White-colored horses are born with unpigmented pink skin and white hair, usually with dark eyes.
However, most of the currently-known alleles can be linked to a documented spontaneous mutation that began with a single ancestor born of non-dominant white parents.
[11][12] In some cases, foals born with residual non-white hair may lose some or all of this pigment with age, without the help of the gray factor.
As such, the only reliable way to find out whether a horse has one of the known white spotting patterns from an allele on KIT is to have it genetically tested.
The original or "normal" form of KIT, which is expected in horses without dominant white spotting, is called the "wild type" allele.
Both dominant white and "Sabino-White" horses are identified by all-white or near-white coats with underlying pink skin and dark eyes, often with residual pigment along the dorsal midline.
[59] However, not all KIT alleles currently identified as "dominant white" have been proven lethal,[21] and in fact W20 is known to be viable in the homozygous form.
[60] The similarities between Dominant White and Sabino 1 reflect their common molecular origin: The W series and SB1 have both been mapped to KIT.
These messages are used during embryonic development to signal the migration of early melanocytes (pigment cells) from the neural crest tissue to their eventual destinations in the dermal layer.
[63] The stochastic element of development is partly responsible for the eventual appearance of white on a horse, potentially accounting for nearly a quarter of the phenotype.
[64] The research team that studied dominant white cited "subtle variations in the amount of residual KIT protein" as a potential cause for the variability in phenotype of horses with the same allele.
They also speculated that variability in the phenotype of horses with W1 might be caused by "different efficacies of [nonsense-mediated decay] in different individuals and in different body regions."
Homozygous embryos from alleles of certain missense and splice site mutations are sometimes viable, apparently because they have less effect on gene function.
A 2013 study also located horses that were compound W5/W20 heterozygotes, almost completely white, essentially with greater depigmentation than could be accounted for by either allele alone.
[69] Also, a diagnosis of albinism in humans is based on visual impairment, which has not been described in horses with dominant white nor similar coat colors.
However, unlike dominant white horses, foals with LWS are born with an underdeveloped colon that is untreatable, and if not euthanized, invariably die of colic within a few days of birth.
[83] Horses that carry only one allele of the LWS gene are healthy and typically exhibit the "frame overo" spotting pattern.
They concluded, based on test matings and progeny phenotype ratios, that the white coat was dominantly inherited and embryonic lethal in the homozygous state.
[93] Wriedt described a range of what he considered to be homozygote phenotypes: all-white, white with pigmented flecks, or weißgraue, which transliterates to "white-gray.
[8] In a 1969 work on horse coat colors, A los colores del caballo, Miguel Odriozola suggested that various forms of dominantly inherited white spotting might be arranged sequentially along one chromosome, thus allowing for the varied expression of dominant white.
[97] The embryonic lethality hypothesis was originally supported by Pulos and Hutt's 1969 study of Mendelian progeny ratios.
[10] Conclusions about Mendelian traits that are controlled by a single gene can be drawn from test breedings with large sample sizes.
"[101] Prior to Pulos and Hutt's work, researchers were split on the mode of inheritance of white and whether it was deleterious (harmful).
[102] Recent research has discovered several possible genetic pathways to a white coat, so disparities in these historical findings may reflect the action of different genes.
Following the mapping of the KIT gene to the W locus in 1988, researchers began identifying other mutations as part of an allelic series of W.[106] There are dozens of known alleles, each representing a unique mutation on the KIT gene, which primarily produce white spotting from tiny head spots to fully white coats, macrocytic anemia from mild to lethal, and sterility.
[105] Some alleles, such as splash produce white spotting alone, while others affect the health of the animal even in the heterozygous state.
Presently, no anecdotal or research evidence has suggested that equine KIT mutations affect health or fertility.
[13] Each of these dominant white conditions had occurred separately and spontaneously in the past 75 years, and each represents a different allele (variation or form) of the same gene.
[7] In humans, a skin condition called piebaldism is caused by more than a dozen distinct mutations in the KIT gene.
Piebaldism in humans is characterized by a white forelock, and pigmentless patches of skin on the forehead, brow, face, ventral trunk and extremities.