Triplication of several par1 genes and part of the homo sapiens-specific Yp11.2/Xq21.3 region of homology in 46, X,t(X;Y)(p22.3;p11.2) male with a schizophrenia

Journal article

Background: No genes for psychosis including schizophrenia have been identified but cytogenetic anomalies provide a lead to the identification of disease-related genes. A 46, X, t(X; Y)(p22.3; p11.2) male with schizophrenia has been identified and the Yp breakpoint has previously been shown to lie within the Yp11.2/Xq21.3 homology block. Aim: To characterise the junction fragment in this XX male with schizophrenia. Methods: Sequence analysis of STSs within the Yp11.2/Xq21.3 block to further define the position of the breakpoint in Yp. Inverse PCR to clone the junction fragment and identify the Xp sequence. Results: Illegitimate recombination was shown to have occurred between retroviral long terminal repeats (LTRs) which resulted in the transfer of 4Mb of Yp to the short arm of the X chromosome. Transfer of Yp to Xp was confirmed by fluorescence in situ hybridisation (FISH). An STS was designed from the Xp sequence and used to radiation hybrid map the Xp breakpoint between the framework markers DXYS233 and DXYS228. Further refinement positioned the breakpoint point close to ASMTL and distal to ASMT within the pseudoautosomal region 1 (PAR1). The translocation results in the triplication of several genes in proximal PAR1 and sequences within the distal segment of the Yp11.2/Xq21.3 homologous region. Conclusions: If schizophrenia in this case is related to the breakpoint it may be the result of triplication of genes in PAR1 as in Klinefelter's syndrome, triplication of sequences within the distal Yp11.2/Xq21.3 region (which has not previously been associated with psychosis in XX males), or some epigenetic interaction between genes in these regions.

Authors: Ross, N; Yang, J; Sargent, C; Boucher, C; Nanko, S

• Journal: American Journal of Medical Genetics - Neuropsychiatric Genetics
• Volume: 105
• Issue: 7
• Pages: 606-607
• Publication date: 2001-10-08
• EISSN: 1552-485X
• ISSN: 1552-4841
• Language: English