male HD gene-positive members of a large Venezuelan cohort to investigate the factors associated with repeat instability. We confirm previous observations that CAG repeat length is the strongest predictor of repeat-length variability in sperm, but we did not find any correlation between CAG repeat instability and either age at the time of sperm donation or affectedness status. We also investigated transmission instability for 184 father-offspring and 311 mother-offspring pairs in this Venezuelan pedigree. Repeat-length changes were dependent upon the sex of the transmitting parent and parental CAG repeat length but not parental age or birth order. Unexpectedly, in maternal transmissions, repeat-length changes were also dependent upon the sex of the offspring, with a tendency for expansion in male offspring and contraction in female offspring.
CONCLUSION: Significant sibling-sibling correlation for repeat instability suggests that genetic factors play a role in intergenerational CAG repeat instability.
Authors:
V C Wheeler; F Persichetti; S M McNeil; J S Mysore; S S Mysore; M E MacDonald; R H Myers; J F Gusella; N S Wexler;
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-07-27
Journal Detail:
Title:  Journal of medical genetics     Volume:  44     ISSN:  1468-6244     ISO Abbreviation:  J. Med. Genet.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-02     Completed Date:  2007-11-29     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  2985087R     Medline TA:  J Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  695-701     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Birth Order
Child
Fathers
Female
Heterozygote
Humans
Huntington Disease / epidemiology,  genetics*
Male
Microsatellite Instability*
Minisatellite Repeats / genetics*
Mothers
Nerve Tissue Proteins / genetics*
Nuclear Proteins / genetics*
Parents
Pedigree
Sex Factors
Siblings
Spermatozoa / chemistry
Venezuela / epidemiology
Grant Support
ID/Acronym/Agency:
NS049206/NS/NINDS NIH HHS; P50 NS016367/NS/NINDS NIH HHS; P50 NS016367-28/NS/NINDS NIH HHS; R01 NS049206/NS/NINDS NIH HHS; R01 NS049206-04/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/HTT protein, human; 0/Nerve Tissue Proteins; 0/Nuclear Proteins
Comments/Corrections
Comment In:
J Med Genet. 2008 Nov;45(11):766   [PMID:  18978336 ]

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


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