SCHIZOPHRENIA - A GENOME SCAN TARGETS CHROMOSOMES 3P AND 8P AS POTENTIAL SITES OF SUSCEPTIBILITY GENES
SCHIZOPHRENIA - A GENOME SCAN TARGETS CHROMOSOMES 3P AND 8P AS POTENTIAL SITES OF SUSCEPTIBILITY GENES
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DOI：
10.1002/ajmg.1320600316
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发表时间：
1995-06-19
期刊：
影响因子：
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通讯作者：
KAZAZIAN, HH
中科院分区：
文献类型：
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作者：
PULVER, AE;LASSETER, VK;KAZAZIAN, HH
利用系统确定的57个家系样本，每个家系有2个或更多成员具有一致的精神分裂症诊断(DSM-III-R标准)，我们进行了520个基因座的连锁研究，覆盖了大约70%的精神分裂症易感基因座的基因组。基于我们样本模拟研究的Lod得分阈值的两阶段策略确定了进一步探索的区域。在每个区域中，使用显性、隐性和仅受影响的模型和非参数同胞对血统同一性的方法分析了高信息量的二核苷酸重复序列(杂合度大于0.70)的密集图谱。对于一个区域，8p22-p21，受影响的同胞对分析给出的P值=0.0001，对应的LOD分数大约等于3.00。对于8p22-p21，最大两点Lod得分出现在‘’只受影响‘’隐性模型中(Z(Max)=2.35；theta(M)=theta(F))；考虑到在参考家系中发现的重组比例的性别差异，Z(Max)=2.78(theta(M)/theta(F)=3)。对于第二个区域，3p26-p24，最大两点Lod得分为2.34(仅受影响的显性模式)，受影响的同胞对P值为0.01。这两个区域是精神分裂症的潜在易感基因位点，值得进一步探索。(C)1995年Wiley-Liss公司
Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and ''affected only'' models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gave a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22-p21, the maximum two-point lod score occurred using the ''affected only'' recessive model (Z(MAX) = 2.35; theta(M) = theta(F)); allowing for a constant sex difference in recombination fractions found in reference pedigrees, Z(MAX) = 2.78 (theta(M)/theta(F) = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 (''affected only'' dominant model), and the affected sib-pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia. (C) 1995 Wiley-Liss, Inc.