X-chromosome markers and manic-depressive illness. Rejection of linkage to Xq28 in nine bipolar pedigrees.

Numerous reports have been published concerning linkage of X-chromosome markers of the q28 region (including protan and deutan color blindness [CB] and glucose-6-phosphate dehydrogenase deficiency) to manic-depressive illness. We studied nine bipolar pedigrees (in which there was no male-to-male transmission) in an attempt to detect linkage, using three tightly linked polymorphic DNA loci, DXS15, DXS52 and F8C (factor 8 gene), all of which are closely linked to the CB and glucose 6-phosphate dehydrogenase classic Xq28 markers. Linkage to this region of Xq28 could be excluded unequivocally in these nine families. When these data were combined with our earlier series of bipolar pedigrees, informative for either protan or deutan CB, a total of 14 bipolar pedigrees have been studied, with no evidence of linkage or heterogeneity. At a recombination fraction (theta) of 1%, this series had greater than 95% power to detect linkage if only 50% of the pedigrees studied were linked to the CB region. Our failure to confirm the previously reported linkage of manic-depressive illness to the CB region of the X chromosome indicates that this linkage is not as common as previously suggested.