MET (embryonic lethal)

Crossing two of them

What it reads like in play

A pairing that keeps refusing: two horses that will breed with anything else and never with each other. The chat line naming the cause is what turns that from a bug report into a clue.

Its gene carrot

Gene key

horsegenetics.met

Priority

92

Alleles

met N

Outcomes

wild, met-carrier, met-embryonic-lethal

Coat effect

none — every outcome is a wild type

Default allele

N

Wild population

3.0% 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

A different code path, and worth being precise about

The Mendelian draw happens exactly as it always does — Genotype.breedWith knows nothing about viability and is not touched — and then the breeding handler reads the genotype it just drew and cancels the birth. So the odds are the ordinary one-in-four for two carriers, the draw stays a pure function of the two parents and the RNG, and the check is one branch in one place.

Two consequences of “no horse is ever born with it”

• canOccur is false for met/met, so the genotype catalogue gives it no entry and does not count it. That is the same rule that rules out a Y/Y horse — and the exact opposite of overo lethal white, which is born and therefore does get one.
• expressionOf still answers for it, because parsing is tolerant and a hand-written code can name any combination.

The variant

MET is the MET proto-oncogene, receptor tyrosine kinase. It encodes a cell-surface signalling receptor that responds to hepatocyte growth factor. In mammals, HGF–MET signalling has large developmental roles: cell survival, cell migration, tissue growth, placental biology, migration of muscle precursor cells, and the development of several organs.

A 14-base deletion shifts the reading frame from around amino acid 392 onward, giving a short wrong sequence and then an early stop. The likely result is a truncated, non-functional receptor, or destruction of the abnormal mRNA by nonsense-mediated decay — which is what makes the deletion a credible causal candidate rather than a linked marker. OMIA 003064

A gene whose only visible symptom is an absence

This is an autosomal recessive embryonic lethal. The field observation that anchors it is a roughly 25% reduction in insemination success in carrier-by-carrier Friesian matings — exactly the loss of the one-quarter of conceptions expected to be homozygous. The disorder is therefore inferred to act before birth, probably early enough that it presents as a failure to establish or maintain pregnancy rather than as a malformed foal.

The 25% is an expectation across many pregnancies, not a promise that a carrier pair loses exactly one in four. Chance, mare fertility, semen quality, timing, uterine health and every other cause of embryo loss still apply to each attempt.

Carriers

Coat. No coat phenotype is known or expected. The distinction matters because “embryonic lethal” in horse genetics summons very different conditions: frame overo lethal white involves EDNRB, produces frame spotting in many heterozygotes, and kills homozygous foals with intestinal disease; some KIT-associated dominant white alleles produce dramatic white patterns and may be lethal homozygous. Separate genes, mechanisms and clinical pictures. The MET allele explains nothing about a Friesian’s black coat or its markings.

Build and size. No published evidence that one copy changes adult height or growth rate, frame, bone, topline, muscling, head or neck conformation, limb conformation, body mass, condition, metabolism, or Friesian type. This is worth stating precisely: a gene can have broad developmental functions without a particular naturally occurring allele producing an observable trait in healthy heterozygotes. The evidence supports a normal carrier versus non-viable homozygote model, not a graded spectrum.

Health and lifespan. No disease syndrome, health deficit or shortened lifespan has been reported in carriers. Carrier status is a reproductive-management finding.

Performance. No evidence that the deletion improves or impairs jump scope or technique, gallop speed, trot or canter mechanics, acceleration, endurance, muscle power, recovery, soundness, trainability or temperament. Nor is there any demonstrated heterozygote advantage: a recessive lethal can become common through founder effects, drift, heavy use of popular sires, small population size and linkage with selected lines, without doing carriers any good at all.

Why MET is plausible, and where the proof stops

Population-genetic evidence. Researchers analysed more than 8,000 Friesians on a 70K SNP dataset and found several haplotypes strikingly deficient in homozygotes. Three related chromosome-4 haplotypes — FH2, FH3 and FH4 — were associated with the deletion. A missing homozygote class is the classic signature of a recessive allele that removes individuals before they can be sampled.

Functional evidence. The deletion disrupts the coding sequence directly and is predicted to frameshift and stop early. A major truncation of a receptor tyrosine kinase is a plausible route to embryonic lethality given how broadly MET signalling matters in development.

Plausible is not proven. The study identifies a likely causal variant, and the curated OMIA entry notes that formal animal-variant pathogenicity classification had not yet been completed.

Breed and frequency

The only breed documented for this deletion is the Friesian, and the available source material gives no published carrier percentage or allele frequency. The 8,000-plus horses are the discovery population, which is a different thing from a reported frequency.

The mod’s WILD_CARRIER_PERCENT of 3.0 therefore has no published number to be checked against — unlike every other gene on this layer, where the mod’s figure can at least be set beside a measured breed frequency. It is a design choice, sized against the other disorders rather than against the literature.

What is settled, and what is not

Established or strongly supported. The variant is a naturally occurring 14-bp MET deletion on chromosome 4; it is predicted to cause a disruptive frameshift, p.(P392Lfs*3); the phenotype is autosomal recessive; risk matings between carriers show about a 25% reduction in insemination success, consistent with the loss of homozygous embryos; the association is documented in Friesians; and healthy carriers have no reported coat, conformation, health or performance phenotype.

Reasonable but unproven. That the embryo dies very early, perhaps around implantation or early placental development, since the visible outcome is reduced pregnancy success rather than a syndrome in live foals. That the loss follows from insufficient MET receptor function in embryonic or extraembryonic tissue. That FH2, FH3 and FH4 are overlapping linked haplotypes carrying the same deletion rather than three independent diseases.

Not known. The exact stage at which homozygous conceptions fail; the tissue-level defect — implantation, trophoblast and placenta, organogenesis, vascular development or something else; whether every homozygous embryo is lost or whether rare later fetal losses occur; whether the variant exists outside Friesians; its true carrier frequency anywhere; any carrier effect on fertility outside carrier-by-carrier matings; and any relationship at all to performance, locomotion, size, coat or conformation.

The one-line version, and it is very close to what the mod implements: a Friesian-specific, likely loss-of-function MET deletion on ECA4, inherited recessively, associated with early embryonic loss in homozygotes and no demonstrated visible or athletic effect in carriers.