? The human genome is remarkably variable and understanding this variation is a vital component of promised advances in human health. Publicly available human and model organism reference genomic sequences provide a foundation for revolutionary advances in population genomics, the genomic-scale detection of DNA sequence variants and investigation of their role in affecting disease risk. However, even as the first population genomic data emerge, solid paradigms of description and analysis have not yet appeared. For example, integration of population genomic polymorphism and associated phenotypic variation into genomic annotations is an essential yet daunting task. To directly address the basic challenge of population genomics we are proposing to begin an effort to obtain the complete sequence of 50 Drosophila melanogaster genomes. The Drosophila strains and their associated genomic polymorphisms will become objects of intense and diverse functional analyses and annotation. The goals of this proposal are (1) to develop and validate an appropriate resequencing technology, (2) to establish a sustainable, high quality resequencing capacity, and (3) to provide preliminary results and analysis that demonstrate the high added value of genomic coverage of population polymorphism. ? ? ?
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