title: Regions of homozygosity identified by SNP microarray analysis aid in the diagnosis of autosomal recessive disease and incidentally detect parental blood relationships.
abstract: OBJECTIVE
  The purpose of this study was to document the ability of single-nucleotide polymorphism microarray to identify copy-neutral regions of homozygosity, demonstrate clinical utility of regions of homozygosity, and discuss ethical/legal implications when regions of homozygosity are associated with a parental blood relationship.
  
  
  METHODS
  Study data were compiled from consecutive samples sent to our clinical laboratory over a 3-year period. A cytogenetics database identified patients with at least two regions of homozygosity >10 Mb on two separate chromosomes. A chart review was conducted on patients who met the criteria.
  
  
  RESULTS
  Of 3,217 single-nucleotide polymorphism microarrays, 59 (1.8%) patients met inclusion criteria. The percentage of homozygosity ranged from 0.9 to 30.1%, indicating parental relationships from distant to first-degree relatives. First-degree kinship was suspected in the parents of at least 11 patients with regions of homozygosity covering >21.3% of their autosome. In four patients from two families, homozygosity mapping discovered a candidate gene that was sequenced to identify a clinically significant mutation.
  
  
  CONCLUSIONS
  This study demonstrates clinical utility in the identification of regions of homozygosity, as these regions may aid in diagnosis of the patient. This study establishes the need for careful reporting, thorough pretest counseling, and careful electronic documentation, as microarray has the capability of detecting previously unknown/unreported relationships.
authors.affiliation: Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Kristen.Sund@cchmc.org
authors.forename: Kristen Lipscomb
authors.initials: KL
authors.lastname: Sund
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Zimmerman
authors.forename: Cameron
authors.initials: C
authors.lastname: Thomas
authors.forename: Anna L
authors.initials: AL
authors.lastname: Mitchell
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Prada
authors.forename: Lauren
authors.initials: L
authors.lastname: Grote
authors.forename: Liming
authors.initials: L
authors.lastname: Bao
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Smolarek
mesh_terms: D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000175:diagnosis*; D006720:Homozygote; D006801:Humans; D008297:Male; D008499:Medical Records; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D035781:Siblings