David C. Page: Difference between revisions
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'''David C. Page''', MD, is a professor of [[biology]] at the [[Massachusetts Institute of Technology]] (MIT) and the director of the [[Whitehead Institute]], and is best known for his work on mapping the [[Y-chromosome]] and on its evolution in mammals and expression during development. |
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'''David C. Page''', MD, is a professor of [[biology]] at the [[Massachusetts Institute of Technology]] (MIT) and the director of the [[Whitehead Institute]], where he has a laboratory devoted to the study of the [[Y-chromosome]]. His lab mapped the human Y chromosome in 1992. In 2003, his research group sequenced the human Y chromosome.<ref>{{Cite journal | last1 = Skaletsky | first1 = H. | last2 = Kuroda-Kawaguchi | first2 = T. | last3 = Minx | first3 = P. J. | last4 = Cordum | first4 = H. S. | last5 = Hillier | first5 = L. | last6 = Brown | first6 = L. G. | last7 = Repping | first7 = S. | last8 = Pyntikova | first8 = T. | last9 = Ali | first9 = J. | last10 = Bieri | doi = 10.1038/nature01722 | first10 = T. | last11 = Chinwalla | first11 = A. | last12 = Delehaunty | first12 = A. | last13 = Delehaunty | first13 = K. | last14 = Du | first14 = H. | last15 = Fewell | first15 = G. | last16 = Fulton | first16 = L. | last17 = Fulton | first17 = R. | last18 = Graves | first18 = T. | last19 = Hou | first19 = S. F. | last20 = Latrielle | first20 = P. | last21 = Leonard | first21 = S. | last22 = Mardis | first22 = E. | last23 = Maupin | first23 = R. | last24 = McPherson | first24 = J. | last25 = Miner | first25 = T. | last26 = Nash | first26 = W. | last27 = Nguyen | first27 = C. | last28 = Ozersky | first28 = P. | last29 = Pepin | first29 = K. | last30 = Rock | first30 = S. | title = The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes | journal = Nature | volume = 423 | issue = 6942 | pages = 825–837 | year = 2003 | pmid = 12815422| pmc = }}</ref><ref>[http://www.wi.mit.edu/research/faculty/page.html Whitehead Institute Faculty Page]</ref><ref>[http://mit.edu/biology/www/facultyareas/facresearch/page.html MIT Department of Biology Faculty Page]</ref> |
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== |
== Education and Career == |
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Page was born in Harrisburg, PA in 1956 and grew up in the rural outskirts of [[Pennsylvania Dutch Country|Pennsylvania Dutch country]].<ref>{{Cite journal|title = Profile of David C. Page|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413862/|journal = Proceedings of the National Academy of Sciences of the United States of America|date = 2006-02-21|issn = 0027-8424|pmc = 1413862|pmid = 16481618|pages = 2471–2473|volume = 103|issue = 8|doi = 10.1073/pnas.0600615103|first = Bijal|last = Trivedi}}</ref><ref name=":0">{{Cite web|title = Why, Oh Y? {{!}} The Scientist Magazine®|url = http://www.the-scientist.com/?articles.view/articleNo/41689/title/Why--Oh-Y-/|website = The Scientist|access-date = 2016-02-04}}</ref><ref>{{Cite journal|url = http://d3fnt9hd6tfohz.cloudfront.net/assets/issues/MURJ29_full.pdf|title = MURJ Spotlight: Professor David C. Page, Director of the Whitehead Institute|last = Jagetia|first = Riya|date = Spring 2015|journal = MIT Undergraduate Research Journal|doi = |pmid = |access-date = 4 February 2016|last2 = Berg|first2 = Elizabeth|last3 = Kim|first3 = Jae Hyun|last4 = Jones|first4 = Brianna}}</ref> The first of his family to go to college, Page attended [[Swarthmore College]], where he graduated with a BA with highest honors in chemistry in 1978.<ref name=":0" /><ref name=":1">{{Cite web|title = DAVID PAGE LABORATORY|url = http://pagelab.wi.mit.edu/|website = pagelab.wi.mit.edu|access-date = 2016-02-04}}</ref> During his final year at Swarthmore, Page attended class just one day a week and spent the rest of his time researched [[chromatin]] structure in the laboratory of molecular biologist Robert Simpson at the [[National Institutes of Health]].<ref name=":0" /><ref name=":1" /> In 1978, Page enrolled at [[Harvard Medical School]] and the [[Harvard–MIT Division of Health Sciences and Technology|Harvard-MIT Health Sciences Program]], where he worked in the laboratories of [[David Botstein]] at MIT and Raymond White at the [[University of Massachusetts Medical School]].<ref name=":1" /> In White’s lab, Page worked on a project to develop a [[Genetic linkage|genetic linkage map]] of the human genome that would become a precursor to the [[Human Genome Project]].<ref name=":2">{{Cite journal |
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Page graduated from [[Swarthmore College]] with a degree in chemistry. He received his MD from [[Harvard Medical School]] in 1984 and was appointed a Whitehead Fellow. He was awarded a [[MacArthur Fellowship]] (a "genius" grant) two years later. He joined the faculty of the Whitehead Institute and MIT in 1988. In 1997, Page was awarded an Amory Prize for advances in [[reproductive biology]] by the [[American Academy of Arts and Sciences]]. In 2003, he received the [[Curt Stern Award]]<ref>{{Cite journal |
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|last1 = Trivedi|first1 = B.|title = Profile of David C. Page|doi = 10.1073/pnas.0600615103|journal = Proceedings of the National Academy of Sciences|volume = 103|issue = 8|pages = 2471–2473|year = 2006|pmid = 16481618|pmc = 1413862}}</ref> The work relied on locating [[Restriction fragment length polymorphism|restriction fragment length polymorphisms]] (RFLP). The first RFLP that Page found was from a site of homology between the [[X chromosome]] and Y chromosome, a coincidence that would set the direction of his subsequent career.<ref name=":2" /> |
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| last1 = Page | first1 = D. C. |
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| title = 2003 Curt Stern Award address. On low expectation exceeded; or, the genomic salvation of the Y chromosome |
