Arthur L. Beaudet, M.D.
M.I.N.D. Institute Distinguished Lecturer Series: November 8, 2006
Arthur L. Beaudet, M.D., is the Henry and Emma Meyer Distinguished Service Professor and Chair of the Department of Molecular and Human Genetics at Baylor College of Medicine in Houston. Dr. Beaudet received his B.S. in Biology magna cum laude from College of the Holy Cross and M.D. cum laude from Yale University. Following a pediatrics residency at Johns Hopkins University and two years as a Research Associate at the National Institutes of Health in Bethesda, he joined the Baylor College of Medicine in 1971, where he has remained to the present.
Dr. Beaudet has published over 200 original research articles in diverse aspects of mammalian genetics. His contributions included the demonstration of mutations in cultured somatic cells in the 1970s at a time when such evidence was still considered novel. He published extensively on inborn errors of metabolism, particularly on urea cycle disorders. His group was the first to describe uniparental disomy in humans in 1988. He has had long-standing interests in somatic gene therapy and in cystic fibrosis. More recently his major focus has been on genomic imprinting as it relates to Prader-Willi and Angelman syndromes, including identification of the gene causing Angelman syndrome.
Dr. Beaudet is well known as one of the editors of Metabolic and Molecular Bases of Inherited Disease for the 6th through 8th editions, and has served on many editorial boards and national review panels. A past president of the American Society of Human Genetics, he is an elected member of the Association of American Physicians and the Institute of Medicine of the National Academy of Sciences.
A Mixed Epigenetic/Genetic and DeNovo/Inherited (MEGDI) Model for Autism (4 pm)
The genetic contribution to autism is often attributed to the combined effects of many loci (ten or more). This conclusion is based in part on the much lower concordance for dizygotic than for monozyotic twins, and is consistent with the failure to find strong evidence for linkage in genome-wide studies. We propose that the twin data are compatible with oligogenic inheritance (two or more loci) combined with a major, genetic or epigenetic, de novo component to the etiology. Based on evidence that maternal but not paternal duplications of chromosome 15q cause autism, we attempted to test the hypothesis that autism involves oligogenic inheritance and that the Angelman gene, which encodes the E6-AP ubiquitin ligase, is one of the contributing genes. Based on evidence for allele sharing in 15q among sib-pairs, abnormal DNA methylation downstream from Angelman gene coding region in one of 17 autism brains, and decreased E6-AP protein in some autism brains, we propose a mixed epigenetic and genetic model for autism with both de novo and inherited contributions. A mixed epigenetic and genetic and mixed de novo and inherited (MEGDI) model could also be relevant to other “complex disease traits.”
If the Incidence of Autism Is Increasing, What Could Be the Cause? (6 pm)
Reports of a dramatic increase in the incidence of autism over the last 30 years have lead to considerable debate as to whether the apparent increase is real or artifact. Some researchers believe that more children per capita are being born with autism. Other researchers agree that many more children are receiving a diagnosis of autism, but argue that this is a reflection of changing use of diagnostic categories, greater awareness of autism, and increased services available to children with a diagnosis of autism. I will review this debate and address some of the relevant issues, including whether a final answer to this controversy is currently available. Whether or not a real increase exists has very important implications for research and prevention, and possibly for treatment. For example, a real increase in autism would point to some environmental change/factor, probably produced by human activities, which is interacting with the genetic makeup of infants. Along these lines, I will discuss a number of possible factors, including the intake of folic acid by the population and exposure to prenatal ultrasound.