Retroelements As Potential Pathogens in Neuropyschiatric Diseases

Retroelements As Potential Pathogens in Neuropyschiatric


H-S Kim, R Wadekar, J-Y Choi, B-H Hyun, H-M Kit, O Takenaks

and TJ Crow

The hypothesis that the predisposing gene has the structure of a

retrovirus or retrotransposon (Crow, 1984) explains some aspects of psychosis

(e.g. episodicity), and is susceptible to investigation through molecular

homologies.  We have employed a combination of a PCR search based upon

known sequences and phylogenetic analysis of these sequences in Hopo sapiens and

hominoid primates to investigate this hypothesis.  We have identified three

classes of element that have been subject to recent change in the course of

primate evolution and that include members that are specific to the human

genome: (1) the SINE.C2 element that has been associated with Fukuyama-type

muscular dystrophy (Kim et al, in press,a) and long terminal repeat (LTR)

structures associated with the human endogenous retroviruses (HERVs) in the (2)

HERV-K and (3) HERV-W classes (Kim et al, in press, b, c).  Each of these

classes has the capacity to active adjacent genes and includes members that have

been subject to recent transposition in the human genome.  We have

investigated elements in these classes that are present within the region of

Xq21.3/Yp region of homology that was generated by a transposition from the X to

the Y chromosome that occurred after the separation of the chimpanzee and Homo

sapiens lineages.  These elements are of interest in relation to the

hypothesis that a gene for cerebral asymmetry is present within this region, and

is associated with variations that is relevant to predisposition to

neuropsychiatric diseases (Crow, 1999).

We envisage that a strategy that combines the phylogenetic

approach across primate species (to select those elements are are labile in

evolution) with what is know about the origin of the human capacity for language

(that it depended upon a change that allowed the brain to develop with an

asymmetrical torque across the fronto-occipital axis through a change in an X-Y

homologous gene) together with knowledge of the recent evolutionary history of

the sex chromosomes, may succeed in defining the critical genomic element when

these strategies pursued independently might fail.

Crow TJ.  A re-evaluation of the viral hypothesis: is

psychosis the result of retroviral integration at a site close to the cerebral

dominance gene?  Brit J Psychiat 1984;145:243-253.

Crow TJ. The case for an Xq21.3/Yp homologous locus in the

evolution of language and the origins of psychosis.  Acta Neuropsychiatrica


Kim H-S, Wadekar T, Takenaka O, et al.  SINE-R.C2 (a Homo

sapiens specific retroposon) is homologous to cDNA from post-mortem brain in

schizophrenia and to two loci in the Xq21.3/Yp block linked to handedness and

psychosis.  Am J Med Genet (Neuropsychiatric Genetics) in press.

Kim H-S, Takenaka O, Crow TJ.  Isolation and phylogeny of

endogenous retroviral sequences belonging to the HERV-W family in primate. J Gen

Virol (in press)

Kim H-S, Crow TJ.  Identification and phylogeny ofnovel

human endogenous retroviral sequences belonging to the HERV-W family on the

human X chromosome.  Arch Virol (in press).