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When Page finished his MD degree in the spring of 1984, he started his own lab as the first Whitehead Fellow at the [[Whitehead Institute|Whitehead Institute for Biomedical Research]] researching the genetics of [[XX male syndrome]], or de la Chapelle Syndrome.<ref name=":1" /><ref name=":2" /> After Page won the [[MacArthur Fellows Program|MacArthur “Genius Grant”]] in 1986, Page was promoted to the faculty of the Whitehead Institute and the [[MIT Department of Biology]] in 1988.<ref name=":1" /><ref>{{Cite journal|url = http://bulletin.swarthmore.edu/bulletin-issue-archive/wp-content/archived_issues_pdf/Bulletin_1999_09.pdf|title = Save the males: David Page '78 reveals the evolutionary roots of sex and gender|last = Cruzan Morton|first = Carol|date = September 1999|journal = Swarthmore Bulletin|doi = |pmid = |access-date = 4 February 2016}}</ref> In 1990, Page was named a Howard Hughes Medical Institute Investigator, and in 2005 he was named as director of the Whitehead Institute.<ref name=":1" /> |
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| journal = American Journal of Human Genetics |
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| volume = 74 |
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== Research == |
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| issue = 3 |
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| pages = 399–402 |
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=== Mapping the Y Chromosome === |
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| year = 2004 |
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In his work on de la Chapelle Syndrome in 1986, Page collaborated with the geneticist who originally identified the first XX male, [[Albert de la Chapelle]], and geneticist [[Jean Weissenbach]] to show that XX males carry a small piece of the Y chromosome.<ref name=":2" /><ref>{{Cite journal|title = Chromosome Y-specific DNA in related human XX males|url = http://www.ncbi.nlm.nih.gov/pubmed/2987697|journal = Nature|date = 1985-05-16|issn = 0028-0836|pmid = 2987697|pages = 224–226|volume = 315|issue = 6016|first = D. C.|last = Page|first2 = A.|last2 = de la Chapelle|first3 = J.|last3 = Weissenbach}}</ref><ref>{{Cite journal|title = Chromosome Y-specific DNA is transferred to the short arm of X chromosome in human XX males|url = http://www.ncbi.nlm.nih.gov/pubmed/3738510|journal = Science (New York, N.Y.)|date = 1986-08-15|issn = 0036-8075|pmid = 3738510|pages = 786–788|volume = 233|issue = 4765|first = M.|last = Andersson|first2 = D. C.|last2 = Page|first3 = A.|last3 = de la Chapelle}}</ref> |
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| pmid = 15053010 |
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| pmc = 1182254 |
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In the following year, he reported that the gene [[ZFY]] induced the development of the [[testes]], a finding which received a great deal of media attention since it putatively resolving a decade-long search for the sex-determining gene.<ref name=":2" /><ref>{{Cite journal|title = The sex-determining region of the human Y chromosome encodes a finger protein|url = http://www.ncbi.nlm.nih.gov/pubmed/3690661|journal = Cell|date = 1987-12-24|issn = 0092-8674|pmid = 3690661|pages = 1091–1104|volume = 51|issue = 6|first = D. C.|last = Page|first2 = R.|last2 = Mosher|first3 = E. M.|last3 = Simpson|first4 = E. M.|last4 = Fisher|first5 = G.|last5 = Mardon|first6 = J.|last6 = Pollack|first7 = B.|last7 = McGillivray|first8 = A.|last8 = de la Chapelle|first9 = L. G.|last9 = Brown}}</ref> In 1989, a British team of scientists led by [[Peter Goodfellow]] and [[Robin Lovell-Badge]] began to report that the testis-determining gene was not ZFY, which led Page to review his data. Page found that he had misinterpreted his data because one of the XY females in his study had a second deletion at the site which proved to be the location of the real sex-determining gene. Launching a second round of media attention, [[Nature (journal)|Nature]] published his findings together with a paper from the British group that identified the sex-determining gene, which they termed [[Testis determining factor|SRY]].<ref name=":2" /><ref>{{Cite journal|title = The sex-determining region of the human Y chromosome encodes a finger protein|url = https://www.ncbi.nlm.nih.gov/pubmed/3690661|journal = Cell|date = 1987-12-24|issn = 0092-8674|pmid = 3690661|pages = 1091–1104|volume = 51|issue = 6|first = D. C.|last = Page|first2 = R.|last2 = Mosher|first3 = E. M.|last3 = Simpson|first4 = E. M.|last4 = Fisher|first5 = G.|last5 = Mardon|first6 = J.|last6 = Pollack|first7 = B.|last7 = McGillivray|first8 = A.|last8 = de la Chapelle|first9 = L. G.|last9 = Brown}}</ref><ref>{{Cite journal|title = A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif|url = http://www.ncbi.nlm.nih.gov/pubmed/1695712|journal = Nature|date = 1990-07-19|issn = 0028-0836|pmid = 1695712|pages = 240–244|volume = 346|issue = 6281|doi = 10.1038/346240a0|first = A. H.|last = Sinclair|first2 = P.|last2 = Berta|first3 = M. S.|last3 = Palmer|first4 = J. R.|last4 = Hawkins|first5 = B. L.|last5 = Griffiths|first6 = M. J.|last6 = Smith|first7 = J. W.|last7 = Foster|first8 = A. M.|last8 = Frischauf|first9 = R.|last9 = Lovell-Badge}}</ref> |
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| doi=10.1086/382659 |
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}}</ref> from the [[American Society of Human Genetics]]. He has also won the [[March of Dimes Prize in Developmental Biology]].<ref>{{Cite journal |
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Despite a belief among geneticists that the Y chromosome contained few genes other than the sex-determining gene, Page continued to map the Y chromosome. He had already published [[Deletion mapping|DNA-based deletion maps]] of the Y chromosome in 1986,<ref>{{Cite journal|title = A deletion map of the human Y chromosome based on DNA hybridization.|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684749/|journal = American Journal of Human Genetics|date = 1986-02-01|issn = 0002-9297|pmc = 1684749|pmid = 3004206|pages = 109–124|volume = 38|issue = 2|first = G|last = Vergnaud|first2 = D C|last2 = Page|first3 = M C|last3 = Simmler|first4 = L|last4 = Brown|first5 = F|last5 = Rouyer|first6 = B|last6 = Noel|first7 = D|last7 = Botstein|first8 = A|last8 = de la Chapelle|first9 = J|last9 = Weissenbach}}</ref> and went on to develop comprehensive clone-based physical maps of the chromosome in 1992<ref>{{Cite journal|url = http://pagelab.wi.mit.edu/pdf/1992%20-%20The%20human%20Y%20chromosome%20-%20a%2043-interval%20map%20based%20on%20naturally%20occurring%20deletions.pdf|title = The Human Y Chromosome: A 43-Interval Map Based on Naturally Occurring Deletions|last = Vollrath|first = Douglas|date = 2 October 1992|journal = Science|doi = |pmid = |access-date = 4 February 2016|last2 = Foote|first2 = Simon|last3 = Hilton|first3 = Adrienne|last4 = Brown|first4 = Laura G.