High-resolution homozygosity mapping is a powerful tool to detect novel mutations causative of autosomal recessive RP in the Dutch population

Rob W.J. Collin, L. Ingeborgh van den Born, B. Jeroen Klevering, Marta de Castro-Miró, Karin W. Littink, Kentar Arimadyo, Maleeha Azam, Volkan Yazar, Marijke N. Zonneveld, Codrut C. Paun, Anna M. Siemiatkowska, Tim M. Strom, Jayne Y. Hehir-Kwa, Hester Y. Kroes, Jan Tjeerd H.N. de Faber, Mary J. van Schooneveld, John R. Heckenlively, Carel B. Hoyng, Anneke I. den Hollander, Frans P.M. Cremers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

62 Citaten (Scopus)


PURPOSE. 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.

Originele taal-2Engels
Pagina's (van-tot)2227-2239
Aantal pagina's13
TijdschriftInvestigative Ophthalmology and Visual Science
Nummer van het tijdschrift5
StatusGepubliceerd - apr. 2011
Extern gepubliceerdJa


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