Pattern 1 (PATN1)

General Description

Leopard Complex Spotting (LP), also known as Appaloosa spotting, is a variant of the TRPM1 gene that results in a collect of unique pigmentation patterns. LP-associated traits include mottled skin, white sclera, striped hooves, progressive roaning, and white markings centered over the hips. The extent of white patterning present at birth is highly variable and is likely the result of multiple genetic factors. Leopard complex spotting is an example of an incompletely dominant trait, indicating that horses with one copy (LP/lp) appear different than horses with two copies (LP/LP). Within areas of white patterning, heterozygous horses (LP/lp) show fully pigmented oval spots, whereas homozygous horses (LP/LP) have few to no spots.

Congenital Stationary Night Blindness (CSNB) is a recessive disorder caused by LP. Homozygotes (LP/LP) are born with a non-progressive lack of vision in low light conditions. Horses tend to adapt very well to CSNB, and often times owners may not realize their horse has a vision problem. However, CSNB affected horses can be more prone to injury at night if a lighted area is not provided, and may be more difficult to handle in low light conditions. Coat pattern is not always sufficient to identify CSNB affected horses, especially in minimally patterned individuals, and thus genetic testing is recommended to verify a horse’s LP genotype.

Pattern-1 (PATN1) is strongly association with a variant of the RFWD3 gene that modifies the expression of leopard complex spotting. Horses that inherit PATN1 are generally born with a large amount (>60%) of LP-associated white spotting, whereas those without tend to have lower amounts (<40%). However, PATN1 has no apparent effect on any other white markings or spotting, and thus effectively “hides” in lp/lp horses. PATN1 is an example of a dominant trait, with both homozygous (PATN1/PATN1) and heterozygous (PATN1/patn1) displaying the same effect on patterning. Other minor variants further modify the extent of white patterning present at birth. The adult color is not a good indicator of PATN1 genotype as some low pattern horses “roan out” to large amounts of white patterning.

Genotype and Phenotype (Color Names)

Double leopard with pattern-1 (LP/LP PATN1/n): fewspot, near fewspot with CSNB

Single leopard with pattern-1 (LP/lp PATN1/n): leopard, near leopard

Non-leopard with pattern-1 (lp/lp PATN1/n):  no leopard complex spotting

Double leopard without pattern-1 (LP/LP patn1/patn1): snowcap, varnish with CSNB

Single leopard without pattern-1 (LP/lp patn1/patn1): spotted blanket, varnish

Non-leopard without pattern-1 (lp/lp patn1/patn1): no leopard complex spotting

* Spotting patterns generally follow after the color of the pigmented regions, for example “dun leopard” or “black silver snowcap.”

* LP associated patterning exists in the full spectrum from 0-100% white spotting, and thus does not always fit in discrete categories. We have not named all commonly used pattern classifications above, but rather have provided examples for each genotype.

* Other color variants can mask leopard spots, resulting in a LP/lp horse that appears homozygous.

* It can be very difficult to difficult to visually distinguish LP/LP from LP/lp (and thus possibility of CSNB) in the lower ranges of patterning.

Gene Information

TRPM1 is a gated ion channel receptor involved in signaling in the retina and melanocytes. Mutations in other species have been associated with congenital stationary night blindness, though only the horse displays pigmentation differences. The LP mutation is a large insertion within TRPM1 that leads to absence of the protein.

RFWD3 is a ubiquitin ligase that functions in the DNA damage response and DNA replication control. There are no known mutations in other species. The PATN1 associated variant is located within the 3' untranslated region and thus may regulate the expression of RFWD3.

References

Bellone RR et al., “Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse.” (2013) PLoS One. 8 :e78280. PMID: 24167615

Holl H et al., “Variant in the RFWD3 Gene Associated with PATN1, a Modifier of Leopard Complex Spotting.” (2015) Anim Genet. 47: 91-101.

Druml T et al., "Phenotypic and genetic analysis of the leopard complex spotting in Noriker horses." (2017) J Hered. doi: 10.1093/jhered/esx039.