Genome Representation and Variant Identification
Deanna M. Church
ISCA Consortium Conference
From Green ED et al. Nature 2011
http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes
CEPH: A=1.000 G=0
YRI: A=0.5852 G=0.4148
Multiple submissions
FrequencyData
1000G
Suspect
Sudmant et al., 2010
Kidd et al, 2007 APOBEC cluster
BLACK: DeletionWhite: Insertion
http://www.ncbi.nlm.nih.gov/dbvar
Variant Call Ambiguitystart stop
Inner start Inner stop
Outer start Outer stop
Probes with decreased signal intensityProbes with expected signal intensity
breakpoint breakpoint
Inner start Inner stop
Variant Call AmbiguityOuter start Outer stop
Fosmid clone (40 Kb +/- 1 Kb)
20Kb Clone has an insertionrelative to the genome
Clone has a deletionrelative to the genome 60 Kb
Large-Scale Variation Complicates Genome Assembly
Sequences from haplotype 1Sequences from haplotype 2
Old Assembly model: compress into a consensus
New Assembly model: represent both haplotypes
MHC (chr6)Chr 6 representation (PGF)
Alt_Ref_Locus_2 (COX)
Church et al., 2011 PLoS Biology
http://genomereference.org
GRCh37 (hg19)
http://genomereference.org
7 alternate haplotypesat the MHC
Alternate loci released as:FASTA
AGPAlignment to chromosome
UGT2B17 MHC MAPT
Richa AgarwalaEugene Yaschenko
70 Fix PATCHES: Chromosome will update in GRCh3871 Novel PATCHES: Additional sequence added
Releasing patches quarterly
Summer of 2013
GRCh37 chr17
GRCh37 Myo19 Fix Patch
Dennis et al., 2012
1q32 1q21 1p21
1p21 patch alignment to chromosome 1
Thanks!
For Slides: Evan Eichler
The Genome Reference ConsortiumThe Genome Center at Washington University The Wellcome Trust Sanger InstituteThe European Bioinformatics InstituteThe National Center for Biotechnology Information
Church group at NCBIValerie SchneiderNathan BoukHsiu-Chuan ChenPeter MericVictor AnanievChao ChenJohn LopezJohn GarnerTim HefferonCliff Clausen NCBI
Alt-Aware Alignments: Richa Agarwala Eugene Yaschenko Chunlin Xiao Steve Sherry
1000 Genome browser: Doug Slotta Eugene Yaschenko Victor Ananiev Lon Phan Steve Sherry Rob Cohen Deanna Church