DOI: 10.5061/dryad.z08kprrk6
title: Frameshift variant in AMPD2 in Cirneco dell’ Etna with retinopathy and tremors

description: Many retinal conditions have non-syndromic manifestations, but many can be
 part of a syndrome.  The majority of these syndromic retinal
 disorders are thought to be recessively inherited. Several tissues are
 affected other than the retina, including the nervous system. A litter of
 four Cirneco dogs, all males, show signs of retinal degeneration, along
 with tremors and signs that could be described preliminarily as atypical
 seizures or paroxysmal dyskinesias. The other two littermates were normal.
 A genetic etiology for this oculo-neurological syndrome was suspected,
 which we named CONS (Cirneco Oculo-neurological syndrome). Homozygosity
 mapping and whole-genome sequencing detected in CFA6 a 1-bp deletion in
 the canine AMPD2, an adenosine monophosphate deaminase converting
 adenosine 5'-monophosphate (AMP) and to inosine 5'-monophosphate
 (IMP), causing a frameshift and premature stop codon. Genotyping of the
 available Cirneco population suggests perfect segregation between cases
 and controls for the variant, which is also absent in thousands of
 unaffected dogs in canine genomic databases. AMPD2 mutation we propose
 adds to the spectrum of neurological manifestations associated with AMPD2,
 in a canine model which also presents retinal manifestations, therefore
 expanding the phenotype spectrum.
description: SNPdata: genotype data Type from
 <em>220k</em> CanineHD array (<em>Illumina</em>).
 DNA was extracted from blood and processed by Neogen.
 NovaSeq6000 paired-end reads (2x100 bp)  whole genome sequencing
 (as for company instructions). The PCR-free library was prepared as
 follows. Libraries of 300 bp insert size were prepared and Illumina
 NovaSeq6000 paired-end reads (2 × 100 bp) were collected. Fastq files were
 generated using Casava 1.8. A total of 1,521,125,559 reads (100 bp
 paired-end reads) were collected in total for the sequenced dogs
 (corresponding to an approximate average coverage of the genome of 32× for
 VB260 and 45× for V259.
description: # Frameshift variant in AMPD2 in Cirneco dell’ Etna with retinopathy and
 tremors
 [https://doi.org/10.5061/dryad.z08kprrk6](https://doi.org/10.5061/dryad.z08kprrk6) Whole Genome Sequencing - 2 cases of Cirneco dog (*Canis lupus familiaris)* affected with a retinal and neurological syndrome (CONS). Paired-end, 300bp, Illumina novaseq6000. Compatible with whole-genome mappers like bwa. VB259_R1.fastq.gz VB259_R2.fastq.gz VB260_R1.fastq.gz VB260_R2.fastq.gz SNP chip genotyping - cases and controls marked as plink document (transposed format). Two cases of whole genome sequenced (see other part of the submission) are also contained here.  CIRN_PENN.tfam CIRN_PENN.tped ## Data details The fastq.gz are gzipped fastq files. Definition (wiki): "FASTQ format is a text-based format for storing both a biological sequence (usually nucleotide sequence) and its corresponding quality scores. Both the sequence letter and quality score are each encoded with a single ASCII character for brevity." More info [https://knowledge.illumina.com/software/general/software-general-reference_material-list/000002211](https://knowledge.illumina.com/software/general/software-general-reference_material-list/000002211) (accessed Nov 24 2024) tfam is a list of identifications (one dog each) used to read the tped file. The tped file contains information about the genotype of each locus, two bases per marker, used for GWAS, homozygosity mapping, and linkage. More information about [https://www.cog-genomics.org/plink/](https://www.cog-genomics.org/plink/) (accessed Nov 24 2024).