A putative silencer variant in a spontaneous canine model of retinitis pigmentosa

PLoS Genetics
Maria KaukonenDoGA Consortium

Abstract

Retinitis pigmentosa (RP) is the leading cause of blindness with nearly two million people affected worldwide. Many genes have been implicated in RP, yet in 30-80% of the RP patients the genetic cause remains unknown. A similar phenotype, progressive retinal atrophy (PRA), affects many dog breeds including the Miniature Schnauzer. We performed clinical, genetic and functional experiments to identify the genetic cause of PRA in the breed. The age of onset and pattern of disease progression suggested that at least two forms of PRA, types 1 and 2 respectively, affect the breed, which was confirmed by genome-wide association study that implicated two distinct genomic loci in chromosomes 15 and X, respectively. Whole-genome sequencing revealed a fully segregating recessive regulatory variant in type 1 PRA. The associated variant has a very recent origin based on haplotype analysis and lies within a regulatory site with the predicted binding site of HAND1::TCF3 transcription factor complex. Luciferase assays suggested that mutated regulatory sequence increases expression. Case-control retinal expression comparison of six best HAND1::TCF3 target genes were analyzed with quantitative reverse-transcriptase PCR assay and indicated overex...Continue Reading

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Citations

Oct 13, 2020·Nucleic Acids Research·Wanwen ZengRui Jiang
Nov 6, 2020·PLoS Genetics·Gustavo D AguirreLeonardo Murgiano

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Methods Mentioned

BETA
GTPase
genotyping
PCR
biopsies
immunoprecipitation
Assay
RNA-seq
transfection
biopsy
transfections

Software Mentioned

ANNOVAR
UCSC liftOver
Genotype Query Tools ( GQT )
Mobile Element Locator Tool ( MELT )
HISAT1 mapper
R
Burrows
gnomAD
featureCounts
Sequencher

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