title: Development of a diagnostic DNA chip to screen for 30 autosomal recessive disorders in the Hutterite population.
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.
authors.affiliation: Departments of Biochemistry & Medical GeneticsUniversity of ManitobaWinnipegCanada; Pediatrics & Child HealthUniversity of Manitoba745 Bannatyne Ave.WinnipegMB R3E 0J9Canada; The Manitoba Institute of Child Health513-715 McDermot Ave.WinnipegMB R3E 3P4Canada.
authors.forename: Barbara
authors.identifier: 0000-0003-4719-6779
authors.initials: B
authors.lastname: Triggs-Raine
authors.affiliation: Clinical Biochemistry and Genetics Diagnostic Services Manitoba at Health Sciences Centre Winnipeg MB R3A 1R9 Canada.
authors.forename: Tamara
authors.initials: T
authors.lastname: Dyck
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa ON K1H 8L1 Canada.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Department of Medical Genetics Alberta Children's Hospital and Alberta Children's Hospital Research Institute for Child and Maternal Health Cumming School of Medicine University of Calgary Calgary Alberta Canada.
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
authors.affiliation: Departments of Human Genetics and Obstetrics and Gynecology The University of Chicago Chicago Illinois.
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.affiliation: Department of Medical Genetics Alberta Children's Hospital and Alberta Children's Hospital Research Institute for Child and Maternal Health Cumming School of Medicine University of Calgary Calgary Alberta Canada.
authors.forename: Jillian S
authors.initials: JS
authors.lastname: Parboosingh
authors.affiliation: Pediatrics & Child Health University of Manitoba 745 Bannatyne Ave. Winnipeg MB R3E 0J9 Canada.
authors.forename: Alexis
authors.initials: A
authors.lastname: Botkin
authors.affiliation: Departments of Biochemistry & Medical GeneticsUniversity of ManitobaWinnipegCanada; Pediatrics & Child HealthUniversity of Manitoba745 Bannatyne Ave.WinnipegMB R3E 0J9Canada; The Manitoba Institute of Child Health513-715 McDermot Ave.WinnipegMB R3E 3P4Canada.
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: Greenberg
authors.affiliation: Departments of Biochemistry & Medical GeneticsUniversity of ManitobaWinnipegCanada; Pediatrics & Child HealthUniversity of Manitoba745 Bannatyne Ave.WinnipegMB R3E 0J9Canada; Clinical Biochemistry and GeneticsDiagnostic Services Manitoba at Health Sciences CentreWinnipegMB R3A 1R9Canada.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Spriggs
keywords: APEX array; Hutterite; carrier screening; chip; diagnostic; mutation