The copy number variant involving part of the α7 nicotinic receptor gene contains a polymorphic inversion

被引：33

作者：

Flomen, Rachel H. ^{[1
]}

Davies, Angela F. ^{[2
]}

Di Forti, Marta ^{[1
]}

La Cascia, Caterina ^{[1
]}

Mackie-Ogilvie, Caroline ^{[2
]}

Murray, Robin ^{[1
]}

Makoff, Andrew J. ^{[1
]}

机构：

[1] Kings Coll London, Dept Psychol Med, Div Psychol Med, Inst Psychiat, London SE5 8AF, England

[2] Guys Hosp, Dept Cytogenet, London, ON, Canada

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2008年 / 16卷 / 11期

关键词：

inversion; schizophrenia; bipolar disorder; 15q13-q14; CHRNA7; segmental duplication;

D O I：

10.1038/ejhg.2008.112

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The alpha 7 nicotinic acetylcholine receptor gene (CHRNA7) is located at 15q13-q14 in a region that is strongly linked to the P50 sensory gating deficit, an endophenotype of schizophrenia and bipolar disorder. Part of the gene is a copy number variant, due to a duplication of exons 5-10 and 3' sequence in CHRFAM7A, which is present in many but not all humans. Maps of this region show that the two genes are in opposite orientation in the individual mainly represented in the public access human DNA sequence database (Build 36), suggesting that an inversion had occurred since the duplication. We have used fluorescent in situ hybridization to investigate this putative inversion. Analysis of interphase chromosomes in 12 individuals confirms the occurrence of an inversion and indicates that CHRFAM7A exists in both orientations with similar frequency. We showed that the 2bp deletion polymorphism in exon 6 of CHRFAM7A is in strong linkage disequilibrium with the inversion polymorphism (r(2) = 0.82, CI 0.53-1.00, P = 0.00003), which can therefore be used as a surrogate marker. Previous associations of endophenotypes of schizophrenia with the 2bp deletion might therefore be due to the orientation of the duplicon containing CHRFAM7A. European Journal of Human Genetics (2008) 16, 1364-1371; doi:10.1038/ejhg.2008.112; published online 11 June 2008

引用

页码：1364 / 1371

页数：8

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