Protein variation in ADH and ADH-RELATED in Drosophila pseudoobscura

Linkage disequilibrium between single nucleotide polymorphisms and protein alleles

Stephen Wade Schaeffer, C. Scott Walthour, Donna M. Toleno, Anna T. Olek, Ellen L. Miller

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10%.

Original languageEnglish (US)
Pages (from-to)673-687
Number of pages15
JournalGenetics
Volume159
Issue number2
StatePublished - 2001

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Alcohol Dehydrogenase
Linkage Disequilibrium
Drosophila
Single Nucleotide Polymorphism
Alleles
Haplotypes
Proteins
Genetic Recombination
Genes
Chromosome Mapping
Gene Frequency
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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abstract = "A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10{\%}.",
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Protein variation in ADH and ADH-RELATED in Drosophila pseudoobscura : Linkage disequilibrium between single nucleotide polymorphisms and protein alleles. / Schaeffer, Stephen Wade; Scott Walthour, C.; Toleno, Donna M.; Olek, Anna T.; Miller, Ellen L.

In: Genetics, Vol. 159, No. 2, 2001, p. 673-687.

Research output: Contribution to journalArticle

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