church isca2012
DESCRIPTION
Presentation given at the ISCA consortium meeting May 2012 in Bethesda, MDTRANSCRIPT
![Page 1: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/1.jpg)
Genome Representation and Variant Identification
Deanna M. Church
ISCA Consortium Conference
![Page 2: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/2.jpg)
From Green ED et al. Nature 2011
![Page 3: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/3.jpg)
http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes
CEPH: A=1.000 G=0
![Page 4: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/4.jpg)
YRI: A=0.5852 G=0.4148
Multiple submissions
FrequencyData
1000G
Suspect
Sudmant et al., 2010
![Page 5: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/5.jpg)
Kidd et al, 2007 APOBEC cluster
BLACK: DeletionWhite: Insertion
![Page 6: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/6.jpg)
http://www.ncbi.nlm.nih.gov/dbvar
![Page 7: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/7.jpg)
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
![Page 8: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/8.jpg)
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
![Page 9: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/9.jpg)
![Page 10: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/10.jpg)
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
![Page 11: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/11.jpg)
MHC (chr6)Chr 6 representation (PGF)
Alt_Ref_Locus_2 (COX)
![Page 12: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/12.jpg)
Church et al., 2011 PLoS Biology
http://genomereference.org
![Page 13: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/13.jpg)
GRCh37 (hg19)
http://genomereference.org
7 alternate haplotypesat the MHC
Alternate loci released as:FASTA
AGPAlignment to chromosome
UGT2B17 MHC MAPT
![Page 14: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/14.jpg)
Richa AgarwalaEugene Yaschenko
![Page 15: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/15.jpg)
70 Fix PATCHES: Chromosome will update in GRCh3871 Novel PATCHES: Additional sequence added
Releasing patches quarterly
Summer of 2013
![Page 16: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/16.jpg)
![Page 17: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/17.jpg)
GRCh37 chr17
GRCh37 Myo19 Fix Patch
![Page 18: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/18.jpg)
Dennis et al., 2012
1q32 1q21 1p21
1p21 patch alignment to chromosome 1
![Page 19: Church isca2012](https://reader035.vdocuments.net/reader035/viewer/2022062703/55502ca7b4c905de2d8b4c29/html5/thumbnails/19.jpg)
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