Diminished Support for Linkage Between Manic Depressive Illness and
X-chromosome Markers in Three Israeli Pedigrees
M. Baron, N.F. Freimer, N. Risch, B. Lerer, J.R. Alexander,
R.E. Straub, S. Asokan, K. Das, A. Peterson, J. Amos, J. Endicott,
J. Ott, C. Gilliam
Nature Genetics , 3(1), 49--55 (1993 Jan)
Abstract
The hypothesis that chromosomal region Xq27-28 harbours a gene for
manic-depression has been a focus of interest in human genetics.
X-linked inheritance of manic depressive illness has been
re-examined in 3 multigeneration Israeli kindreds. Extension and
re-evaluation of pedigree data, including new individuals,
diagnostic follow-up, and analysis with DNA markers, shows greatly
diminished support for linkage to Xq28. The peak lod scores in two
of the pedigrees have dropped several lod units to clearly negative
values at the RCP-F8-G6PD gene cluster. On the other hand, positive
lod scores (Zmax = 2.09) are sustained in another pedigree at the
same map location. None of the pedigrees show linkage to more
proximal markers, including the Xq27 locus DXS98. Our analysis
underscores the uncertainties in studying complex disorders.
Comment in: Nat Genet 1993 Jan;3(1):4-5;
Comment in: Nat Genet 1994 Mar;6(3):224
