Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

Haplotyping germline and cancer genomes with high-throughput linked-read sequencing. Nature biotechnology Zheng, G. X., Lau, B. T., Schnall-Levin, M., Jarosz, M., Bell, J. M., Hindson, C. M., Kyriazopoulou-Panagiotopoulou, S., Masquelier, D. A., Merrill, L., Terry, J. M., Mudivarti, P. A., Wyatt, P. W., Bharadwaj, R., Makarewicz, A. J., Li, Y., Belgrader, P., Price, A. D., Lowe, A. J., Marks, P., Vurens, G. M., Hardenbol, P., Montesclaros, L., Luo, M., Greenfield, L., Wong, A., Birch, D. E., Short, S. W., Bjornson, K. P., Patel, P., Hopmans, E. S., Wood, C., Kaur, S., Lockwood, G. K., Stafford, D., Delaney, J. P., Wu, I., Ordonez, H. S., Grimes, S. M., Greer, S., Lee, J. Y., Belhocine, K., Giorda, K. M., Heaton, W. H., McDermott, G. P., Bent, Z. W., Meschi, F., Kondov, N. O., Wilson, R., Bernate, J. A., Gauby, S., Kindwall, A., Bermejo, C., Fehr, A. N., Chan, A., Saxonov, S., Ness, K. D., Hindson, B. J., Ji, H. P. 2016; 34 (3): 303-311

Abstract

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.

View details for DOI 10.1038/nbt.3432

View details for PubMedID 26829319

View details for PubMedCentralID PMC4786454