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RESEARCH
My work is focused on Ultraconserved elements (UCEs). These are regions of the genome that show exceptionally high sequence conservation between different species. Sequence conservation between different species is often used as an indicator for DNA that has important functions. However, the function(s) that cause the highest levels of conservation in the genome are yet to be elucidated.
The Wu laboratory has proposed the hypothesis that UCEs may take part in pairing between UCE copies on the two homologous chromosomes. This could allow comparison between the two copies, such that base pair differences, or deletion of one copy, could lead to loss-of-fitness. In this way UCEs could be thought of as ‘guardians’ of genome integrity, with a possible role in cancer. Aneuploidy and DNA loss and rearrangement are very common in cancer cells, although the ultimate cause of these problems is still not fully understood.
The study of UCEs is in its infancy. Different hypotheses for UCE function have been proposed, such as pairing, or the presence of multiple overlapping functions, which would constrain DNA sequence. Even so, no idea provides a totally satisfying and complete explanation for ultraconservation. I am also seeking to understand the properties and behavior of UCEs more fully, in order to test existing hypotheses and formulate new ones about what they may be for.
PUBLICATIONS
Short interspersed element (SINE) depletion and long interspersed element (LINE) abundance are not features universally required for imprinting.
Cowley M, de Burca A, McCole RB, Chahal M, Saadat G, Oakey RJ, Schulz R.
PLoS One. 2011 Apr 20;6(4):e18953.
A case-by-case evolutionary analysis of four imprinted retrogenes.
McCole RB, Loughran NB, Chahal M, Fernandes LP, Roberts RG, Fraternali F, O'Connell MJ, Oakey RJ.
Evolution. 2011 May;65(5):1413-27. doi: 10.1111/j.1558-5646.2010.01213.x. Epub 2011 Jan 10.
Unwitting hosts fall victim to imprinting.
McCole RB, Oakey RJ.
Epigenetics. 2008 Sep;3(5):258-60. Epub 2008 Sep 19. No abstract available.
Transcript- and tissue-specific imprinting of a tumour suppressor gene.
Schulz R, McCole RB, Woodfine K, Wood AJ, Chahal M, Monk D, Moore GE, Oakey RJ.
Hum Mol Genet. 2009 Jan 1;18(1):118-27. Epub 2008 Oct 4.
Lateral line, otic and epibranchial placodes: developmental and evolutionary links?
Baker CV, O'Neill P, McCole RB.
J Exp Zool B Mol Dev Evol. 2008 Jun 15;310(4):370-83. Review.
A molecular analysis of neurogenic placode and cranial sensory ganglion development in the shark, Scyliorhinus canicula.
O'Neill P, McCole RB, Baker CV.
Dev Biol. 2007 Apr 1;304(1):156-81. Epub 2006 Dec 19. Erratum in: Dev Biol. 2009 Aug;332(1):186-8.
General Audience:
Cellular error correction – a new way to treat genetic disease?
https://sitn.hms.harvard.edu/sitnflash_wp/2011/07/issue97/
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