Garver D L, Holcomb J, Mapua F M, Wilson R, Barnes B
Department of Psychiatry and Behavioral Science, University of Louisville School of Medicine, Louisville, KY, USA.
Schizophr Res. 2001 Dec 1;52(3):145-60. doi: 10.1016/s0920-9964(01)00157-8.
Genome-wide linkage studies, examining the relationship between the schizophrenia syndrome(s) and possible susceptibility regions within the human genome have identified multiple regions within which linkage to the syndrome may be explored. No regions have been found to provide supportive evidence for linkage in all cohorts. These findings are consistent with the schizophrenia syndrome being genetically heterogeneous, with genetic susceptibility arising from multiple sites which are differentially distributed in from pedigree to pedigree. The authors present data from an autosomal-wide scan of 30 multiplex pedigrees, each with a mean of 4.1 members affected with a schizophrenia spectrum disorder with respect to regions of interest for linkage with the schizophrenia spectrum disease(s). Partial, though not significant replications of susceptibility sites at D1S518 (P=0.029) described by Shaw et al. (1998: Shaw, S.H., Kelly, M., Smith, A.B., Shields, G., Hopkins, P.J., Loftus, J., Laval, S.H., Vita, A., DeHert, M., Cardon, L.R., Crow, T.J., Sherrington, R., DeLisi, L.E., 1998. A Genome-wide search for schizophrenia susceptibility genes. Am. J. Med. Genet. (Neuropsychiatric Genet.) 81, 364-376.), and at D5S426 (P=0.015) described by : Silverman, J.M., Greenberg, D.A., Altstiel, L.D., Siever, L.J., Mohs, R.C., Smith, C.J., Zhou, G., Hollander, T.Y., Yang, X.-P., Kedache, M., Li, G., Zaccario, M.L., Davis, K.L., 1996. Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree. Am. J. Med. Genet. 67, 162-171.) were documented using multipoint non-parametric (NPL) statistics. Two additional novel regions worthy of further investigation were identified at D1S1150 (P=0.004) and at D20S171 (P=0.009). Previously reported genomic regions of interest for the schizophrenias are reviewed in the context of the same/flanking markers utilized with the present cohort of pedigrees. The data further suggests that only a fraction of pedigrees multiplex for schizophrenia link at any single susceptibility region.
全基因组连锁研究旨在探究精神分裂症综合征与人类基因组中可能的易感区域之间的关系，已确定了多个可能与该综合征存在连锁关系的区域。尚未发现有区域能在所有队列中为连锁提供支持性证据。这些发现与精神分裂症综合征具有遗传异质性相一致，即遗传易感性源于多个位点，这些位点在不同家系中的分布存在差异。作者展示了对30个多重家系进行常染色体全扫描的数据，每个家系平均有4.1名成员患有精神分裂症谱系障碍，涉及与精神分裂症谱系疾病连锁的感兴趣区域。使用多点非参数（NPL）统计方法记录了肖等人（1998年：肖，S.H.，凯利，M.，史密斯，A.B.，希尔兹，G.，霍普金斯，P.J.，洛夫特斯，J.，拉瓦尔，S.H.，维塔，A.，德赫特，M.，卡尔顿，L.R.，克罗，T.J.，谢林顿，R.，德利西，L.E.，1998年。全基因组搜索精神分裂症易感基因。《美国医学遗传学杂志》（神经精神遗传学）81，364 - 376）所描述的位于D1S518处（P = 0.029）的易感位点以及西尔弗曼等人（1996年：西尔弗曼，J.M.，格林伯格，D.A.，阿尔斯蒂尔，L.D.，西弗，L.J.，莫赫斯，R.C.，史密斯，C.J.，周，G.霍兰德，T.Y.，杨，X.-P.，凯达切，M.，李，G.，扎卡里奥，M.L.，戴维斯，K.L.，1996年。一个大型家系中5号染色体短臂上存在精神分裂症及相关疾病位点的证据。《美国医学遗传学杂志》67，162 - 171）所描述的位于D5S426处（P = 0.015）的易感位点的部分（尽管不显著）重复情况。还在D1S1150处（P = 0.004）和D20S171处（P = 0.009）确定了另外两个值得进一步研究的新区域。在与本家系队列使用相同/侧翼标记的背景下，对先前报道的精神分裂症相关感兴趣基因组区域进行了综述。数据进一步表明，在任何单个易感区域，只有一小部分精神分裂症多重家系存在连锁关系。
