Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results
Abstract Background The mapping resolution of genome-wide association studies (GWAS) is limited by historic recombination events and effects are often assigned to haplotype blocks rather than individual SNPs. It is not clear how many of the SNPs in the block, and which ones, are causative. Drosophil...
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doaj-1a1d87580065427fbfba4beb8951aee82020-11-24T21:10:31ZengBMCGenome Biology1474-760X2017-07-011811610.1186/s13059-017-1262-7Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies resultsJean-Michel Gibert0Jorge Blanco1Marlies Dolezal2Viola Nolte3Frédérique Peronnet4Christian Schlötterer5Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie du Développement Paris Seine-Institut de Biologie Paris Seine (LBD-IBPS)Institut für Populationsgenetik, Vetmeduni ViennaInstitut für Populationsgenetik, Vetmeduni ViennaInstitut für Populationsgenetik, Vetmeduni ViennaSorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie du Développement Paris Seine-Institut de Biologie Paris Seine (LBD-IBPS)Institut für Populationsgenetik, Vetmeduni ViennaAbstract Background The mapping resolution of genome-wide association studies (GWAS) is limited by historic recombination events and effects are often assigned to haplotype blocks rather than individual SNPs. It is not clear how many of the SNPs in the block, and which ones, are causative. Drosophila pigmentation is a powerful model to dissect the genetic basis of intra-specific and inter-specific phenotypic variation. Three tightly linked SNPs in the t-MSE enhancer have been identified in three D. melanogaster populations as major contributors to female abdominal pigmentation. This enhancer controls the expression of the pigmentation gene tan (t) in the abdominal epidermis. Two of the three SNPs were confirmed in an independent study using the D. melanogaster Genetic Reference Panel established from a North American population. Results We determined the functional impact of SNP1, SNP2, and SNP3 using transgenic lines to test all possible haplotypes in vivo. We show that all three candidate SNPs contribute to female Drosophila abdominal pigmentation. Interestingly, only two SNPs agree with the effect predicted by GWAS; the third one goes in the opposite direction because of linkage disequilibrium between multiple functional SNPs. Our experimental design uncovered strong additive effects for the three SNPs, but we also found significant epistatic effects explaining up to 11% of the total variation. Conclusions Our results suggest that linked causal variants are important for the interpretation of GWAS and functional validation is needed to understand the genetic architecture of traits.http://link.springer.com/article/10.1186/s13059-017-1262-7Genome-wide associations studies (GWAS)Genetic architectureAdditivityEpistasisPigmentationDrosophila |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jean-Michel Gibert Jorge Blanco Marlies Dolezal Viola Nolte Frédérique Peronnet Christian Schlötterer |
spellingShingle |
Jean-Michel Gibert Jorge Blanco Marlies Dolezal Viola Nolte Frédérique Peronnet Christian Schlötterer Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results Genome Biology Genome-wide associations studies (GWAS) Genetic architecture Additivity Epistasis Pigmentation Drosophila |
author_facet |
Jean-Michel Gibert Jorge Blanco Marlies Dolezal Viola Nolte Frédérique Peronnet Christian Schlötterer |
author_sort |
Jean-Michel Gibert |
title |
Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results |
title_short |
Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results |
title_full |
Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results |
title_fullStr |
Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results |
title_full_unstemmed |
Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results |
title_sort |
strong epistatic and additive effects of linked candidate snps for drosophila pigmentation have implications for analysis of genome-wide association studies results |
publisher |
BMC |
series |
Genome Biology |
issn |
1474-760X |
publishDate |
2017-07-01 |
description |
Abstract Background The mapping resolution of genome-wide association studies (GWAS) is limited by historic recombination events and effects are often assigned to haplotype blocks rather than individual SNPs. It is not clear how many of the SNPs in the block, and which ones, are causative. Drosophila pigmentation is a powerful model to dissect the genetic basis of intra-specific and inter-specific phenotypic variation. Three tightly linked SNPs in the t-MSE enhancer have been identified in three D. melanogaster populations as major contributors to female abdominal pigmentation. This enhancer controls the expression of the pigmentation gene tan (t) in the abdominal epidermis. Two of the three SNPs were confirmed in an independent study using the D. melanogaster Genetic Reference Panel established from a North American population. Results We determined the functional impact of SNP1, SNP2, and SNP3 using transgenic lines to test all possible haplotypes in vivo. We show that all three candidate SNPs contribute to female Drosophila abdominal pigmentation. Interestingly, only two SNPs agree with the effect predicted by GWAS; the third one goes in the opposite direction because of linkage disequilibrium between multiple functional SNPs. Our experimental design uncovered strong additive effects for the three SNPs, but we also found significant epistatic effects explaining up to 11% of the total variation. Conclusions Our results suggest that linked causal variants are important for the interpretation of GWAS and functional validation is needed to understand the genetic architecture of traits. |
topic |
Genome-wide associations studies (GWAS) Genetic architecture Additivity Epistasis Pigmentation Drosophila |
url |
http://link.springer.com/article/10.1186/s13059-017-1262-7 |
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