HomeResearchIntramural ResearchResearch Branches at NHGRIInherited Disease Research Branch Wilson Lab

Alexander Wilson, Ph.D. Co-Chief & Senior Investigator Inherited Disease Research Branch Head Genometrics Section B.A. Western Maryland College, 1975 Ph.D. Indiana University, 1980 (410) 550-7510 (410) 550-7513 afw@mail.nih.gov Johns Hopkins University 333 Cassell Dr, Suite 2000 Baltimore, MD 21224 Selected Publications Genometric Analysis Simulation Program (GASP)

Along with his background in medical genetics and biology, Dr. Wilson uses statistics, mathematics, and computer science to develop new methodologies for performing statistical genetic analysis. Most of the traits he studies are multifactorial, not Mendelian single-gene diseases. By analyzing the patterns of genetic markers in people with a disease and people who are healthy, Dr. Wilson's group identifies chromosomal regions where disease genes most likely reside..

Dr. Wilson's research covers a wide range of disorders, ranging from scoliosis (extreme curvature of the spine) to obesity and cardiovascular disease. Working with investigators at The Johns Hopkins University, Dr. Wilson's group recently determined that at least some cases of scoliosis are linked to a gene on the X chromosome, paving the way for research to identify the causative gene (or genes). This is a significant discovery, because scoliosis affects about one in 200 people, most often girls between 10 and 16 years of age. Although most cases are mild, some can be crippling.

Similarly, by analyzing data from an ongoing genotyping study of traits related to obesity in the Old Order Amish in Pennsylvania, Dr. Wilson's group recently found candidate regions for obesity-related genes on five chromosomes. The strongest signal was found on a region on chromosome 7- in an area that holds a dozen or more genes encoding taste and smell receptors. Moreover, Dr. Wilson's group has collaborated in other studies that provided evidence for the presence of genetic factors influencing body mass index (BMI), the standard measure of obesity. Ironically, BMI was once considered the prime example of a purely environmental factor that contributed to heart disease; researchers can now begin to elucidate the influence of genetics on an individual's BMI.

Dr. Wilson also helps to develop important new methodologies to bolster statistical geneticists' toolkits. For example, he combined a traditional test of heritability with a standard analysis of variance test in a way that simplifies and significantly reduces the cost of testing for the heritability of quantitative traits. This methodology is called regression of offspring on midparent (ROMP). Tests of association for quantitative traits traditionally have required genotyping parents and offspring in large numbers of families, a process that can be extremely costly. However, ROMP requires investigators only to genotype the offspring while phenotyping the parents. In a study of high blood pressure, for example, scientists would use ROMP to genotype the offspring while only checking the parents' blood pressures. When a series of computerized calculations is performed, ROMP can use these tests to estimate the heritability of the trait and determine whether the locus being studied contains a gene that affects the trait.

Dr. Wilson also created a software program called GASP (for Genometric Analysis Simulation Program), which enables scientists to create models of populations or of families with different mixtures of genetic and environmental influenced diseases. Because such data are often "noisy," GASP allows the creation of sample situations without extraneous factors, with one or more genes plugged in for analysis by various statistical methods. In this way, statistical geneticists can use GASP to try out new analytical approaches. Investigators at more than 70 institutions in at least 14 countries are using GASP to test new methodologies and as a teaching tool.

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Last Updated: May 27, 2008