Abstract

Project 3: One of the major difficulties of characterizing structural variation in a large number of individuals has been the lack of an accurate, cost-effective, high-throughput genotyping method. This project focuses on developing methods for genotyping structural variation and assessing their genetic characteristics in the four major HapMap populations. Our strategy is to develop specific high-throughput assays according to the type of structural variation. During the course of this project, we propose to: 1) develop a robust assay to genotype -400 simple insertion/deletion events within 480 HapMap samples using a fluorescent oligonucleotide-extension microbead assay;2) assess the utility of the oligonucleotide array comparative genomic hybridization by genotyping 300 structural variants within segmental duplications and calibrating these results against corresponding sequence;3) develop PCR breakpoint assays to genotype 200 complex/inversion rearrangements and 4) assess linkage disequilibrium of structural variation and flanking SNPs. The results of this analysis will provide an assessment of heritability and allele frequency spectrum data for a large subset of structural variation. In addition, these data will allow integration of structural variation data in the HapMap and provide a set of experimentally validated genotyping assays for 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 #
5P01HG004120-03
Application #
7799372
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Project Start
Project End
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
3
Fiscal Year
2009
Total Cost
$327,320
Indirect Cost

  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