一个精神分裂症多发家系染色体候选区域的连锁分析

A linkage study of schizophrenia candidate regions in a Chinese multiplex pedigree

目的探讨1q21-22,1q32-44,5q21-33,6p24-22,8p22-21,10p15-11,11q23-24,11p15,12q23-24,13q32-34,22q11-12,9q34,16p13,12q13,17q25及19q13等染色体候选区域与精神分裂症的连锁关系。方法选择候选染色体区域的微卫星标志,对湖南省永州市一个汉族精神分裂症多发家系进行基因组扫描。用Linkage 5.1软件包及Genehunter 2.1软件包进行参数和非参数连锁分析,并构建最可能的单体型。结果在染色体11q23.2-24.2区域获得3个连续高的多点非参数分析LOD值,在D11s925处获得的峰值为4.33(P=0.016),超过显著性连锁的阈值。与D11s925相邻的D11s898及D11s4151在多点非参数分析中的LOD值分别为1.57和3.82。对11号染色体上的6个微卫星标志进行单体型分析,D11s902与D11s898之间存在重组,提示可能的疾病基因在D11s902远端。结论11q22.1-24.2区域可能包含有精神分裂症的易感基因。

Objective This study was to explore the molecular genetic relationship between chromosome regions and susceptibility genes for familial schizophrenia in Chinese Han population. Methods A multiplex schizophrenia family including 5 schizophrenia patients and their 21 relatives was included. The patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders 4th Edition criteria for schizophrenia. A genome-wide scan was carried out by using 72 microsatellite markers. Parametric and nonparametric linkage was performed to evaluate regions of the genome demonstrating increased allele sharing, as measured by a led score. Haplotype analysis was carried out to ascertained the interval of the disease locus. Results A region with multipoint maximum led scores was on chromosome 11 q23.1-24. 2 （peak led score of 4. 33 at marker D11s925） in this family. Evaluation of recombinants suggested that the disease gene was in the interval between D11s902 and 11q qter. No evidence of linkage was obtained at several locations reported in previous studies, including chromosomes 1q21-22, 1q32-44, 5q21-33, 6p24- 22, 8p22-21, 10p15-11, 11q23-24, 11p15, 12q23-24, 13q32-34, 22q11-12, 9q34, 16p13, 12q13, 17q25 and 19q13. Conclusion The results support that a susceptibility locus for schizophrenia is possiblly on chromosome 11 q22. 1-24. 2.