SINE-R.C2 (a homo sapiens specific retroposon) is homologous to cDNA from postmortem brain in schizophrenia and to two loci in the Xq21.3/Yp flock linked to handedness and psychosis

We investigated the retroviral/retroposon hypothesis of schizophrenia by ge nerating sequences with PCR primers based on a retroviral sequence recovere d by Yee et al, [1998: Schizophr Res 29:92] from a cDNA library from postmo rtem brain tissue from an individual with psychosis in a genomic region (Xq 21.3) that has been tentatively linked to schizophrenia and schizoaffective disorder by Laval et al, [1998: Am. J. Med. Genet, (Neuropsychiatr. Genet, ) 81:420-427], Within the block of homology with Yp that was generated by a transposition between the chimpanzee and Homo sapiens we find two sequence s, HS307 and HS408, with a high degree of homology to but not identity with the schizophrenic brain cDNA, The closest match of these three sequences i s to a family of retroposons, that has evolved from the HERV-K family of en dogenous retroviruses, some members of which (e.g., SINE-R.C2) appear to be specific to the human genome. This element has been reported as a cause of Fukuyama-type muscular dystrophy [Kobayashi et al,, 1998: Nature 394:388-3 92]. Such retroposons, as agents of change in the human genome, provide a s trategy for investigating pathogenesis. On account of their genomic locatio n in a region that has been subject to change in the course of hominid evol ution, and that may have a relationship to psychosis and/or cerebral asymme try, we conclude that these particular insertions deserve further investiga tion. (C) 1999 Wiley-Liss, Inc.