Li Jian-Liang, Hayden Michael R, Almqvist Elisabeth W, Brinkman Ryan R, Durr Alexandra, Dodé Catherine, Morrison Patrick J, Suchowersky Oksana, Ross Christopher A, Margolis Russell L, Rosenblatt Adam, Gómez-Tortosa Estrella, Cabrero David Mayo, Novelletto Andrea, Frontali Marina, Nance Martha, Trent Ronald J A, McCusker Elizabeth, Jones Randi, Paulsen Jane S, Harrison Madeline, Zanko Andrea, Abramson Ruth K, Russ Ana L, Knowlton Beth, Djoussé Luc, Mysore Jayalakshmi S, Tariot Suzanne, Gusella Michael F, Wheeler Vanessa C, Atwood Larry D, Cupples L Adrienne, Saint-Hilaire Marie, Cha Jang-Ho J, Hersch Steven M, Koroshetz Walter J, Gusella James F, MacDonald Marcy E, Myers Richard H
Department of Neurology, Boston University School of Medicine, and Bioinformatics Program, School of Public Health, Boston University, Boston, MA, USA.
Am J Hum Genet. 2003 Sep;73(3):682-7. doi: 10.1086/378133. Epub 2003 Aug 1.
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.
亨廷顿舞蹈病（HD）是由位于4p16.3上一个新基因编码区内的CAG重复序列扩增所致。尽管发病年龄的差异部分可由扩增重复序列的大小来解释，但发病年龄中无法解释的差异具有很强的遗传性（h2 = 0.56），这表明其他基因会影响HD的发病年龄。为了鉴定这些修饰基因座，我们对629对患病同胞对（295个家系和695名个体）进行了全基因组扫描，扫描密度为10 cM，使用根据扩增和正常CAG重复序列大小调整后的发病年龄。由于所有研究对象均为HD患者，因此通过位置加权法对HD基因座及其周围区域通过血缘共享的等位基因估计值进行了调整，以校正4p处增加的等位基因共享。在4p16（LOD = 1.93）、6p21 - 23（LOD = 2.29）和6q24 - 26（LOD = 2.28）发现了连锁的提示性证据，这可能有助于研究影响HD发病年龄的基因。
