David C. Page, MD

Director, Whitehead Institute Professor of Biology, MIT Investigator of the Howard Hughes Medical Institute 617.258.5203 page_admin@wi.mit.edu

Whitehead Institute Director David C. Page has conducted fundamental studies of mammalian sex chromosomes and their roles in germ cell development, with special attention to the function, structure, and evolution of the Y chromosome. His laboratory recently completed the sequencing of the human Y chromosome in conjunction with the Washington University Genome Sequencing Center. Page’s laboratory first reported DNA-based deletion maps of the Y chromosome in 1986, comprehensive clone-based physical maps of the chromosome in 1992, and systematic catalogs of Y-linked genes in 1997 [ page research 220 kbps QuickTime].

These genomic studies have led to unanticipated biological insights. The Page laboratory reconstructed the evolution of today's X and Y chromosomes from an ancestral pair of autosomes that existed 300 million years ago. His laboratory discovered molecular evolutionary mechanisms by which the Y chromosome became functionally specialized, in male germ cell development and spermatogenesis. The lab discovered and characterized the most common genetic cause of spermatogenic failure in humans, the deletion of the AZFc region of the Y chromosome.

In conjunction with colleagues at Washington University, the Page lab discovered that most of the Y chromosome’s testis genes exist as mirror-image pairs on massive palindromes. They determined that these palindromes are sites of frequent gene conversion and, thus, that the male-specific chromosome is intensely recombinogenic despite the absence of conventional crossing over to a partner chromosome. Page and his colleagues have also been sequencing the chimpanzee Y chromosome. While this is still a work in progress, their initial findings have shown that while the human Y has remained intact, the chimpanzee Y has in fact been losing genes over the last 10 million years.

Having explored the chromosomal basis of human sex reversal (XX maleness) in the 1980s, Page is now turning his attention to the question of germ cell sex determination in mammals, and to the development of the embryonic ovary.

Page is Director of the Whitehead Institute, professor of biology at the Massachusetts Institute of Technology, and Investigator at the Howard Hughes Medical Institute. In 1992, he founded the Whitehead Task Force on Genetics and Public Policy. He is editor (with Matthew Scott) of Current Opinion in Genetics and Development and associate editor of the Annual Review of Human Genetics and Genomics.

Page trained in the laboratory of David Botstein, at MIT, while earning an M.D. magna cum laude from Harvard Medical School and the Harvard-MIT Health Sciences and Technology Program.

Selected Publications

Hughes, J.F., Skaletsky, H., Pyntikova T., Minx, P.J., Graves, T., Rozen, S., Wilson, R.K., Page, D.C. (2005) Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee. Nature, Vol 436, (7055) 101-104.

Cordum, H.S., Hillier, L., Brown, L.G., Repping, S., Pyntikova, T., Ali, T.J., Bieri, T., Chinwalla, A., Delehaunty, A., Delehaunty, K., Du, H., Fewell, G., Fulton, L., Fulton, R., Graves, T., Hou, S.-F., Latrielle, P., Leonard, S., Mardis, E., Maupin, R., McPherson, J., Miner, T., Nash, W., Nguyen, C., Ozersky, P., Pepin, K., Rock, S., Rohlfing, T., Scott, K., Schultz, B., Strong, C., Tin-Wollam, A., Yang, S.-P., Waterston, R.H., Wilson, R.K., Rozen, S., Page, D.C. (2003). The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature, 423, 825-837.

Rozen, S., Skaletsky, H., Marszalek, J.D., Minx, P.J., Cordum, H.S., Waterston, R.H., Wilson, R.K., Page, D.C. (2003). Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature, 423, 873-876.

Menke, D.B., Koubova, J., Page, D.C. (2003). Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave. Developmental Biology, 262, 303-313.

Repping, S., Skaletsky, H., Brown, K., van Daalen, S.K.M., Korver, C.M., Pyntikova, T., Kuroda-Kawaguchi, T., de Vries, J.W.A., Oates, R.D., Silber, S., van der Veen, F., Page, D.C., Rozen, S. (2003). Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between mutation and haploid selection.
Nature Genetics, 35, 247-251.

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