| Literature DB >> 12900792 |
Jian-Liang Li1, Michael R Hayden, Elisabeth W Almqvist, Ryan R Brinkman, Alexandra Durr, Catherine Dodé, Patrick J Morrison, Oksana Suchowersky, Christopher A Ross, Russell L Margolis, Adam Rosenblatt, Estrella Gómez-Tortosa, David Mayo Cabrero, Andrea Novelletto, Marina Frontali, Martha Nance, Ronald J A Trent, Elizabeth McCusker, Randi Jones, Jane S Paulsen, Madeline Harrison, Andrea Zanko, Ruth K Abramson, Ana L Russ, Beth Knowlton, Luc Djoussé, Jayalakshmi S Mysore, Suzanne Tariot, Michael F Gusella, Vanessa C Wheeler, Larry D Atwood, L Adrienne Cupples, Marie Saint-Hilaire, Jang-Ho J Cha, Steven M Hersch, Walter J Koroshetz, James F Gusella, Marcy E MacDonald, Richard H Myers.
Abstract
Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.Entities:
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Year: 2003 PMID： 12900792 PMCID： PMC1180695 DOI： 10.1086/378133
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025