|last5 = Beer-Romero|first5 = Peggy|last6 = Bogan|first6 = Jonathan|last7 = Page|first7 = David C.|issue = 5079|volume = 258|pages = 52-59}}</ref><ref>{{Cite journal|url = http://pagelab.wi.mit.edu/pdf/1992%20-%20The%20human%20Y%20chromosome%20-%20overlapping%20DNA%20clones%20spanning%20the%20euchromatic%20region.pdf|title = The Human Y Chromosome: Spanning the Euchromatic Region|last = Foote|first = Simon|date = 2 October 1992|journal = Science|doi = |pmid = |access-date = 4 February 2016|last2 = Vollrath|first2 = Douglas|last3 = Hilton|first3 = Adrienne|last4 = Page|first4 = David C.|issue = 5079|volume = 258|pages = 60-66}}</ref> and systematic catalogs of Y-linked genes in 1997.<ref>{{Cite journal|url = http://pagelab.wi.mit.edu/pdf/1997%20-%20Functional%20coherence%20of%20the%20human%20Y%20chromosome.pdf|title = Functional Coherence of the Human Y Chromosome|last = Lahn|first = Bruce|date = 24 October 1997|journal = Science|doi = |pmid = |access-date = 4 February 2016|last2 = Page|first2 = David C.|issue = 5338|volume = 278|pages = 675-680}}</ref> Page collaborated with a team at the [[McDonnell Genome Institute|Genome Institute]] at [[Washington University in St. Louis|Washington University]] to make a complete map of the Y chromosome, which they achieved in 2003.<ref name=":3">{{Cite journal |last1 = Skaletsky|first1 = H.|last2 = Kuroda-Kawaguchi|first2 = T.|last3 = Minx|first3 = P. J.|last4 = Cordum|first4 = H. S.|last5 = Hillier|first5 = L.|last6 = Brown|first6 = L. G.|last7 = Repping|first7 = S.|last8 = Pyntikova|first8 = T.|last9 = Ali|first9 = J.|last10 = Bieri|doi = 10.1038/nature01722|first10 = T.|last11 = Chinwalla|first11 = A.|last12 = Delehaunty|first12 = A.|last13 = Delehaunty|first13 = K.|last14 = Du|first14 = H.|last15 = Fewell|first15 = G.|last16 = Fulton|first16 = L.|last17 = Fulton|first17 = R.|last18 = Graves|first18 = T.|last19 = Hou|first19 = S. F.|last20 = Latrielle|first20 = P.|last21 = Leonard|first21 = S.|last22 = Mardis|first22 = E.|last23 = Maupin|first23 = R.|last24 = McPherson|first24 = J.|last25 = Miner|first25 = T.|last26 = Nash|first26 = W.|last27 = Nguyen|first27 = C.|last28 = Ozersky|first28 = P.|last29 = Pepin|first29 = K.|last30 = Rock|first30 = S.|title = The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes|journal = Nature|volume = 423|issue = 6942|pages = 825–837|year = 2003|pmid = 12815422|pmc = }}</ref> To do so, Page and his colleagues developed a new sequencing technique, single-haplotype iterative mapping and sequencing (SHIMS), since mammalian sex chromosomes contain too many repetitive sequences to be sequenced by conventional approaches.<ref name=":0" /> The development of SHIMS allowed Page to identify long palindromic sequences on the long arm of the Y chromosome, which he would go on to show made the Y chromosome vulnerable to the deletions that cause spermatogenic failure (an inability to produce sperm).<ref>{{Cite journal|title = Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure|url = http://www.ncbi.nlm.nih.gov/pubmed/12297986|journal = American Journal of Human Genetics|date = 2002-10-01|issn = 0002-9297|pmc = 419997|pmid = 12297986|pages = 906–922|volume = 71|issue = 4|doi = 10.1086/342928|first = Sjoerd|last = Repping|first2 = Helen|last2 = Skaletsky|first3 = Julian|last3 = Lange|first4 = Sherman|last4 = Silber|first5 = Fulco|last5 = Van Der Veen|first6 = Robert D.|last6 = Oates|first7 = David C.|last7 = Page|first8 = Steve|last8 = Rozen}}</ref> In 2012, Page characterized the most common genetic cause of spermatogenic failure, the deletion of the AZFc region of the Y chromosome.<ref name=":4">[http://www.wi.mit.edu/research/faculty/page.html Whitehead Institute Faculty Page]</ref><ref>{{Cite journal|title = AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes|url = http://www.ncbi.nlm.nih.gov/pubmed/23103232|journal = American Journal of Human Genetics|date = 2012-11-02|issn = 1537-6605|pmc = 3487143|pmid = 23103232|pages = 890–896|volume = 91|issue = 5|doi = 10.1016/j.ajhg.2012.09.003|first = Steven G.|last = Rozen|first2 = Janet D.|last2 = Marszalek|first3 = Kathryn|last3 = Irenze|first4 = Helen|last4 = Skaletsky|first5 = Laura G.|last5 = Brown|first6 = Robert D.|last6 = Oates|first7 = Sherman J.|last7 = Silber|first8 = Kristin|last8 = Ardlie|first9 = David C.|last9 = Page}}</ref> The lab also found that aberrant crossing over within the Y chromosome’s palindromes underlies a wide range of disorders of sexual differentiation, including Turner syndrome.<ref name=":4" /> |
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| last1 = Page | first1 = D. |
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| title = David Page |
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=== Evolution of the Y Chromosome === |
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| doi = 10.1038/nrg3025 |
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With the development of more detailed maps of the Y chromosome, in the mid-1990s Page began to find genetic evidence confirming the theory that both the X and Y chromosomes had evolved from [[Autosome|autosomes]], beginning with the 1996 discovery that a family of genes called [[DAZ associated protein 1|DAZ]] (deleted in azoospermia) had been transposed from an autosome to the Y chromosome.<ref name=":0" /><ref>{{Cite journal|title = The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned|url = https://www.ncbi.nlm.nih.gov/pubmed/8896558|journal = Nature Genetics|date = 1996-11-01|issn = 1061-4036|pmid = 8896558|pages = 292–299|volume = 14|issue = 3|doi = 10.1038/ng1196-292|first = R.|last = Saxena|first2 = L. G.|last2 = Brown|first3 = T.|last3 = Hawkins|first4 = R. K.|last4 = Alagappan|first5 = H.|last5 = Skaletsky|first6 = M. P.|last6 = Reeve|first7 = R.|last7 = Reijo|first8 = S.|last8 = Rozen|first9 = M. B.|last9 = Dinulos}}</ref> In 1999, Page and his then-graduate student [[Bruce Lahn]] showed that the X and Y chromosomes had diverged in four steps, beginning 200-300 million years ago.<ref>{{Cite journal|title = Four evolutionary strata on the human X chromosome|url = http://www.ncbi.nlm.nih.gov/pubmed/10542153|journal = Science (New York, N.Y.)