Data from: A naturally occurring canine model of syndromic congenital microphthalmia
Data files
Dec 27, 2023 version files 26.45 GB
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MICR_PWD_GWAS.tfam
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MICR_PWD_GWAS.tped
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MICR_PWD_R1.fastq.gz
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MICR_PWD_R2.fastq.gz
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README.md
Feb 12, 2024 version files 26.45 GB
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MICR_PWD_GWAS.tfam
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MICR_PWD_GWAS.tped
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MICR_PWD_R1.fastq.gz
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MICR_PWD_R2.fastq.gz
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README.md
Abstract
In humans, the prevalence of congenital microphthalmia is estimated to be 0.2 to 3.0 every 10,000 individuals, with non-ocular involvement reported in ~80% of cases. Inherited eye diseases have been widely and descriptively characterized in dogs, and canine models of ocular diseases have played an important role in understanding the pathophysiology and development of new therapies. A naturally occurring canine model of a syndromic disorder characterized by microphthalmia was discovered in the Portuguese Water Dogmodel of a syndromic disorder characterized by microphthalmia in the Portuguese Water Dog (PWD). As non-ocular findings included tooth enamel malformations, stunted growth, anemia, and thrombocytopenia, we hence termed this disorder Canine Congenital Microphthalmos with Hematopoietic Defects (cCMHD). GWAS and homozygosity mapping detected a 2-Mb candidate region on canine chromosome 4. Whole genome sequencing and mapping against the Canfam4 reference revealed a SINE element insertion in exon 2 of the DNAJC1 gene (g.74,274,883ins[T70]TGCTGCTTGGATT). Subsequent Real-Time PCR-based mass genotyping of a larger PWD population found the homozygous mutant genotype perfectly associated with the cCMHD phenotype. Biallelic variants in DNAJC21 are mostly found to be associated with bone marrow failure (BMF) syndrome type 3, with a phenotype that has a certain degree of overlap with Fanconi anemia, dyskeratosis congenita, Shwachman–Diamond syndrome, Diamond–Blackfan anemia, and reports of individuals showing thrombocytopenia, microdontia and microphthalmia. We therefore propose cCMHD as a naturally occurring model for DNAJC21-associated syndromes.
README: Data from: A naturally occurring canine model of syndromic congenital microphthalmia
Whole Genome Sequencing, Portuguese water dog, HiSeq2500 paired-end reads (2x 150 bp), of a microphtalmia case:
"MICR_PWD_R1.fastq.gz" Forward reads
"MICR_PWD_R2.fastq.gz" Reverse reads
Illumina 220k canine SNP chip genotyping:
Files:
"MICR_PWD_GWAS.tped" transposed ped file (tped), SNP data in plink format
"MICR_PWD_GWAS.tfam" transposed tfam file, ID data in plink format
Following: sample list, cases and controls described in the tfam file
MP001 Case
MP001 Case
MP003 Case
MP004 Case
MP006 Case
MP007 Case
MP008 Case
MP009 Case
MP011 Case
MP012 Case
MP013 Case
MP015 Case
MP016 Case
MP018 Case
MP025 Case
MP026 Case
MP029 Case
MP037 Case
MP038 Case
MP028 Control
MP002 Control
MP010 Control
MP014 Control
MP017 Control
MP027 Control
MP030 Control
MP031 Control
MP032 Control
MP036 Control
MP039 Control
MP040 Control
MP041 Control
MP042 Control
MP043 Control
MP044 Control
MP045 Control
MP046 Control
MP052 Control
MP053 Control
PWD01 Control
PWD02 Control
PWD03 Control
PWD04 Control
PWD05 Control
PWD06 Control
PWD07 Control
PWD08 Control
PWD09 Control
PWD10 Control
PWD11 Control
PWD12 Control
PWD13 Control
PWD14 Control
PWD15 Control
PWD16 Control
PWD17 Control
PWD18 Control
PWD19 Control
PWD20 Control
PWD21 Control
PWD22 Control
PWD23 Control
BWA_GATK_Pipel_Base.sh is the GATK variant calling pipeline plus the Delly commands.
GWAS.GENAB.Microph.R is the GWAS script with genable script
Methods
Blood samples were gathered of cases and controls - Portuguese Water Dogs affected and unaffected by syndromic congenital microphthalmia. DNA was extracted with standard methods.
A subset of these was genotyped on 220k illumina canine SNP chip for homozygosity mapping and GWAS.
Whole genome sequencing (Illumina Hiseq2000) of a single case was carried out to explore the candidate region.
Usage notes
SNP chip data are in plink format, easily convertible to vcf through plink 1.9 or plink 2.0. Also readable as-is (or easily processed) by several R packages.
Whole Genome data are in fastq format, which can be mapped to a reference using standard mappers like BWA.