Homozygosity mapping guided next generation sequencing to identify the causative genetic variation in inherited retinal degenerative diseases.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 9808008 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-232X (Electronic) Linking ISSN: 14345161 NLM ISO Abbreviation: J Hum Genet Subsets: MEDLINE
    • Publication Information:
      Publication: 2009- : London : Nature Pub. Group
      Original Publication: Tokyo : Springer-Verlag, c1998-
    • Subject Terms:
      Chromosome Mapping* ; Genetic Association Studies* ; Genetic Variation* ; High-Throughput Nucleotide Sequencing* ; Homozygote*; Leber Congenital Amaurosis/*diagnosis ; Leber Congenital Amaurosis/*genetics; Adolescent ; Adult ; Aged ; Consanguinity ; DNA Mutational Analysis ; Female ; Fluorescein Angiography ; Genotype ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Young Adult
    • Abstract:
      Inherited retinal degeneration (IRD) are a group of genetically heterogeneous disease of which retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are the most common and severe type. In our study we had taken three unrelated South Indian consanguineous IRD families. Homozygosity mapping was done using Affymetrix 250K Nsp1 GeneChip in each of LCA, Cone-Rod dystrophy (CRD) and autosomal recessive RP (arRP) families followed by targeted re-sequencing by next generation sequencing (NGS) on Illumina MiSeq. Known candidate genes ranging from 1-8 in numbers within the homozygous blocks were identified by homozygosity mapping and targeted NGS revealed the causative mutations; RDH12 c.832A>C, ABCA4 c.1462G>T, CDHR1c.1384_1392delCTCCTGGACinsG, in the LCA, CRD and arRP families, respectively. The identified mutations were validated by Sanger sequencing, segregation in the families and their absence in 200 control chromosomes. Homozygosity mapping guided targeted NGS, especially when more numbers of known candidate genes within the homozygous blocks are observed is a comprehensive method for mutation identification. Molecular data from a larger retinal degenerative disease cohort would reveal the spectrum and prevalence of mutations and genes in Indian population. Molecular diagnosis also aids in genetic counseling, offering carrier and prenatal testing to family members.
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    • Publication Date:
      Date Created: 20160708 Date Completed: 20170406 Latest Revision: 20181113
    • Publication Date:
      20221213
    • Accession Number:
      10.1038/jhg.2016.83
    • Accession Number:
      27383656