Prospects for identifying functional variation across the genome. Export

@article{citeulike:3078549, abstract = {The genetic factors contributing to complex trait variation may reside in regulatory, rather than protein-coding portions of the genome. Within noncoding regions, SNPs in regulatory elements are more likely to contribute to phenotypic variation than those in nonregulatory regions. Thus, it is important to be able to identify and annotate noncoding regulatory elements. DNA conservation among diverged species successfully identifies noncoding regulatory regions. However, because rapidly evolving regulatory regions will not generally be conserved across species, these will not detected by using purely conservation-based methods. Here we describe additional approaches that can be used to identify putative regulatory elements via signatures of nonneutral evolution. An examination of the pattern of polymorphism both within and between populations of Drosophila melanogaster, as well as divergence with its sibling species Drosophila simulans, across 24.2 kb of noncoding DNA identifies several nonneutrally evolving regions not identified by conservation. Because different methods tag different regions, it appears that the methods are complementary. Patterns of variation at different elements are consistent with the action of selective sweeps, balancing selection, or population differentiation. Together with regions conserved between D. melanogaster and Drosophila pseudoobscura, we tag 5.3 kb of noncoding DNA as potentially regulatory. Ninety-seven of the 408 common noncoding SNPs surveyed are within putatively regulatory regions. If these methods collectively identify the majority of functional noncoding polymorphisms, genotyping only these SNPs in an association mapping framework would reduce genotyping effort for noncoding regions 4-fold.}, address = {Department of Ecology and Evolutionary Biology, University of California, Irvine, 92697-2525, USA. sjm@uci.edu}, author = {Macdonald, S. J. and Long, A. D.}, citeulike-article-id = {3078549}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0501990102}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15851675}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15851675}, day = {3}, doi = {10.1073/pnas.0501990102}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, month = {May}, pages = {6614--6621}, posted-at = {2008-09-14 05:20:00}, priority = {3}, title = {Prospects for identifying functional variation across the genome.}, url = {http://dx.doi.org/10.1073/pnas.0501990102}, volume = {102 Suppl 1}, year = {2005} }

TY - JOUR ID - citeulike:3078549 L3 - citeulike-article-id:3078549 N2 - The genetic factors contributing to complex trait variation may reside in regulatory, rather than protein-coding portions of the genome. Within noncoding regions, SNPs in regulatory elements are more likely to contribute to phenotypic variation than those in nonregulatory regions. Thus, it is important to be able to identify and annotate noncoding regulatory elements. DNA conservation among diverged species successfully identifies noncoding regulatory regions. However, because rapidly evolving regulatory regions will not generally be conserved across species, these will not detected by using purely conservation-based methods. Here we describe additional approaches that can be used to identify putative regulatory elements via signatures of nonneutral evolution. An examination of the pattern of polymorphism both within and between populations of Drosophila melanogaster, as well as divergence with its sibling species Drosophila simulans, across 24.2 kb of noncoding DNA identifies several nonneutrally evolving regions not identified by conservation. Because different methods tag different regions, it appears that the methods are complementary. Patterns of variation at different elements are consistent with the action of selective sweeps, balancing selection, or population differentiation. Together with regions conserved between D. melanogaster and Drosophila pseudoobscura, we tag 5.3 kb of noncoding DNA as potentially regulatory. Ninety-seven of the 408 common noncoding SNPs surveyed are within putatively regulatory regions. If these methods collectively identify the majority of functional noncoding polymorphisms, genotyping only these SNPs in an association mapping framework would reduce genotyping effort for noncoding regions 4-fold. JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 AD - Department of Ecology and Evolutionary Biology, University of California, Irvine, 92697-2525, USA. sjm@uci.edu EP - 6621 TI - Prospects for identifying functional variation across the genome. VL - 102 Suppl 1 SP - 6614 AU - Macdonald, SJ AU - Long, AD PY - 2005/05/03/ UR - http://dx.doi.org/10.1073/pnas.0501990102 ER -