Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny
Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Director. Office of Science. Office of Biological andEnvironmental Research, Lawrence Livermore National Laboratory, LosAlamos National Laboratory; National Institutes of Health Grant NHLBIU1HL66681B; Canadian Institutes for Health ResearchFellowship
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 862170
- Report Number(s):
- LBNL-57715; R&D Project: 626809; BnR: KP1103010; TRN: US200602%%80
- Journal Information:
- Human Molecular Genetics, Vol. 14, Issue 20; Related Information: Journal Publication Date: 10/15/2005
- Country of Publication:
- United States
- Language:
- English
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