Comparative genomics of the vertebrate ParaHox gene cluster. (360G-Wellcome-081233_B_06_Z)

£18,349

The clustered Hox genes comprise only 39 of the > 200 homeobox genes in the human genome. The non-Hox homeobox genes are usually studied in isolation, but in fact some are in gene clusters. We found that three (Gsx, Xlox/Pdx, Cdx) form the ParaHox cluster in amphioxus, human, mouse, Xenopus and basal ray-finned fish, but not in zebrafish and pufferfish (where the constituent genes have dispersed). We will use a combination of comparative genomics and experimental assays to ask: (1) How conserved is the ParaHox gene cluster? To test, we will analyse two species chosen for their positions in vertebrate diversity. (2) When, how and why did the ParaHox cluster disintegrate in teleost fish evolution? We hypothesize that whole genome duplication (WGD) at the base of the teleosts allowed interdigitated ParaHox genes to be dissociated. We will test by comparison between fish branching before and after the WGD, including zebrafish and some non-traditional models. (3) What is the functional reason for the cluster? We hypothesize the genes are trapped by shared enhancers and overlapping gene organisation; we will test this by determining the activity of conserved non-coding regions using Xenopus transgenics. (4) What are the implications for zebrafish as a model?

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Grant Details

Amount Awarded 18349
Applicant Surname Isaacs
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2006-11-01T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Project Grant
Internal ID 081233/B/06/Z
Lead Applicant Dr Harry Isaacs
Other Applicant(s) Prof Peter Holland
Partnership Value 18349
Planned Dates: End Date 2010-03-31T00:00:00+00:00
Planned Dates: Start Date 2007-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Yorkshire and the Humber