Article
Effects of natural selection on interpopulation divergence at polymorphic sites in human protein-coding Loci.
Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208, USA.
Genetics (impact factor:
4.01).
08/2005;
170(3):1181-7.
DOI:10.1534/genetics.104.037077
Source: PubMed
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Article: Near-neutrality in evolution of genes and gene regulation.
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ABSTRACT: The nearly neutral theory contends that the interaction of drift and selection is important and occurs at various levels, including synonymous and nonsynonymous substitutions in protein coding regions and sequence turnover of regulatory elements. Recent progress of the theory is reviewed, and the interaction between drift and selection is suggested to differ at these different levels. Weak selective force on synonymous changes is stable, whereas its consequence on nonsynonymous changes depends on environmental factors. Selection on differentiation of regulatory elements is even more dependent on environmental factors than on amino acid changes. Of particular significance is the role of drift in the evolution of gene regulation that directly participates in morphological evolution. The range of near neutrality depends on the effective size of the population that is influenced by selected linked loci. In addition to the effective population size, molecular chaperones such as heat shock protein 90 have significant effects on the range of near neutrality.Proceedings of the National Academy of Sciences 01/2003; 99(25):16134-7. · 9.68 Impact Factor -
Article: Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease.
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ABSTRACT: The past two decades have witnessed an explosion in the identification, largely by positional cloning, of genes associated with mendelian diseases. The roughly 1,200 genes that have been characterized have clarified our understanding of the molecular basis of human genetic disease. The principles derived from these successes should be applied now to strategies aimed at finding the considerably more elusive genes that underlie complex disease phenotypes. The distribution of types of mutation in mendelian disease genes argues for serious consideration of the early application of a genomic-scale sequence-based approach to association studies and against complete reliance on a positional cloning approach based on a map of anonymous single nucleotide polymorphism haplotypes.Nature Genetics 04/2003; 33 Suppl:228-37. · 35.53 Impact Factor -
Article: Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus.
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ABSTRACT: Interleukin-8 (IL8) is believed to play a role in the pathogenesis of bronchiolitis, a common viral disease of infancy, and a recent U.K. family study identified an association between this disease and the IL8-251A allele. In the present study we report data, from a different set of families, which replicate this finding; combined analysis of 194 nuclear families through use of the transmission/disequilibrium test gives P = .001. To explore the underlying genetic cause, we identified nine single-nucleotide polymorphisms (SNPs) in a 7.6-kb segment spanning the IL8 gene and its promoter region and used six of these SNPs to define the haplotypic structure of the IL8 locus. The IL8-251A allele resides on two haplotypes, only one of which is associated with disease, suggesting that this may not be the functional allele. Europeans show an unusual haplotype genealogy that is dominated by two common haplotypes differing at multiple sites, whereas Africans have much greater haplotypic diversity. These marked haplotype-frequency differences give an F(ST) of.25, and, in the European sample, both Tajima's D statistic (D = 2.58, P = .007) and the Hudson/Kreitman/Aguade test (chi(2) = 4.9, P = .03) reject neutral equilibrium, suggesting that selective pressure may have acted on this locus.The American Journal of Human Genetics 09/2001; 69(2):413-9. · 10.60 Impact Factor
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Keywords
396 protein-coding genes
biological processes relevant
complex human diseases
diverged populations
divergent selection pressures
gene diversity
genetic associations
interpopulation divergence
interpopulation genetic distance
intrapopulation gene diversity
loci
new strategies
nonsynonymous SNPs
protein structure
purifying selection
SNP loci
SNP sites
SNPs
three major historic human populations
turn causes
