OMIA 002229-9685 : Hypotrichosis, HR-related in Felis catus

In other species: bottlenosed dolphin , beluga whale , minke whale , sheep , Indo-Pacific finless porpoise , long-beaked common dolphin , Yangtze River dolphin , Omura's baleen whale

Possibly relevant human trait(s) and/or gene(s) (MIM number): 146550

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Also known as Hairless

Species-specific description: " A recently developed breed, the lykoi (a.k.a. werewolf cat), 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 a 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. . . . The breeding program was established in 2011 by a veterinarian who has constantly monitored health in the cats [http://lykoikitten.com/history/]. No health concerns have been identified in the lykoi other than the lymphocytic mural folliculitis." (Buckley et al., 2020)

History: Buckley et al. (2020): "The lykoi is a very recently developed novelty breed with a sparse hair coat and black and white hair roaning, hence named from the Greek term lycos for wolf. To maintain diversity in the founding population, the breeders have actively recruited cats with similar phenotypes for the breeding program, resulting in six different “foundation” lineages identified in this study from 16 potential founders. The breed is growing in popularity due to the novelty of the appearance, the lack of concern for health problems and the charismatic name and nature. The breed was accepted for full championship showing by TICA [The International Cat Association. Available online: https://tica.org/] in May 2017".

Molecular basis: Buckley et al. (2020): "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) (HR lysine demethylase and nuclear receptor corepressor) as candidate causal gene 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".

Clinical features: Buckley et al. (2020): "A recently developed breed of cat, termed the lykoi . . . , presents a unique form of hypotrichia . . . . Lykoi have a 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. Individual hairs of the coat are either normal coloration or all white, producing a roaning effect. The undercoats are sparse."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
HRhairless Felis catus - no genomic information (-..-) HRhairless Ensembl

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Lykoi Hypotrichia and Roaning HRhairless hr^TN duplication Felis_catus_9.0 B1 g.36040783dupGT c.1255_1256dupGT p.(Gln420Serfs*100) 2020 32580512
Lykoi Hypotrichia and Roaning HRhairless hr^Fr splicing Felis_catus_9.0 B1 g.36040933delTinsGT c.1404+2delTinsGT "This variant should extend and change the reading frame, including an additional 24 amino acids in the aberrant protein before a stop codon is recognized. Alternatively, a cryptic splice site may be used from within intron 4." (Buckley et al., 2020) 2020 32580512
Lykoi Hypotrichia and Roaning HRhairless hr^TX splicing Felis_catus_9.0 B1 g.36045776G>A c.2112G>A "This variant likely disrupts the splice donor allowing read-through for an additional 12 amino acids until a stop codon is encountered and is designated hrTX allele. Alternatively, a cryptic splice site may be used from within intron 8." (Buckley et al., 2020) 2020 32580512
Lykoi Hypotrichia and Roaning HRhairless hr^NC nonsense (stop-gain) Felis_catus_9.0 B1 g.36047047C>T c.2243C>T p.(Arg748X) 2020 32580512
Lykoi Hypotrichia and Roaning HRhairless hr^Ca nonsense (stop-gain) Felis_catus_9.0 B1 g.36047518C>T c.2593C>T p. (Gln865X) 2020 32580512
Lykoi Hypotrichia and Roaning HRhairless hr^VA insertion, small (<=20) Felis_catus_9.0 B1 g.36051556insGACA c.3389insGACA p.(Ser1130Argfs*29) 2020 32580512

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2020 Buckley, R.M., Gandolfi, B., Creighton, E.K., Pyne, C.A., Bouhan, D.M., LeRoy, M.L., Senter, D.A., Gobble, J.R., Abitbol, M., Lyons, L.A. :
Werewolf, There Wolf: Variants in <i>Hairless</i> Associated with Hypotrichia and Roaning in the Lykoi Cat Breed. Genes (Basel) 11:, 2020. Pubmed reference: 32580512. DOI: 10.3390/genes11060682.
2016 LeRoy, M.L., Senter, D.A., Kim, D.Y., Gandolfi, B., Middleton, J.R., Trainor, K.E., Bouhan, D.M., Lyons, L.A. :
Clinical and Histologic Description of Lykoi Cat Hair Coat and Skin Japanese Journal of Veterinary Dermatology 22:179-191, 2016.

Edit History


  • Created by Frank Nicholas on 27 Jan 2020
  • Changed by Frank Nicholas on 27 Jan 2020
  • Changed by Frank Nicholas on 30 Jun 2020