Microarrays: a Queensland first for Mater Pathology

Industry leader Mater Pathology is the first laboratory in Queensland to offer high-resolution microarrays—also known as array comparative genome hybridisation (CGH) or molecular karyotyping—as a diagnostic tool in genetics. The test uses the Affymetrix® GeneChip® System and is a significant advancement in the diagnosis of cytogenetic and other genetic abnormalities.

This novel test utilises the combined expertise of Mater Pathology’s Omics team (under Chief Scientist, Gareth Price) and the Cytogenetics division (under Chief Scientist, Marylou Doody). The project is headed by Director of Mater Pathology, Professor Deon Venter.

The Affymetrix® GeneChip® System is one of several systems in Mater Pathology’s Omics laboratory—the first of its kind in Australia to consolidate expertise in advanced molecular technologies such as genomics, proteomics and advanced metabolic mass spectrometry.

Gareth Price explained the diagnostic advancement.

“The system uses advanced hardware and software designed for targeted genotyping,” he said.

“The gene chip has 2.7 million probes enriched with subtelometric and centromeric probes for increased analytic capacity. To put that into context, the human genome has 3.2 billion base pairs, so the gene chip allows us to map gains and losses throughout the human genome in far greater depth than what is currently achievable by conventional cytogenetics.”

Marylou Doody elaborated on the advantages for Mater Pathology’s cytogenetics laboratory.

“In the diagnosis of problems in children, array testing will increase our pickup rate from two to three per cent using conventional karyotyping, to 10 to 15 per cent,” she said.

“This is very exciting, as our capacity to identify chromosomal abnormalities in children with intellectual disabilities, developmental delay and congenital abnormalities will benefit from the much higher resolution achieved by microarray testing.

“It will also further reduce the very few mistakes made in the demanding but subjective conventional cytogenetics analysis. Although we will continue to use the standard cytogenetics techniques such as karyotyping and Fluorescent In-Situ Hybridisation (FISH), microarrays will significantly improve our diagnostic service,” Ms Doody continued.

Microarray testing in cytogenetics is currently available by consultation. For more information, contact Marylou Doody on 07 3163 8212.

Case study

A six month-old with dysmorphic features and microcephaly was found by conventional cytogenetic karyotype analysis to have a very subtle change at the telomere of the short arm of a C-group chromosome. Fluorescent In-Situ Hybridisation (FISH) studies confirmed genetic material was missing (deleted) from the terminal region of the chromosome.

Loss of the terminal regions of either the short or long arms of many chromosomes are well described as being associated with specific phenotypes. These simple deletions are usually de novo (non-recurrent) and the recurrence risk for parents is very low. However, apparent simple deletions can arise from the inheritance of a familial balanced translocation in a genetically imbalanced form. In these cases there is both loss of genetic material at the deleted region and gain of material from another chromosome—deletion/duplication syndromes. The phenotypic effect in these cases is often greater than simple deletions and the recurrence risk for the parents (and extended family) is high.

Using conventional cytogenetics to distinguish between these two scenarios is labour intensive, time consuming and expensive.

High resolution molecular karyotyping using microarrays on the Affymetrix® Cytochip 2.7M was undertaken to provide more information than achievable by conventional karyotyping. The test confirmed the previously detected deletion, but also revealed a subtle duplication of material from the terminal region of a B-group chromosome.

The use of array testing excluded the possibility of a simple deletion syndrome and confirmed a diagnosis of a duplication/deletion syndrome. What appeared by conventional cytogenetics to be a de novo event was shown to be a complex inherited imbalance. This had major implications for the child as the phenotype was expected to be more severe than a simple deletion case. As the child’s abnormal chromosomes are inherited, there is also a major effect on the family’s reproductive risk.

Thanks to the power of array technology, the clinician can now provide appropriate genetic counselling to the family and assist them to make informed decisions about their future.