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  • 1
    Publication Date: 2012-02-10
    Description: A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683990/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mackay, Trudy F C -- Richards, Stephen -- Stone, Eric A -- Barbadilla, Antonio -- Ayroles, Julien F -- Zhu, Dianhui -- Casillas, Sonia -- Han, Yi -- Magwire, Michael M -- Cridland, Julie M -- Richardson, Mark F -- Anholt, Robert R H -- Barron, Maite -- Bess, Crystal -- Blankenburg, Kerstin Petra -- Carbone, Mary Anna -- Castellano, David -- Chaboub, Lesley -- Duncan, Laura -- Harris, Zeke -- Javaid, Mehwish -- Jayaseelan, Joy Christina -- Jhangiani, Shalini N -- Jordan, Katherine W -- Lara, Fremiet -- Lawrence, Faye -- Lee, Sandra L -- Librado, Pablo -- Linheiro, Raquel S -- Lyman, Richard F -- Mackey, Aaron J -- Munidasa, Mala -- Muzny, Donna Marie -- Nazareth, Lynne -- Newsham, Irene -- Perales, Lora -- Pu, Ling-Ling -- Qu, Carson -- Ramia, Miquel -- Reid, Jeffrey G -- Rollmann, Stephanie M -- Rozas, Julio -- Saada, Nehad -- Turlapati, Lavanya -- Worley, Kim C -- Wu, Yuan-Qing -- Yamamoto, Akihiko -- Zhu, Yiming -- Bergman, Casey M -- Thornton, Kevin R -- Mittelman, David -- Gibbs, Richard A -- GM 45146/GM/NIGMS NIH HHS/ -- R01 GM 059469/GM/NIGMS NIH HHS/ -- R01 GM 085183/GM/NIGMS NIH HHS/ -- R01 GM045146/GM/NIGMS NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Feb 8;482(7384):173-8. doi: 10.1038/nature10811.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA. trudy_mackay@ncsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318601" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Centromere/genetics ; Chromosomes, Insect/genetics ; Drosophila melanogaster/*genetics ; *Genome-Wide Association Study ; *Genomics ; Genotype ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/*genetics ; Selection, Genetic/genetics ; Starvation/genetics ; Telomere/genetics ; X Chromosome/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-09-16
    Description: Here we present computational machinery to efficiently and accurately identify transposable element (TE) insertions in 146 next-generation sequenced inbred strains of Drosophila melanogaster . The panel of lines we use in our study is composed of strains from a pair of genetic mapping resources: the Drosophila Genetic Reference Panel (DGRP) and the Drosophila Synthetic Population Resource (DSPR). We identified 23,087 TE insertions in these lines, of which 83.3% are found in only one line. There are marked differences in the distribution of elements over the genome, with TEs found at higher densities on the X chromosome, and in regions of low recombination. We also identified many more TEs per base pair of intronic sequence and fewer TEs per base pair of exonic sequence than expected if TEs are located at random locations in the euchromatic genome. There was substantial variation in TE load across genes. For example, the paralogs derailed and derailed-2 show a significant difference in the number of TE insertions, potentially reflecting differences in the selection acting on these loci. When considering TE families, we find a very weak effect of gene family size on TE insertions per gene, indicating that as gene family size increases the number of TE insertions in a given gene within that family also increases. TEs are known to be associated with certain phenotypes, and our data will allow investigators using the DGRP and DSPR to assess the functional role of TE insertions in complex trait variation more generally. Notably, because most TEs are very rare and often private to a single line, causative TEs resulting in phenotypic differences among individuals may typically fail to replicate across mapping panels since individual elements are unlikely to segregate in both panels. Our data suggest that "burden tests" that test for the effect of TEs as a class may be more fruitful.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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  • 3
    Publication Date: 2013-12-11
    Description: Drosophila suzukii Matsumura (spotted wing drosophila) has recently become a serious pest of a wide variety of fruit crops in the United States as well as in Europe, leading to substantial yearly crop losses. To enable basic and applied research of this important pest, we sequenced the D. suzukii genome to obtain a high-quality reference sequence. Here, we discuss the basic properties of the genome and transcriptome and describe patterns of genome evolution in D. suzukii and its close relatives. Our analyses and genome annotations are presented in a web portal, SpottedWingFlyBase, to facilitate public access.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 4
    Publication Date: 2014-06-26
    Description: We have used whole genome paired-end Illumina sequence data to identify tandem duplications in 20 isofemale lines of Drosophila yakuba and 20 isofemale lines of D. simulans and performed genome wide validation with PacBio long molecule sequencing. We identify 1,415 tandem duplications that are segregating in D. yakuba as well as 975 duplications in D. simulans , indicating greater variation in D. yakuba . Additionally, we observe high rates of secondary deletions at duplicated sites, with 8% of duplicated sites in D. simulans and 17% of sites in D. yakuba modified with deletions. These secondary deletions are consistent with the action of the large loop mismatch repair system acting to remove polymorphic tandem duplication, resulting in rapid dynamics of gain and loss in duplicated alleles and a richer substrate of genetic novelty than has been previously reported. Most duplications are present in only single strains, suggesting that deleterious impacts are common. Drosophila simulans shows larger numbers of whole gene duplications in comparison to larger proportions of gene fragments in D. yakuba . Drosophila simulans displays an excess of high-frequency variants on the X chromosome, consistent with adaptive evolution through duplications on the D. simulans X or demographic forces driving duplicates to high frequency. We identify 78 chimeric genes in D. yakuba and 38 chimeric genes in D. simulans , as well as 143 cases of recruited noncoding sequence in D. yakuba and 96 in D. simulans , in agreement with rates of chimeric gene origination in D. melanogaster . Together, these results suggest that tandem duplications often result in complex variation beyond whole gene duplications that offers a rich substrate of standing variation that is likely to contribute both to detrimental phenotypes and disease, as well as to adaptive evolutionary change.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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