McClellan Jon M, King Mary-Claire
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Neuron. 2021 May 5;109(9):1411-1413. doi: 10.1016/j.neuron.2021.04.002.
Severe neuropsychiatric disorders are so genetically heterogeneous that virtually every unrelated patient harbors different clinically significant alleles. By studying schizophrenia in the Ashkenazi Jewish founder population, Lencz and co-authors identified rare severe alleles each shared by a few patients. Experimental evaluation of an implicated protocadherin allele revealed failure to form homophilic cellular aggregates as a possible mechanism for defective development of neural circuits.
严重的神经精神疾病在基因上具有高度异质性，几乎每个无亲缘关系的患者都携带不同的具有临床意义的等位基因。通过对阿什肯纳兹犹太奠基人群体中的精神分裂症进行研究，伦茨及其合著者发现了一些罕见的严重等位基因，每个等位基因都为少数患者所共有。对一种涉及的原钙黏蛋白等位基因进行实验评估后发现，无法形成同嗜性细胞聚集体可能是神经回路发育缺陷的一种机制。
