OMIA 002021-9796 : Brindle 1 in Equus caballus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 300918 , 308205 , 308800

Mendelian trait/disorder: yes

Mode of inheritance: X-linked semi-dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2016

Species-specific symbol: BR1

History: This coat colour was first defined by Murgiano et al. (2016), who describe it as "irregular vertical stripes in their hair coat texture along the neck, back, hindquarters, and upper legs", this being a phenotype described by breeders as "brindle". Brindle involves a specific coat color (pigmentation) phenotype, but also subtle changes in the hair texture and morphology.

Mapping: By genotyping 36 descendants of a Quarter Horse mare, with the Illumina 70 k SNP chip, Murgiano et al. (2016) mapped the BR1 locus to "a 5 Mb segment on chromosome X spanning from positions 13,601,933 to 18,711,357 (EquCab2 assembly; markers BIEC2-1111129 - BIEC2-1112988)" which includes 41 annotated genes.

Molecular basis: Analysis of whole-genome sequence from "4 female genomes predicted to be heterozygous at the BR1 locus and 60 control genomes, which should be either hemizygous or homozygous wildtype at the causative variant" enabled Murgiano et al. (2016) to identify "61 private variants in the critical interval, none of them located in an exon of an annotated gene. However, one of the private variants was close to an exon/intron boundary in intron 10 of the MBTPS2 gene encoding the membrane bound transcription factor peptidase, site 2 (c.1437+4T>C). Different coding variants in this gene lead to three related genodermatoses in human patients [see entries for "Possible human homologues" above]. We therefore analyzed MBTPS2 transcripts in skin and identified an aberrant transcript in a BR1 horse, which lacked the entire exon 10 and parts of exon 11. The MBTPS2:c1437+4T>C variant showed perfect co-segregation with the brindle phenotype in the investigated family and was absent from 457 control horses of diverse breeds. . . . The mutant transcript contained an open reading frame lacking 32 codons, which encode parts of the third luminal and the entire sixth transmembrane domain of the MBTPS2 protein (p.422_453del). . . . The variant designation on the transcript level . . . is r.[=, 1265_1360del]".

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MBTPS2 membrane bound transcription factor peptidase, site 2 Equus caballus X NC_009175.3 (17255391..17297613) MBTPS2 Homologene, Ensembl, NCBI gene

Variants

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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
Quarter Horse Coat colour, brindle 1 MBTPS2 splicing c.1437+4T>C 2016 27449517

Reference


2016 Murgiano, L., Waluk, D., Towers, R., Wiedemar, N., Dietrich, J., Jagannathan, V., Drögemüller, M., Balmer, P., Druet, T., Galichet, A., Penedo, M.C., Müller, E.J., Roosje, P., Welle, M.M., Leeb, T. :
An Intronic MBTPS2 Variant Results in a Splicing Defect in Horses with Brindle Coat Texture. G3 (Bethesda) :, 2016. Pubmed reference: 27449517. DOI: 10.1534/g3.116.032433.

Edit History


  • Created by Frank Nicholas on 04 Aug 2016
  • Changed by Frank Nicholas on 04 Aug 2016
  • Changed by Tosso Leeb on 12 Aug 2016
  • Changed by Frank Nicholas on 13 Aug 2016