title: High-resolution homozygosity mapping is a powerful tool to detect novel mutations causative of autosomal recessive RP in the Dutch population.
abstract: OBJECTIVE
  To determine the genetic defects underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch population and in a subset of patients originating from other countries. The hypothesis was that, because there has been little migration over the past centuries in certain areas of The Netherlands, a significant fraction of Dutch arRP patients carry their genetic defect in the homozygous state.
  
  
  METHODS
  High-resolution genome-wide SNP genotyping on SNP arrays and subsequent homozygosity mapping were performed in a large cohort of 186 mainly nonconsanguineous arRP families living in The Netherlands. Candidate genes residing in homozygous regions were sequenced.
  
  
  RESULTS
  In ~94% of the affected individuals, large homozygous sequences were identified in their genome. In 42 probands, at least one of these homozygous regions contained one of the 26 known arRP genes. Sequence analysis of the corresponding genes in each of these patients revealed 21 mutations and two possible pathogenic changes, 14 of which were novel. All mutations were identified in only a single family, illustrating the genetic diversity within the Dutch population.
  
  
  CONCLUSIONS
  This report demonstrates that homozygosity mapping is a powerful tool for identifying the genetic defect underlying genetically heterogeneous recessive disorders like RP, even in populations with little consanguinity.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, Nijmegen, The Netherlands. r.collin@antrg.umcn.nl
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
authors.forename: Marta
authors.initials: M
authors.lastname: de Castro-Miró
authors.forename: Karin W
authors.initials: KW
authors.lastname: Littink
authors.forename: Kentar
authors.initials: K
authors.lastname: Arimadyo
authors.forename: Maleeha
authors.initials: M
authors.lastname: Azam
authors.forename: Volkan
authors.initials: V
authors.lastname: Yazar
authors.forename: Marijke N
authors.initials: MN
authors.lastname: Zonneveld
authors.forename: Codrut C
authors.initials: CC
authors.lastname: Paun
authors.forename: Anna M
authors.initials: AM
authors.lastname: Siemiatkowska
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Jayne Y
authors.initials: JY
authors.lastname: Hehir-Kwa
authors.forename: Hester Y
authors.initials: HY
authors.lastname: Kroes
authors.forename: Jan-Tjeerd H N
authors.initials: JT
authors.lastname: de Faber
authors.forename: Mary J
authors.initials: MJ
authors.lastname: van Schooneveld
authors.forename: John R
authors.initials: JR
authors.lastname: Heckenlively
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D002874:Chromosome Mapping; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics*; D009426:Netherlands; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000235:genetics*