A genome scan for modifiers of age at onset in Huntington disease:: The HD MAPS study
A genome scan for modifiers of age at onset in Huntington disease:: The HD MAPS study
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DOI：
10.1086/378133
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发表时间：
2003-09-01
影响因子：
9.8
通讯作者：
Myers, RH
中科院分区：
文献类型：
--
作者：
Li, JL;Hayden, MR;Myers, RH
亨廷顿病（HD）是由4p16.3上一个新基因编码区内CAG重复扩增引起的。虽然发病年龄的变化部分可以用扩增重复序列的大小来解释，但无法解释的发病年龄变化具有很强的遗传性（h(2) = 0.56），这表明其他基因改变了HD的发病年龄。为了确定这些修饰位点，我们对629对受影响的兄弟姐妹（295个家系和695个个体）进行了10厘米密度全基因组扫描，并根据扩展和正常CAG重复序列大小调整发病年龄。由于所有研究对象都受HD影响，因此通过位置加权方法调整HD位点上和周围的等位基因共享相同的估计值，以校正在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）位点上发现了相关的提示证据，这可能有助于研究改变HD发病年龄的基因。
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 (h(2) = 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.