Quantitation of X-Y homologous genes in patients with schizophrenia by multiplex polymerase chain reaction.
OBJECTIVE
The genetic basis of schizophrenia is obscure. In an XX male patient with schizophrenia we previously showed that one X;Y translocation breakpoint was in pseudoautosomal region 1 (PAR1) with the effect that the proximal segment of PAR1 from the PAR1 boundary to acetylserotonin N-methyl transferase (ASMT) distally was triplicated in this patient. This study determined whether dosage imbalances of X-Y homologous regions in general are associated with schizophrenia.


METHODS
A multiplex semi-quantitative polymerase chain reaction assay was developed to quantify MIC2 gene as a representative of PAR1 and compare it with the SYBL1 gene which maps in pseudoautosomal region 2 (PAR2) and protocadherin XY (PCDHXY), located at Xq21.3. Each of these three loci was co-amplified with the autosomal gene MSX2 using Cy5-labelled primers and the products separated by electrophoresis in polyacrylamide gels. Results were expressed as ratios of peak area of the target gene to MSX2 which served as an internal dosage control.


RESULTS
Using genomes with sex chromosome aneuploidies, the method was found sensitive enough to detect a two-fold difference in gene copy number. We confirmed the MIC2 triplication in the XX male patient but found no significant difference in gene dosage of MIC2, PCDHXY and SYBL1 in a panel of 17 patients with schizophrenia compared to controls.


CONCLUSIONS
No evidence was obtained for gene dosage imbalances in MIC2, PCDHXY and SYBL1 in patients with schizophrenia.
Ross
Norman L J
NL
University of Oxford, Department of Psychiatry, Warneford Hospital, Oxford, UK. norman.ross@psychiatry.ox.ac.uk
Mavrogiannis
Lampros A
LA
Sargent
Carole A
CA
Knight
Samantha J L
SJ
Wadekar
Rekha
R
DeLisi
Lynn E
LE
Crow
Timothy J
TJ
D000071443:12E7 Antigen; D000782:Aneuploidy; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D017931:DNA Primers; D018628:Gene Dosage; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D050683:R-SNARE Proteins; D012559:Schizophrenia / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D008565:Membrane Proteins; D050683:R-SNARE Proteins; C121241:VAMP7 protein, human