Understanding Genomic Variations in the Context of Health and Disease: Annotation, Interpretation, and Challenges
An extensive variability exists in humans – no two genomes are exactly alike. To separate “functional” variants from other bystanders is a Herculean task, complicated by the contextual nature of these variations. While a large number of well-maintained repositories of variation data exist, a systematic method to obtain information from different sources and collate them coherently toward prioritization of functional variants is the dire need of the hour. We begin this chapter with a brief classification of genomic variations and discuss the factors that govern such widespread variability, methods which are in practice to study genomic variations, and the potential uses of studying them. Moreover, we provide a short description of the different resources that have cataloged variation data and discuss the studies that have meaningfully annotated variations in specific contexts. We conclude the chapter by proposing strategies for variant prioritization, including how one should go about ascertaining the functionality of non-coding variants.
KeywordsVariation Genomics GWAS Functional Contextual Missing heritability eQTL
Project funding from the Council of Scientific and Industrial Research (CMM-0016 and MLP-901), DST Inspire and D.S. Kothari Postdoctoral Fellowship to AN, and CSIR-Senior Research Fellowship to AB are duly acknowledged. We acknowledge the efforts of Uma Anwardekar for fruitful comments and discussions.
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