Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica
Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica
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DOI：
10.1002/ajmg.10538
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发表时间：
2002-07-08
期刊：
影响因子：
--
通讯作者：
Sherrington, R
中科院分区：
文献类型：
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作者：
DeLisi, LE;Mesen, A;Sherrington, R
遗传分离物已成为寻找未知病理疾病的基因的有用群体。这样的一个群体被认为存在于哥斯达黎加圣何塞市周围的中央山谷。先前的研究人员在这一人群中发现了一种罕见的遗传性耳聋显性基因，另一项研究也报道了严重双相精神障碍的暗示联系。99个至少有一对兄弟姐妹患有精神分裂症或被诊断为精神分裂症谱系的家庭进行了临床评估，并收集了DNA进行基因分型。Marshfield医学研究基金会（NHLBI）哺乳动物基因分型服务使用404个平均间隔10 cM的短串联重复多态性标记（STRPs）进行所有基因分型。使用非参数程序GeneHunterPlus分析数据。采用STRUCT程序对种群结构进行了调查。未发现具有全基因组连锁意义的区域。使用精神分裂症加分裂情感性障碍的表型，观察到的最高似然评分（MLS）为1.78 (P < 0.004)，距离染色体5q上的pter 176.6 cM，该区域先前与其他一些群体有关。此外，1p、2p、2q、14p和8p染色体上有5个区域的mss大于1.0。其他所有地区的得分都低于1.0。种群遗传分析没有显示出种群亚结构、与其他种群（如美洲印第安人）混合或亲代近亲繁殖的证据。尽管有证据表明后代之间存在近亲繁殖，但后者使人们对这个种群是否是孤立的产生了一些怀疑。(C) 2002 Wiley-Liss, Inc。
Genetic isolates have been useful cohorts in which to search for genes underlying disorders of unknown pathology. One such cohort is thought to exist in the Central Valley of Costa Rica surrounding the city of San Jose. Previous investigators identified a rare dominant gene for hereditary deafness in this population, and a suggestive linkage of severe bipolar psychosis has been reported in another study. Ninety-nine families with at least one pair of siblings affected with schizophrenia or a schizophrenia-spectrum diagnosis had clinical evaluations and DNA collected for genotyping. The Marshfield Medical Research Foundation (NHLBI) Mammalian Genotyping Service performed all genotyping using 404 short-tandem repeat polymorphic markers (STRPs) spaced on average 10 cM apart. Data were analyzed using the nonparametric program, GeneHunterPlus. The population structure was investigated using the STRUCT program. No region was found with genome-wide significance for linkage. Using a phenotype of schizophrenia plus schizoaffective disorder, the highest maximum likelihood score (MLS) observed was 1.78 (P < 0.004) at 176.6 cM from pter on chromosome 5q, an area previously implicated by some other groups. In addition, five regions on chromosomes 1p, 2p, 2q, 14p, and 8p had MLSs above 1.0. All other regions produced scores below 1.0. Population genetic analysis reveals no evidence for population substructure, for admixture with other populations, such as Amerindians, or for inbreeding in the parental generation. The latter casts some doubt on this population being an isolate, although there was evidence of inbreeding among the offspring. (C) 2002 Wiley-Liss, Inc.