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PMID: 16339379 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Selective sweep mapping of genes with large phenotypic effects.

Genome research ·Vol. 15 ·No. 12 ·2005-12-00 ·Pages 1809-19

Pollinger JP, Bustamante CD, Fledel-Alon A, Schmutz S, Gray MM, Wayne RK

Abstract

Many domestic dog breeds have originated through fixation of discrete mutations by intense artificial selection. As a result of this process, markers in the proximity of genes influencing breed-defining traits will have reduced variation (a selective sweep) and will show divergence in allele frequency. Consequently, low-resolution genomic scans can potentially be used to identify regions containing genes that have a major influence on breed-defining traits. We model the process of breed formation and show that the probability of two or three adjacent marker loci showing a spurious signal of selection within at least one breed (i.e., Type I error or false-positive rate) is low if highly variable and moderately spaced markers are utilized. We also use simulations with selection to demonstrate that even a moderately spaced set of highly polymorphic markers (e.g., one every 0.8 cM) has high power to detect regions targeted by strong artificial selection in dogs. Further, we show that a gene responsible for black coat color in the Large Munsterlander has a 40-Mb region surrounding the gene that is very low in heterozygosity for microsatellite markers. Similarly, we survey 302 microsatellite markers in the Dachshund and find three linked monomorphic microsatellite markers all within a 10-Mb region on chromosome 3. This region contains the FGFR3 gene, which is responsible for achondroplasia in humans, but not in dogs. Consequently, our results suggest that the causative mutation is a gene or regulatory region closely linked to FGFR3.

MeSH Terms
Animals Breeding Chromosome Mapping/methods Computer Simulation Dogs/genetics Female Genetic Markers/genetics Genetic Variation/genetics Genome Heterozygote Male Models, Genetic Mutation/genetics Phenotype Polymorphism, Genetic Receptor, Fibroblast Growth Factor, Type 3/genetics Selection, Genetic
Chemicals
Genetic Markers Receptor, Fibroblast Growth Factor, Type 3
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pollinger John P
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095-1606, USA. [email protected]
Bustamante Carlos D
Fledel-Alon Adi
Schmutz Sheila
Gray Melissa M
Wayne Robert K
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.4374505
Email
[email protected]
Published
2005-12-00
Pages
1809-19
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC1356119
Subset
IM
Grants
NHGRI NIH HHS · R01 HG003229 · United States
NHGRI NIH HHS · 1R01HG003229-01 · United States
External Links
PubMed source DOI: 10.1101/gr.4374505 PMC Full Text View journal details
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