Premium
ProtocadherinX / Y , a candidate gene‐pair for schizophrenia and schizoaffective disorder: A DHPLC investigation of genomic sequence
Author(s) -
Giouzeli Maria,
Williams Nic A.,
Lonie Lorne J.,
DeLisi Lynn E.,
Crow Timothy J.
Publication year - 2004
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.30036
Subject(s) - protocadherin , biology , genetics , coding region , psychosis , homo sapiens , gene , exon , psychology , cadherin , psychiatry , sociology , cell , anthropology
Abstract Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell‐surface adhesion molecules expressed predominantly in the brain. The PCDHX / Y gene‐pair was generated by an X–Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens ‐specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY . However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X–Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX / Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X‐inactivation. Further investigation of the epigenetic control of PCDHX / Y in relation to psychosis is warranted. © 2004 Wiley‐Liss, Inc.