Dominant white

This dominant white Thoroughbred stallion (W2/+) has one form of dominant white. His skin, hooves, and coat lack pigment cells, giving him a pink-skinned white coat.

Dominant white is a group of genetically related coat color conditions in the horse, best known for producing an all-white coat, but also for producing some forms of white spotting and white markings. Dominant white horses are born with unpigmented pink skin and white hair with dark eyes, although the amount of white hair or spotting can vary depending on which genetic mutation is involved. Dominant white is a rare condition, and under normal conditions, at least one parent must be dominant white to produce dominant white offspring. However, most of the currently-known alleles of dominant white can be linked to a documented spontaneous mutation in a single ancestor.

Dominant white can occur in any breed, and has been studied in many different breeds. Two color breeds, the American White Horse and Camarillo White Horse are characterized by their dominant white coats.

There are many different forms of dominant white; in genetics, as of 2013 they are labeled W1 through W20. All known dominant white coat colors are associated with the KIT gene. As the name suggests, these known white coats are inherited dominantly, meaning that a horse only needs one copy of a W allele to have the white or white spotted coat.

Dominant white is genetically distinct from Sabino and both genetically and visually distinct from gray and cremello. Dominant white is not the same as lethal white syndrome, nor are dominant white horses "albinos". Albinism has never been documented in horses. Some forms of dominant white are thought to result in nonviable embryos when a zygote has two W alleles (is homozygous). However, this has not been verified for all dominant white genetic variations.

Identification

The dark skin under a white hair coat, easily seen at the muzzle and genitals, shows that this white-looking horse is actually a gray. Most horses that look "white" are actually grays.

Dominant white horses are born with pink skin and a white coat, which they retain throughout their lives. Although the term "dominant white" is typically associated with a pure white coat, such horses may be all-white, near-white, partially white, or exhibit an irregular spotting pattern similar to that of sabino horses. The amount of white hair depends on which mutation of W is involved. Non-white areas of skin and hair are most commonly seen along the dorsal midline of the horse, known as the topline, and are especially common in the mane and on the ears. They may also have interspersed specks or spots of non-white skin and hair. In addition, the hooves are most often white, but may have striping if there is pigmented skin on the coronary band just above the hoof. 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. Dominant white spotting does not affect eye color, and most dominant white horses have brown eyes. The pink skin is devoid of pigment cells (melanocytes), and appears pink from the underlying network of capillaries. White hair is rooted in unpigmented pink skin. There are many other genetic factors that produce white, near-white, and off-white coat colors in horses, some of which are visually very similar to dominant white.

Prevalence

Dominant white is one of several potential genetic causes for horses with near-white or completely white coats; it may occur through spontaneous mutation, and thus may be found unexpectedly in any breed, even those that discourage excessive white markings. To date, dominant white has been identified in multiple families of Thoroughbreds, American Quarter Horses, Frederiksborg horses, Icelandic horses, Shetland ponies, Franches Montagnes horses, South German Draft horses, and in one family of the Arabian horse. The American White Horse, which is descended primarily from one dominant white stallion crossed on non-white mares, is known for its dominant white coat, as is the Camarillo White Horse.

Inheritance

The W locus was mapped to the KIT gene in 2007. The terms "Kit oncogene" and "dominant spotting" gene, symbolized by KIT and W respectively, can be used interchangeably. Current research has now shown that there are multiple forms, or alleles, of the W gene. All horses possess the KIT gene, as it is necessary for survival even at the earliest stages of development. The presence or absence of dominant white is based on the presence of certain altered forms of KIT. Each unique form is called an allele, and for every trait, all animals inherit one allele from each parent. The original or "normal" form of KIT, which is expected in horses without dominant white spotting, is called the "wild type" allele. Thus, a dominant white horse has one KIT allele with a mutation associated with dominant white spotting, and one wild type KIT allele.

History of dominant white research

Dominant white horses were first described in scientific literature in 1912. Horse breeder William P. Newell described his family of white and near-white horses to researcher A. P. Sturtevant of Columbia University:

This dominant white Franches Montagnes colt (W1/+) lost almost all his residual pigment by the time he was 3 years old (below)

The same foal as an adult horse. 100% unpigmented skin and hair is not necessary for a horse to be considered "dominant white." Some dominant white horses lose pigment with age, even though they do not possess the gray gene.

