Categories: Pigmentation phene , Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613216 (trait) , 603576 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0013183: congenital stationary night blindness 1C

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Leopard complex; Appaloosa; Congenital stationary night blindness

Species-specific symbol: LP; CSNB

Inheritance: As summarised by Bellone et al. (2013): "Leopard complex spotting is a group of white spotting patterns in horses caused by an incompletely dominant gene (LP) . . . homozygotes (LP/LP) are also affected with congenital stationary night blindness". Thus, a single mutation is autosomal incompletely dominant for Leopard Complex/Appaloosa and autosomal recessive for stationary congenital night blindness.

Mapping: A genome scan on 27 half-sibs segregating this trait, each genotyped with 102 microsatellites, enabled Terry et al. (2004) to linkage-map this trait to chromosome ECA1. Linkage analyses with additional markers on additional horses in the candidate region enabled Terry et al. (2004) to refine the location to a region of approximately 6cM "between microsatellite markers ASB08 and 1CA43". Comparative mapping analysis enabled Terry et al. (2004) to suggest TRPM1 (encoding transient receptor potential cation channel, subfamily M, member 1) as a potential comparative positional candidate gene. By judicial sequencing and SNP genotyping, Bellone et al. (2010) narrowed the candidate region to "A single 173 kb haplotype associated with LP and CSNB (ECA1: 108,197,355- 108,370,150)" which contains TRPM1. From segregation analysis, Holl et al. (2016) concluded there is a major gene that modifies the extent of white in Leopard complex spotting. They mapped this gene, which they named PATN1 (for pattern-1), to a 15Mb region on chromosome ECA3p.

Molecular basis: RNA sequencing "from five samples (three from skin and two from retina)" enabled Bellone et al. (2011) to identify the causal mutation as a retroviral long terminal repeat (LTR) insertion in TRPM1. Details were provided by Bellone et al. (2013): the causal mutation is "a 1378 bp insertion in intron 1 of TRPM1" [omia.variant:725].

Breeds: American Miniature Horse (Horse) (VBO_0000896), Appaloosa (Horse) (VBO_0000904), British Spotted Pony, Spotted Pony, United Kingdom of Great Britain and Northern Ireland (Horse) (VBO_0011461), English Spotted Pony, Australia (Horse) (VBO_0011165), Knabstrupper (Horse) (VBO_0001008), Noric (Horse) (VBO_0001030), Pony Of the Americas, Germany (Horse) (VBO_0011370), Thoroughbred (Horse) (VBO_0001083).
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: