Biology subjects

Creighton, E. K.

Publications and source records attributed to Creighton, E. K..

3 recordsLinked to original sources

bioRxiv2020

A deletion in GDF7 is associated with a heritable forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts in cats.

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 99 Lives 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.

genetics↗

bioRxiv2020

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

A variety of cat breeds have been developed via novelty selection on aesthetic, dermatological traits, such as coat colors and fur types. A recently developed breed, the lykoi, was bred from cats with a sparse hair coat with roaning, implying full color and all white hairs. The lykoi phenotype is a form of hypotrichia, presenting as significant reduction in the average numbers of follicles per hair follicle group as compared to domestic shorthair cats, a mild to severe perifollicular to mural lymphocytic infiltration in 77% of observed hair follicle groups, and the follicles are often miniaturized, dilated, and dysplastic. Whole genome sequencing was conducted on a single lykoi cat that was a cross between two independently ascertained lineages. Comparison to the 99 Lives dataset of 194 non-lykoi cats suggested two variants in the cat homolog for Hairless (HR: lysine demethylase and nuclear receptor corepressor) as candidate causal variants. The lykoi cat was a compound heterozygote for two loss of function variants in HR, an exon 3 c.1255_1256dupGT (chrB1:36040783), which should produce a stop codon at amino acid 420 (p.Gln420Serfs*100) and, an exon 18 c.3389insGACA (chrB1:36051555), which should produce a stop codon at amino acid position 1130 (p.Ser1130Argfs*29). Ascertainment of 14 additional cats from founder lineages from Canada, France and different areas of the USA identified four additional loss of function HR variants likely causing the highly similar phenotypic hair coat across the diverse cats. The novel variants in HR for cat hypotrichia can now be established between minor differences in the phenotypic presentations.

genetics↗

bioRxiv2018

A highly divergent picornavirus infecting the gut epithelia of zebrafish (Danio rerio) in research institutions world-wide

Zebrafish have been extensively used as a model system for research in vertebrate development and pathogen-host interactions. We describe the complete genome of a novel picornavirus identified during a viral metagenomics analysis of zebrafish gut tissue. The closest relatives of this virus showed identity of [≤]19.8% in their P1 capsids and [≤]35.4% in their RdRp qualifying zebrafish picornavirus 1 (ZfPV1) as member of a novel genus with a proposed name of Cyprivirus. RT-PCR testing of zebrafish from 41 institutions from North America, Europe, and Asia showed ZfPV1 to be highly prevalent world-wide. In situ hybridization of whole zebrafish showed viral RNA was restricted to a subset of enterocytes and cells in the subjacent lamina propria of the intestine and the intestinal mucosa. This naturally occurring and apparently asymptomatic infection (in wild type zebrafish lineage AB) provides a natural infection system to study picornavirus-host interactions in an advanced vertebrate model organism. Whether ZfPV1 infection affects any immunological, developmental or other biological processes in wild type or mutant zebrafish lineages remains to be determined.

microbiology↗