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Updated: Aug 22, 2026

Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
Sequence-based linkage analysis
Itay Furman1, Mark J Rieder, Suzanne Da Ponte
1Division of Human Biology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109-1024, USA.
Abstract:
The rapid decrease in the cost of DNA sequencing will enable its use for novel applications. Here, we investigate the use of DNA sequencing for simultaneous discovery and genotyping of polymorphisms in family linkage studies. In the proposed approach, short contiguous segments of genomic DNA, regularly spaced across the genome, are resequenced in each pedigree member, and all sequence polymorphisms discovered within a pedigree are used as genetic markers. We use computer simulations consistent with observed human sequence diversity to show that segments of 500-1,000 base pairs, spaced at intervals of 1-2 Mb across the genome, provide linkage information that equals or exceeds that of traditional marker-based approaches. We validate these results experimentally by implementing the sequence-based linkage approach for chromosome 19 in CEPH pedigrees.
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