Chromosome 1 loci in Finnish schizophrenia families
Chromosome 1 loci in Finnish schizophrenia families
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DOI：
10.1093/hmg/10.15.1611
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发表时间：
2001-07-15
影响因子：
3.5
通讯作者：
Peltonen, L
中科院分区：
文献类型：
--
作者：
Ekelund, J;Hovatta, I;Peltonen, L
我们早些时候报道了在芬兰两项独立研究中收集的精神分裂症家庭中染色体1q32-q42上两个区域的关联证据。在这里，我们报告了一个精细的绘图工作的结果，旨在进一步定义的染色体区域的兴趣使用一个大的，基于人群的研究样本（221个家庭，557个受影响的个体）。大多数患者（78%）患有DSM-IV型精神分裂症诊断，其余患者患有精神分裂症谱系障碍。我们在1q染色体45 cM宽区域共对147个微卫星标记进行了基因分型。结果分别对来自芬兰内部孤立的家庭和来自芬兰其他地区的家庭以及所有家庭进行了分析。我们使用了传统的两点联动分析、SimWalk2多点联动分析和一种新颖的博弈-竞争关联/联动方法。在组合样本（Z(max) = 2.71, D1S2709）和内部分离物外的核心家族（Z(max) = 3.21, D1S2709）中获得了一个位点的连锁证据。在来自内部分离物的家族中，最有力的证据是在该标记的22 cM着丝粒处获得的标记（Z(max) 2.30, D1S245）。多点分析也发现了这些位点。用配子竞争法观察到与几个标记相关的证据。有趣的是，在联合研究样本中，最有力的连锁证据是标记D1S2709，这是D1SC1基因的一个基因内标记，之前被认为是精神分裂症的易感基因。这些结果与易感基因在该染色体区域的存在是一致的，这一结果也暗示了最近其他精神分裂症的家庭研究。
We have earlier reported evidence for linkage to two regions on chromosome 1q32-q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Z(max) 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the D1SC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.