|date = 1999-10-29|issn = 0036-8075|pmid = 10542153|pages = 964–967|volume = 286|issue = 5441|first = B. T.|last = Lahn|first2 = D. C.|last2 = Page}}</ref> Later cross-species comparisons would show that while ancestral genes on the Y chromosome initially underwent rapid decay,<ref name=":3" /><ref>{{Cite journal|title = Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition|url = http://www.ncbi.nlm.nih.gov/pubmed/20622855|journal = Nature|date = 2010-07-29|issn = 1476-4687|pmc = 2943333|pmid = 20622855|pages = 612–616|volume = 466|issue = 7306|doi = 10.1038/nature09172|first = Daniel W.|last = Bellott|first2 = Helen|last2 = Skaletsky|first3 = Tatyana|last3 = Pyntikova|first4 = Elaine R.|last4 = Mardis|first5 = Tina|last5 = Graves|first6 = Colin|last6 = Kremitzki|first7 = Laura G.|last7 = Brown|first8 = Steve|last8 = Rozen|first9 = Wesley C.|last9 = Warren}}</ref> the remaining genes have remained stable for the last 25 million years,<ref>{{Cite journal|title = Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes|url = http://www.nature.com/nature/journal/v483/n7387/full/nature10843.html|journal = Nature|date = 2012-03-01|issn = 0028-0836|pmc = 3292678|pmid = 22367542|pages = 82–86|volume = 483|issue = 7387|doi = 10.1038/nature10843|language = en|first = Jennifer F.|last = Hughes|first2 = Helen|last2 = Skaletsky|first3 = Laura G.|last3 = Brown|first4 = Tatyana|last4 = Pyntikova|first5 = Tina|last5 = Graves|first6 = Robert S.|last6 = Fulton|first7 = Shannon|last7 = Dugan|first8 = Yan|last8 = Ding|first9 = Christian J.|last9 = Buhay}}</ref> overturning the long-held view that the Y chromosome was going extinct.<ref name=":0" /> In a 2014 study, Page concluded that the conserved genes on the Y chromosome played an important role in male viability, since they were dosage-dependent genes with similar but not identical counterparts on the X chromosome that all have regulatory roles in transcription, translation, and protein stability. Because these genes are expressed throughout the body, Page further concluded that these genes give rise to differences in the biochemistry of male and female tissues.<ref>{{Cite journal|title = Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators|url = http://www.nature.com/nature/journal/v508/n7497/full/nature13206.html|journal = Nature|date = 2014-04-24|issn = 0028-0836|pmc = 4139287|pmid = 24759411|pages = 494–499|volume = 508|issue = 7497|doi = 10.1038/nature13206|language = en|first = Daniel W.|last = Bellott|first2 = Jennifer F.|last2 = Hughes|first3 = Helen|last3 = Skaletsky|first4 = Laura G.|last4 = Brown|first5 = Tatyana|last5 = Pyntikova|first6 = Ting-Jan|last6 = Cho|first7 = Natalia|last7 = Koutseva|first8 = Sara|last8 = Zaghlul|first9 = Tina|last9 = Graves}}</ref> |
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| journal = Nature Reviews Genetics |
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| volume = 12 |
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In super-resolution studies of the sex chromosomes, Page has found evidence of an evolutionary “arms race” between the X and Y chromosomes for transmission to the next generation. In one study, Page found that human X and mouse Y chromosomes have converged, independently acquiring and amplifying gene families expressed in testicular germ cells.<ref>{{Cite journal|title = Independent specialization of the human and mouse X chromosomes for the male germ line|url = http://www.nature.com/ng/journal/v45/n9/full/ng.2705.html|journal = Nature Genetics|date = 2013-09-01|issn = 1061-4036|pmc = 3758364|pmid = 23872635|pages = 1083–1087|volume = 45|issue = 9|doi = 10.1038/ng.2705|language = en|first = Jacob L.|last = Mueller|first2 = Helen|last2 = Skaletsky|first3 = Laura G.|last3 = Brown|first4 = Sara|last4 = Zaghlul|first5 = Susan|last5 = Rock|first6 = Tina|last6 = Graves|first7 = Katherine|last7 = Auger|first8 = Wesley C.|last8 = Warren|first9 = Richard K.|last9 = Wilson}}</ref> Another study found that the mouse Y chromosome had acquired and massively amplified genes homologous to the testis-expressed gene families on the mouse X chromosome.<ref>{{Cite journal|title = Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes|url = http://www.ncbi.nlm.nih.gov/pubmed/25417157|journal = Cell|date = 2014-11-06|issn = 1097-4172|pmc = 4260969|pmid = 25417157|pages = 800–813|volume = 159|issue = 4|doi = 10.1016/j.cell.2014.09.052|first = Y. Q. Shirleen|last = Soh|first2 = Jessica|last2 = Alföldi|first3 = Tatyana|last3 = Pyntikova|first4 = Laura G.|last4 = Brown|first5 = Tina|last5 = Graves|first6 = Patrick J.|last6 = Minx|first7 = Robert S.|last7 = Fulton|first8 = Colin|last8 = Kremitzki|first9 = Natalia|last9 = Koutseva}}</ref> |
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| issue = 7 |
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| pages = 458 |
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=== The Genetics of Germ Cells === |
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| year = 2011 |
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Page used the mouse as a model to study the genetics of [[Meiosis|meiotic]] initiation, showing that [[retinoic acid]] (RA) is the key factor which induces meiosis, as well as identifying several important genes crucial to the meiotic initiation pathway, including Stra8 and [[DAZL]].<ref>{{Cite journal|title = In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication|url = http://www.ncbi.nlm.nih.gov/pubmed/17115059|journal = Nature Genetics|date = 2006-12-01|issn = 1061-4036|pmid = 17115059|pages = 1430–1434|volume = 38|issue = 12|doi = 10.1038/ng1919|first = Andrew E.|last = Baltus|first2 = Douglas B.|last2 = Menke|first3 = Yueh-Chiang|last3 = Hu|first4 = Mary L.|last4 = Goodheart|first5 = Anne E.|last5 = Carpenter|first6 = Dirk G.|last6 = de Rooij|first7 = David C.|last7 = Page}}</ref><ref>{{Cite journal|title = Germ Cell-Intrinsic and -Extrinsic Factors Govern Meiotic Initiation in Mouse Embryos|url = http://science.sciencemag.org/content/322/5908/1685|journal = Science|date = 2008-12-12|issn = 0036-8075|pmid = 19074348|pages = 1685–1687|volume = 322|issue = 5908|doi = 10.1126/science.1166340|language = en|first = Yanfeng|last = Lin|first2 = Mark E.|last2 = Gill|first3 = Jana|last3 = Koubova|first4 = David C.