OMIA 002326-9615 : Deafness, KLF7-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 604865 (gene)

Mendelian trait/disorder: unknown

Considered a defect: yes

Year key variant first reported: 2021

Mapping: Xu et al. (2021): "performed a genome-wide association study (GWAS) and whole genome sequencing (WGS) of affected and normal individuals. For GWAS, 3 bilateral deaf ASCDs [Australian stumpy tail cattle dogs], 43 herding dogs, and one unaffected ASCD were used, resulting in 13 significantly associated loci on 6 chromosomes, i.e., CFA3, 8, 17, 23, 28, and 37. CFA37 harbored a region with the most significant association (−log10(9.54 × 10−21) = 20.02) as well as 7 of the 13 associated loci."

Molecular basis: Xu et al. (2021): "For whole genome sequencing, the same three affected ASCDs [Australian stumpy tail cattle dogs] and one unaffected ASCD were used. ... Using effect prediction tools, two variants remained with predicted deleterious effects within the Heart development protein with EGF like domains 1 (HEG1) gene (NC_006615.3: g.28028412G>C; XP_022269716.1: p.His531Asp) and Kruppel-like factor 7 (KLF7) gene (NC_006619.3: g.15562684G>A; XP_022270984.1: p.Leu173Phe). Due to its function as a regulator in heart and vessel formation and cardiovascular development, HEG1 was excluded as a candidate gene. On the other hand, KLF7 plays a crucial role in the nervous system, is expressed in the otic placode, and is reported to be involved in inner ear development. 55 additional ASCD samples (28 deaf and 27 normal hearing dogs) were genotyped for the KLF7 variant, and the variant remained significantly associated with deafness in ASCD (p = 0.014). Furthermore, 24 dogs with heterozygous or homozygous mutations were detected, including 18 deaf dogs. The penetrance was calculated to be 0.75 ...."

Breed: Australian Stumpy Tail Cattle Dog.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KLF7 Kruppel-like factor 7 (ubiquitous) Canis lupus familiaris 37 NC_051841.1 (15543812..15452165) KLF7 Homologene, Ensembl, NCBI gene

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.
2021 Xu, F., Shan, S., Sommerlad, S., Seddon, J.M., Brenig, B. :
A missense mutation in the KLF7 gene is a potential candidate variant for congenital deafness in Australian Stumpy Tail Cattle dogs. Genes (Basel) 12:467, 2021. Pubmed reference: 33805165. DOI: 10.3390/genes12040467.
2010 Sommerlad, S., McRae, AF., McDonald, B., Johnstone, I., Cuttell, L., Seddon, JM., O'Leary, CA. :
Congenital sensorineural deafness in Australian Stumpy-Tail Cattle dogs is an autosomal recessive trait that maps to CFA10. PLoS One 5:e13364, 2010. Pubmed reference: 20967282. DOI: 10.1371/journal.pone.0013364.

Edit History


  • Created by Imke Tammen2 on 14 Apr 2021
  • Changed by Imke Tammen2 on 14 Apr 2021