Development of a diagnostic DNA chip to screen for 30 autosomal recessive disorders in the Hutterite population. Issue 3 (19th January 2016)

• Record Type: Journal Article
• Authors: Triggs‐Raine, Barbara; Dyck, Tamara; Boycott, Kym M.; Innes, A. Micheil; Ober, Carole; Parboosingh, Jillian S.; Botkin, Alexis; Greenberg, Cheryl R.; Spriggs, Elizabeth L.
• Is Part Of: Molecular genetics & genomic medicine. Volume 4:Issue 3(2016)
• Page Start: 312
• Page End: 321
• Publication Date: 2016-01-19
• Subjects: chip -- Hutterite -- diagnostic -- mutation -- APEX array -- carrier screening; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.206
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: The Hutterites are a religious isolate living in colonies across the North American prairies. This population originated from approximately 90 founders, resulting in a number of genetic diseases that are overrepresented, underrepresented, or unique. The founder effect in this population increases the likelihood that Hutterite couples carry the same recessive mutations. We have designed a diagnostic chip on a fee‐for‐service basis with Asper Biotech to provide Hutterites with the option of comprehensive carrier screening. Methods: A total of 32 disease‐causing mutations in 30 genes were selected and primers were designed for array primer extension‐based testing. Selected mutations were limited to those leading to autosomal recessive disorders, maintaining its primary use as a test for determining carrier status. Results: The DNA chip was developed and validated using 59 DNA controls for all but one of the mutations, for which a synthetic control was used. All mutations were readily detected except for a duplication causing restrictive dermopathy where heterozygotes and homozygotes could only be distinguished by sequencing. Blinded testing of 12 additional samples from healthy Hutterites was performed by Asper Biotech using chip testing. All known mutations from previous molecular testing were detected on the chip. As well, additional mutations identified by the chip in these 12 samples were subsequently verified by a second method. Conclusions: Our analysis indicates that the chip is a sensitive and specific means of carrier testing in the Hutterite population and can serve as a model for other founder populations. Abstract : Hutterites, a religious isolate located in North America, have a number of genetic disorders that are unique and/or over‐represented. A diagnostic chip that simultaneously tests for 30 autosomal recessive disorders of significance to this population was developed and validated in partnership with Asper Biotech. We have determined that this diagnostic chip provides a sensitive and specific means for carrier testing and has the potential to provide information that may empower future decision making in the Hutterite community.