Hypothesis-Free Data Gathering
“Chromosome microarray analysis is showing clinical utility in a proportion of individuals with autism,” states Stephen W. Scherer, Ph.D., director of the Centre for Applied Genomics, Hospital for Sick Children, University of Toronto. “In autism about 5 to 10% of idiopathic cases are found to carry de novo CNVs, and some genes involved have also been implicated using other experimental approaches. Tests are available for some genes and loci.” Though, he cautions, that when analyzing results, autism is a complex disorder so any data interpretation needs to be viewed in that context.
“Notwithstanding, for some of CNV regions being identified, the general lessons of medical genetics seem to apply and diagnoses are being made.”
Dr. Scherer, another speaker at the Cambridge Healthtech conference, says that enabling technologies like array CGH allow genome-wide hypothesis-free data gathering. “From these comprehensive genomic datasets one can focus in and generate informed hypotheses based on knowledge of complete data. It is just this type of algorithm of analysis that has led to such rapid progress in this field.”
New Genetic Paradigm
“The concept of copy number variation as the etiology of human disease is increasingly being driven by technology and revealing a completely new part of genetics,” states Charles Strom, M.D., Ph.D., medical director of the genetic testing center of Quest Diagnostics Nichols Institute.
Quest Diagnostics’ ClariSure™ array CGH postnatal test was approved for patient testing in New York in March 2009. It uses a single 10 mL blood sample to detect CNVs implicated in neuropsychiatric conditions including mental retardation, birth defects, autism spectrum, and developmental disorders, which conventional laboratory tests may not detect.
Mental retardation is defined as having an intelligence quotient of less than 70, and affects from 1 to 3% of the population. Initial investigations using karyotyping found an etiology in about 3.7% of patients tested. FISH with probes specific to subtelomeric regions can detect chromosomal aberrations in another 4% of individuals, though for other chromosomal regions additional probes are required. Array CGH can detect cytogenetic abnormalities throughout the genome in a single assay in 5 to 11% of individuals with mental retardation.
Dr. Strom considers the technological advances in genomics today analogous to the invention of the telescope and the impact it had on driving advances in astronomy. “We are still collecting and sorting out information. Then it will take the clinic and time to better understand the full etiologic implications of these neuropsychiatric conditions. With these tools, diseases that have defied description will be able to be described and explained.”