7号染色体q臂上自闭症易感基因座AUTS1的进一步特征分析。

Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q.

出版信息

Hum Mol Genet. 2001 Apr 15;10(9):973-82. doi: 10.1093/hmg/10.9.973.

DOI:10.1093/hmg/10.9.973

Abstract

Autism is a neurodevelopmental disorder that usually arises on the basis of a complex genetic predisposition. The most significant susceptibility region in the first whole genome screen of multiplex families was on chromosome 7q, although this linkage was evident only in UK IMGSAC families. Subsequently all other genome screens of non-UK families have found some evidence of increased allele sharing in an overlapping 40 cM region of 7q. To further characterize this susceptibility locus, linkage analysis has now been completed on 170 multiplex IMGSAC families. Using a 5 cM marker grid, analysis of 125 sib pairs meeting stringent inclusion criteria resulted in a multipoint maximum LOD score (MLS) of 2.15 at D7S477, whereas analysis of all 153 sib pairs generated an MLS of 3.37. The 71 non-UK sib pairs now contribute to this linkage. Linkage disequilibrium mapping identified two regions of association-one lying under the peak of linkage, the other some 27 cM distal. These results are supported in part by findings in independent German and American singleton families.

摘要

自闭症是一种神经发育障碍，通常在复杂的遗传易感性基础上出现。在多重家庭的首次全基因组筛查中，最显著的易感区域位于7号染色体长臂（7q），不过这种连锁仅在英国IMGSAC家庭中明显。随后，对非英国家庭进行的所有其他基因组筛查都发现，在7q一个重叠的40厘摩区域内，存在等位基因共享增加的一些证据。为了进一步描述这个易感基因座，现已对170个多重IMGSAC家庭完成了连锁分析。使用一个5厘摩的标记网格，对符合严格纳入标准的125对同胞进行分析，在D7S477处得到多点最大对数优势分数（MLS）为2.15，而对所有153对同胞进行分析得到的MLS为3.37。现在71对非英国家庭的同胞对也参与了此次连锁分析。连锁不平衡图谱确定了两个关联区域，一个位于连锁峰值之下，另一个在其远端约27厘摩处。这些结果部分得到了德国和美国独立单病例家庭研究结果的支持。