Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells

作者：Peters Brock A^*; Kermani Bahram G; Sparks Andrew B; Alferov Oleg; Hong Peter; Alexeev Andrei; Jiang Yuan; Dahl Fredrik; Tang Y Tom; Haas Juergen; Robasky Kimberly; Zaranek Alexander Wait; Lee Je Hyuk; Ball Madeleine Price; Peterson Joseph E; Perazich Helena; Yeung George; Liu Jia; Chen Linsu; Kennemer Michael I; Pothuraju Kaliprasad; Konvicka Karel; Tsoupko Sitnikov Mike; Pant Krishna P; Ebert Jessica C; Nilsen Geoffrey B; Baccash Jonathan; Halpern Aaron L

来源：Nature, 2012, 487(7406): 190-195.

DOI：10.1038/nature11236

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 similar to 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.

• 出版日期2012-7-12