DOI: 10.5061/dryad.z08kprrk3
title: Data from: A naturally occurring canine model of syndromic congenital microphthalmia

description: 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.
description: 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.
description: 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.
description: # 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