What breeds need what genetic tests?

***Presented are the personal opinions of Dr. Lyons.

Below are tables to help cat breeders understand which genetic tests they should be requesting and what to do with the test results.  Many laboratories now offer big panels of genetic tests, however, many of the genetic tests are not appropriate for every breed and many are not appropriate for any breed. 

A genetic test is valid only for the breed(s) in which the allele (a.k.a. variant, mutation) was discovered and for which published information is available.  Genetic tests should be validated within a new breed because the “genetic background” is different between breeds and the different genetic background can cause a genetic mutation to act differently.  Documentation of a DNA variant in a breed is NOT validation.  Validation implies the DNA variant is proven to cause a health problem or the trait of interest.

Some tests are obviously appropriate for different and new breeds when known outcrossing is allowed by the registries or when a new breed is developing from a mixture of established breeds.  Breed outcrossing is a scenario when large genetic panels can be useful as DNA mutations that suddenly show up in different breeds are most likely present due to outcrossing (intentional or unintentional).  Thus, large DNA panels testing can help identify intentional or unintentional outcrossing.

The scientific information for all the DNA variants (mutations) in cats can be found at the website: Inline Mendelian Inheritance in Animals (OMIA) – https://www.omia.org

As of today – 01 December 2023 -the cat has basically 188 DNA variants, however not all of them need to be genetically tested.  The allele is a specific variant (mutation) within a gene that causes a trait or disease.  Many genes have more than one allele, especially for traits / phenotypes.

Table 1. Summary of Cat DNA Variants (188)​ See OMIA: www.OMIA.org

Variant Type​Allele CountGenes​ or countBreed – related​ alleles)Genes Count​
Disease – phenotyp​e9​Tailless, folded ear, dwarfism, polydactyl94​
Blood Type​14​CMAH>4?​1​
VUS or Modifier​4​ALMS1, TNNT2, TPOARSB (MPS VI mild)?​4​
Cancer​2​STAT5B, EXT10​2​
Felid specific​2​TAS1R2, UGT1A6N/A​2​

Points to Consider and Counseling Advice:

  1. Once foundation or breeding cats have been genetically tested and are “clear” of a DNA variant (not present), no further testing is required as the offspring will not inherit the variant.  All new cats entering a breeding program should be genetically tested to be certain an unwanted DNA variant does not get introduced. Note – for new breed development (Transylvanian, Highlander, munchkin varieties and more) – all genetic tests should be monitored to document healthy foundation lines.
  2. “Monitor” implies this variant, by itself, does not cause disease but should be monitored and spread prevented.  Examples are MPS VI (mild) and F11.
  3. To eradicate a variant, do not breed affected cats, do not breed carrier to carrier, AND IMPORTANTLY, work to remove carriers by selecting better cats for breeding in the next generation.  Retire carriers early, do not conduct extensive breeding with carriers.
  4. Be aware of breeding practices in different cat registries.  Breeders know more about how the breeds are related and outcrossed with different breeds.  In the tables below are DNA variants known to be in specific breeds.  All longhaired or shorthaired and color varieties of breeds should be considered (which may not be listed below) and to need to be genetically tested.
  5. Beware of outcrosses with “similar” breeds.  Ragdolls, Siberians and Maine coons lines have been identified with common variants that were not originally identified within the breed but in the similar breed, likely due to outcrossing.
  6. Approximately 45 variants are found in many different breeds or are specific to breeds.  These variants affect the appearance of the cat and the cat’s phenotype (coat color, fur type, pattern).  These variants cause no (or minimal) health concerns and are desired or undesired by different breeds or breeding programs within a breed.  See Table 2.
  7. Approximately 112 are DNA variants that causes diseases and health problems.  Only 36 variants are important to cat breeders and should be closely monitored for health.  The other ~ 76 DNA variants were discovered in random bred cats and will be very unlikely to become established in cat breeds.  See Table 3.
  8. CEP290, PKLR variants have spread to many breeds, work to eradicate!  Most all breeds should now genetically test for these two variants until the breed is established as clear.
  9. Four variants (ALMS1, one TPO variant, TNNT2, ARSB (MPS VI – mild)) are specifically under review by the cat genetics scientific community and the role of these four variants in cat health is uncertain.  These variants – known as variant of unknown significance (VUS) need special consideration as they could be modifiers of disease, such as the case for MPS VI (mild).  This variant is harmless unless present with other MPS variants.  Monitor these variants.
  10. All cats should be tested for blood type and monitor F11!  The gene (CMAH) that causes the major cat blood type has many (14) variants listed although only a few define the Type B and Type AB blood types.  Investigators are working to define the best set of variants to test.  Currently, as many variants as possible should be tested to clarify which DNA variants in CMAH are the most important.  Look for DNA testing laboratories that perform the most CMAH variants and perhaps also serology.  The UC Davis Veterinary Genetics Laboratory (www.vgl.ucdavis.edu) has robust CMAH testing.  Blood type variants should be monitored in all cats.
  11. Nine DNA variants are known in four genes that cause desired phenotypes in cats that are associated with potential health concerns.  Tailless in the Manx breed the Folded variant for Scottish folds need to be considered for retirement from cat breeding.  Polydactyla cats and dwarf cats are under scrutiny, but health concerns are less obvious.  These variants will be less harmful is good breeding practices are followed that consider the long-term health of the cat, such as minimal extra toes and dwarf cats that have longer and straighter legs and healthy joints.  Cats with polydactyla and folded ears should be tested to confirm if one or two copies of the variant is present.  Cats with Tailless and dwarfism will only have one copy of a variant.  However, Manx cats have four possible variants for Tailless therefore Manx / Cymric cats should be tested to monitor which variant is present because one variant may cause more health problems.
  12. The variants found in cancer types (STAT5B and EXT1) are found in the tumors and will not be present in the normal DNA of the cat.  These variants should not be used for breeding decisions.
  13. The two variants (TAS1R2, UGT1A6) are found in all felids making cats different from other species. These variants should not be used for breeding decisions.

Table 2. Phenotypes found in cat breeds and random bred cats.

The allele with a “+” sign is the normal, wildtype, allele as defined by random bred cats.  An allele with a capital letter is the dominant allele while alleles with lower case letters are recessive.  The equal sign “=” implies alleles that are co-dominant to others and a different presentation is evident in the heterozygous cat.  Co-dominance effects are not known for many alleles since the heterozygotes have never been documented.

!!!All alleles for a gene must be tested to know if a trait will be absent or present.

If your breed does not have the trait, then it is wildtype, a genetic test is not required.

LocusGeneAllelesVariant presentation
Agouti, AASIPA+, a, APBSolid, charcoal*
Brown, BTYRP1B+, b, blBrown, cinnamon coloration
Color, CTYRC+, cm, cb = cs, c, caTemperature-sensitive color (Siamese, Burmese), mocha, full albinism
Dilute, DMLPHD+, dUneven color distribution (dilution)
Extension, EMC1RE+, e, er, ecIncreased pheomelanin
Folded earTRPV4Fd, fd+Scottish fold ear
Glitter, GltrFGFR2Gltr+, gltrSheen in fur
GlovesKITG+, gGloves (Birman)
HairlessKRT71Hr, hr+Hairless (sphynx)
Inhibitor, IUnknownI, i+No pheomelanin
Japanese, Kurilian BobtailHES7JBT, jbt+Bobbed or kinked tail
Long, LFGF5L, lRAG, lNFC, lMCC, l, lMCC2Long hair
LykoiHRHr+,hrTN, hrCA, hrFr, hrNC, hrTX, hrVAAbsent undercoat
Orange, OUnknownXO, Xo+Color & Pattern
Manx – TaillessTBX1Mx1, Mx2, Mx3, Mx4, mx+No or short tail
PolydactlaLMBR1PdH, PdUK1, PdUK2, pd+Extra toes (Maine Coon)
SpottingKITS, s+Bi-color (Ss), Van (SS) color – pattern
Rex (Cornish, German) R, r+Curly coat
Rex (Devon) Re, re+Curly coat
Rex (Selkirk) Rs, rs+Curly coat
Rex (Ural)LIPHRu, ru+Curly coat
Ticked, TiDKK4ti+, TiA, TiCK,Pattern, no pattern
Tabby, TLVRNTM+, tb1, tb2, tb3,tbasBlotched – classic
Variable Wideband, VWBCORINVWB+, vwbSIB, vwbeSIB, vwbBSHColor & Pattern?
WhiteKITW, w+No pigmentation

*Charcoal presents when a cat has both a domestic cat non-agouti allele, a, and an allele from the leopard cat, APB (a/APB)

Table 3.  Diseases to be monitored in cat breeds.

Abyssinian, SomaliCRX***, CEP290, PKLRBlindness, blindness, pyruvate kinase deficiency
American shorthairPKD1, ALX1Polycystic kidney disease, craniofacial defect
Asian, Australian Mist, Burmese, Burmilla, Bombay, SingapuraALX1, CLCN1, COL5A1, HEXB, WNK4Craniofacial defect, myotonia congenita, Ehlers-Danlos Syndrome (EDS), gangliosidosis, hypokalemia
BengalCOL5A1, CEP290, KIF3B, PKLREhlers-Danlos Syndrome (EDS), blindness (2), pyruvate kinase deficiency
BirmanFOXN1Hypotrichosis (hair loss) with shortened life span
British ShorthairFASLG, LTBP3Autoimmune lymphoproliferative syndrome, Skeletal dysplasia
Devon Rex, Selkirk rex, SphynxCOLQ, SLC7A9Spasticity, cystinuria
KoratGLB1, HEXBGangliosidosis GM1, GM2
Norwegian ForestGBE1Glycogen storage disease
Maine Coon (also polydactyls)DMD, F11**, LIX1, MTM1, MYBPC3, SLC7A9Muscular dystrophy, bleeding, spinal muscular atrophy, myotubular myopathy, HCM, cystinuria
Persian, Exotic, Scottish Fold, Himalayan, Selkirk RexAIPL1, LYST***, PKD1Blindness, Chediak-Higashi, polycystic kidney disease
Orientals, Siamese, Colorpoints, PeterbaldsARSB (2)*,CEP290, GLB1, LTBP2, NPC2, PKLR, SLC7A9MPS IV, blindness, gangliosidosis (GM1), glaucoma, Niemann-Pick C2, pyruvate kinase deficiency, cystinuria
Russian BlueTPOHypothyroidism
SiberianPKD2Polycystic kidney disease
Turkish VanSLC39A4Acrodermatitis enteropathica

Breeders should work to eradicate these DNA variants from their breeding lines, except the following: *MPS IV – includes the mild modifier variant – monitor, other MPS variants must be present to cause disease.  **F11 – test if cat needs surgery – be sure to monitor. ***CRX & LYST is now likely eradicated in breeds.  CEP290, PKLR variants have spread to many breeds, work to eradicate!