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Chunk #4 — INTRODUCTION

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Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence.
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To achieve our goal, we employ targeted capture (Gnirke et al., 2009) of 71 AD candidate genes in combination with deep, massively-parallel next-generation sequencing (McKernan et al., 2009). This approach is technically similar to exome sequencing, but captures the entire gene and its flanking regions, including putative regulatory regions. This method can identify several types of genetic variants, including common and rare variants, which allowed us to investigate the role these variants may play in AD. To our knowledge this is the first sequencing study of AD to examine entire genes, including introns and gene promoters, regions upstream of genes that assist with gene transcription, and regulatory regions; areas not previously covered by alcohol exome studies. Publically available resources, such as the Roadmap Epigenomics Project (Kundaje et al., 2015), will be used to aid in the interpretation of AD findings outside exons (Edwards et al., 2013).