Paired-end mapping reveals extensive structural variation in the human genome.
Structural variation of the genome involves kilobase- to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements. We introduce high-throughput and massive paired-end mapping (PEM), a large-scale genome-sequencing method to identify structural variants (SVs) approximately 3 kilobases (kb) or larger that combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and a computational approach to map DNA reads onto a reference genome. PEM was used to map SVs in an African and in a putatively European individual and identified shared and divergent SVs relative to the reference genome. Overall, we fine-mapped more than 1000 SVs and documented that the number of SVs among humans is much larger than initially hypothesized; many of the SVs potentially affect gene function. The breakpoint junction sequences of more than 200 SVs were determined with a novel pooling strategy and computational analysis. Our analysis provided insights into the mechanisms of SV formation in humans.
Korbel
Jan O
JO
Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.
Urban
Alexander Eckehart
AE
Affourtit
Jason P
JP
Godwin
Brian
B
Grubert
Fabian
F
Simons
Jan Fredrik
JF
Kim
Philip M
PM
Palejev
Dean
D
Carriero
Nicholas J
NJ
Du
Lei
L
Taillon
Bruce E
BE
Chen
Zhoutao
Z
Tanzer
Andrea
A
Saunders
A C Eugenia
AC
Chi
Jianxiang
J
Yang
Fengtang
F
Carter
Nigel P
NP
Hurles
Matthew E
ME
Weissman
Sherman M
SM
Harkins
Timothy T
TT
Gerstein
Mark B
MB
Egholm
Michael
M
Snyder
Michael
M
D007446:Chromosome Inversion; D002874:Chromosome Mapping; D019295:Computational Biology; D005260:Female; D050939:Gene Fusion; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D016254:Mutagenesis, Insertional; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D018626:Retroelements; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D018626:Retroelements