|last4 = Page}}</ref><ref>{{Cite journal|title = Retinoic acid regulates sex-specific timing of meiotic initiation in mice|url = http://www.pnas.org/content/103/8/2474|journal = Proceedings of the National Academy of Sciences of the United States of America|date = 2006-02-21|issn = 0027-8424|pmc = 1413806|pmid = 16461896|pages = 2474–2479|volume = 103|issue = 8|doi = 10.1073/pnas.0510813103|language = en|first = Jana|last = Koubova|first2 = Douglas B.|last2 = Menke|first3 = Qing|last3 = Zhou|first4 = Blanche|last4 = Capel|first5 = Michael D.|last5 = Griswold|first6 = David C.|last6 = Page}}</ref> Page further discovered that the differentiation germ cells into [[Gametocyte|gametocytes]] ([[Oocyte|oocytes]] in females or [[Spermatocyte|spermatocytes]] in males) does not depend on meiotic initiation, as commonly thought, showing that germ cells deficient in Stra8, a gene that activates the meiotic pathway, are still capable of growth and differentiation.<ref>{{Cite journal|title = Periodic retinoic acid-STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis|url = http://www.ncbi.nlm.nih.gov/pubmed/25902548|journal = Proceedings of the National Academy of Sciences of the United States of America|date = 2015-05-05|issn = 1091-6490|pmc = 4426408|pmid = 25902548|pages = E2347–2356|volume = 112|issue = 18|doi = 10.1073/pnas.1505683112|first = Tsutomu|last = Endo|first2 = Katherine A.|last2 = Romer|first3 = Ericka L.|last3 = Anderson|first4 = Andrew E.|last4 = Baltus|first5 = Dirk G.|last5 = de Rooij|first6 = David C.|last6 = Page}}</ref><ref>{{Cite journal|title = Oocyte differentiation is genetically dissociable from meiosis in mice|url = http://www.nature.com/ng/journal/v45/n8/full/ng.2672.html|journal = Nature Genetics|date = 2013-08-01|issn = 1061-4036|pmc = 3747777|pmid = 23770609|pages = 877–883|volume = 45|issue = 8|doi = 10.1038/ng.2672|language = en|first = Gregoriy A.|last = Dokshin|first2 = Andrew E.|last2 = Baltus|first3 = John J.|last3 = Eppig|first4 = David C.|last4 = Page}}</ref> |
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| pmid = 21606932 |
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| pmc = |
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== Awards and Honors == |
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}}</ref> In 2005 he was elected to the [[United States National Academy of Sciences|National Academy of Sciences]].<ref>{{Cite journal |
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* 1986 [[MacArthur Fellows Program|MacArthur Prize Fellowship]]<ref>{{Cite web|title = David C. Page — MacArthur Foundation|url = https://www.macfound.org/fellows/282/|website = www.macfound.org|access-date = 2016-02-04}}</ref> |
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| last1 = Trivedi | first1 = B. |
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* 1989 [[Searle Scholars Program|Searle Scholar Award]]<ref>{{Cite web|title = Searle Scholars Program : David C. Page (1989)|url = http://www.searlescholars.net/person/313|website = www.searlescholars.net|access-date = 2016-02-04}}</ref> |
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| title = Profile of David C. Page |
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* 1990 Serono Award, American Society of Andrology for advances in reproductive biology |
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| doi = 10.1073/pnas.0600615103 |
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* 1997 Francis Amory Prize, [[American Academy of Arts and Sciences]] (for genetic studies of mammalian sex determination; prize shared with Peter Goodfellow and Robin Lovell-Badge) |
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| journal = Proceedings of the National Academy of Sciences |
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* 2003 [[Curt Stern Award]], [[American Society of Human Genetics]] (for outstanding scientific achievement in human genetics)<ref>{{Cite journal|title = On Low Expectations Exceeded; or, The Genomic Salvation of the Y Chromosome|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182254/|journal = American Journal of Human Genetics|date = 2004-03-01|issn = 0002-9297|pmc = 1182254|pmid = 15053010|pages = 399–402|volume = 74|issue = 3|first = David C.|last = Page}}</ref> |
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| volume = 103 |
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* 2005 Member, [[National Academy of Sciences]]<ref name=":2" /> |
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| issue = 8 |
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* 2007 Fellow, [[American Association for the Advancement of Science]]<ref name=":1" /> |
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| pages = 2471–2473 |
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* 2008 Member, [[National Academy of Medicine|Institute of Medicine]]<ref>{{Cite web|title = MIT Office of the Provost, Institutional Research|url = http://web.mit.edu/ir/pop/awards/iom.html|website = web.mit.edu|access-date = 2016-02-04}}</ref> |
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| year = 2006 |
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* 2010 Pioneer in Reproduction Research Award, [[Woods Hole Marine Biological Laboratory]] |
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| pmid = 16481618 |
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* 2011 [[March of Dimes Prize in Developmental Biology]] (prize shared with Patricia Jacobs) |
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| pmc =1413862 |
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* 2011 Fellow, [[American Academy of Arts and Sciences]] (Class Speaker, Biological Sciences)<ref>{{Cite web|title = Press Releases - American Academy of Arts & Sciences|url = https://www.amacad.org/content/news/pressReleases.aspx?pr=133|website = www.amacad.org|access-date = 2016-02-04}}</ref> |
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}}</ref> Later that same year he became the director of the Whitehead Institute at MIT. |
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==References== |
==References== |
Revision as of 18:22, 4 February 2016
David C. Page, MD, is a professor of biology at the Massachusetts Institute of Technology (MIT) and the director of the Whitehead Institute, and is best known for his work on mapping the Y-chromosome and on its evolution in mammals and expression during development.