"The colour of skin is white or so-called pink, usually with a few small dark specks in skin. Some have a great many dark spots in skin. These latter usually have a few dark stripes in hoofs; otherwise the hoofs are almost invariably white. Those that do not have dark specks in skin usually have glass or watch eyes, otherwise dark eyes ... I have one colt coming one year old that is pure white, not a coloured speck on him, not a coloured hair on him, and with glass [blue] eyes."

Sturtevant and his contemporaries agreed that this colt's blue eyes were inherited separately from his white coat. In 1912, Sturtevant assigned the "white" trait to the White or W locus. At the time there was no means of assigning W to a position on the chromosome, or to a gene.

This family of white horses produced Old King in 1908, a dark-eyed white stallion that was purchased by Caleb R. and Hudson B. Thompson. Old King was bred to Morgan mares to produce a breed of horse known today as the American White Horse. A grandson of Old King, Snow King, was at the center of the first major study of the dominant white coat color in horses, conducted in 1969 by Dr. William L. Pulos of Alfred University and Dr. Frederick B. Hutt of Cornell. They concluded, based on test matings and progeny phenotype ratios, that the white coat was dominantly inherited and embryonic lethal in the homozygous state. Other factors, such as variations in expressivity and the influence of multiple genes, may have influenced the progeny ratios that Pulos and Hutt observed. The white coat of the American White Horse has not yet been mapped.

A 1924 study by C. Wriedt identified a heritable white coat color in the Frederiksborg horse. 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." The German term for gray horse is schimmel, not weißgraue. Heterozygotes, according to Wriedt, ranged from roaned or diluted to more or less solid white horses. Reviewers, such as Miguel Odriozola, reinterpreted Wriedt's data in successive years, while Pulos and Hutt felt that his work had been "erroneous" because Wriedt never concluded that white was lethal when homozygous.

Other researchers prior to modern DNA analysis developed remarkably prescient theories. The gene itself was first proposed and named W in 1948. 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. He also proposed that other, distant genes might also influence the amount of white present.

This mare comes from a family of white Thoroughbreds.

Between the time of Pulos and Hutt's study in 1969 and the beginning of molecular-level research into dominant white in the 21st century, a pattern known as "Sabino" became regarded by some as a more likely cause of white phenotypes. Sabino is a type of white spotting, and the one allele now mapped, the dominantly inherited Sabino-1 (SB-1), is genetically related, though distinct. When homozygous, SB-1 can produce nearly all-white horses that resemble dominant white. Other genes responsible for all possible patterns labeled "Sabino" have not yet been identified, though some forms of the splashed white gene may be responsible for certain patterns.

In 2007, researchers from Switzerland and the United States published a paper identifying the genetic cause of dominant white spotting in horses from the Franches Montagnes horse, Camarillo White Horse, Arabian horse and Thoroughbred breeds. 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. These same researchers identified a further seven unique causes of dominant white in 2009: three in distinct families of Thoroughbreds, one Icelandic horse, one Holsteiner, a large family of American Quarter Horses and a family of South German Draft horses.

Allelic series

The KIT gene contains over 2000 base pairs, and a change in any of those base pairs results in a mutant allele. Over forty such alleles have been identified by sequencing the KIT genes of various horses. The resultant phenotype of most of these alleles is not yet known, but 20 have been linked to dominant white. To date, DNA tests can identify if a horse carries the various identified W alleles, some commercially available.

