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PMID: 14628290 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Comparative linkage-disequilibrium analysis of the beta-globin hotspot in primates.

American journal of human genetics ·Vol. 73 ·No. 6 ·2003-12-00 ·Pages 1330-40

Wall JD, Frisse LA, Hudson RR, Di Rienzo A

Abstract

Recombination rates vary both across the genome and between different species, but little information is available about the temporal and physical scales over which such rates change. To shed light on these questions, we performed a high-resolution analysis of a genomic region within the beta-globin gene cluster that is known to experience elevated recombination rates in humans. For this purpose, we developed new linkage disequilibrium-based methods that thoroughly search for subsets of the data with unusually high or unusually low estimated values of the population-recombination parameter (4Nr, where N is the effective population size and r is the crossover rate between adjacent base pairs). By resequencing a 15-kb segment in a human population sample, we were able to narrow the recombinational hotspot to a segment <2 kb in length that coincides with the beta-globin replication origin. In addition, we analyzed the orthologous region in samples of rhesus macaques and common chimpanzees. Whereas the analysis of the chimpanzee data is complicated by the sample structure, the macaque data imply that this region may not be a hotspot in that species. These results suggest a time scale for the evolution of hotspots in primates. Furthermore, they allow us to propose diverged sequence elements that may contribute to the differences in the recombinational landscape in the two species.

MeSH Terms
Animals Base Sequence Beta-Globulins/genetics Chromosome Mapping Humans Likelihood Functions Linkage Disequilibrium/genetics Models, Genetic Molecular Sequence Data Polymorphism, Genetic/genetics Primates/genetics Recombination, Genetic/genetics Sequence Analysis, DNA
Chemicals
Beta-Globulins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wall Jeffrey D
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Frisse Linda A
Hudson Richard R
Di Rienzo Anna
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/380311
Published
2003-12-00
Epub
2003-00-18
Pages
1330-40
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1180398
Subset
IM
Grants
NHGRI NIH HHS · HG 02098 · United States
NHGRI NIH HHS · F32 HG000219 · United States
NHGRI NIH HHS · HG 00219 · United States
NHGRI NIH HHS · HG 2772 · United States
NHGRI NIH HHS · R01 HG002772 · United States
Databases
GENBANK
AF205410, AF339362, AF339363, J00327, J00334, M18797, X02345, X05665
External Links
PubMed source DOI: 10.1086/380311 PMC Full Text View journal details
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