Alternative phenotypes for the complex genetics of schizophrenia
Alternative phenotypes for the complex genetics of schizophrenia
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DOI：
10.1016/s0006-3223(98)00321-7
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发表时间：
1999-03-01
影响因子：
10.6
通讯作者：
Leonard, S
中科院分区：
文献类型：
--
作者：
Freedman, R;Adler, LE;Leonard, S
精神分裂症遗传学的复杂性已经被许多研究者描述过。在缺乏简单孟德尔遗传的情况下，遗传连锁并没有取得在其他疾病中发现的明确结果，这些方法已经导致了责任基因的鉴定。连锁分析的替代表型提出了这个问题的一个解决方案。这些表型代表了精神分裂症中离散的生物学缺陷，可能比疾病本身更能反映单个基因的作用。一种替代表型的孟德尔遗传，未能抑制对重复刺激的P50听觉诱发反应，导致缺陷与候选基因的位点成功连锁，该候选基因是染色体15 q14上的α 7-烟碱乙酰胆碱受体。最近在NIMH精神分裂症遗传学倡议的家庭中发现了对这种联系的进一步支持，使用精神分裂症作为表型。基于精神分裂症离散生物学缺陷的替代表型增强了连锁分析的能力。这样的分析不仅可以促进精神分裂症的遗传传递的理解，但他们也提供了进一步的支持精神分裂症的病理生理学的神经生物学特征，但是，确定负责的基因突变是必要的，才能得出明确的结论。生物精神病学1999;45：551-558（C）1999年生物精神病学学会。
The complexity of the genetics of schizophrenia has been described by many investigators. In the absence of simple Mendelian inheritance, genetic linkage has not achieved the definitive results found in other illnesses, where such methods have led to the identification of responsible genes. Alternative phenotypes for linkage analysis are proposed as one solution to this problem. These phenotypes, representative of discrete biological deficits in schizophrenia, may more closely reflect the effect of a single gene than the illness itself The Mendelian inheritance of one alternative phenotype, failure to inhibit the P50 auditory evoked response to repeated stimuli, has resulted in successful linkage of the deficit to the locus of a candidate gene, the alpha 7-nicotinic acetylcholine receptor on chromosome 15q14. Further support for this linkage has recently been found in families from the NIMH Schizophrenia Genetics Initiative, using schizophrenia as the phenotype. Alternative phenotypes based on discrete biological deficits in schizophrenia have enhanced power for linkage analysis. Such analyses can not only facilitate understanding of the genetic transmission of schizophrenia, but they also provide further support for neurobiological characterizations of the pathophysiology of schizophrenia; however, identification of responsible genetic mutations is necessary before definitive conclusions can be reached. Biol Psychiatry 1999;45: 551-558 (C) 1999 Society of Biological Psychiatry.