• W1 is found in Franches Montagnes horses descended from a white mare named Cigale born in 1957. Cigale's parents' coats were not extensively marked. A single nucleotide polymorphism (SNP), a type of mutation in which a single nucleotide is accidentally exchanged for another, is thought to have occurred with Cigale. This mutation (c.2151C>G) is thought to severely affect the function of KIT. It is a nonsense mutation located on Exon15 of KIT Some horses with the W1 mutation are born pure white, but many have residual pigment along the topline, which they may then lose over time. Based on studies of KIT mutations in mice, the severity of this mutation suggests that it may be nonviable in the homozygous state. However, horses with the W1 mutation have been found to have normal blood parameters and do not suffer from anemia.
• W2 is found in Thoroughbred horses descended from KY Colonel, a stallion born in 1946. While KY Colonel was described as a chestnut with extensive white markings, he is known for siring a family of pure white horses through his white daughter, White Beauty, born in 1963. The W2 allele is also linked to a single nucleotide polymorphism (c.1960G>A), but it is a missense mutation located on Exon17.
• W3 is found in Arabian horses descended from R Khasper, a near-white stallion born in 1996. Neither of his parents were white, and the causative mutation (c.706A>T) is thought to have originated with this horse. It is a nonsense mutation on Exon4. Horses with the W3 allele often retain interspersed flecks or regions of pigmented skin and hair, which may fade with time. Some members of this family possess blue eyes, but these are thought to be inherited separately from the white coat. Based on similar studies in mice, researchers have named W3 as potentially homozygous nonviable.

The Camarillo White Horse breed has a dominant white coat owed to the W4 mutation.

• W4 is found in Camarillo White Horses, a breed characterized by a white coat, beginning with a spontaneous white stallion born in 1912 named Sultan. Like W1 and W3, horses with this type of dominant white may be pure white or near-white, with pigmented areas along the topline that fade with time. This mutation is also an SNP (c.1805C>T), a missense mutation on Exon12.
• W5 is found in Thoroughbreds descending from Puchilingui, a 1984 stallion with sabino-like white spotting and roaning. Horses with the W5 allele exhibit a huge range in white phenotype: a few have been pure white or near-white, while others have sabino-like spotting limited to high, irregular stockings and blazes that covered the face. Twenty-two members of this family were studied, and the 12 with some degree of dominant white spotting were found to have a deletion in exon 15 (p.T732QfsX9), in the form of a frameshift mutation. A later study found that the members of this family with the greatest depigmentation were compound heterozygotes who also carried the W20 allele.
• W6 is found in one near-white Thoroughbred born to non-white parents in 2004. The potential range of expressivity, therefore, is not yet known. The mutation (c.856G>A) is thought to have occurred spontaneously in this horse. It is a messense mutation on Exon5.
• W7 is found in another near-white Thoroughbred born in 2005 to a dam that had nine other offspring, all non-white. She did not possess the W7 allele, which results from a splice site mutation (c.338-1G>C), located on Intron2 of KIT.
• W8 is found in one Icelandic horse with sabino-like white spotting, mottling, and roaning. Both parents and four maternal half-siblings, all non-white, were found without the W8 allele. The W8 allele is also a splice site mutation (c.2222-1G>A), located on Intron15.
• W9 is found in one all-white Holsteiner horse with a single nucleotide polymorphism (c.1789G>A). No relatives were studied, but both parents are non-white. It is a missense mutation on Exon12.
• W10 was found in a study of 27 horses in a family of American Quarter Horses, 10 of which are white or spotted and 17 that were solid and non-white. The 10 family members with W10 had a deletion in exon 7 (c.1126_1129delGAAC). Like W5, a wide range of phenotypes were observed. The most modestly marked had large amounts of white on the face and legs and some medium-sized belly spots, while another was nearly all-white. It is a frameshift mutation on Exon7. The founder of this line was GQ Santana, foaled in 2000.
• W11 is found in a family of South German Draft horses descending from a single white stallion, in which the causative mutation is thought to have originated. The mutation responsible for the W11 phenotype is a splice site mutation of intron 20 (c.2684+1G>A).
• W12 is found in Thoroughbreds, and is a deletion mutation found on Exon3.
• W13 is found in Quarter Horses, and is a splice site mutation on Intron17.
• W14 is a deletion mutation on Exon17, found in Thoroughbreds.
• W15 is found in Arabians, and is a missense mutation on Exon10.
• W16 is found in the Oldenburger and is a missense mutation on Exon18.
• W17 is found in a Japanese Draft horse and is a missense mutation on Exon14.
• W18 is a splice site mutation on Intron8 (c.1346 +1G>A) found in a bay Swiss Warmblood with extensive speckling. Both parnts were solid-colored and had no extended head or leg markings.
• W19 was found in three part-Arabians with bald face markings, white leg markings extending above the knees and hocks, and irregular belly spots. All three horses tested negative for sabino-1, frame overo and splashed white. W19 is a missense mutation on Exon 8 (c.1322A.G; p.Tur41Cys). This gene is predicted to be "probably damaging" and one of the three horses has solid-colored offspring that do not carry the allele.
• W20 is a missense mutation on Exon14 (c.2045G>A; p.Arg682His) originally discovered in 2007 but not recognized for having a subtle role in increasing white markings and white pigmentation. It appears in many breeds, but its effects were first recognized in the W5 family of Thoroughbreds and was determined to be the causative factor in the most extensively-depigmented ("white") horses.

