Below is an update of genetic tests for the domestic cat (30 July 2013). Text is modified from: Lyons LA. Genetic testing in domestic cats. Mol Cell Probes. 2012;26(6):224–230. doi: 10.1016/j.mcp.2012.04.004. Epub 2012 Apr 21.

Introduction

Genetic testing has been available in the domestic cat since the 1960s, but as like other species, over the past 50 years, the level of resolution has improved from the chromosome level to the sequence level. Knowing the direct causative mutation for a trait or disease assists cat breeders with the breeding programs and can help clinicians determine heritable presentations versus idiopathic versions of a health concern. Genetic tests cover all the various forms of DNA variants, including chromosomal abnormalities, mtDNA variation, gene loss, translocations, large inversions, small insertions and deletions and the simple nucleotide substitutions. Higher throughput technologies have made genetic testing cheaper, simpler, and faster, thereby making cat genetic testing affordable to the lay public and small animal practice clinicians. The genetic resources for cats and other animal species have also opened the doors for animal evidence to be supportive in criminal investigations. This presentation will highlight the various tests available for the domestic cat and their specific capabilities and roles in cat health and management.

Cat Chromosomes

Some of the earliest genetic testing for any species was the examination of the chromosomes to determine the presence of the normal and complete genomic complement. Early studies of mitotic chromosomes of the domestic cat revealed an easily distinguishable karyotype consisting of 18 autosomal chromosomes and the XY sex chromosome pair, resulting in a 2N complement of 38 chromosomes for the cat genome.¹ Sex chromosome aneuploidies and trisomies of small acrocentric chromosomes were typically associated with cases of decreased fertility and syndromes that displayed distinct morphological presentations. Turner's Syndrome (XO), Klinefelter's Syndrome (XXY) and chimerism have been documented in the domestic cat. Because cat has a highly recognizable X-linked trait,^2-5 Orange, and the X-inactivation process was recognized,⁶ tortoiseshell and calico male cats were the first feline suspects of chromosomal abnormalities. Karyotypic and now gene-based assays are common methods to determine if a cat with ambiguous genitalia⁷ or a poor reproductive history has a chromosomal abnormality. Karyotypic studies of male tortoiseshell cats have shown that they are often mosaics, or chimeras, being XX/XY in all or some tissues.^5,8-15 The minor chromosomal differences that are cytogenetically detectable between a domestic cat and an Asian leopard cat are likely the cause of fertility problems in the Bengal cat breed, which is a hybrid between these two species.¹⁶ Other significant chromosomal abnormalities causing common "syndromes" are not well documented in the cat. Several research and commercial laboratories can perform cat chromosomal analyses when provided a living tissue, such as a fibroblast biopsy or whole blood for the analysis of white blood cells.

Inherited Disease Tests

The candidate gene approach has been fruitful in domestic cat investigations for the identification of many diseases and trait mutations. The first mutations identified were for a gangliosidosis and muscular dystrophy, discovered in the early and mid-1990s,^17,18 as these diseases have well-defined phenotypes and known genes with mutations that were found in humans. Most of the common diseases, coat colors, and coat types were deciphered in the cat following the same candidate gene approach.

Most of the identified disease tests in cats that are very specific to breeds and populations are available as commercial genetic tests (Table 1). Typically, diseases are identified in cat breeds, which are a small percentage of the cat population of the world, perhaps at most 10–15% in the USA.¹⁹ However, some mutations that were found in a specific breed, such as mucopolysaccharidosis in the Siamese,^20,21 were found in a specific individual, and the mutation is not of significant prevalence in the breed (Table 2). These genetic mutations should not be part of routine screening by cat breeders and registries, but clinicians should know that genetic tests are available for diagnostic purposes, especially from research groups with specialized expertise, such as at the University of Pennsylvania (http://research.vet.upenn.edu/penngen). Other diseases, such as polycystic kidney disease (PKD), are prevalent; PKD in Persians is estimated at 30–38% worldwide.^22-24 Because of cross-breeding with Persians, many other breeds - such as British Shorthairs, American Shorthairs, Selkirk Rex, and Scottish Folds - also need to be screened for PKD.^25-27 As PKD testing begins to become less common, as breeders remove positive cats, other genetic tests are becoming more popular, such as coat color and other disease traits (Figure 1).

Table 1. Common commercialized DNA tests for domestic cats

* Mode of inheritance of the non-wild-type variant
** Long fur variants are more or less common depending on the breed. Not all transcripts for a given gene may have been discovered or well documented in the cat; mutations presented as interpreted from original publication.

Table 2. Other mutations for inherited domestic cat diseases*

* The presented conditions are not prevalent in breeds or populations but may have been established into research colonies.
** Not all transcripts for a given gene may have been discovered or well documented in the cat; mutations presented as interpreted from original publication.

Figure 1. Trends of genetic testing in the domestic cat DNA-based genetic tests are presented for the cat. Parentage and individual identification (DNA) has not increased, as cats do not require testing for registration. One of the most popular tests, PKD, is presented separately to show that the testing requests are decreasing as breeders are eliminating positive cats from breeding programs. Other disease tests and color tests are becoming more popular tests in the cat market.

Genetic Testing Concerns in Hybrid Cat Breeds

Several cat breeds were formed by crossing with different species of cats. The Bengal breed is acknowledged worldwide and has become a highly popular breed. To create Bengals, Asian leopard cats (Felis bengalensis) were and are bred with domestic cat breeds like Egyptian Mau, Abyssinian and other cats to form a very unique breed in both color and temperament.²⁸ An Asian leopard cat had a common ancestor with the domestic cat about 6 million years ago, the bobcat about 8 million years ago, the Serval about 9.5 million years ago.²⁹ The Jungle cat is more closely related to a domestic cat than the leopard cat to the domestic cat. In addition, for some of these wild felid species, different subspecies were incorporated into the breed. The DNA sequence between a domestic cat and one of these wild felid species will have many genetic differences, less for the Jungle cat, more for Serval as compared to a domestic cat. The genetic differences are most likely silent mutations, but the variation will interplay with genetic assays and may cause more allelic dropout than what would be normally anticipated. No genetic tests are validated in the hybrid cat breeds, although the tests are typically used very frequently in Bengal cats. Thus, the accuracy for any genetic test is not known for hybrid cat breeds. A genetic test for the charcoal coloration in Bengals will likely soon be available and is unique due to the hybridization with leopard cats.

Race and Breed Identification

A newly developing test for the domestic cat is a race and breed identification panel. Based on the studies by Lipinski et al. (2008)³⁰ and Kurushima et al. (2012, submitted), STRs have been tested in a variety of random-bred cats from around the world and a majority of the major cat breeds of the USA and other regions. The genetic studies have been able to differentiate eight worldwide populations of cats - races - and can distinguish the major breeds. Analyses of the present-day random-bred cat populations suggest that the regional populations are highly genetically distinct, hence analogous to humans, different races of cats. The regional genetic differentiation is captured and displayed within the breeds that developed later from those populations. The foundation population (race) of the Asian breeds, such as Burmese and Siamese, is comprised of the street cats of Southeast Asia, whereas the foundation population (race) of the Maine Coon and Norwegian Forest cat is comprised of Western European cats. Phenotypic markers help to delineate breeds within specific breed families, such as the Persian, Burmese, and Siamese families. The cat race and breed identification tests are similar to tests that have been developed for the dog, such as the Mars, Inc. Wisdom Panel (www.wisdompanel.com). Although similar, domestic cats are random-bred cats and not a concoction of pedigreed breed cats. Cat breeds developed from the random-bred populations that have existed in different regions of the world for thousands of years. Therefore, the claims of the cat race and breed identification tests are different than the dog tests, not claiming that most household cats are recent offspring of pedigreed cats.

Implications for Cat Health & Breeding

To date, most cat genetic tests have been for traits that have nearly complete penetrance, having little variability in expression, and early onset. These aspects are important when considering management in the breed. If your cat has the PKD mutation, it will get kidney cysts, but the development of renal failure is variable (variable expression). Therefore, some recognized mutations in cats might be considered risk factors, predisposing an individual to health problems. Excellent examples of mutations that confer a risk in cats are the DNA variants associated with cardiac disease in cats. Hypertrophic cardiomyopathy (HCM) is a recognized genetic condition.³¹ In 2005, Drs. Meurs, Kittleson and colleagues published that a DNA alteration, A31P, in the gene cardiac myosin-binding protein C 3 (MYBPC3) was strongly associated with HCM in a long-term research colony of Maine Coon cats at UC Davis.³² Recent studies have shown that not all Maine Coon cats with the A31P mutation get HCM,^33,34 and one of those papers has mistakenly interpreted this lack of penetrance as being evidence that the A31P mutation is not causal³⁴. This interpretation is misleading, causing debate as to the validity of the Maine Coon HCM test. As true in humans with cardiac disease, the finding that not all cats with the A31P mutation in MYBPC3 get HCM is actually usual in the field of HCM genetic testing.

Like cat HCM mutations, other disease mutations have shown variation in penetrance and expression, such as the CEP290 PRA mutation in Abyssinians, and some cats with the pyruvate kinase deficiency can have very mild and subclinical presentations.³⁵ Thus, disease or trait causing mutations may not be 100% penetrant; thus, they do not always cause clinically detectable disease.

Conclusion

Many aspects of the population and the specific mutation must be considered during management of a disease. Diseases with a low frequency in a large population could likely be eliminated. Diseases in a very high frequency or present in a very small population need to be slowly removed from the population with great care. Genetic testing is an important diagnostic tool for the veterinarian, breeder, and owner. Genetic tests are not 100% foolproof, and the accuracy of the test procedure and the reputation and customer service of the genetic testing laboratory need to be considered. Some traits are highly desired, and genetic testing can help breeders to more accurately determine appropriate breedings, potentially becoming more efficient breeders, thus lowering costs and excess cat production. Other traits or diseases are undesired, thus genetic testing can be used to prevent disease, potentially eradicating the concern from the population. Genetic tests for simple genetic traits are more consistent with predicting the trait or disease presentation, but, as genomics progress for the cat, more tests that confer risk will become more common.

Figure 2. The slippery slope of mutation lethality Some mutations are so severe, they cause death in utero, such as PKD and taillessness. Some have high and severe penetrance, while others have low and mild penetrance. All these factors and others should be considered when managing a cat population.

Table References

1.  Eizirik E, et al. Molecular genetics and evolution of melanism in the cat family. Curr Biol. 2003;13(5):448–453.

2.  Peterschmitt M, et al. Mutation in the melanocortin 1 receptor is associated with amber colour in the Norwegian forest cat. Anim Genet. 2009;40(4):547–552.

3.  Lyons LA, et al. Chocolate coated cats: TYRP1 mutations for brown color in domestic cats. Mamm Genome. 2005;16(5):356–366.

4.  Schmidt-Kuntzel A, et al. Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci. J Hered. 2005;96(4):289–301.

5.  Imes DL, et al. Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation. Anim Genet. 2006;37(2):175–178.

6.  Lyons LA, et al. Tyrosinase mutations associated with Siamese and Burmese patterns in the domestic cat (Felis catus). Anim Genet. 2005;36(2):119–126.

7.  Ishida Y, et al. A homozygous single-base deletion in MLPH causes the dilute coat color phenotype in the domestic cat. Genomics. 2006;88:698–705.

8.  Gandolfi B, et al. Off with the gloves: mutation in KIT implicated for the unique white spotting phenotype of Birman cats. Submitted, 2010.

9.  Gandolfi B, et al. The naked truth: Sphynx and Devon Rex cat breed mutations in KRT71. Mamm Genome. 2010;21(9–10):509–515.

10. Drogemuller C, et al. Mutations within the FGF5 gene are associated with hair length in cats. Anim Genet. 2007;38(3):218–221.

