Haplotype-resolved diverse human genomes and integrated analysis of structural variation

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Item Type:	Article
Title:	Haplotype-resolved diverse human genomes and integrated analysis of structural variation
Creators Name:	Ebert, P., Audano, P. A., Zhu, Q., Rodriguez-Martin, B., Porubsky, D., Bonder, M.J., Sulovari, A., Ebler, J., Zhou, W., Serra Mari, R., Yilmaz, F., Zhao, X., Hsieh, P.H., Lee, J., Kumar, S., Lin, J., Rausch, T., Chen, Y., Ren, J., Santamarina, M., Höps, W., Ashraf, H., Chuang, N.T., Yang, X., Munson, K.M., Lewis, A.P., Fairley, S., Tallon, L.J., Clarke, W.E., Basile, A.O., Byrska-Bishop, M., Corvelo, A., Evani, U.S., Lu, T.Y., Chaisson, M.J.P., Chen, J., Li, C., Brand, H., Wenger, A.M., Ghareghani, M., Harvey, W.T., Raeder, B., Hasenfeld, P., Regier, A.A., Abel, H.J., Hall, I.M., Flicek, P., Stegle, O., Gerstein, M.B, Tubio, J.M.C., Mu, Z., Li, Y.I., Shi, X., Hastie, A.R., Ye, K., Chong, Z., Sanders, A.D., Zody, M.C., Talkowski, M.E., Mills, R. E., Devine, S.E., Lee, C., Korbel, J.O., Marschall, T. and Eichler, E.E.
Abstract:	Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent-child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average contig N50: 26 Mbp) integrate all forms of genetic variation even across complex loci. We identify 107,590 structural variants (SVs), of which 68% are not discovered by short-read sequencing, and 278 SV hotspots (spanning megabases of gene-rich sequence). We characterize 130 of the most active mobile element source elements and find that 63% of all SVs arise by homology-mediated mechanisms. This resource enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1,526 expression quantitative trait loci as well as SV candidates for adaptive selection within the human population.
Keywords:	DNA Sequence Analysis, Genetic Variation, Genotype, Haplotypes, High-Throughput Nucleotide Sequencing, Human Genome, INDEL Mutation, Interspersed Repetitive Sequences, Population Groups, Quantitative Trait Loci, Retroelements, Sequence Inversion, Whole Genome Sequencing
Source:	Science
ISSN:	0036-8075
Publisher:	American Association for the Advancement of Science
Volume:	372
Number:	6537
Page Range:	eabf7117
Date:	25 February 2021
Official Publication:	https://doi.org/10.1126/science.abf7117
PubMed:	View item in PubMed

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