Education and Career
Page was born in Harrisburg, PA in 1956 and grew up in the rural outskirts of Pennsylvania Dutch country.[1][2][3] The first of his family to go to college, Page attended Swarthmore College, where he graduated with a BA with highest honors in chemistry in 1978.[2][4] During his final year at Swarthmore, Page attended class just one day a week and spent the rest of his time researched chromatin structure in the laboratory of molecular biologist Robert Simpson at the National Institutes of Health.[2][4] In 1978, Page enrolled at Harvard Medical School and the Harvard-MIT Health Sciences Program, where he worked in the laboratories of David Botstein at MIT and Raymond White at the University of Massachusetts Medical School.[4] In White’s lab, Page worked on a project to develop a genetic linkage map of the human genome that would become a precursor to the Human Genome Project.[5] The work relied on locating restriction fragment length polymorphisms (RFLP). The first RFLP that Page found was from a site of homology between the X chromosome and Y chromosome, a coincidence that would set the direction of his subsequent career.[5]
When Page finished his MD degree in the spring of 1984, he started his own lab as the first Whitehead Fellow at the Whitehead Institute for Biomedical Research researching the genetics of XX male syndrome, or de la Chapelle Syndrome.[4][5] After Page won the MacArthur “Genius Grant” in 1986, Page was promoted to the faculty of the Whitehead Institute and the MIT Department of Biology in 1988.[4][6] In 1990, Page was named a Howard Hughes Medical Institute Investigator, and in 2005 he was named as director of the Whitehead Institute.[4]
Research
Mapping the Y Chromosome
In his work on de la Chapelle Syndrome in 1986, Page collaborated with the geneticist who originally identified the first XX male, Albert de la Chapelle, and geneticist Jean Weissenbach to show that XX males carry a small piece of the Y chromosome.[5][7][8]
In the following year, he reported that the gene ZFY induced the development of the testes, a finding which received a great deal of media attention since it putatively resolving a decade-long search for the sex-determining gene.[5][9] In 1989, a British team of scientists led by Peter Goodfellow and Robin Lovell-Badge began to report that the testis-determining gene was not ZFY, which led Page to review his data. Page found that he had misinterpreted his data because one of the XY females in his study had a second deletion at the site which proved to be the location of the real sex-determining gene. Launching a second round of media attention, Nature published his findings together with a paper from the British group that identified the sex-determining gene, which they termed SRY.[5][10][11]
Despite a belief among geneticists that the Y chromosome contained few genes other than the sex-determining gene, Page continued to map the Y chromosome. He had already published DNA-based deletion maps of the Y chromosome in 1986,[12] and went on to develop comprehensive clone-based physical maps of the chromosome in 1992[13][14] and systematic catalogs of Y-linked genes in 1997.[15] Page collaborated with a team at the Genome Institute at Washington University to make a complete map of the Y chromosome, which they achieved in 2003.[16] To do so, Page and his colleagues developed a new sequencing technique, single-haplotype iterative mapping and sequencing (SHIMS), since mammalian sex chromosomes contain too many repetitive sequences to be sequenced by conventional approaches.[2] The development of SHIMS allowed Page to identify long palindromic sequences on the long arm of the Y chromosome, which he would go on to show made the Y chromosome vulnerable to the deletions that cause spermatogenic failure (an inability to produce sperm).[17] In 2012, Page characterized the most common genetic cause of spermatogenic failure, the deletion of the AZFc region of the Y chromosome.[18][19] The lab also found that aberrant crossing over within the Y chromosome’s palindromes underlies a wide range of disorders of sexual differentiation, including Turner syndrome.[18]
Evolution of the Y Chromosome
With the development of more detailed maps of the Y chromosome, in the mid-1990s Page began to find genetic evidence confirming the theory that both the X and Y chromosomes had evolved from autosomes, beginning with the 1996 discovery that a family of genes called DAZ (deleted in azoospermia) had been transposed from an autosome to the Y chromosome.[2][20] In 1999, Page and his then-graduate student Bruce Lahn showed that the X and Y chromosomes had diverged in four steps, beginning 200-300 million years ago.[21] Later cross-species comparisons would show that while ancestral genes on the Y chromosome initially underwent rapid decay,[16][22] the remaining genes have remained stable for the last 25 million years,[23] overturning the long-held view that the Y chromosome was going extinct.[2] In a 2014 study, Page concluded that the conserved genes on the Y chromosome played an important role in male viability, since they were dosage-dependent genes with similar but not identical counterparts on the X chromosome that all have regulatory roles in transcription, translation, and protein stability. Because these genes are expressed throughout the body, Page further concluded that these genes give rise to differences in the biochemistry of male and female tissues.[24]
