Comparison of polymorphisms in the alpha7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects.
The hypothesis that the 15q13-15 region of chromosome 15 contains a gene that contributes to the etiology of schizophrenia is supported by multiple genetic linkage studies. The alpha7 neuronal nicotinic acetylcholine receptor (CHRNA7) gene was selected as the best candidate gene in this region for molecular investigation, based on these linkage findings and biological evidence in both human and rodent models. CHRNA7 receptors are decreased in expression in postmortem brain of schizophrenic subjects. A dinucleotide marker, D15S1360, in intron two of the CHRNA7 gene is genetically linked to an auditory gating deficit found in schizophrenics and half of the first-degree relatives of patients. Single strand conformation polymorphism (SSCP) and sequence analyses of DNA from schizophrenic and control individuals identified 33 variants in the coding region and intron/exon borders of the CHRNA7 gene and its partial duplication, dupCHRNA7; common polymorphisms were mapped. Twenty-one variants were found in the exons, but non-synonymous changes were rare. Although the expression of CHRNA7 is decreased in schizophrenia, the general structure of the remaining receptors is likely to be normal.
Gault
Judith
J
Department of Psychiatry, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Hopkins
Janet
J
Berger
Ralph
R
Drebing
Carla
C
Logel
Judith
J
Walton
Catherine
C
Short
Margaret
M
Vianzon
Ruby
R
Olincy
Ann
A
Ross
Randal G
RG
Adler
Lawrence E
LE
Freedman
Robert
R
Leonard
Sherry
S
D001483:Base Sequence; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005091:Exons / Q000235:genetics; D020440:Gene Duplication; D008040:Genetic Linkage / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor