Year: 2021
Type: article
Abstract: Evaluating the impact of genetic variants on transcriptional regulation is a central goal in biological science that has been constrained by reliance on a single reference genome. To address this, we constructed phased, diploid genomes for four cadaveric donors (using long-read sequencing) and systematically charted noncoding regulatory elements and transcriptional activity across more than 25 tissues from these donors. Integrative analysis revealed over a million variants with allele-specific activity, coordinated, locus-scale allelic imbalances, and structural variants impacting proximal chromatin structure. We relate the personal genome analysis to the ENCODE encyclopedia, annotating allele- and tissue-specific elements that are strongly enriched for variants impacting expression and disease phenotypes. These experimental and statistical approaches, and the corresponding EN-TEx resource, provide a framework for personalized functional genomics.
Authors: Rozowsky, Joel, Moore, Jill E., Pratt, Henry E., Weng, Zhiping, Gerstein, Mark
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7011659629