Genomic variation and its impact on gene expression in Drosophila melanogaster

Article Article scientifique Article Genomic variation and its impact on gene expression in Drosophila melanogaster eng 2012 author Massouras Andreas 810345 author Waszak Sebastian M author Albarca-Aguilera Monica author Hens Korneel author Holcombe Wiebke author Ayroles Julien F author Dermitzakis Emmanouil 542683 author Stone Eric A author Jensen Jeffrey D author Mackay Trudy F C author Deplancke Bart 703941 e1003055 10.1371/journal.pgen.1003055 23189034 1553-7390 Understanding the relationship between genetic and phenotypic variation is one of the great outstanding challenges in biology. To meet this challenge, comprehensive genomic variation maps of human as well as of model organism populations are required. Here, we present a nucleotide resolution catalog of single-nucleotide, multi-nucleotide, and structural variants in 39 Drosophila melanogaster Genetic Reference Panel inbred lines. Using an integrative, local assembly-based approach for variant discovery, we identify more than 3.6 million distinct variants, among which were more than 800,000 unique insertions, deletions (indels), and complex variants (1 to 6,000 bp). While the SNP density is higher near other variants, we find that variants themselves are not mutagenic, nor are regions with high variant density particularly mutation-prone. Rather, our data suggest that the elevated SNP density around variants is mainly due to population-level processes. We also provide insights into the regulatory architecture of gene expression variation in adult flies by mapping cis-expression quantitative trait loci (cis-eQTLs) for more than 2,000 genes. Indels comprise around 10% of all cis-eQTLs and show larger effects than SNP cis-eQTLs. In addition, we identified two-fold more gene associations in males as compared to females and found that most cis-eQTLs are sex-specific, revealing a partial decoupling of the genomic architecture between the sexes as well as the importance of genetic factors in mediating sex-biased gene expression. Finally, we performed RNA-seq-based allelic expression imbalance analyses in the offspring of crosses between sequenced lines, which revealed that the majority of strong cis-eQTLs can be validated in heterozygous individuals. Allelic Imbalance/genetics Animals Chromosome Mapping Drosophila melanogaster/genetics Gene Expression Genetic Variation Genome INDEL Mutation Phenotype Polymorphism, Single Nucleotide Quantitative Trait Loci/genetics Dewey 576.5 135 Département de médecine génétique et développement 21D false 551 Population Genomics and Genetics of Complex Traits 892 PLOS genetics 8 11 4980610f-3067-4a20-85f6-d7797d645c8c Article (Published version) Public PMID23189034.pdf 1274940 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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Genomic variation and its impact on gene expression in Drosophila melanogaster	PLOS genetics			2012	674	363

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Massouras, Andreas