University of Connecticut
Department of Molecular & Cell Biology
354 Mansfield Road, Unit 1131
Beach Hall 343
Storrs, CT 06269-1131
Education: Ph.D.- University of Texas at Austin: Post-doctoral study- University of Melbourne, Princeton University
Research Interests: Epigenetic inheritance, defined as the transmission of traits independent of DNA sequence, takes many forms and is widely seen in both plants and animals. Epigenetic marks may take the form of specific patterns of DNA methylation or heterochromatinization and may be evinced as differential transcriptional states in developing embryos. Three well-studied examples of epigenetic inheritance are paramutation in maize, transvection in Drosophila and genomic or gametic imprinting in mammals and seed-bearing plants. Imprinting can be broadly defined as the unequal representation or function of genes or chromosomes based on parental origin. This broad definition of imprinting includes mechanisms of chromosome expulsion or diminution seen in embryonic development of several invertebrates. The primary focus of research in my lab is genomic imprinting that is manifest as the unequal expression of alleles of a gene based on parental origin. To date, this type of imprinting has only been seen in mammals. We currently know of about 40 genes that show parent of origin effects on transcription and there are likely to be many more in the genome. Some of these genes are transcriptionally silent when inherited from the father; others are transcriptionally silent when inherited from the mother.
Despite more than ten years of molecular genetic research focused on imprinted genes, the evolutionary origins and, indeed, the function of genomic imprinting remain obscure. Disruptions in imprinted gene expression are associated with several inherited diseases and certain types of cancer in humans. To advance our understanding of genomic imprinting my laboratory addresses three fundamental questions: 1) How and why did genomic imprinting evolve? 2) What are the consequences of genomic imprinting for embryonic development, specifically neurological development? 3) What are the molecular mechanisms that render a gene transcriptionally silent in a parent specific manner?
Waugh-O’Neill, R.J., O’Neill, M.J., and Graves, J.A.M. (1999) Genome evolution. Role of methylation in eutherian hybrids. Nature 401: 131-132.
Vrana, P.B., Fossella, J.A., Matteson, P., del Rio, T., O’Neill, M.J. and Tilghman, S.M. (2000) Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in peromyscus. Nat Genet. 25:120-4.
O’Neill, M.J., Binder, M.D., Smith C.A., Reed K., Smith M.J., Millar C., Lambert D. and Sinclair, A.H. (2000) ASW: a Gene with Conserved Avian W-linkage and Female Specific Expression in Chick Embryonic Gonad. Development Genes and Evolution 210:243-249.
O’Neill, M.J., Ingram, R.S., Vrana, P.B. and Tilghman, S.M. (2000) Allelic expression of IGF2 in marsupials and birds. Development Genes and Evolution 210:18-20.
O’Neill, M., Brewer, W., Thornley, C., Copolov, D., Warne, G., Forrest, S., Sinclair, A. and Williamson, B. (1999) The Kallmann Syndrome Gene (KA L-X) Is Not Mutated in Schizophrenia. American Journal of Medical Genetics (Neuropsychiatric Genetics) 88: 34-37.
Waugh-O’Neill, R.J., O’Neill, M.J., and Graves, J. M. Undermethylation Associated with Retroelement Activation and Chromosome Remodelling in an Interspecific Mammalian Hybrid. Nature 397: 68-72.
O’Neill, M.J., Tridjaja, B., Smith, M.J., Bell, K.M., Warne, G.L. and Sinclair, A.H. (1998) Familial Kallmann Syndrome: A Novel Splice Acceptor Mutation in the KAL gene. Human Mutation 11(4):340-342.
O’Neill, M.J. and Sinclair, A.H. (1997) Isolation of Rare Transcripts by Representational Difference Analysis. Nucleic Acids Research 25,13: 2681-2682.