Kohn Yoav, Danilovich Eduardo, Filon Dvorah, Oppenheim Ariella, Karni Osnat, Kanyas Kyra, Turetsky Neil, Korner Mira, Lerer Bernard
Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120.
Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):65-70. doi: 10.1002/ajmg.b.30044.
Several genes have been reported recently to be associated with schizophrenia and bipolar disorder. Because of the complexity of the inheritance of these disorders, there is an urgent need to replicate these findings and to search for additional candidate genes. The study of genetic isolates is a powerful technique that may overcome some of the obstacles caused by genetic heterogeneity and ambiguity of phenotype definition. Identity by descent (IBD) haplotype sharing analysis in these populations may be used to detect mutations within shared haplotypes in smaller samples of affected individuals. In this study, we used IBD haplotype sharing analysis to replicate positive linkage and association findings in psychotic disorders, and to identify other regions of interest. Fifty-two patients with major psychiatric disorders from a genetically isolated village in Israel were studied. By studying eight Y chromosome markers, we were able to confirm the oral tradition of members of this isolate regarding a common paternal origin. Three hundred fifty nine microsatellite markers on 9 candidate chromosomes were genotyped, and haplotypes were reconstructed using information from family members. Two highly significant (P < 0.0001) peaks of haplotype sharing were found. One was for psychotic patients with any diagnosis at the location of dysbindin, a gene previously associated with schizophrenia. The other peak was for patients with schizophrenia on chromosome 1p36. Thus, this study both replicates an earlier finding and points to a novel region of interest, which might be unique to this population.
最近有报道称，有几个基因与精神分裂症和双相情感障碍有关。由于这些疾病遗传方式的复杂性，迫切需要重复这些研究结果，并寻找其他候选基因。对遗传隔离人群的研究是一项强大的技术，它可能会克服一些由遗传异质性和表型定义模糊性所带来的障碍。在这些人群中，通过血缘相同（IBD）单倍型共享分析，可以在受影响个体的较小样本中检测共享单倍型内的突变。在本研究中，我们使用IBD单倍型共享分析来重复在精神障碍中阳性连锁和关联的研究结果，并识别其他感兴趣的区域。我们对来自以色列一个遗传隔离村庄的52名患有严重精神疾病的患者进行了研究。通过研究8个Y染色体标记，我们得以证实该隔离人群成员关于共同父系起源的口述传统。对9条候选染色体上的359个微卫星标记进行了基因分型，并利用家庭成员的信息重建了单倍型。发现了两个高度显著（P < 0.0001）的单倍型共享峰。一个是在dysbindin基因位置上，针对任何诊断的精神病患者，该基因先前已被证明与精神分裂症有关。另一个峰是在1p36染色体上，针对精神分裂症患者。因此，本研究既重复了早期的研究结果，又指出了一个新的感兴趣区域，这可能是该人群所特有的。