These alleles do not account for all dominantly inherited white spotting in horses. More KIT alleles are expected to be found with roles in white spotting. Most W alleles each occur within a specific breed or family and arise as spontaneous mutations. The KIT gene itself seems prone to mutation, and so new alleles of W could occur in virtually any breed.

Skin biopsies of non-white (left) and white horses. Blue staining identifies Kit protein activity, while melanin is visible in the non-white sample as brown granules. The sample from the white horse shows reduced Kit activity, no melanocytes, and no melanin.

Molecular genetics

Main article: CD117

The KIT gene encodes a protein called steel factor receptor, which is critical to the differentiation of stem cells into blood cells, sperm cells, and pigment cells. A process called alternative splicing, which uses the information encoded in the KIT gene to make slightly different proteins (isoforms) for use in different circumstances, may impact whether a mutation on KIT affects blood cells, sperm cells, or pigment cells. Steel factor receptor interacts chemically with steel factor or stem cell factor to relay chemical messages. 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. The neural crest is a transient tissue in the embryo that lies along the dorsal line. Melanocytes migrate along the dorsal line to a number of specific sites: near the eye, near the ear, and the top of the head; six sites along each side of the body, and a few along the tail. At these sites, the cells undergo a few rounds of replication and differentiation, and then migrate down and around the body from the dorsal aspect towards the ventral aspect and the limb buds.

The timing of this migration is critical; all white markings, from a small star to a pure white coat, are caused by the failed migration of melanocytes.

A certain degree of the eventual amount of white, and its "design", is completely random. The development of an organism from single-celled to fully formed is a process with many, many steps. Even beginning with identical genomes, as in clones and identical twins, the process is unlikely to occur the same way twice. A process with this element of randomness is called a stochastic process, and cell differentiation is, in part, a stochastic process. 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. 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 kind of dominant white.

Lethality

Early embryonal lethality, also known as early embryonic death or a non-viable embryo, may occur when the embryo possesses two dominant white alleles, or have the homozygous genotype. The reason for this is that many mutations for W are caused by nonsense mutations, frameshift mutations or DNA deletions, which, if homozygous, would make it impossible to produce a functional KIT protein. However, it is possible that homozygous embryos from alleles of missense and splice site mutations might be viable because they have less effect on gene function. A 2013 study also unearthed horses that were compound W5/W20 heterozygotes, almost completely white, essentially with greater depigmentation than could be accounted for by either allele alone.

The embryonic lethality hypothesis was originally supported by Pulos and Hutt's 1969 study of Mendelian progeny ratios. Conclusions about Mendelian traits that are controlled by a single gene can be drawn from test breedings with large sample sizes. However, traits that are controlled by allelic series or multiple loci are not Mendelian characters, and are not subject to Mendelian ratios.

Pulos and Hutt knew that if the allele that created a white coat was recessive, then white horses would have to be homozygous for the condition and therefore breeding white horses together would always result in a white foal. However, this did not occur in their study and they concluded that white was not recessive. Conversely, if a white coat was a simple autosomal dominant, ww horses would be non-white, while both Ww and WW horses would be white, and the latter would always produce white offspring. But Pulos and Hutt did not observe any white horses that always produced white offspring, suggesting that homozygous dominant (WW) white horses did not exist. As a result, Pulos and Hutt concluded that white was semidominant and lethal in the homozygous state: ww horses were non-white, Ww were white, and WW died.

