Werewolf, there wolf: variants in Hairless associated with hypotrichia and roaning in the lykoi cat breed

Fulton

et al. 2020

Preprint

Self Cite

Over 94 million domestic cats are considered pets, who, as our companions, are also susceptible to cancers, common and rare diseases. Whole exome sequencing (WES) is a cost-effective strategy to study their putative disease-causing variants. Presented is ~35.8 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. WES was conducted on 41 cats from various breeds with known and unknown diseases and traits, including 10 cats with prior whole genome sequence (WGS) data available, to test WES capture probe performance. A WES and WGS comparison was completed to understand variant discovery capability of each platform. At ~80x exome coverage, the percent of on-target base coverage >20x was 96.4% with an average of 10.4% off-target. For variant discovery, greater than 98% of WGS SNPs were also discovered by WES. Platform specific variants were mainly restricted to a small number of sex chromosome and olfactory receptor genes. Within the 41 cats with ~31 diseases and normal traits, 45 previously known disease or trait causal variants were observed, such as Persian progressive retinal degeneration and hydrocephalus. Novel candidate variants for polycystic kidney disease and atrichia in the Peterbald breed were also identified as well as a new cat patient with a known variant for cystinuria. These results show the discovery potential of deep exome sequencing to validate existing disease gene models and identify novel gene candidate alleles for many common and rare diseases in cats.

Section: Resultsmentioning

confidence: 99%

“…The lysophosphatidic acid receptor 6 (LPAR6) c.250_253delTTTG variant that causes a p.Phe84Glufs*9 and is associated with the autosomal recessive rexoid (marsella wave) coat of the Cornish rex breed was detected in a Peterbald cat, which is a hairless breed 57,53 . However, the hairless trait is considered autosomal dominant by cat breeders.…”

Section: Resultsmentioning

confidence: 99%

A domestic cat whole exome sequencing resource for trait discovery

Rodney

Fulton

et al. 2020

Preprint

Self Cite

“…Cat genomes have been submitted to the NCBI short read archive under BioProject: PRJNA528515; Accessions PRJNA343385; SRX2654400 (Sire), SRX2654398 (dam) and SRX2654399 (offspring). Genome sequence analyses and variant calling for the 99 Lives project has been previously described [37]. Approximately 2.5 million variants were ascertained across 195 cats in the exonic portion of the dataset, which included 21 bp of exon flank sequence.…”

Section: Whole Genome Sequencingmentioning

confidence: 99%

A Deletion in GDF7 is Associated with a Heritable Forebrain Commissural Malformation Concurrent with Ventriculomegaly and Interhemispheric Cysts in Cats

Creighton

et al. 2020

Genes

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An inherited neurologic syndrome in a family of mixed-breed Oriental cats has been characterized as forebrain commissural malformation, concurrent with ventriculomegaly and interhemispheric cysts. However, the genetic basis for this autosomal recessive syndrome in cats is unknown. Forty-three cats were genotyped on the Illumina Infinium Feline 63K iSelect DNA Array and used for analyses. Genome-wide association studies, including a sib-transmission disequilibrium test and a case-control association analysis, and homozygosity mapping, identified a critical region on cat chromosome A3. Short-read whole genome sequencing was completed for a cat trio segregating with the syndrome. A homozygous 7 bp deletion in growth differentiation factor 7 (GDF7) (c.221_227delGCCGCGC [p.Arg74Profs]) was identified in affected cats, by comparison to the 99 Lives Cat variant dataset, validated using Sanger sequencing and genotyped by fragment analyses. This variant was not identified in 192 unaffected cats in the 99 Lives dataset. The variant segregated concordantly in an extended pedigree. In mice, GDF7 mRNA is expressed within the roof plate when commissural axons initiate ventrally-directed growth. This finding emphasized the importance of GDF7 in the neurodevelopmental process in the mammalian brain. A genetic test can be developed for use by cat breeders to eradicate this variant.

“…Cat genomes have been submitted to the NCBI short read archive under BioProject: PRJNA528515; Accessions PRJNA343385; SRX2654400 (Sire), SRX2654398 (dam) and SRX2654399 (offspring). Genome sequence analyses and variant calling for the 99 Lives project has been previously described [36]. Approximately 2.5 million variants were ascertained across 195 cats in the exonic portion of the dataset, which included 21 bp of exon flank sequence.…”

Section: Whole Genome Sequencingmentioning

confidence: 99%

A deletion inGDF7is associated with a heritable forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts in cats

Creighton

et al. 2020

Preprint

Self Cite

An inherited neurologic syndrome in a family of mixed-breed Oriental cats has been characterized as forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts. However, the genetic basis for this autosomal recessive syndrome in cats is unknown. Forty-three cats were genotyped on the Illumina Infinium Feline 63K iSelect DNA Array and used for analyses. Genome-wide association studies, including a sib-transmission disequilibrium test, a case-control association analysis, and homozygosity mapping, identified a critical region on cat chromosome A3. Short-read whole genome sequencing was completed for a cat trio segregating with the syndrome. A homozygous 7 bp deletion in growth differentiation factor 7 (GDF7) (c.221_227delGCCGCGC [p.Arg74Profs]) was identified in affected cats by comparison to the 99 Lives Cat variant dataset, validated using Sanger sequencing, and genotyped by fragment analyses. This variant was not identified in 192 unaffected cats in the 99Lives dataset. The variant segregated concordantly in an extended pedigree. Obligate carrier cats were heterozygous. In mice, GDF7 mRNA is expressed within the roof plate when commissural axons initiate ventrally-directed growth. This finding emphasizes the importance of GDF7 in the neurodevelopmental process in the mammalian brain. A genetic test can be developed for use by cat breeders to eradicate this variant.