Introduction: Retinitis pigmentosa (RP) is a genetically heterogeneous with more than 70 RP loci currently known. A three-generation RP family exhibiting X linked recessive pattern were studied. Materials and Methods: Linkage analysis was performed using 18 microsatellite markers. Whole exome sequencing was used for mutational analysis. Results: Polymorphic microsatellite markers were used to map the disease interval to a 48 Mb region on the X chromosome between the markers DXS1068 and DXS1196. Whole exome sequencing (WES) was performed on a selected sib-pair within the family. Total 1973 SNPs were found to be located within the critical interval. Among these SNPs, 139 were shared between the obligated carrier and the affected male offspring but not the phenotypically normal male offspring. We also utilized the WES identi fi ed polymorphic SNPs mapped within the critical disease interval to construct detailed haplotype for the sib-pair. Additional crossing-over evens were revealed on and the disease interval were mapped into two intervals: chrx: 38,911,177 -68890047; and chr X: 69,155,432-69,261,818). The causative mutation (RP2 c.102G>A; Lys34Lys, a RP2 splicing donor site mutation) was then identi fi ed. Conclusion: We have combined the positional information obtained from the linkage and haplotype analysis to identify the genetic intervals harboring the disease-causing gene, and also utilized DNA polymorphisms identi fi ed from WES as additional genetic markers to further mapped the crossing-over evens as a creative strategy for positional cloning.
Date:
2019-07
Relation:
European Journal of Human Genetics. 2019 Jul;27(Suppl. 1):66-67.