Pulos and Hutt reported that neonatal death rates in white foals were similar to those in non-white foals, and concluded that homozygous white fetuses died during gestation. No aborted fetuses were found, suggesting that death occurred early on in embryonic or fetal development and that the fetus was "resorbed."

Prior to Pulos and Hutt's work, researchers were split on the mode of inheritance of white and whether it was deleterious (harmful). 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. It is also possible that the varied origins of Pulos and Hutt's white horses might be responsible for the lack of homozygotes. Therefore, it remains to be proven whether all equine dominant white mutations cause embryonic lethality in the homozygous state.

The white (W) locus was first recognized in mice in 1908. The mutation of the same name produces a belly spot and interspersed white hairs on the dorsal aspect of the coat in the heterozygote (W/+) and black-eyed white in the homozygote (W/W). While heterozygotes are healthy, homozygous W mice have severe macrocytic anemia and die within days. A mutation which affects multiple systems is "pleiotropic." 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. There are over 90 known W 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. Some alleles, such as sash produce white spotting alone, while others affect the health of the animal even in the heterozygous state. Alleles encoding small amounts of white are no more likely to be linked with anemia and sterility than those encoding conspicuous white. Presently, no anecdotal or research evidence has suggested that equine KIT mutations affect health or fertility. A recent study showed that blood parameters in horses with the W1 mutation were normal.

"White" horses that are not dominant white

See also: White (horse)

Pale blue eyes, rosy-pink skin and cream-colored hair identify the presence of some sort of dilution gene, most often the cream gene. This cremello is neither white nor gray.

White horses are potent symbols in many cultures. An array of horse coat colors may be identified as "white," often inaccurately, and many are genetically distinct from "dominant white."

"Albino" horses have never been documented, despite references to so-called "albino" horses. Dominant white is caused by the absence of pigment cells (melanocytes), whereas albino animals have a normal distribution of melanocytes. 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. In other mammals, the diagnosis of albinism is based on the impairment of tyrosinase production through defects in the Color (C) gene. No mutations of the tyrosinase or C gene are known in horses.

Non-white colors

• Cremello or Blue-eyed cream horses have rosy pink skin, pale blue eyes and cream-colored coats, indicating that pigment cells and pigment are present in the skin, eyes, and coat, but at lower levels. Dominant white horses do not have pigment cells, and thus no pigment, in the skin or coat. In addition, dominant white horses seldom have blue eyes. Other genetic factors, or combinations of genetic factors, such as the pearl gene or champagne gene, can also produce cremello-like coats. These coat colors may be distinguishable from dominant white by their unusually colored eyes.
• Gray horses are born any color and progressively replace their colored coat with gray and white hairs. Most gray horses have dark skin, unless they happen to also carry genes for pink or unpigmented skin. Unlike dominant white horses, grays are not born white, nor is their skin color affected by their coat color change.
• Leopard complex horses, such as the Appaloosa and Knabstrupper breeds, are genetically quite distinct from all other white spotting patterns. The fewspot leopard pattern, however, can resemble white. Two factors influence the eventual appearance of a leopard complex coat: whether one copy or two copies of the Leopard alleles are present, and the degree of dense leopard-associated white patterning that is present at birth. If a foal is homozygous for the LP allele and has extensive dense white patterning, they will appear nearly white at birth, and may continue to lighten with age. In other parts of the world, these horses are called "white born." "White born" foals are less common among Appaloosa horses, which tend to have blankets and varnish roans, than Knabstruppers or Norikers, which tend to be full leopards.

This "white-born" or "fewspot" Appaloosa foal is hard to distinguish from a dominant white without familiarity with the leopard complex and the animal's pedigree.

• Tovero, Medicine hat or War bonnet are terms sometimes applied to Pinto horses with residual non-white areas only around the head, especially the ears and poll, while most the remaining of the coat is white. While dominant white horses may have areas of residual pigment only around the ears and poll, the term "medicine hat" usually refers to horses with more commonly known white spotting genes, most often tobiano, combined with frame overo, sabino or splashed white.

