Authors' recommendations: Chromosome abnormalities are a well-established cause of congenital anomalies, dysmorphic features, developmental delay (DD), intellectual disability (ID), and other neurodevelopmental disorders. However, of individuals with DD, ID, and/or multiple congenital anomalies (MCA), less than 10% will have abnormalities detectable by conventional karyotype analysis or fluorescence in situ hybridization (FISH). Microarray-based comparative genomic hybridization (aCGH), which involves comparing the genomes of two individuals (the patient and a normal control), is able to detect much smaller chromosomal imbalances than standard karyotype and FISH analyses. Because of this increased resolution, aCGH will identify chromosomal imbalances in approximately 10% of patients with a suspected chromosome disorder who have a normal karyotype by conventional cytogenetics. Single nucleotide polymorphism (SNP) microarrays, which analyze thousands of SNPs throughout the genome in order to identify deletions and duplications, are another type of microarray that has been recently developed. SNPs are variants in which a single base pair differs from a specified reference sequence. SNP microarray testing involves hybridizing patient DNA to the microarray and comparing results with those obtained from a given set of control samples. In addition to identifying copy number variants (CNVs; segments of DNA longer than 1 kilobase that differ in copy number from a reference genome), SNP microarrays can detect "copy number neutral" abnormalities. Specifically, SNP microarrays may reveal the presence of uniparental disomy (UPD; when both copies of a chromosome are inherited from the same parent with no contribution from the other parent) or consanguinity (parents are related by blood), which can lead to disease if a recessive gene variant is present (either UPD or consanguinity) or if an imprinted region is involved (UPD only). The resolution of SNP microarrays is determined by the length and spacing between probes and by the statistical algorithms used to identify gains and losses (which differ between the various statistical software packages available for analysis). Like aCGH, SNP microarrays offer a cytogenetic evaluation at a significantly higher resolution than a standard karyotype analysis, as well as the ability to look for genomic imbalances throughout the genome in a single assay. In addition, both types of microarray analysis may be used to evaluate apparently balanced translocations, as up to 40% of these anomalies are found to have submicroscopic imbalances at rearrangement breakpoints. The main issue with microarray testing, including SNP microarray analysis, is the identification of CNVs of unknown clinical significance. In addition, the microarrays will not detect balanced chromosome rearrangements (i.e., balanced translocations or inversions) or imbalances not covered by the probes on the microarray.

Project Status: Completed

Year Published: 2011

URL for published report: http://www.hayesinc.com/hayes/crd/?crd=12937

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2011 Winifred S. Hayes, Inc