title: Genome-wide in situ exon capture for selective resequencing.
abstract: Increasingly powerful sequencing technologies are ushering in an era of personal genome sequences and raising the possibility of using such information to guide medical decisions. Genome resequencing also promises to accelerate the identification of disease-associated mutations. Roughly 98% of the human genome is composed of repeats and intergenic or non-protein-coding sequences. Thus, it is crucial to focus resequencing on high-value genomic regions. Protein-coding exons represent one such type of high-value target. We have developed a method of using flexible, high-density microarrays to capture any desired fraction of the human genome, in this case corresponding to more than 200,000 protein-coding exons. Depending on the precise protocol, up to 55-85% of the captured fragments are associated with targeted regions and up to 98% of intended exons can be recovered. This methodology provides an adaptable route toward rapid and efficient resequencing of any sizeable, non-repeat portion of the human genome.
authors.affiliation: Howard Hughes Medical Institute, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Hodges
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xuan
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Balija
authors.forename: Melissa
authors.initials: M
authors.lastname: Kramer
authors.forename: Michael N
authors.initials: MN
authors.lastname: Molla
authors.forename: Steven W
authors.initials: SW
authors.lastname: Smith
authors.forename: Christina M
authors.initials: CM
authors.lastname: Middle
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rodesch
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Albert
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: W Richard
authors.initials: WR
authors.lastname: McCombie
mesh_terms: D005091:Exons; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009841:Oligonucleotides / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D009841:Oligonucleotides