Jay Shendure talks with
ScienceWatch.com and answers a few questions about
this month's Fast Moving Front Paper in the field of Molecular
Biology & Genetics.
Article: Multiplex amplification of large sets of human
Authors: Porreca, GJ;Zhang, K;Li, JB;Xie, B;Austin, D;Vassallo,
SL;LeProust, EM;Peck, BJ;Emig, CJ;Dahl, F;Gao, Y;Church,
Journal: NAT METHODS, 4 (11): 931-936 NOV 2007
Addresses: Univ Calif San Diego, Dept Bioengn, La Jolla, CA
Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond,
VA 23284 USA.
Agilent Technol, Genom Solut Unit, Santa Clara, CA 95051
(addresses have been
Why do you think your paper is highly
New methods for multiplex amplification of complex subsets of the human
genome are currently in high demand, as they extend the utility of
next-generation DNA sequencing platforms.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
"The research grew out of our earlier involvement in
developing massively parallel DNA sequencing
The paper describes the synthesis of several methodologies and their
extension to a new direction. Specifically, we describe the efficient
generation of tens of thousands of molecular inversion probes by a release
from programmable microarrays, and then use these molecular inversion
probes in a way that has not been utilized before. Specifically, we
demonstrated the capture of approximately 10,000 human exons in a highly
multiplex, solution-phase reaction.
Would you summarize the significance of your paper in
New sequencing technologies have dropped the cost of DNA sequence analysis
by several orders of magnitude. However, the scales at which these
technologies operate are poorly matched to "front end" methods like the
polymerase chain reaction (PCR) that enable targeted resequencing. The
methods that we describe here are aimed at building a better "front end"
for next-generation DNA sequencing platforms.
How did you become involved in this research and were
any particular problems encountered along the way?
The research grew out of our earlier involvement in developing massively
parallel DNA sequencing platforms, as we sought to apply these approaches
to human genetics and ran into a new problem (i.e., the lack of
technologies for multiplex targeted genome amplification).
Where do you see your research leading in the
We are attempting to extend targeted exon capture with molecular inversion
probes to the full human exome, i.e., the approximately 1% of the human
genome that is protein-coding.
Jay Shendure, M.D., Ph.D.
The Shendure Lab
University of Washington
Seattle, WA, USA
KEYWORDS: CODING SEQUENCES; CANCER GENES; GENOME; MUTATION; SNPS.