11. Kehler JS, et al. Four independent mutations in the feline fibroblast growth factor 5 gene determine the long-haired phenotype in domestic cats. J Hered. 2007;98(6):555–566.

12. Gandolfi B, et al. To the root of the curl: a signature of a recent selective sweep identifies a mutation that defines the Cornish Rex cat breed. PLoS One. 2013;8(6):e67105.

13. Gandolfi B, et al. A splice variant in KRT71 is associated with curly coat phenotype of Selkirk Rex cats. Sci Rep. 2013;3:2000.

14. Kaelin CB, et al. Specifying and sustaining pigmentation patterns in domestic and wild cats. Science. 2012;337(6101):1536–1541.

15. Bighignoli B, et al. Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mutations associated with the domestic cat AB blood group. BMC Genet. 2007;8:27.

16. De Maria R, et al. Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis. Acta Neuropathol (Berl). 1998;96:307–314.

17. Bradbury AM, et al. Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency. Mol Genet Metab. 2009;97(1):53–59.

18. Muldoon LL, et al. Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease). Am J Pathol. 1994;144(5):1109–1118.

19. Martin DR, et al. Mutation of the GM2 activator protein in a feline model of GM2 gangliosidosis. Acta Neuropathol. 2005;110(5):443–450.

20. Meurs KM, et al. A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Hum Mol Genet. 2005;14(23):3587–3593.

21. Meurs KM, et al. A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics. 2007;90(2):261–264.

22. Gandolfi B, et al. First WNK4-hypokalemia animal model identified by genome-wide association in Burmese cats. PLoS One. 2012;7(12):e53173.

23. Menotti-Raymond M, et al. Mutation in CEP290 discovered for cat model of human retinal degeneration. J Hered. 2007;98(3):211–220.

24. Menotti-Raymond M, et al. Mutation discovered in a feline model of human congenital retinal blinding disease. Invest Ophthalmol Vis Sci. 2010;51(6):2852–2859.

25. Lyons LA, et al. Feline polycystic kidney disease mutation identified in PKD1. J Am Soc Nephrol. 2004;15(10):2548–2555.

26. Grahn RA, et al. Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats. BMC Vet Res. 2012;8(1):207.

27. Fyfe JC, et al. An approximately 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival. Genome Res. 2006;16(9):1084–1090.

28. Owens SL, et al. Congenital adrenal hyperplasia associated with mutation in an 11beta-hydroxylase-like gene in a cat. J Vet Intern Med. 2012;26(5):1221–1226.

29. He X, et al. Identification and characterization of the molecular lesion causing mucopolysaccharidosis type I in cats. Mol Genet Metab. 1999;67(2):106–112.

30. Yogalingam G, et al. Feline mucopolysaccharidosis type VI. Characterization of recombinant N-acetylgalactosamine 4-sulfatase and identification of a mutation causing the disease. J Biol Chem. 1996;271(44):27259–27265.

31. Yogalingam G, et al. Mild feline mucopolysaccharidosis type VI. Identification of an N-acetylgalactosamine-4-sulfatase mutation causing instability and increased specific activity. J Biol Chem. 1998;273(22):13421–13429.

32. Crawley AC, et al. Two mutations within a feline mucopolysaccharidosis type VI colony cause three different clinical phenotypes. J Clin Invest. 1998;101(1):109–119.

33. Uddin MM, et al. Identification of Bangladeshi domestic cats with GM1 gangliosidosis caused by the c.1448G>C mutation of the feline GLB1 gene: case study. J Vet Med Sci. 2013;75(3):395–397.

34. Martin DR, et al. An inversion of 25 base pairs causes feline GM2 gangliosidosis variant. Exp Neurol. 2004;187(1):30–37.

35. Fyfe JC, et al. Molecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII. Genomics. 1999;58(2):121–128.

36. Kanae Y, et al. Nonsense mutation of feline beta-hexosaminidase beta-subunit (HEXB) gene causing Sandhoff disease in a family of Japanese domestic cats. Res Vet Sci. 2007;82(1):54–60.

