The copy number variant involving part of the alpha7 nicotinic receptor gene contains a polymorphic inversion.
The alpha7 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 2 bp 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 2 bp deletion might therefore be due to the orientation of the duplicon containing CHRFAM7A.
Department of Psychological Medicine, Division of Psychological Medicine, Institute of Psychiatry, King's College London, Denmark Hill, London, UK.
Rachel H
RH
Flomen
Angela F
AF
Davies
Marta
M
Di Forti
Caterina
C
La Cascia
Caroline
C
Mackie-Ogilvie
Robin
R
Murray
Andrew J
AJ
Makoff
D000818:Animals; D001483:Base Sequence / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D002679:Pan troglodytes; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D017384:Sequence Deletion; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D005819:Genetic Markers; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor