Genome Sequencing Scholarly Journal

Genome sequencing projects are discovering millions of human genetic variations, and decoding their functional consequences is important for understanding the genetic basis of human trait variability. Here we present the first reliably collected, high-throughput RNA sequencing data from multiple human populations with high-quality genome sequences from 462 lymphoblastoid cell lines from the 1000 Genomes Project. We discover extremely widespread genetic variability affecting the regulation of most genes, with variance in the transcript structure and level of expression being similarly common but largely separate from genetics. Our analysis of causal regulatory variability sheds light on regulatory and loss-of-function heterogeneity in cellular pathways, and helps us to infer putative causal variants for hundreds of disease-associated loci. This research offers a detailed understanding of the cellular processes of transcriptome variability and the nature of functional variants in the human genome in general. The implementation of these new technologies is expected to lead to the discovery of a host of novel oncogenes and tumor suppressors, which will have a significant effect on our understanding of tumorigenesis and clinical management of cancer patients.