Genomic Variation and Its Impact on Gene Expression in Drosophila melanogaster

被引:87
作者
Massouras, Andreas [1 ]
Waszak, Sebastian M. [1 ]
Albarca-Aguilera, Monica [1 ]
Hens, Korneel [1 ]
Holcombe, Wiebke [1 ]
Ayroles, Julien F. [2 ]
Dermitzakis, Emmanouil T. [3 ]
Stone, Eric A. [4 ]
Jensen, Jeffrey D.
Mackay, Trudy F. C. [4 ]
Deplancke, Bart [1 ]
机构
[1] Ecole Polytech Fed Lausanne, Lab Syst Biol & Genet, Inst Bioengn, Sch Life Sci, CH-1015 Lausanne, Switzerland
[2] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA
[3] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland
[4] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA
来源
PLOS GENETICS | 2012年 / 8卷 / 11期
基金
瑞士国家科学基金会; 美国国家卫生研究院;
关键词
COPY NUMBER VARIATION; NATURAL-SELECTION; MUTATION-RATE; EVO-DEVO; SEQUENCE; NUCLEOTIDE; CIS; POLYMORPHISM; POPULATIONS; INSERTIONS;
D O I
10.1371/journal.pgen.1003055
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:14
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