High-resolution human genome structure by single-molecule analysis.
Variation in genome structure is an important source of human genetic polymorphism: It affects a large proportion of the genome and has a variety of phenotypic consequences relevant to health and disease. In spite of this, human genome structure variation is incompletely characterized due to a lack of approaches for discovering a broad range of structural variants in a global, comprehensive fashion. We addressed this gap with Optical Mapping, a high-throughput, high-resolution single-molecule system for studying genome structure. We used Optical Mapping to create genome-wide restriction maps of a complete hydatidiform mole and three lymphoblast-derived cell lines, and we validated the approach by demonstrating a strong concordance with existing methods. We also describe thousands of new variants with sizes ranging from kb to Mb.
The Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics and Biotechnology Center, University of Wisconsin, 425 Henry Mall, Madison, WI 53706-1580, USA.
Brian
B
Teague
Michael S
MS
Waterman
Steven
S
Goldstein
Konstantinos
K
Potamousis
Shiguo
S
Zhou
Susan
S
Reslewic
Deepayan
D
Sarkar
Anton
A
Valouev
Christopher
C
Churas
Jeffrey M
JM
Kidd
Scott
S
Kohn
Rodney
R
Runnheim
Casey
C
Lamers
Dan
D
Forrest
Michael A
MA
Newton
Evan E
EE
Eichler
Marijo
M
Kent-First
Urvashi
U
Surti
Miron
M
Livny
David C
DC
Schwartz
D000465:Algorithms; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D056972:Optical Restriction Mapping / Q000379:methods* / Q000706:statistics & numerical data; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000235:genetics