A 2-base pair deletion polymorphism in the partial duplication of the alpha7 nicotinic acetylcholine gene (CHRFAM7A) on chromosome 15q14 is associated with schizophrenia.
Multiple genetic linkage studies support the hypothesis that the 15q13-14 chromosomal region contributes to the etiology of schizophrenia. Among the putative candidate genes in this area are the alpha7 nicotinic acetylcholine receptor gene (CHRNA7) and its partial duplication, CHRFAM7A. A large chromosomal segment including the CHRFAM7A gene locus, but not the CHRNA7 locus, is deleted in some individuals. The CHRFAM7A gene contains a polymorphism consisting of a 2 base pair (2 bp) deletion at position 497-498 bp of exon 6. We employed PCR-based methods to quantify the copy number of CHRFAM7A and the presence of the 2 bp polymorphism in a large, multi-ethnic population. The 2 bp polymorphism was associated with schizophrenia in African Americans (genotype p=0.005, allele p=0.015), and in Caucasians (genotype p=0.015, allele p=0.009). We conclude that the presence of the 2 bp polymorphism at the CHRFAM7A locus may have a functional significance in schizophrenia.
Sinkus
Melissa L
ML
Department of Psychiatry, University of Colorado at Denver, Denver, CO 80045, USA.
Lee
Michael J
MJ
Gault
Judith
J
Logel
Judith
J
Short
Margaret
M
Freedman
Robert
R
Christian
Susan L
SL
Lyon
Jennifer
J
Leonard
Sherry
S
D001741:Black or African American / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D015139:Blotting, Southern; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018579:Patient Selection; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D044465:White People / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor