Evidence for linkage to psychosis and cerebral asymmetry (relative hand skill) on the X chromosome.
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.
Laval
S H
SH
Department of Psychiatry, Warneford Hospital, Oxford, UK.
Dann
J C
JC
Butler
R J
RJ
Loftus
J
J
Rue
J
J
Leask
S J
SJ
Bass
N
N
Comazzi
M
M
Vita
A
A
Nanko
S
S
Shaw
S
S
Peterson
P
P
Shields
G
G
Smith
A B
AB
Stewart
J
J
DeLisi
L E
LE
Crow
T J
TJ
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
D005819:Genetic Markers