In super-resolution studies of the sex chromosomes, Page has found evidence of an evolutionary “arms race” between the X and Y chromosomes for transmission to the next generation. In one study, Page found that human X and mouse Y chromosomes have converged, independently acquiring and amplifying gene families expressed in testicular germ cells.[25] Another study found that the mouse Y chromosome had acquired and massively amplified genes homologous to the testis-expressed gene families on the mouse X chromosome.[26]
The Genetics of Germ Cells
Page used the mouse as a model to study the genetics of meiotic initiation, showing that retinoic acid (RA) is the key factor which induces meiosis, as well as identifying several important genes crucial to the meiotic initiation pathway, including Stra8 and DAZL.[27][28][29] Page further discovered that the differentiation germ cells into gametocytes (oocytes in females or spermatocytes in males) does not depend on meiotic initiation, as commonly thought, showing that germ cells deficient in Stra8, a gene that activates the meiotic pathway, are still capable of growth and differentiation.[30][31]
Awards and Honors
- 1986 MacArthur Prize Fellowship[32]
- 1989 Searle Scholar Award[33]
- 1990 Serono Award, American Society of Andrology for advances in reproductive biology
- 1997 Francis Amory Prize, American Academy of Arts and Sciences (for genetic studies of mammalian sex determination; prize shared with Peter Goodfellow and Robin Lovell-Badge)
- 2003 Curt Stern Award, American Society of Human Genetics (for outstanding scientific achievement in human genetics)[34]
- 2005 Member, National Academy of Sciences[5]
- 2007 Fellow, American Association for the Advancement of Science[4]
- 2008 Member, Institute of Medicine[35]
- 2010 Pioneer in Reproduction Research Award, Woods Hole Marine Biological Laboratory
- 2011 March of Dimes Prize in Developmental Biology (prize shared with Patricia Jacobs)
- 2011 Fellow, American Academy of Arts and Sciences (Class Speaker, Biological Sciences)[36]
References
- ^ Trivedi, Bijal (2006-02-21). "Profile of David C. Page". Proceedings of the National Academy of Sciences of the United States of America. 103 (8): 2471–2473. doi:10.1073/pnas.0600615103. ISSN 0027-8424. PMC 1413862. PMID 16481618.
- ^ a b c d e f "Why, Oh Y? | The Scientist Magazine®". The Scientist. Retrieved 2016-02-04.
- ^ Jagetia, Riya; Berg, Elizabeth; Kim, Jae Hyun; Jones, Brianna (Spring 2015). "MURJ Spotlight: Professor David C. Page, Director of the Whitehead Institute" (PDF). MIT Undergraduate Research Journal. Retrieved 4 February 2016.
- ^ a b c d e f g "DAVID PAGE LABORATORY". pagelab.wi.mit.edu. Retrieved 2016-02-04.
- ^ a b c d e f g Trivedi, B. (2006). "Profile of David C. Page". Proceedings of the National Academy of Sciences. 103 (8): 2471–2473. doi:10.1073/pnas.0600615103. PMC 1413862. PMID 16481618.
- ^ Cruzan Morton, Carol (September 1999). "Save the males: David Page '78 reveals the evolutionary roots of sex and gender" (PDF). Swarthmore Bulletin. Retrieved 4 February 2016.
- ^ Page, D. C.; de la Chapelle, A.; Weissenbach, J. (1985-05-16). "Chromosome Y-specific DNA in related human XX males". Nature. 315 (6016): 224–226. ISSN 0028-0836. PMID 2987697.
- ^ Andersson, M.; Page, D. C.; de la Chapelle, A. (1986-08-15). "Chromosome Y-specific DNA is transferred to the short arm of X chromosome in human XX males". Science (New York, N.Y.). 233 (4765): 786–788. ISSN 0036-8075. PMID 3738510.
- ^ Page, D. C.; Mosher, R.; Simpson, E. M.; Fisher, E. M.; Mardon, G.; Pollack, J.; McGillivray, B.; de la Chapelle, A.; Brown, L. G. (1987-12-24). "The sex-determining region of the human Y chromosome encodes a finger protein". Cell. 51 (6): 1091–1104. ISSN 0092-8674. PMID 3690661.
- ^ Page, D. C.; Mosher, R.; Simpson, E. M.; Fisher, E. M.; Mardon, G.; Pollack, J.; McGillivray, B.; de la Chapelle, A.; Brown, L. G. (1987-12-24). "The sex-determining region of the human Y chromosome encodes a finger protein". Cell. 51 (6): 1091–1104. ISSN 0092-8674. PMID 3690661.
- ^ Sinclair, A. H.; Berta, P.; Palmer, M. S.; Hawkins, J. R.; Griffiths, B. L.; Smith, M. J.; Foster, J. W.; Frischauf, A. M.; Lovell-Badge, R. (1990-07-19). "A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif". Nature. 346 (6281): 240–244. doi:10.1038/346240a0. ISSN 0028-0836. PMID 1695712.
- ^ Vergnaud, G; Page, D C; Simmler, M C; Brown, L; Rouyer, F; Noel, B; Botstein, D; de la Chapelle, A; Weissenbach, J (1986-02-01). "A deletion map of the human Y chromosome based on DNA hybridization". American Journal of Human Genetics. 38 (2): 109–124. ISSN 0002-9297. PMC 1684749. PMID 3004206.
- ^ Vollrath, Douglas; Foote, Simon; Hilton, Adrienne; Brown, Laura G.; Beer-Romero, Peggy; Bogan, Jonathan; Page, David C. (2 October 1992). "The Human Y Chromosome: A 43-Interval Map Based on Naturally Occurring Deletions" (PDF). Science. 258 (5079): 52–59. Retrieved 4 February 2016.
- ^ Foote, Simon; Vollrath, Douglas; Hilton, Adrienne; Page, David C. (2 October 1992). "The Human Y Chromosome: Spanning the Euchromatic Region" (PDF). Science. 258 (5079): 60–66. Retrieved 4 February 2016.
- ^ Lahn, Bruce; Page, David C. (24 October 1997). "Functional Coherence of the Human Y Chromosome" (PDF). Science. 278 (5338): 675–680. Retrieved 4 February 2016.
- ^ a b Skaletsky, H.; Kuroda-Kawaguchi, T.; Minx, P. J.; Cordum, H. S.; Hillier, L.; Brown, L. G.; Repping, S.; Pyntikova, T.; Ali, 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. (2003). "The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes". Nature. 423 (6942): 825–837. doi:10.1038/nature01722. PMID 12815422.
