Premium
Extending the scope of diagnostic chromosome analysis: Detection of single gene defects using high‐resolution SNP microarrays
Author(s) -
Bruno Damien L.,
Stark Zornitza,
Amor David J.,
Burgess Trent,
Butler Kathy,
Corrie Sylvea,
Francis David,
Ganesamoorthy Devika,
Hills Louise,
James Paul A.,
O'Rielly Darren,
Oertel Ralph,
Savarirayan Ravi,
Prabhakara Krishnamurthy,
Salce Nicholas,
Slater Howard R.
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21581
Subject(s) - biology , genetics , dna microarray , snp array , microarray , snp , genotype , single nucleotide polymorphism , chromosome , copy number variation , phenotype , gene , genotype phenotype distinction , computational biology , bioinformatics , genome , gene expression
Microarray analysis has provided significant advances in the diagnosis of conditions resulting from submicroscopic chromosome abnormalities. It has been recommended that array testing should be a “first tier” test in the evaluation of individuals with intellectual disability, developmental delay, congenital anomalies, and autism. The availability of arrays with increasingly high probe coverage and resolution has increased the detection of decreasingly small copy number changes (CNCs) down to the intragenic or even exon level. Importantly, arrays that genotype SNPs also detect extended regions of homozygosity. We describe 14 examples of single gene disorders caused by intragenic changes from a consecutive set of 6,500 tests using high‐resolution SNP microarrays. These cases illustrate the increased scope of cytogenetic testing beyond dominant chromosome rearrangements that typically contain many genes. Nine of the cases confirmed the clinical diagnosis, that is, followed a “phenotype to genotype” approach. Five were diagnosed by the laboratory analysis in the absence of a specific clinical diagnosis, that is, followed a “genotype to phenotype” approach. Two were clinically significant, incidental findings. The importance of astute clinical assessment and laboratory‐clinician consultation is emphasized to optimize the value of microarrays in the diagnosis of disorders caused by single gene copy number and sequence mutations. 32:1500–1506, 2011. ©2011 Wiley Periodicals, Inc.