OMIA 001402-9685 : Multidrug resistance 1, ABCB1-related in Felis catus

In other species: dog , cattle , goat

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 171050 (gene) , 120080 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: MDR1

Molecular basis: By sequencing the most obvious functional candidate gene in 8 cats that showed "adverse reactions to P-glycoprotein substrate drugs" (including one sensitive to ivermectin), Mealey and Burke (2015) discovered a 2bp deletion in the ABCB1 gene (11930_1931del TC) that was homozygous in the one cat sensitive to ivermectin. However, the other 7 sensitive cats were homozygous for a normal functional ABCB1 allele. In addition, "14 missense mutations were identified in one or more phenotyped cats".

Mealey et al. (2021) investigated “whether ABCB11930_1931del TC predisposed cats to macrocyclic-lactone toxicosis and the frequency of the ABCB11930_1931del TC gene mutation in banked feline DNA samples. … 4 of the 5 cats with neurologic signs presumed to be associated with macrocyclic-lactone exposure were homozygous for ABCB11930_1931del TC. The other cat had unilateral vestibular signs not typical of macrocyclic-lactone toxicosis. … Results suggested a strong relationship between homozygosity for ABCB11930_1931del TC and neurologic toxicosis after topical application with eprinomectin-containing antiparasitic products labeled for use in cats … .”

Prevalence: Mealey et al. (2021): "The distribution of genotypes from the banked feline DNA samples was as follows: 0 homozygous for ABCB11930_1931del TC, 47 heterozygous for ABCB11930_1931del TC, and 959 homozygous for the wild-type ABCB1 allele. Among the 47 cats with the mutant ABCB1 allele, only 3 were purebred (Ragdoll, Russian Blue, and Siamese)."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1 Felis catus A2 NC_058369.1 (91762620..91528480) ABCB1 Homologene, Ensembl, NCBI gene

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.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1322 Adverse reaction to certain drugs ABCB1 deletion, small (<=20) Naturally occurring variant Felis_catus_9.0 A2 g.93144355_93144356del c.1930_1931del NM_001171064.2; published as ABCB1:1930_1931delTC; resuling in a frameshift generating a series of stop codons immediately downstream from the deletion. The protein product is predicted to be severely truncated (~50%) and non functional. (Mealey and Burke, 2015) 2015 25660379 Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley.

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.
2022 Mealey, K.L., Owens, J.G., Freeman, E. :
Canine and feline P-glycoprotein deficiency: What we know and where we need to go. J Vet Pharmacol Ther :, 2022. Pubmed reference: 36326478. DOI: 10.1111/jvp.13102.
2021 Mealey, K.L., Burke, N.S., Connors, R.L. :
ABCB11930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone-induced neurologic toxicosis in cats associated with products labeled for companion animal use. J Am Vet Med Assoc 259:72-76, 2021. Pubmed reference: 34125616. DOI: 10.2460/javma.259.1.72.
Nürnberger, D., Wagner, L., Müller, S.F., Leiting, S., Leidolf, R., Alber, J., Hamann, M., Geyer, J. :
Detection of the <i>ABCB1</i>1930_1931del TC Mutation in Two Suspected Ivermectin-Sensitive Cats and Their Relatives by a Novel TaqMan Allelic Discrimination Assay. Front Vet Sci 8:808392, 2021. Pubmed reference: 35265692. DOI: 10.3389/fvets.2021.808392.
2015 Mealey, K.L., Burke, N.S. :
Identification of a nonsense mutation in feline ABCB1. J Vet Pharmacol Ther 38:429-33, 2015. Pubmed reference: 25660379. DOI: 10.1111/jvp.12212.

Edit History


  • Created by Frank Nicholas on 14 Nov 2015
  • Changed by Frank Nicholas on 14 Nov 2015
  • Changed by Imke Tammen2 on 18 Jun 2021
  • Changed by Imke Tammen2 on 19 Feb 2022