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 block linked to handedness and psychosis.
We investigated the retroviral/retroposon hypothesis of schizophrenia by generating sequences with PCR primers based on a retroviral sequence recovered by Yee et al. [1998: Schizophr Res 29:92] from a cDNA library from postmortem brain tissue from an individual with psychosis in a genomic region (Xq21.3) 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 sequences, 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 is to a family of retroposons, that has evolved from the HERV-K family of endogenous 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 394:388-392]. Such retroposons, as agents of change in the human genome, provide a strategy for investigating pathogenesis. On account of their genomic location in a region that has been subject to change in the course of hominid evolution, and that may have a relationship to psychosis and/or cerebral asymmetry, we conclude that these particular insertions deserve further investigation.
Kim
H S
HS
POWIC, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.
Wadekar
R V
RV
Takenaka
O
O
Winstanley
C
C
Mitsunaga
F
F
Kageyama
T
T
Hyun
B H
BH
Crow
T J
TJ
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D003175:Complement C2 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics; D019143:Evolution, Molecular; D007839:Functional Laterality / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D000882:Haplorhini; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D011618:Psychotic Disorders / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014960:X Chromosome; D014998:Y Chromosome
D003175:Complement C2; D018076:DNA, Complementary; D018626:Retroelements