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 diversit y associated with the evolution of language generates the prediction t hat illness will be linked to a gene determining cerebral asymmetry, w hich, from the evidence of sex chromosome aneuploidies, is present in homologous form on the X and Y chromosomes. We investigated evidence o f linkage to markers on the X chromosome in 1) 178 families multiply a ffected with schizophrenia or schizoaffective disorder with a series o f 16 markers spanning the centromere (study 1), and 2) 180 pairs of le ft-handed brothers with 14 markers spanning the whole chromosome (stud y 2), In study 1, excess allele-sharing was observed in brother-brothe r pairs (but not brother-sister or a small sample of sister-sister pai rs) 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 d egree of left-handedness was observed extending over approximately 60 cM, with a maximum lod score of 2.8 at DXS990 (approximately 20 cM fro m DXS991). Within the overlap of allele-sharing is located a block in Xq21 that transposed to the Y chromosome in recent hominid evolution a nd is now represented as two segments on Yp. In one of two MI males wi th psychosis we found that the breakpoint on the Y is located within t he distal region of homology to the block in Xq21, These findings are consistent with the hypothesis that an X-Y homologous determinant of c erebral asymmetry carries the variation that contributes to the predis position to psychotic illness. (C) 1998 Wiley-Liss, Inc.