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Type of publication: Journal Article
Type of document: Full Paper

Year: 2017

Authors: Gibert, JM; Blanco, J; Dolezal, M; Nolte, V; Peronnet, F; Schlötterer, C

Title: Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results.

Source: Genome Biol. 2017; 18(1):126



Authors Vetmeduni Vienna:

Dolezal Marlies
Nolte Viola
Schlötterer Christian

Vetmed Research Units
Institute of Population Genetics


Project(s): NGS Speed Mapping

ERC ADG: The architecture of adaptation


Abstract:
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.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.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.

Keywords Pubmed: Animals
Animals, Genetically Modified
Drosophilagenetics
Epistasis, Genetic
Female
Genes, Insect
Genetic Linkage
Genome-Wide Association Study
Pigmentationgenetics
Polymorphism, Single Nucleotide
Quantitative Trait Loci

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