title: Evidence for linkage to psychosis and cerebral asymmetry (relative hand skill) on the X chromosome.
abstract: The hypothesis that psychosis arises as a part of the genetic diversity associated with the evolution of language generates the prediction that illness will be linked to a gene determining cerebral asymmetry, which, from the evidence of sex chromosome aneuploidies, is present in homologous form on the X and Y chromosomes. We investigated evidence of linkage to markers on the X chromosome in 1) 178 families multiply affected with schizophrenia or schizoaffective disorder with a series of 16 markers spanning the centromere (study 1), and 2) 180 pairs of left-handed brothers with 14 markers spanning the whole chromosome (study 2). In study 1, excess allele-sharing was observed in brother-brother pairs (but not brother-sister or a small sample of sister-sister pairs) over a region of approximately 20 cM, with a maximum LOD score of 1.5 at DXS991. In study 2, an association between allele-sharing and degree of left-handedness was observed extending over approximately 60 cM, with a maximum lod score of 2.8 at DXS990 (approximately 20 cM from DXS991). Within the overlap of allele-sharing is located a block in Xq21 that transposed to the Y chromosome in recent hominid evolution and is now represented as two segments on Yp. In one of two XX males with psychosis we found that the breakpoint on the Y is located within the distal region of homology to the block in Xq21. These findings are consistent with the hypothesis that an X-Y homologous determinant of cerebral asymmetry carries the variation that contributes to the predisposition to psychotic illness.
authors.affiliation: Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: S H
authors.initials: SH
authors.lastname: Laval
authors.forename: J C
authors.initials: JC
authors.lastname: Dann
authors.forename: R J
authors.initials: RJ
authors.lastname: Butler
authors.forename: J
authors.initials: J
authors.lastname: Loftus
authors.forename: J
authors.initials: J
authors.lastname: Rue
authors.forename: S J
authors.initials: SJ
authors.lastname: Leask
authors.forename: N
authors.initials: N
authors.lastname: Bass
authors.forename: M
authors.initials: M
authors.lastname: Comazzi
authors.forename: A
authors.initials: A
authors.lastname: Vita
authors.forename: S
authors.initials: S
authors.lastname: Nanko
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: P
authors.initials: P
authors.lastname: Peterson
authors.forename: G
authors.initials: G
authors.lastname: Shields
authors.forename: A B
authors.initials: AB
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Stewart
authors.forename: L E
authors.initials: LE
authors.lastname: DeLisi
authors.forename: T J
authors.initials: TJ
authors.lastname: Crow
mesh_terms: D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D014960:X Chromosome
chemical_list: D005819:Genetic Markers