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Fri., June 25, 2010, 10 a.m. Osborne Conference Room (ECSS 3.503)

 

 

 

 

 

 

 

 

 

 

 

“A Singular View of the Genome”
Dr. David C. Schwartz, University of Wisconsin-Madison

Abstract
Technological advances broaden our understanding of genomes, and new approaches employing single molecule analytes offer unique advantages for the discovery and characterization of genomic alterations complementing discernment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). CNVs commonly represent genomic events, such as amplifications and deletions usually found by DNA hybridization. Although such measures of genomic alteration are relatively comprehensive and have characterized small populations, CNVs effectively flag broad classes of genomic alterations but do not readily discern genomic structural alterations embodied as translocations, gene-fusion events, insertions or rearrangements – both large- and small-scale (sub-genic). Next-generation sequencing also offers limited structural insights due to short read lengths, which attenuate genome coverage and discernment of complex events.

The optical mapping system, developed at the University of Wisconsin-Madison, exploits the detection range afforded by restriction fragment length polymorphism analysis, but with high throughput and single-DNA molecule precision engendered by automated fluorescence microscopy. Optical mapping enables the construction of genome-wide physical maps (consensus maps) from ensembles of ordered, single-DNA molecule restriction maps developed from genomic sources, obviating clone libraries, PCR and hybridization. Comparisons of optical consensus maps against a reference map reveals structural alterations as “differences,” in the form of novel restriction sites (missing or extra cuts; MCs or ECs), or indels (insertions or deletions), which are statistically assessed, in part, based on the number of single-DNA molecule optical maps collectively represented by the consensus map. Since high-resolution restriction maps intrinsically reveal genome structure, elusive differences such as indels are discoverable and physically characterized.

In this talk I will describe the workings of the optical mapping system and single molecule sequencing approaches, and I will present numerous applications covering normal and cancer genomes.

Bio
David C. Schwartz is a professor of chemistry and genetics at the University of Wisconsin-Madison, where he is director of the Laboratory for Molecular and Computational Genetics. His work is funded by the National Institutes for Health and the National Science Foundation. He holds a bachelor’s degree (1976) from Hampshire College and a Ph.D. (1985) from Columbia University.