Lethal White

Main article: Lethal white syndrome

Foals with Lethal white syndrome (LWS) have two copies of the Frame overo gene and are born with white or nearly white coats and pink skin. 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. Horses that carry only one allele of the LWS gene are healthy and typically exhibit the "frame overo" spotting pattern. In cases of "solid" horses with frame overo ancestry, uncertain "overo" (non-tobiano) phenotype, or horses with multiple patterns, the LWS allele can be detected by DNA test.

Sabino

Main article: Sabino horse

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. However, there are genetic differences. The term "dominant white" is reserved for known W alleles. Dominant white horses are heterozygous for any one of 11 known alleles of the KIT gene (e.g. W8/+). Homozygosity for some of the 11 known alleles may not create a viable embryo. In contrast, Sabino-White horses are homozygous for the Sabino 1 allele of the KIT gene (SB1/SB1).

The arrangement of irregular white markings on this Paso Fino is typical of Sabino-1, other sabino-like patterns, and some types of dominant white. Such ambiguous white markings are usually called "sabino" even in the absence of a positive SB1 DNA test.

Another type of sabino patterning, called simply "sabino," "minimal sabino" if slight, or if particularly dramatic, "maximum sabino," refers to horses that test negative for any of the Dominant White alleles, negative for Sabino 1, and also negative for Tobiano and Frame overo. Initially, dominant white was separated from sabino on the grounds that the former had to be entirely white, while the latter could possess some pigment. However, the 2007 and 2009 studies of dominant white showed that many dominant white alleles produce a range of white phenotypes that include horses with pigmented spots in hair and skin. Each of the larger families of dominant white studied included pure-white horses, horses described as having "sabino-like" white markings, as well as white horses described as "maximal sabino."

More recently, dominant white and sabino were distinguished from one another on the grounds that dominant white alleles produce nonviable embryos in the homozygous state, while Sabino 1 was viable when homozygous. However, not all KIT alleles currently identified as "dominant white" have been proven lethal.

The similarities between Dominant White, Sabino 1, and other forms of sabino may reflect their common molecular origin: The W1-W11 series and SB1 have been mapped to KIT. The researchers who mapped Sabino 1 suggested that other sabino-like patterns might also map to KIT. Similarly, major alleles for white leg and facial markings have also been mapped to or near to the KIT gene.

Mosaicism

Mosaicism in horses is thought to account for some spontaneous occurrences of white, near-white, spotted, and roan horses. Mosaicism refers to mutations that occur after the single-cell stage, and therefore affect only a portion of the adult cells. Mosaicism may be one possible cause for the rare occurrence of brindle coloring in horses. Mosaic-white horses would be visually indistinguishable from dominant whites. Mosaicism could produce white or partially white foals if a stem cell in the developing foal underwent a mutation, or change to the DNA, that resulted in unpigmented skin and hair. The cells that descend from the affected stem cell will exhibit the mutation, while the rest of the cells are unaffected.

A mosaic mutation may or may not be inheritable, depending on the cell populations affected. Though this is not always the case, genetic mutations can occur spontaneously in one sex cell of a parent during gametogenesis. In these cases, called germline mutations, the mutation will be present in the single-celled zygote conceived from the affected sperm or egg cell, and the condition can be inherited by the next generation.

Homologous conditions

See also: Homology (biology)

Some spotted patterns on pigs, such as this one, are caused by polymorphisms of the porcine KIT gene.

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. Outside of pigmentation, piebaldism is an otherwise benign condition. In pigs, the "patch," "belted," and commercial "white" colors are caused by mutations on the KIT gene. The best-known model for KIT gene function is the mouse, in which over 90 alleles have been described. The various alleles produce everything from white toes and blazes to black-eyed white mice, panda-white to sashed and belted. Many of these alleles are lethal in the homozygous state, lethal when combined, or sublethal due to anemia. Male mice with KIT mutations are often sterile. To date, no such pleiotropic effects have been described in horses with KIT mutations.