Following the footprints of polymorphic inversions on SNP data: from detection to association tests.
Nucleic Acids Res
; 43(8): e53, 2015 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-25672393
ABSTRACT
Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Haplótipos
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Polimorfismo de Nucleotídeo Único
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Técnicas de Genotipagem
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Inversão Cromossômica
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Child, preschool
/
Humans
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article