Editor—There have been a number of claims for linkage to schizophrenia but none has been reliably established. The findings of genome scans have been inconsistent between studies.1 2 On the basis of an association of psychosis with sex chromosome aneuploidies and a relationship between sex and diagnosis within families (the “same sex concordance” effect), a gene for psychosis in a region of X-Y homology was suggested.3 4 In addition, there is an argument that psychosis is related to cerebral asymmetry, a putative defining feature of the human brain, and that a determinant of asymmetry is in the X-Y homologous class.4 Searches for linkage on the X chromosome have yielded weak evidence for linkage in Xp115 and on the proximal long arm,6-8but, arguably, these findings have been no more consistent than those on the autosomes.9

In the absence of consistent linkage, one approach to finding genes associated with psychosis is through analysis of cytogenetic anomalies. One such anomaly is the case of an XX male with schizophrenia.10 11 In general, XX maleness is the result of the transfer of the testis determining factor (SRY) to the X chromosome12 as a result of an abnormal X-Y interchange involving the non-recombining region of Yp and homologous sequences in Xp.13 14 We showed previously that the breakpoint on the Y in this case is within the distal Yp11.2/Xq21.3 region of homology.8

In this study we have characterised the Y breakpoint using a sequencing approach and fluorescence in situ hybridisation (FISH). We have shown that the abnormal X-Y interchange occurred between retroviral long terminal repeats (LTR). This is distinct from previously described translocations, which frequently involve hot spots such as the protein kinase gene PRK that has homologues on both Yp and …