1 / 32

Genome representation and variant identification

Genome representation and variant identification. Deanna M. Church, NCBI. The Reference Assembly is NOT Static. NCBI35 (hg17). NCBI36 (hg18). GRCh37 (hg19). GRCh37.p9. Image credit: http :// www.tohlejokes.com. http://genomereference.org. Resolved: 716 Open: 697.

nardo
Download Presentation

Genome representation and variant identification

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Genome representation and variant identification Deanna M. Church, NCBI

  2. The Reference Assembly is NOT Static NCBI35 (hg17) NCBI36 (hg18) GRCh37 (hg19) GRCh37.p9

  3. Image credit: http://www.tohlejokes.com

  4. http://genomereference.org

  5. Resolved: 716 Open: 697

  6. http://www.ncbi.nlm.nih.gov/dbvar

  7. Studies Methods Analysis Publications Samples Submitted assembly Variant Region nsv531833 type: CNV Variant Regions Variant Calls: nssv577112 type: copy number gain Method: OligoaCGH Analysis: Probe signal intensity phenotype: Autism; etc. Clinical: Pathogenic Copy Number: 3 Variant Calls: nssv580124 type: copy number loss Method: OligoaCGH Analysis: Probe signal intensity phenotype: Autism. Clinical: Pathogenic Copy Number: 1 Variant Calls

  8. Variant Call Ambiguity start stop Probes with decreased signal intensity Probes with expected signal intensity breakpoint breakpoint Inner start Inner stop Outer start Outer stop Inner start Inner stop

  9. Variant Call Ambiguity Fosmid clone (40 Kb +/- 1 Kb) Clone has an insertionrelative to the genome 20Kb Clone has a deletionrelative to the genome 60 Kb Outer start Outer stop

  10. Assembly, Mis-assembly, Biology and Variant Interpretation

  11. Shotgun sequence Assemble GAPS “finishers” go in to manually fill the gaps, often by PCR BAC insert BAC vector

  12. GRCh37 (hg19) NCBI36 (hg18)

  13. AL139246.20 NCBI35 (hg17) GRCh37 (hg19) AL139246.21

  14. Build sequence contigs based on contigs defined in TPF (Tiling Path File). Check for orientation consistencies Select switch points Instantiate sequence for further analysis Switch point Consensus sequence

  15. NCBI36

  16. nsv832911 (nstd68) Submitted on NCBI35 (hg17)

  17. Moved approximately 2 Mb distal on chr15 NCBI35 (hg17) Tiling Path NC_0000015.8 (chr15) Gap Inserted Removed from assembly GRCh37 (hg19) Tiling Path Added to assembly NC_0000015.9 (chr15) HG-24

  18. Sequences from haplotype 1 Sequences from haplotype 2 Old Assembly model: compress into a consensus New Assembly model: represent both haplotypes

  19. nsv532126 (nstd37) NCBI36NC_000004.10 (chr4) Tiling Path TMPRSS11E2 TMPRSS11E2 TMPRSS11E TMPRSS11E GRCh37NC_000004.11 (chr4) Tiling Path AC147055.2 AC079749.5 AC021146.7 AC134921.1 AC074378.4 AC093720.2 AC079749.5 AC147055.2 AC019173.4 AC021146.7 AC134921.2 AC140484.1 AC093720.2 AC074378.4 GRCh37: NT_167250.1 (UGT2B17 alternate locus) AC021146.7 AC019173.4 AC074378.4 AC226496.2 AC140484.1 Xue Y et al, 2008

  20. GRCh37

  21. GRCh37.p9 81 FIX Patches 71 NOVEL Patches

  22. 1q32 1q21 1p21 1p21 patch alignment to chromosome 1 Dennis et al., 2012

  23. Finding the data

  24. How dbVar* manages data Search Term *and most other NCBI databases too

  25. Variant submitted on NCBI35 (hg17) Failed to remap to NCBI36 (hg18) Successful remap to GRCh37 (hg19)

  26. No results in ‘normal’ dbVar search Genome Sensor predicts this is a location -> points to dbVar Genome Browser

  27. Acknowledgements dbVar GRC NCBI NCBI John Lopez Tim Hefferon John Garner Chao Chen George Zhou Victor Ananiev Valerie Schneider Nathan Bouk Hsiu-Chuan Chen Collaborators Collaborators DGVa DGV TGI-WU WTSI EBI ISCA NCBI Genomes, Viewers and Variation groups

More Related