Ontology highlight
ABSTRACT: Purpose
Chromosomal microarray analysis to assess copy-number variation has become a first-tier genetic diagnostic test for individuals with unexplained neurodevelopmental disorders or multiple congenital anomalies. More than 100 cytogenetic laboratories worldwide use the new ultra-high resolution Affymetrix CytoScan-HD array to genotype hundreds of thousands of samples per year. Our aim was to develop a copy-number variation resource from a new population sample that would enable more accurate interpretation of clinical genetics data on this microarray platform and others.Methods
Genotyping of 1,000 adult volunteers who are broadly representative of the Ontario population (as obtained from the Ontario Population Genomics Platform) was performed with the CytoScan-HD microarray system, which has 2.7 million probes. Four independent algorithms were applied to detect copy-number variations. Reproducibility and validation metrics were quantified using sample replicates and quantitative-polymerase chain reaction, respectively.Results
DNA from 873 individuals passed quality control and we identified 71,178 copy-number variations (81 copy-number variations/individual); 9.8% (6,984) of these copy-number variations were previously unreported. After applying three layers of filtering criteria, from our highest confidence copy-number variation data set we obtained >95% reproducibility and >90% validation rates (73% of these copy-number variations overlapped at least one gene).Conclusion
The genotype data and annotated copy-number variations for this largely Caucasian population will represent a valuable public resource enabling clinical genetics research and diagnostics.
SUBMITTER: Uddin M
PROVIDER: S-EPMC4752593 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
Uddin Mohammed M Thiruvahindrapuram Bhooma B Walker Susan S Wang Zhuozhi Z Hu Pingzhao P Lamoureux Sylvia S Wei John J MacDonald Jeffrey R JR Pellecchia Giovanna G Lu Chao C Lionel Anath C AC Gazzellone Matthew J MJ McLaughlin John R JR Brown Catherine C Andrulis Irene L IL Knight Julia A JA Herbrick Jo-Anne JA Wintle Richard F RF Ray Peter P Stavropoulos Dimitri J DJ Marshall Christian R CR Scherer Stephen W SW
Genetics in medicine : official journal of the American College of Medical Genetics 20141211 9
<h4>Purpose</h4>Chromosomal microarray analysis to assess copy-number variation has become a first-tier genetic diagnostic test for individuals with unexplained neurodevelopmental disorders or multiple congenital anomalies. More than 100 cytogenetic laboratories worldwide use the new ultra-high resolution Affymetrix CytoScan-HD array to genotype hundreds of thousands of samples per year. Our aim was to develop a copy-number variation resource from a new population sample that would enable more a ...[more]