Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice.
The role of gene deletion and duplication in the aetiology of disease has become increasingly evident over the last decade. In addition to the classical deletion/duplication disorders diagnosed using molecular techniques, such as Duchenne Muscular Dystrophy and Charcot-Marie-Tooth Neuropathy Type 1A, the significance of partial or whole gene deletions in the pathogenesis of a large number single-gene disorders is becoming more apparent. A variety of dosage analysis methods are available to the diagnostic laboratory but the widespread application of many of these techniques is limited by the expense of the kits/reagents and restrictive targeting to a particular gene or portion of a gene. These limitations are particularly important in the context of a small diagnostic laboratory with modest sample throughput. We have developed a gene-targeted, custom-designed comparative genomic hybridisation (CGH) array that allows twelve clinical samples to be interrogated simultaneously for exonic deletions/duplications within any gene (or panel of genes) on the array. We report here on the use of the array in the analysis of a series of clinical samples processed by our laboratory over a twelve-month period. The array has proven itself to be robust, flexible and highly suited to the diagnostic environment.
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. renate.mn@gmail.com.
Renate
R
Marquis-Nicholson
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. DProsser@adhb.govt.nz.
Debra
D
Prosser
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. JLove@adhb.govt.nz.
Jennifer M
JM
Love
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. DonaldL@adhb.govt.nz.|School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. DonaldL@adhb.govt.nz.
Donald R
DR
Love
Cowden syndrome; array comparative genomic hybridisation (aCGH); dosage analysis; familial phaeochromocytoma/paraganglioma syndrome; maturity-onset diabetes of the young (MODY); molecular diagnosis; targeted microarray