LINKAGE STUDIES IN BIPOLAR AFFECTIVE-DISORDER WITH MARKERS ON CHROMOSOME-21

Straub et al. (1994; Nature Genet. 8: 291-296) have suggested that a s usceptibility gene for bipolar affective disorder is located at chromo some 21q22.3, on the basis of linkage analysis in one large family. Th is result has been supported by Gurling et al. (1995; Nature Genet. 10 , 8-9) who also found some evidence for linkage to this region under l ocus heterogeneity. In order to investigate the validity of these resu lts and to estimate how broadly applicable they are, we performed a li nkage study between bipolar affective disorder and two DNA markers (D2 1S171 and PFKL) from 21q22.3 using 60 bipolar pedigrees from three Eur opean centres and Brazil. The most positive result obtained was a maxi mised admixture lod score of 1.2 for the marker PFKL under the assumpt ion of locus heterogeneity, dominant transmission and a diagnostic cla ssification which included recurrent unipolar depression. However,sinc e lod scores obtained for both markers were substantially negative ove rall, we conclude that there is no common major gene for bipolar affec tive disorder at 21q22.3, It remains possible that a gene of major eff ect in this region operates in a minority of families.