Nature Genetics
3, 49 - 55 (1993)
doi:10.1038/ng0193-49
Diminished support for linkage between manic depressive illness and X−chromosome markers in three Israeli pedigreesMiron Baron1, Nelson F. Freimer1, 5, Neil Risch2, Bernard Lerer3, Joyce R. Alexander3, Richard E. Straub1, Susha Asokan1, Kamna Das1, Amy Peterson1, 5, Jean Amos4, Jean Endicott1, Jurg Ott1
& T. Conrad Gilliam1
1New York State Psychiatric Institute and Departments of Psychiatry and Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
2Departments of Epidemiology and Public Health and of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
3Department of Psychiatry, Hadassah−Hebrew University Medical Center, Jerusalem 91120, Israel
4Center for Human Genetics, Boston University Medical Center, Boston, Massachusetts 02118, USA
5current address: Langley Porter Psychiatric Institute and Department of Psychiatry, University of California at San Francisco, San Francisco, California 94143, USA Correspondence should be addressed to M.B. The hypothesis that chromosomal region Xq27−28 harbours a gene for manicdepression 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 DMA 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.
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