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Array comparative genomic hybridisation

The type of chromosomal microanalysis using arrays referred to in the previous article in the thread is developing. A method known as array comparative genomic hybridization has potential uses in both pre-natal diagnosis and in evaluation in adults and children. For example, in a Danish study, a high-resolution whole genome array comparative genomic hybridization method was used on foetuses with abnormal ultrasound. An 80-kb resolution oligonucleotide array-based comparative genomic hybridization (aCGH) was used. The discovery of clinically significant copy number variations in 11 foetuses with structural malformations and three foetuses with uncertain clinical significant variations led the authors to propose that array comparative genomic hybridization is a valuable diagnostic tool in the context of detection of foetal abnormalities.

The method has potential in a number of disorders, including autism as mentioned in the original article in this thread. A study from the University of Washington used retrospective array comparative genomic hybridization on patients who had been referred for genetic testing for autism spectrum disorders. Among the patients in whom a diagnosis of autism spectrum disorder was confirmed and in whom array comparative genomic hybridization was performed , 8.7% had ‘pathogenic or presumed pathogenic abnormalities’ while another 8.7% had’ likely pathogenic copy-number variants’ and another 22% had variants which are not yet sub-classified and whose significance is not yet understood. In another study from the University of Colorado, adults with an unexplained intellectual disability were considered. Out of 45 patients, three had abnormal high-resolution chromosome studies, which were confirmed by array comparative genomic hybridization while another 7 had ‘novel genomic losses identified only by array comparative genomic hybridization’. This is a method with a lot of potential.

Sources

STOBBE, G. et al., 2013. Diagnostic yield of array comparative genomic hybridization in adults with autism spectrum disorders. Genetics In Medicine: Official Journal Of The American College Of Medical Genetics

TAYLOR, M.R.G. et al., 2010. High prevalence of array comparative genomic hybridization abnormalities in adults with unexplained intellectual disability. Genetics In Medicine: Official Journal Of The American College Of Medical Genetics, 12(1), pp. 32-38

VESTERGAARD, E.M. et al., 2013. Prenatal diagnosis: array comparative genomic hybridization in fetuses with abnormal sonographic findings. Acta Obstetricia et Gynecologica Scandinavica, 92(7), pp. 762-768