Chromosomal Microarray (aCGH) Applications in the Clinical Setting
Lisa D. White – Baylor College of Medicine
Work shown here is the work of a large number of people.
Conflict of interest statement. Baylor does get revenue from it’s sequencing services.
Custom targeted arrays. 180k postnatal CMA – high resolution, related to MR, DD, DF, autism, heart defects, seizure disorder. entire mitochondria genome. Recently upgraded to a 400kb postnatal array, has same coverage as other array, but includes 120k new snps across the genome.
Interested in detecting absense of heterozygosity. eg, consanguinity.
How does it work? uses same label protocol w restriction digestion. SNPs are recognized by whether it is cut or not.
Absense of heterozygosity is not loss of heterozygosity. Happens with consanguinity, eg, identical regions inherited, not loss of a chromosome.
Also, Uniparental disomy, when one parent gives you both copies of the same chromosome, rather than one from each parent. [is that correct?]
Examples given, showing Illumina 610 Quad vs Agilent custom. Looks good.
Discovery of incest in assessment of AOH detection. In clinical setting, it’s possible to identify cases of incest based on chromosomal data, eg. consanguinity. Raises ethical issues, however.
Limits to the array. [general array stats, like regions it doesn’t cover, situations like balanced translocations. etc.]
Other situations: DNA extraction of uncultured Amniocytes. Informed Consent. MD collects sample and ships to lab. DNA extraction is done (Bi et al, 2008 Prenatal diagnosis.). 3-5ml. Do three thingsÆ Maternal cell contamination test, gender PCR and Quantitation. Average turn around time is 6 days. (some info about back up culture, from set aside portion of the sample, but it’s rarely needed)
Prenatal example… indication of abnormal hands and feed… found a 500kb duplication detected. Able to show it was de novo, not tied to either parent.
- Arrays are important for diagnostics, even given NGS.
- Can do valuable work, and can be offered more uniersally for all pregnancies.
- Recently launched a cancer genetics lab, which will also use array CGH and NGS as part of the test.
Also developing NGS tests as well, moving forward. Looking for diagnostic tests that can move into the CLIA lab for proper applications.
Big effort with lots of people working on it.