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.
Teague
Brian
B
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.
Waterman
Michael S
MS
Goldstein
Steven
S
Potamousis
Konstantinos
K
Zhou
Shiguo
S
Reslewic
Susan
S
Sarkar
Deepayan
D
Valouev
Anton
A
Churas
Christopher
C
Kidd
Jeffrey M
JM
Kohn
Scott
S
Runnheim
Rodney
R
Lamers
Casey
C
Forrest
Dan
D
Newton
Michael A
MA
Eichler
Evan E
EE
Kent-First
Marijo
M
Surti
Urvashi
U
Livny
Miron
M
Schwartz
David C
DC
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