Margaret Ann Pericak-Vance

The focus of my work is the genetic mapping and gene identification of inherited disorders of both a single gene and complex etiology. The emphasis is on the genetic epidemiology aspects of locating genes. The first step in this process is family ascertainment and sampling. I employ linkage analysis techniques in order to localize both causative as well as susceptibility genes for genetic disease. In Mendelian disorders such as Huntington disease, myotonic dystrophy, etc., I identify the narrowest region where the gene could lie and hence where the molecular biologist can focus. For common complex disorders such as Alzheimer disease and multiple sclerosis, we identify susceptibility loci that can have a major effect on risk of developing the disease. I am interested in the connection between genotype and it's expression as a phenotype, and in the interaction of genes and/or the environment in the resultant phenotype. I am also involved in the extension and development of new methodological approaches towards the mapping of complex diseases. My research to date has involved the genetic mapping of human disease genes. Specifically, I have mapped the genes for late onset Alzheimer disease (APOE on chromosome 19 and the recently identified locus on chromosome 12), Lou Gehrig's disease (amyotrophic lateral sclerosis; SOD1 on chromosome 21), various muscular dystrophies, and several Mendelian eye disorders. Most recently I have been involved in identifying potential susceptibility genes in multiple sclerosis, autism, primary-open-angle glaucoma and age-related macular degeneration. I have pioneered the application of genetic epidemiological tools in the mapping of complex common disease genes.

The approaches and techniques used in my research include clinical diagnosis, elements of statistical evaluation of the data, application of statistical genetic techniques of gene mapping and gene identification. The specific techniques include model dependent (LOD score) and model independent (sibpair, affected relative pair) linkage analysis as well as family-based and case/control association studies.

The areas of expertise in which I have national recognition is the genetic mapping and identification of genes in both Mendelian as well as complex common genetic disorders. In addition to the above specific areas or diseases that I am often asked to review or counsel on are Alzheimer disease, multiple sclerosis, general neurogenetics, ophthalmological genetics, autism, genetic counseling for risk assessment and human genetics in general.