Article
作者: Zheng, Grace X. Y. ; Lau, Billy T. ; Schnall-Levin, Michael ; Jarosz, Mirna ; Bell, John M. ; Hindson, Christopher M. ; Kyriazopoulou-Panagiotopoulou, Sofia ; Masquelier, Donald A. ; Merrill, Landon ; Terry, Jessica M. ; Mudivarti, Patrice A. ; Wyatt, Paul W. ; Bharadwaj, Rajiv ; Makarewicz, Anthony J. ; Li, Yuan ; Belgrader, Phillip ; Price, Andrew D. ; Lowe, Adam J. ; Marks, Patrick ; Vurens, Gerard M. ; Hardenbol, Paul ; Montesclaros, Luz ; Luo, Melissa ; Greenfield, Lawrence ; Wong, Alexander ; Birch, David E. ; Short, Steven W. ; Bjornson, Keith P. ; Patel, Pranav ; Hopmans, Erik S. ; Wood, Christina ; Kaur, Sukhvinder ; Lockwood, Glenn K. ; Stafford, David ; Delaney, Joshua P. ; Wu, Indira ; Ordonez, Heather S. ; Grimes, Susan M. ; Greer, Stephanie ; Lee, Josephine Y. ; Belhocine, Kamila ; Giorda, Kristina M. ; Heaton, William H. ; McDermott, Geoffrey P. ; Bent, Zachary W. ; Meschi, Francesca ; Kondov, Nikola O. ; Wilson, Ryan ; Bernate, Jorge A. ; Gauby, Shawn ; Kindwall, Alex ; Bermejo, Clara ; Fehr, Adrian N. ; Chan, Adrian ; Saxonov, Serge ; Ness, Kevin D. ; Hindson, Benjamin J. ; Ji, Hanlee P.
Haplotyping of human chromosomes is a prerequisite for cataloguing the full repertoire of genetic variation. We present a microfluidics-based, linked-read sequencing technology that can phase and haplotype germline and cancer genomes using nanograms of input DNA. This high-throughput platform prepares barcoded libraries for short-read sequencing and computationally reconstructs long-range haplotype and structural variant information. We generate haplotype blocks in a nuclear trio that are concordant with expected inheritance patterns and phase a set of structural variants. We also resolve the structure of the EML4-ALK gene fusion in the NCI-H2228 cancer cell line using phased exome sequencing. Finally, we assign genetic aberrations to specific megabase-scale haplotypes generated from whole-genome sequencing of a primary colorectal adenocarcinoma. This approach resolves haplotype information using up to 100 times less genomic DNA than some methods and enables the accurate detection of structural variants.