title: A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications.
abstract: We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
authors.affiliation: Department of Genetics and Pathology, Rudbeck laboratory, Uppsala University, 751 85 Uppsala, Sweden
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Buckley
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Mantripragada
authors.forename: Magdalena
authors.initials: M
authors.lastname: Benetkiewicz
authors.forename: Isabel
authors.initials: I
authors.lastname: Tapia-Páez
authors.forename: Teresita
authors.initials: T
authors.lastname: Diaz De Ståhl
authors.forename: Magnus
authors.initials: M
authors.lastname: Rosenquist
authors.forename: Haider
authors.initials: H
authors.lastname: Ali
authors.forename: Caroline
authors.initials: C
authors.lastname: Jarbo
authors.forename: Cecilía
authors.initials: C
authors.lastname: De Bustos
authors.forename: Carina
authors.initials: C
authors.lastname: Hirvelä
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sinder Wilén
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Fransson
authors.forename: Charlotte
authors.initials: C
authors.lastname: Thyr
authors.forename: Britt-Inger
authors.initials: BI
authors.lastname: Johnsson
authors.forename: Carl E G
authors.initials: CE
authors.lastname: Bruder
authors.forename: Uwe
authors.initials: U
authors.lastname: Menzel
authors.forename: Martin
authors.initials: M
authors.lastname: Hergersberg
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blennow
authors.forename: Anna
authors.initials: A
authors.lastname: Wedell
authors.forename: David M
authors.initials: DM
authors.lastname: Beare
authors.forename: John E
authors.initials: JE
authors.lastname: Collins
authors.forename: Ian
authors.initials: I
authors.lastname: Dunham
authors.forename: Donna
authors.initials: D
authors.lastname: Albertson
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinkel
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
authors.forename: A Fawad
authors.initials: AF
authors.lastname: Faruqi
authors.forename: Roger S
authors.initials: RS
authors.lastname: Lasken
authors.forename: Koichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: V Peter
authors.initials: VP
authors.lastname: Collins
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
mesh_terms: D002874:Chromosome Mapping / Q000379:methods; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*