Mapping of structural variants using functional genomics

CREATED: 200808140304 Speaker: Jan Korbel ** Human genome variation *SNPs, structural variants eg. copy number variants, indel, inversions *>12% of the genome prone to SVs (Redon et al., Nature 2006) *resolution of SVs usually ~50kb, breakpoints are unknown ** Fine-mapping of SVs using high resolution tiling MA *Break-Pointer algorithm for SV breakpoint detection, based on HMM (Korbel et al., PNAS 2007) *Novel tech (HR-CGH) and scoring approach (Break-Pointer) for fine mapping of SVs *Abundance of SVs < 50kbs ** Genome-wide mapping of SVs in two human genomes using 454 sequencing high-resolution and massive paired-end mapping (PEM), Korbel et. al., Science 2007 #mapping of paired ends against reference genome #comparison of paired-end span against expected distribution #categorization of outliers into groups *** Results *17% of SVs in both genomes affect genes *13% of affected genes (355) have altered gene structures *validation against HR-CGH, Fiber-FISH, PCR spanning PEM-predicted breakpoints *14% of SVs formed through non-allelic homologous recombination *30% of SVs formed through retrotransposition *56% of SVs formed through non-homologous end-joining *examples of SVs: gene fusion of 2 olfactory receptor genes on chr11 ** Future work *scaling up to multiple human genomes, www.1000genomes.org