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10.1186/s13059-017-1262-7 http://scihub22266oqcxt.onion/10.1186/s13059-017-1262-7 C5496195!5496195 !28673357     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28673357 &cmd=llinks): Failed to open stream: HTTP request failed! 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Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results |pdf=|usr=}}{{28673357 }} gab.com Text Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results JO: Genome Biol http://www.kidney.de/pget.php?&tw=1&pmid=28673357 #FOAvip 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. Twit Text FOAVip Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results ????Genome Biol http://www.kidney.de/pget.php?&tw=1&pmid=28673357 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28673357 #FOAvip English Wikipedia <ref>{{Cite pmid|28673357 }}</ref> Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results #MMPMID28673357 Gibert JM ; Blanco J ; Dolezal M ; Nolte V ; Peronnet F ; Schlötterer C Genome Biol 2017[Jul]; 18 (1 ): 126 PMID28673357 show ga 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. |*Epistasis, Genetic [MESH] |*Genetic Linkage [MESH] |*Genome-Wide Association Study [MESH] |*Polymorphism, Single Nucleotide [MESH] |Animals [MESH] |Animals, Genetically Modified [MESH] |Drosophila/*genetics [MESH] |Female [MESH] |Genes, Insect [MESH] |Pigmentation/*genetics [MESH]Strong epistatic and additive effects of linked candidate SNPs for Dro(epmc).pdf DeepDyve Pubget Overpricing