- ^ Repping, Sjoerd; Skaletsky, Helen; Lange, Julian; Silber, Sherman; Van Der Veen, Fulco; Oates, Robert D.; Page, David C.; Rozen, Steve (2002-10-01). "Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure". American Journal of Human Genetics. 71 (4): 906–922. doi:10.1086/342928. ISSN 0002-9297. PMC 419997. PMID 12297986.
- ^ a b Whitehead Institute Faculty Page
- ^ Rozen, Steven G.; Marszalek, Janet D.; Irenze, Kathryn; Skaletsky, Helen; Brown, Laura G.; Oates, Robert D.; Silber, Sherman J.; Ardlie, Kristin; Page, David C. (2012-11-02). "AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes". American Journal of Human Genetics. 91 (5): 890–896. doi:10.1016/j.ajhg.2012.09.003. ISSN 1537-6605. PMC 3487143. PMID 23103232.
- ^ Saxena, R.; Brown, L. G.; Hawkins, T.; Alagappan, R. K.; Skaletsky, H.; Reeve, M. P.; Reijo, R.; Rozen, S.; Dinulos, M. B. (1996-11-01). "The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned". Nature Genetics. 14 (3): 292–299. doi:10.1038/ng1196-292. ISSN 1061-4036. PMID 8896558.
- ^ Lahn, B. T.; Page, D. C. (1999-10-29). "Four evolutionary strata on the human X chromosome". Science (New York, N.Y.). 286 (5441): 964–967. ISSN 0036-8075. PMID 10542153.
- ^ Bellott, Daniel W.; Skaletsky, Helen; Pyntikova, Tatyana; Mardis, Elaine R.; Graves, Tina; Kremitzki, Colin; Brown, Laura G.; Rozen, Steve; Warren, Wesley C. (2010-07-29). "Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition". Nature. 466 (7306): 612–616. doi:10.1038/nature09172. ISSN 1476-4687. PMC 2943333. PMID 20622855.
- ^ Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Graves, Tina; Fulton, Robert S.; Dugan, Shannon; Ding, Yan; Buhay, Christian J. (2012-03-01). "Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes". Nature. 483 (7387): 82–86. doi:10.1038/nature10843. ISSN 0028-0836. PMC 3292678. PMID 22367542.
- ^ Bellott, Daniel W.; Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Cho, Ting-Jan; Koutseva, Natalia; Zaghlul, Sara; Graves, Tina (2014-04-24). "Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators". Nature. 508 (7497): 494–499. doi:10.1038/nature13206. ISSN 0028-0836. PMC 4139287. PMID 24759411.
- ^ Mueller, Jacob L.; Skaletsky, Helen; Brown, Laura G.; Zaghlul, Sara; Rock, Susan; Graves, Tina; Auger, Katherine; Warren, Wesley C.; Wilson, Richard K. (2013-09-01). "Independent specialization of the human and mouse X chromosomes for the male germ line". Nature Genetics. 45 (9): 1083–1087. doi:10.1038/ng.2705. ISSN 1061-4036. PMC 3758364. PMID 23872635.
- ^ Soh, Y. Q. Shirleen; Alföldi, Jessica; Pyntikova, Tatyana; Brown, Laura G.; Graves, Tina; Minx, Patrick J.; Fulton, Robert S.; Kremitzki, Colin; Koutseva, Natalia (2014-11-06). "Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes". Cell. 159 (4): 800–813. doi:10.1016/j.cell.2014.09.052. ISSN 1097-4172. PMC 4260969. PMID 25417157.
- ^ Baltus, Andrew E.; Menke, Douglas B.; Hu, Yueh-Chiang; Goodheart, Mary L.; Carpenter, Anne E.; de Rooij, Dirk G.; Page, David C. (2006-12-01). "In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication". Nature Genetics. 38 (12): 1430–1434. doi:10.1038/ng1919. ISSN 1061-4036. PMID 17115059.
- ^ Lin, Yanfeng; Gill, Mark E.; Koubova, Jana; Page, David C. (2008-12-12). "Germ Cell-Intrinsic and -Extrinsic Factors Govern Meiotic Initiation in Mouse Embryos". Science. 322 (5908): 1685–1687. doi:10.1126/science.1166340. ISSN 0036-8075. PMID 19074348.
- ^ Koubova, Jana; Menke, Douglas B.; Zhou, Qing; Capel, Blanche; Griswold, Michael D.; Page, David C. (2006-02-21). "Retinoic acid regulates sex-specific timing of meiotic initiation in mice". Proceedings of the National Academy of Sciences of the United States of America. 103 (8): 2474–2479. doi:10.1073/pnas.0510813103. ISSN 0027-8424. PMC 1413806. PMID 16461896.
- ^ Endo, Tsutomu; Romer, Katherine A.; Anderson, Ericka L.; Baltus, Andrew E.; de Rooij, Dirk G.; Page, David C. (2015-05-05). "Periodic retinoic acid-STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis". Proceedings of the National Academy of Sciences of the United States of America. 112 (18): E2347–2356. doi:10.1073/pnas.1505683112. ISSN 1091-6490. PMC 4426408. PMID 25902548.
- ^ Dokshin, Gregoriy A.; Baltus, Andrew E.; Eppig, John J.; Page, David C. (2013-08-01). "Oocyte differentiation is genetically dissociable from meiosis in mice". Nature Genetics. 45 (8): 877–883. doi:10.1038/ng.2672. ISSN 1061-4036. PMC 3747777. PMID 23770609.
- ^ "David C. Page — MacArthur Foundation". www.macfound.org. Retrieved 2016-02-04.
- ^ "Searle Scholars Program : David C. Page (1989)". www.searlescholars.net. Retrieved 2016-02-04.
- ^ Page, David C. (2004-03-01). "On Low Expectations Exceeded; or, The Genomic Salvation of the Y Chromosome". American Journal of Human Genetics. 74 (3): 399–402. ISSN 0002-9297. PMC 1182254. PMID 15053010.
- ^ "MIT Office of the Provost, Institutional Research". web.mit.edu. Retrieved 2016-02-04.
- ^ "Press Releases - American Academy of Arts & Sciences". www.amacad.org. Retrieved 2016-02-04.
External links
- New York Times article on Y chromosome sex anomalies
- More on David Page from the Howard Hughes Medical Institute