High-Resolution Homozygosity Mapping Is a Powerful Tool to Detect Novel Mutations Causative of Autosomal Recessive RP in the Dutch Population

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

来源：Investigative Ophthalmology & Visual Science, 2011, 52(5): 2227-2239.

DOI：10.1167/iovs.10-6185

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 similar to 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. (Invest Ophthalmol Vis Sci. 2011;52:2227-2239) DOI:10.1167/iovs.10-6185

• 出版日期2011-4