37. Somers K, et al. Mutation analysis of feline Niemann-Pick C1 disease. Mol Genet Metab. 2003;79:99–103.

38. Lettice LA, et al. Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum Mol Genet. 2008;17(7):978–985.

39. Goree M, et al. Characterization of the mutations causing hemophilia B in 2 domestic cats. J Vet Intern Med. 2005;19(2):200–204.

40. Clavero S, et al. Feline congenital erythropoietic porphyria: two homozygous UROS missense mutations cause the enzyme deficiency and porphyrin accumulation. Mol Med. 2010;16(9–10):381–388.

41. Goldstein R, et al. Primary hyperoxaluria in cats caused by a mutation in the feline GRHPR gene. J Hered. 2009;100(Supplement 1):S2–S7.

42. Clavero S, et al. Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations. Hum Mol Genet. 2010;19(4):584–596.

43. Ginzinger DG, et al. A mutation in the lipoprotein lipase gene is the molecular basis of chylomicronemia in a colony of domestic cats. J Clin Invest. 1996;97(5):1257–1266.

44. Geisen V, Weber K, Hartmann K. Vitamin D-dependent hereditary rickets type I in a cat. J Vet Intern Med. 2009;23(1):196–199.

45. Berg T, et al. Purification of feline lysosomal alpha-mannosidase, determination of its cDNA sequence and identification of a mutation causing alpha-mannosidosis in Persian cats. Biochem J. 1997;328(3):863–870.

46. Grahn R, et al. A novel CYP27B1 mutation causes a feline vitamin D-dependent rickets type IA. J Feline Med Surg. 2012;14(8):587–590.

47. Mazrier H, et al. Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease. J Hered. 2003;94(5):363–373.

Other References

1.  Wurster-Hill DH, Gray CW. Giemsa banding patterns in the chromosomes of twelve species of cats (Felidae). Cytogenet Cell Genet. 1973;12(6):388–397.

2.  Bamber RC, Herdman EC. The inheritance of black, yellow and tortoiseshell coat colour in cats. J Genetics. 1927;18:87–97.

3.  Little CC. Colour inheritance in cats, with special reference to colours, black, yellow and tortoiseshell. J Genetics. 1919;8:279–290.

4.  Ibsen HL. Tricolor inheritance. III. Tortoiseshell cats. Genetics. 1916;1:377–386.

5.  Doncaster L. On the inheritance of tortoiseshell and related colours in cats. In: Proc Cambridge Philosophical Soc. 1904;13:35–38.

6.  Lyon MF. Sex chromatin and gene action in mammalian X-chromosome. Am J Hum Genet. 1962;14:135–148.

7.  Schlafer DH, et al. A case of SRY-positive 38,XY true hermaphroditism (XY sex reversal) in a cat. Vet Pathol. 2011;48(4):817–822.

8.  Ishihara T. Cytological studies on tortoiseshell male cats. Cytologia. 1956;21:391–398.

9.  Chu EHY, Thuline HC, Norby DE. Triploid-diploid chimerism in a male tortoiseshell cat. Cytogenetics. 1964;3:1–18.

10. Thuline HC. Male tortoiseshell, chimerism and true hermaphroditism. J Cat Genetics. 1964;4:2–3.

11. Pyle RL, et al. XXY sex chromosome constitution in a Himalayan cat with tortoise-shell points. J Hered. 1971;62(4):220–222.

12. Gregson NM, Ishmael J. Diploid triploid chimerism in three tortoiseshell cats. Res Vet Sci. 1971;12:275–279.

13. Centerwall WR, Benirschke K. Animal model for the XXY Klinefelter's syndrome in man: tortoiseshell and calico male cats. Am J Vet Res. 1975;36:1275–1280.

14. Kosowska B, et al. Cytogenetic and histologic studies of tortoiseshell cats. Medycyna Weterynaryjna. 2001;57:475–479.

15. Kuiper H, Hewicker-Trautwein M, Distl O. [Cytogenetic and histologic examination of four tortoiseshell cats]. Dtsch Tierarztl Wochenschr. 2003;110(11):457–461.

16. Modi WS, et al. Chromosomal localization of satellite DNA sequences among 22 species of felids and canids (Carnivora). Cytogenet Cell Genet. 1988;48(4):208–213.

17. Winand NJ, et al. Deletion of the dystrophin muscle promoter in feline muscular dystrophy. Neuro Disord. 1994;4(5–6):433–445.

18. Muldoon LL, et al. Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease). Am J Pathol. 1994;144(5):1109–1118.

19. Louwerens M, et al. Feline lymphoma in the post-feline leukemia virus era. J Vet Intern Med. 2005;19(3):329–335.

20. Yogalingam G, et al. Mild feline mucopolysaccharidosis type VI. Identification of an N-acetylgalactosamine-4-sulfatase mutation causing instability and increased specific activity. J Biol Chem. 1998;273(22):13421–13429.

21. Yogalingam G, et al. Feline mucopolysaccharidosis type VI. Characterization of recombinant N-acetylgalactosamine 4-sulfatase and identification of a mutation causing the disease. J Biol Chem. 1996;271(44):27259–27265.

22. Cannon MJ, et al. Prevalence of polycystic kidney disease in Persian cats in the United Kingdom. Vet Rec. 2001;149(14):409–411.

23. Barrs VR, et al. Prevalence of autosomal dominant polycystic kidney disease in Persian cats and related-breeds in Sydney and Brisbane. Aust Vet J. 2001;79(4):257–259.

24. Barthez PY, Rivier P, Begon D. Prevalence of polycystic kidney disease in Persian and Persian related cats in France. J Feline Med Surg. 2003;5(6):345–347.

25. Biller DS, Chew DJ, DiBartola SP. Polycystic kidney disease in a family of Persian cats. J Am Vet Med Assoc. 1990;196(8):1288–1290.

26. Eaton KA, et al. Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats. Vet Pathol. 1997;34(2):117–126.

27. Lyons LA, et al. Feline polycystic kidney disease mutation identified in PKD1. J Am Soc Nephrol. 2004;15(10):2548–2555.

28. Johnson G. The Bengal Cat. Greenwell Springs, LA: Gogees Cattery; 1991.

29. Johnson WE, et al. The late Miocene radiation of modern Felidae: a genetic assessment. Science. 2006;311(5757):73–77.

30. Lipinski MJ, et al. The ascent of cat breeds: genetic evaluations of breeds and worldwide random-bred populations. Genomics. 2008;91(1):12–21.

31. Kittleson MD, et al. Familial hypertrophic cardiomyopathy in Maine Coon cats: an animal model of human disease. Circulation. 1999;99(24):3172–3180.

32. Meurs KM, et al. A cardiac myosin binding protein C mutation in the Maine coon cat with familial hypertrophic cardiomyopathy. Hum Mol Genet. 2005;14(23):3587–3593.

33. Sampedrano C, et al. Prospective echocardiographic and tissue Doppler imaging screening of a population of Maine coon cats tested for the A31P mutation in the myosin-binding protein C gene: a specific analysis of the heterozygous status. J Vet Intern Med. 2009;23:91–99.

34. Wess G, et al. Association of A31P and A74T polymorphisms in the myosin binding protein C3 gene and hypertrophic cardiomyopathy in Maine coon and other breed cats. J Vet Intern Med. 2010;24(3):527–532.

35. Kohn B, Fumi C. Clinical course of pyruvate kinase deficiency in Abyssinian and Somali cats. J Feline Med Surg. 2008;10:143–153.

36. Eizirik E, et al. Molecular genetics and evolution of melanism in the cat family. Curr Biol. 2003;13(5):448–453.

37. Peterschmitt M, et al. Mutation in the melanocortin 1 receptor is associated with amber colour in the Norwegian forest cat. Anim Genet. 2009;40(4):547–552.

38. Lyons LA, et al. Chocolate coated cats: TYRP1 mutations for brown color in domestic cats. Mamm Genome. 2005;6(5):356–366.

39. Schmidt-Kuntzel A, et al. Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci. J Hered. 2005;96(4):289–301.

40. Imes DL, et al. Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation. Anim Genet. 2006;37(2):175–178.

41. Lyons LA, et al. Tyrosinase mutations associated with Siamese and Burmese patterns in the domestic cat (Felis catus). Anim Genet. 2005;36(2):119–126.

42. Ishida Y, et al. A homozygous single-base deletion in MLPH causes the dilute coat color phenotype in the domestic cat. Genomics. 2006;88:698–705.

43. Gandolfi B, et al. Off with the gloves: mutation in KIT implicated for the unique white spotting phenotype of Birman cats. Submitted, 2010.

44. Gandolfi B, et al. The naked truth: Sphynx and Devon Rex cat breed mutations in KRT71. Mamm Genome. 2010;21(9–10):509–515.

45. Drogemuller C, et al. Mutations within the FGF5 gene are associated with hair length in cats. Anim Genet. 2007;38(3):218–221.

46. Kehler JS, et al. Four independent mutations in the feline fibroblast growth factor 5 gene determine the long-haired phenotype in domestic cats. J Hered. 2007;98(6):555–566.

47. Gandolfi B, et al. To the root of the curl: a signature of a recent selective sweep identifies a mutation that defines the Cornish Rex cat breed. PLoS One. 2013;8(6):e67105.

48. Gandolfi B, et al. A splice variant in KRT71 is associated with curly coat phenotype of Selkirk Rex cats. Sci Rep. 2013;3:2000.

49. Kaelin CB, et al. Specifying and sustaining pigmentation patterns in domestic and wild cats. Science. 2012;337(6101):1536–1541.

50. Bighignoli B, et al. Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mutations associated with the domestic cat AB blood group. BMC Genet. 2007;8:27.

51. De Maria R, et al. Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis. Acta Neuropathol (Berl). 1998;96:307–314.

52. Bradbury AM, et al. Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency. Mol Genet Metab. 2009;97(1):53–59.

53. Martin DR, et al. Mutation of the GM2 activator protein in a feline model of GM2 gangliosidosis. Acta Neuropathol. 2005;110(5):443–450.

54. Meurs KM, et al. A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics. 2007;90(2):261–264.

55. Gandolfi B, et al. First WNK4-hypokalemia animal model identified by genome-wide association in Burmese cats. PLoS One. 2012;7(12):e53173.

56. Menotti-Raymond M, et al. Mutation in CEP290 discovered for cat model of human retinal degeneration. J Hered. 2007;98(3):211–220.

57. Menotti-Raymond M, et al. Mutation discovered in a feline model of human congenital retinal blinding disease. Invest Ophthalmol Vis Sci. 2010;51(6):2852–2859.

58. Grahn RA, et al. Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats. BMC Vet Res. 2012;8(1):207.

59. Fyfe JC, et al. An approximately 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival. Genome Res. 2006;16(9):1084–1090.

60. Owens SL, et al. Congenital adrenal hyperplasia associated with mutation in an 11beta-hydroxylase-like gene in a cat. J Vet Intern Med. 2012;26(5):1221–1226.

61. He X, et al. Identification and characterization of the molecular lesion causing mucopolysaccharidosis type I in cats. Mol Genet Metab. 1999;67(2):106–112.

62. Crawley AC, et al. Two mutations within a feline mucopolysaccharidosis type VI colony cause three different clinical phenotypes. J Clin Invest. 1998;101(1):109–119.

63. Uddin MM, et al. Identification of Bangladeshi domestic cats with GM1 gangliosidosis caused by the c.1448G>C mutation of the feline GLB1 gene: case study. J Vet Med Sci. 2013;75(3):395–397.

64. Martin DR, et al. An inversion of 25 base pairs causes feline GM2 gangliosidosis variant. Exp Neurol. 2004;187(1):30–37.

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