title: Application of next-generation sequencing to identify genes and mutations causing autosomal dominant retinitis pigmentosa (adRP).
abstract: The goal of our research is to identify genes and mutations causing autosomal dominant retinitis pigmentosa (adRP). For this purpose we established a cohort of more than 250 independently ascertained families with adRP in the Houston Laboratory for Molecular Diagnosis of Inherited Eye Diseases. Affected members of each family were screened for disease-causing mutations in genes and gene regions that are commonly associated with adRP. By this approach, we detected mutations in 65 % of the families, leaving 85 families that are likely to harbor mutations outside of the "common" regions or in novel genes. Of these, 32 families were tested by several types of next-generation sequencing (NGS), including (a) targeted polymerase chain reaction (PCR) NGS, (b) whole exome NGS, and (c) targeted retinal-capture NGS. We detected mutations in 11 of these families (31 %) bringing the total detected in the adRP cohort to 70 %. Several large families have also been tested for linkage using Afymetrix single nucleotide polymorphism (SNP) arrays.
authors.affiliation: Human Genetics Center, School of Public Health, Univ. of Texas HSC, 1200 Herman Pressler Dr., 77030, Houston, TX, USA, Stephen.P.Daiger@uth.tmc.edusss.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Daiger
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Bowne
authors.forename: Lori S
authors.initials: LS
authors.lastname: Sullivan
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Koboldt
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fulton
authors.forename: David
authors.initials: D
authors.lastname: Larsen
authors.forename: Peter
authors.initials: P
authors.lastname: Humphries
authors.forename: Marian M
authors.initials: MM
authors.lastname: Humphries
authors.forename: Eric A
authors.initials: EA
authors.lastname: Pierce
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
mesh_terms: D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods / Q000639:trends*; D006801:Humans; D008297:Male; D010375:Pedigree; D015995:Prevalence; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*
chemical_list: D005136:Eye Proteins