Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells |
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Authors: | Brock A Peters Bahram G Kermani Andrew B Sparks Oleg Alferov Peter Hong Andrei Alexeev Yuan Jiang Fredrik Dahl Y Tom Tang Juergen Haas Kimberly Robasky Alexander Wait Zaranek Je-Hyuk Lee Madeleine Price Ball Joseph E Peterson Helena Perazich George Yeung Jia Liu Linsu Chen Michael I Kennemer Kaliprasad Pothuraju Karel Konvicka Mike Tsoupko-Sitnikov Krishna P Pant Jessica C Ebert Geoffrey B Nilsen Jonathan Baccash Aaron L Halpern George M Church Radoje Drmanac |
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Affiliation: | Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA. bpeters@completegenomics.com |
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Abstract: | Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100?picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10?megabases. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications. |
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