Abstract

We will apply next-generation sequencing (NGS) technology to assess the genome-wide pattern of structural variation within large (>20 kbp), complex regions of segmental duplication. Combining read-depth and a single-base unique nucleotide (SUN) identifier map, we will generate absolute estimates of diploid copy-number and sequence content for duplicated regions and gene families. We propose to analyze all 2,000 individuals being analyzed as part of the 1000 Genomes Project and to validate regions by a combination of array comparative genomic hybridization (arrayCGH), clone-based sequencing and FISH-based approaches.
This aim will provide the first genotypic assessment of copy and content of these complex regions facilitating future disease association studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Program Projects (P01)
Project #
5P01HG004120-07
Application #
8489317
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
7
Fiscal Year
2013
Total Cost
$362,283
Indirect Cost
$130,049

  Institution

Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Eslami Rasekh, Marzieh; Chiatante, Giorgia; Miroballo, Mattia et al. (2017) Discovery of large genomic inversions using long range information. BMC Genomics 18:65
Watson, Corey T; Steinberg, Karyn Meltz; Graves, Tina A et al. (2015) Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity. Genes Immun 16:24-34
Nuttle, Xander; Itsara, Andy; Shendure, Jay et al. (2014) Resolving genomic disorder-associated breakpoints within segmental DNA duplications using massively parallel sequencing. Nat Protoc 9:1496-513
Lazaridis, Iosif; Patterson, Nick; Mittnik, Alissa et al. (2014) Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature 513:409-13
Huddleston, John; Ranade, Swati; Malig, Maika et al. (2014) Reconstructing complex regions of genomes using long-read sequencing technology. Genome Res 24:688-96
Stong, Nicholas; Deng, Zhong; Gupta, Ravi et al. (2014) Subtelomeric CTCF and cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline. Genome Res 24:1039-50
Antonacci, Francesca; Dennis, Megan Y; Huddleston, John et al. (2014) Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability. Nat Genet 46:1293-302
Steinberg, Karyn Meltz; Schneider, Valerie A; Graves-Lindsay, Tina A et al. (2014) Single haplotype assembly of the human genome from a hydatidiform mole. Genome Res 24:2066-76
Mueller, Michael; Barros, Paula; Witherden, Abigail S et al. (2013) Genomic pathology of SLE-associated copy-number variation at the FCGR2C/FCGR3B/FCGR2B locus. Am J Hum Genet 92:28-40
Nuttle, Xander; Huddleston, John; O'Roak, Brian J et al. (2013) Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions. Nat Methods 10:903-9

Showing the most recent 10 out of 41 publications