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Comparison of polymorphisms in the α7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects
Author(s) -
Gault Judith,
Hopkins Janet,
Berger Ralph,
Drebing Carla,
Logel Judith,
Walton Catherine,
Short Margaret,
Vianzon Ruby,
Olincy Ann,
Ross Randal G.,
Adler Lawrence E.,
Freedman Robert,
Leonard Sherry
Publication year - 2003
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.20061
Subject(s) - biology , genetics , gene , gene duplication , exon , candidate gene , intron , genetic linkage , coding region , single strand conformation polymorphism
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 α7 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. © 2003 Wiley‐Liss, Inc.