Kenneth K. Kidd

Professor of Genetics, Psychiatry, and Molecular, Cellular & Developmental Biology

B.A. University of Southern California, 1965
Ph.D. University of Wisconsin, 1969

Research Interests:

Complex Human Disorders
Neuropsychiatric Disorders
Human Population Genetics
Human Evolution

Honors:

Fellow, American Association for the Advancement of Science
Mellon Distinguished Visiting Professor, University of Witwatersrand, South Africa
Carter Medal and Lecture, British Society of Human Genetics
"Profiles in DNA Courage" award, U.S. National Institute of Justice

Normal DNA sequence variation such as single nucleotide polymorphisms (SNPs), short tandem repeat polymorphisms (STRPs), etc. have made Homo sapiens amenable to many types of genetic analysis. We are using these polymorphisms to search for the genes for several inherited disorders, including neuropsychiatric disorders, and working on statistical methods to analyze the data. We are also studying these polymorphisms on DNA samples from many different human populations with an emphasis on understanding the organization of normal variation including studies of linkage disequilibrium and estimates of the distribution of the variation in the entire species.

Current Research

For the past several years my laboratory has studied the genetics of complex human disorders, those disorders that fail to show a Mendelian pattern but do "run in families". DNA polymorphisms are now being used to search for the genetic loci of major effect in behavioral and other complex disorders. Our efforts to find genes responsible for neuropsychiatric disorders have most recently focussed on Giles de la Tourette syndrome, but studies of schizophrenia are also ongoing. In both cases, we have family data, collected in collaboration with many other investigators, on which extensive diagnostic evaluations have been completed. Complete 10 cM genome scans have been completed on most of the large kindreds and sets of small families but no definitive evidence of major loci has yet emerged.

We are also studying the population genetics of expressed and non-expressed genetic variation at several genes of known neurologic relevance, such as the dopamine receptors D2 and D4. Because of their demonstrated relevance to alcoholism we are studying the genes involved in ethanol metabolism, the ADH genes and ALDH2. Understanding the nature of the common normal variation at these loci provides a background for investigating how they might influence normal and abnormal neurologic/metabolic function and susceptibility to psychiatric disorders.

Several more evolution-oriented projects are also being pursued. These include theoretical studies as well as studying samples from diverse human populations for DNA polymorphisms. For some genes of interest we are also collecting DNA sequence of other great apes to examine the origins of the human lineage. The lab's efforts are currently focused on genome diversity among world populations and understanding how that diversity arose. We have accumulated cell lines on individuals from over 30 different populations and plan to increase this resource in the coming years. On a global basis we are finding that the majority of alleles for nuclear DNA polymorphisms are present in most populations around the world, though sub-Saharan African populations have more genetic variation (alleles), in general, than indigenous populations in any other part of the world. We interpret the data to mean that there was a major founder effect and loss of variation associated with the expansion of modern humans out of Africa. Haplotype data collected on all of the populations we are studying are beginning to reveal patterns that provide a better understanding of that founder effect and the recent evolutionary history of modern humans.

Polymorphic patterns for the alpha satellite repetitive DNA on chromosome 17. The commonly seen polymorphism, using Pvu II to digest genomic DNA of caucasians, is the presence or absence of a tandemly repeated sequence of 2.2kb, as illustrated in the first two lanes. We have found several new variant phenotypes in African pygmies, as illustrated in lanes 3 through 7.

Representative Publications:

Tishkoff, S.A., E. Dietzsch, W. Speed, A.J. Pakstis, K. Cheung, J.R. Kidd, B. Bonne-Tamir, A.S. Santachiara-Benerecetti, P. Moral, E. Watson, M. Krings, S. Paabo, N. Risch, T. Jenkins, and K.K. Kidd, 1996. Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science 271:1380-1387.

Kidd, K.K., B. Morar, C.M. Castiglione, H. Zhao, A.J. Pakstis, W.C. Speed, B. Bonne-Tamir, R.-B. Lu, D. Goldman, C. Lee, Y.S. Nam, D.K. Grandy, T. Jenkins, and J.R. Kidd, 1998. A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus. Human Genetics 103:211-227.

Calafell, F., A. Shuster, W.C. Speed, J.R. Kidd, and K.K. Kidd, 1998. Short tandem repeat polymorphism evolution in humans. European Journal of Human Genetics 6:38-49.

Osier, M., A.J. Pakstis, J.R. Kidd, J.-F. Lee, S.-J. Yin, H.-C. Ko, H.J. Edenberg, R.-B. Lu, and K.K. Kidd, 1999. Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. American Journal of Human Genetics 64:1147-1157.

Palmatier, M.A., A. Min Kang, and K.K. Kidd, 1999. Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles. Biological Psychiatry 46:557-567.

Zhao, H., K.R. Merikangas, and K.K. Kidd, 1999. On a randomization procedure in linkage analysis. American Journal of Human Genetics 65:1449-1456.

The International Tourette Syndrome Genetics Consortium, 1999. A complete genome screen in sib-pairs affected with Gilles de la Tourette syndrome. American Journal of Human Genetics 65:1428-1436.

Kidd, J.R., A.J. Pakstis, H. Zhao, R.-B. Lu, F.E. Okonofua, A. Odunsi, E. Grigorenko, B. Bonne-Tamir, J. Friedlaender, L.O. Schulz, J. Parnas, and K.K. Kidd, 2000. Haplotypes and linkage disequilibrium at the phenylalanine hydroxylase locus (PAH) in a global representation of populations. American Journal of Human Genetics 66:1882-1899.

Updated 19 December 2000