MYO5A (lavender foal syndrome)

Crossing two of them

Born, and then lost

Lethal at birth, so the foal really is born: it gets a name, a record and a place in the family tree, and then dies over a few seconds with a chat line naming what took it.

That is deliberate. A pairing that silently produced nothing would teach a player nothing about the two horses they just bred, and the whole value of a recessive lethal is that it tells you something about both parents at once. The mechanics of the death are on the trait system page.

Its gene carrot

There is none. A disorder locus sets hasGeneCarrot() false — forcing one onto somebody’s line is hostile — and SpliceSafety keeps it out of the random splice as well, derived from the fact that it declares a non-informational Condition rather than from any hand-written list.

Gene key

horsegenetics.myo5a

Priority

97

Alleles

lfs N

Outcomes

wild, myo5a-carrier, lavender-foal-syndrome

Coat effect

none — every outcome is a wild type

Default allele

N

Wild population

2.2% of founders carry one copy; none carries two

Founder draws

1 × nextFloat()

Catalogue entries

1 — it never changes what a horse looks like

The combination table

The dilution is deliberately not painted

MYO5A is the only lethal in the mod whose real presentation includes a colour, and drawing it would be the obvious thing to do. It is not drawn, for two reasons that compound.

The first is that the foal dies within seconds of being born, so a player would essentially never see the coat — a great deal of pipeline work for a horse that exists for one breath. The second is the same problem ST14 has at more length: phase 1 can only remove pigment, so a diluted mane reads as a white mane. That is a different horse and a worse lie than drawing nothing at all.

If a delayed-death path ever lands, this is the first gene that would want a coat — and it would want a real phase-3 pass, not a de-pigmentation.

At a glance

A motor that carries the wrong cargo nowhere

Myosin Va walks selected cellular cargo along actin filaments — the cell’s internal transport tracks. Two of the places that matters most are exactly the two things LFS breaks:

• Melanocytes. It moves melanosomes, the pigment-containing organelles, out to the cell periphery so pigment can be handed to the hair-producing keratinocytes around them.
• Neurons, particularly in dendrites, where it carries mRNAs, glutamate receptors and secretory vesicles.

The causal variant is a single-base deletion in exon 30. It shifts the reading frame and produces a premature stop shortly afterwards, truncating roughly 379 amino acids of the C-terminal globular tail. That is the biologically important part: the tail is what binds the cargo. The motor may keep some of its structure and lose the function it exists for. Brooks et al., PMC2855325

The original work went past association: all seven tested affected foals were homozygous, the available parents were carriers, the affected horses shared a homozygous region on chromosome 1 spanning MYO5A, the deleted region is highly conserved across species, and the clinical picture matches known MYO5A pigment-and-neurology disorders in other mammals.

Why one gene gives both a colour and a seizure

The lavender coat and the neurologic syndrome are two readings of the same transport failure — pleiotropy, one gene reaching two traits that look unrelated.

Pigmentation is not only making melanin. It is moving melanosomes correctly inside the melanocyte and transferring pigment into the developing hair shaft, which myosin Va does as part of a complex with RAB27A and melanophilin (MLPH). Disrupt the motor and delivery goes wrong, and the newborn foal is visibly diluted: described as lavender, pale grey, pewter, silver or pinkish-silver, or a very light chestnut.

The neurologic signs follow myosin Va’s job in neurons. Affected foals show seizures or tetany-like episodes, opisthotonus — severe backward arching of the neck and spine — rigid or paddling limbs, nystagmus, an inability to stand normally, an inability to nurse, and rapid deterioration after birth. Mild leukopenia has sometimes been reported, but the core pathology is neurologic and not the profound immune deficiency seen with the related pathway gene RAB27A. It is “lethal” because the impairment is severe enough that the foal cannot function or feed; there is no curative treatment and euthanasia is frequently necessary.

Affected foal versus carrier

The occasional claim that a “lavender gene” goes with unusual athletic ability or a particular refinement is not supported. A carrier has one functional copy, which appears to be enough for normal pigment trafficking and normal neurology, and that is precisely why carriers look, train, race, jump and breed normally while still transmitting the allele. The mod agrees: the carrier row costs nothing.

Inheritance and breeding maths

Per-conception probabilities, not a guaranteed ratio across a small set of foals. Two carriers can produce several clear foals in a row and then an affected one; earlier outcomes do not change the next draw. The goal is not to purge every carrier — they are clinically normal and can be genetically valuable — but to test and avoid carrier-to-carrier pairings.

Breeds and frequency

Firmly documented in the Arabian horse, and especially in horses of Egyptian Arabian descent. OMIA’s breed listing for the causal variant is Arab alone; related Arab-influenced populations and crossbreds carry it only insofar as they inherit that ancestry, and it is not established as a meaningful allele in unrelated breeds. OMIA 001501

The discovery study put the allele frequency at 5.2% among its Egyptian Arabians and 0.89% among the non-Egyptian sample. The spread from 1.8% to 16% across those rows is the point: quoting one number as “the breed frequency” is not safe, because it moves with country, subpopulation, line concentration, which farms send samples, and how heavily particular families have been used. EVJ 13604

The Egyptian concentration is a founder effect amplified by linebreeding. In the original mapping pedigrees the affected foals shared an ancestor six to eight generations back, though later carrier identification suggested the true origin is older than that conspicuous recent one.

The mod carries 2.2% WILD_CARRIER_PERCENT, applied to every founder horse rather than to one breed — the same distance problem B4GALT7 and GBE1 have.

What is settled, and what is not

Well established. The exon-30 deletion is the causal LFS variant in Arabians; it is a frameshift loss-of-function on ECA1; affected foals are homozygous; inheritance is autosomal recessive; homozygotes show severe neonatal neurologic disease with characteristic dilution; heterozygotes are clinically normal on the available evidence; and the mechanism is consistent with myosin Va’s roles in melanosome and neuronal transport.

Plausible, not fully demonstrated in horses. The cell-by-cell chain from the mutant protein to each clinical sign has not been mapped in equine tissue — it is inferred from the predicted truncation and comparative biology. Whether the mutation reduces total MYO5A protein or produces a dysfunctional truncated one is unresolved in affected foals. The dilution’s exact relationship to base colour and the other pigment loci has never been quantified in a large LFS cohort. And whether the allele exists at meaningful frequency in every Arabian-derived or non-Arabian light breed is unproven — the original authors flagged it for future screening.

Specifically unproven. Any carrier athletic advantage; any carrier conformation effect; any carrier health syndrome, including subclinical dilution or neurologic impairment. And a survivable “mild LFS” in carriers: the 2010 paper noted a rumour that some juvenile, survivable seizure disorders in the same pedigrees might be related, and was explicit that this had not been validated because the samples were unavailable. It should not be treated as a carrier phenotype.