title: Exon array CGH: detection of copy-number changes at the resolution of individual exons in the human genome.
abstract: The development of high-throughput screening methods such as array-based comparative genome hybridization (array CGH) allows screening of the human genome for copy-number changes. Current array CGH strategies have limits of resolution that make detection of small (less than a few tens of kilobases) gains or losses of genomic DNA difficult to identify. We report here a significant improvement in the resolution of array CGH, with the development of an array platform that utilizes single-stranded DNA array elements to accurately measure copy-number changes of individual exons in the human genome. Using this technology, we screened 31 patient samples across an array containing a total of 162 exons for five disease genes and detected copy-number changes, ranging from whole-gene deletions and duplications to single-exon deletions and duplications, in 100% of the cases. Our data demonstrate that it is possible to screen the human genome for copy-number changes with array CGH at a resolution that is 2 orders of magnitude higher than that previously reported.
authors.affiliation: Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: Pawandeep
authors.initials: P
authors.lastname: Dhami
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Coffey
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbs
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Woodward
authors.forename: Robert M
authors.initials: RM
authors.lastname: Andrews
authors.forename: Cordelia
authors.initials: C
authors.lastname: Langford
authors.forename: David
authors.initials: D
authors.lastname: Vetrie
mesh_terms: D005091:Exons; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D030342:Genetic Diseases, Inborn / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results