Chromosomal Microarray

Use of Chromosome Microarrays

High-resolution microarrays are now in common use in identifying genetic defects and patterns in individuals presenting for clinical services with intellectual disability and/or autism spectrum disorders (ASD). Thus, the rise of chromosomal microarrays or array comparative genomic hybridization (aCGH) with copy number probes and later high-resolution microarrays with both copy number and SNP probes have significantly impacted understandings of genetic factors contributing to human disease.

For example, studies have shown that as high as 90% of those with ASD may have causative genetic factors. Furthermore, probes for SNPs, which can detect differences in the DNA pattern from individual to individual, are helpful in identifying regions of homozygosity or areas of DNA that appear identical. These stretches of DNA contain genes that are identical by descent or coming from a common ancestor, thereby supporting consanguinity or inbreeding, particularly when these regions share loss of heterozygosity not due to missing or deleted DNA segments on the other member of the chromosome pair. An example of loss of heterozygosity and not due to inbreeding or a deletion is a genetic phenomenon referred to as uniparental disomy when both members of a chromosome pair come from only one parent as seen in Prader-Willi syndrome (PWS), a classical but rare genetic disorder with maternal disomy 15 being the second most common cause of the disorder. A chromosome 15q11-q13 deletion involving the father’s chromosome 15 is the most common cause (see Figure 1).

Figure 1 Chromosome Microarray Results for Prader-Willi Syndrome

Source: Merlin G. Butler and A. M. Manzardo

Consanguinity is a common occurrence in some cultures, and the offspring from consanguineous or related parents share common gene alleles and are at risk of inheriting genes with defects or mutations that can cause genetic diseases, particularly autosomal recessive conditions such as cystic fibrosis. Consanguinity is termed as a union between individuals who are biologically related at the level of second cousins or closer. The degree of consanguinity can be based on the amount of homozygosity or lack of DNA polymorphic signals [Page 248]in the genome and assessed by using SNP data from high-resolution microarrays to calculate the coefficient of inbreeding. Couples related as second cousins or closer and their progeny account for an estimated 10% of the global population.

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