Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 300918 (trait) , 308205 (trait) , 308800 (trait) , 300294 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked incomplete dominant

Disease-related: 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]".

Breeds: Quarter Horse (Horse) (VBO_0001057), Warmblood (Horse) (VBO_0017483).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: