A Novel Variant in CMAH Is Associated with Blood Type AB in Ragdoll Cats

Abstract

The enzyme cytidine monophospho-N-acetylneuraminic acid hydroxylase is associated with the production of sialic acids on cat red blood cells. The cat has one major blood group with three serotypes; the most common blood type A being dominant to type B. A third rare blood type is known as AB and has an unclear mode of inheritance. Cat blood type antigens are defined, with N-glycolylneuraminic acid being associated with type A and N-acetylneuraminic acid with type B. Blood type AB is serologically characterized by agglutination using typing reagents directed against both A and B epitopes. While a genetic characterization of blood type B has been achieved, the rare type AB serotype remains genetically uncharacterized. A genome-wide association study in Ragdoll cats (22 cases and 15 controls) detected a significant association between blood type AB and SNPs on cat chromosome B2, with the most highly associated SNP being at position 4,487,432 near the candidate gene cytidine monophospho-N-acetylneuraminic acid hydroxylase. A novel variant, c.364C>T, was identified that is highly associated with blood type AB in Ragdoll cats and, to a lesser degree, with type AB in random bred cats. The newly identified variant is probably linked with blood type AB in Ragdoll cats, and is associated with the expression of both antigens (N-glycolylneuraminic acid and N-acetylneuraminic acid) on the red blood cell membrane. Other variants, not identified by this work, are likely to be associated with blood type AB in other breeds of cat.

The Prevalence of Blood Groups in Domestic Cats in the Saskatoon and Calgary Areas of Saskatchewan and Alberta, Canada

“…It is proposed that the A and B red blood cell antigens are sialic N-glycolyl-and N-acetylneuraminic acids, respectively (2, 3). Genetic mutations identified in the cytidine monophosphate-N-acetylneuramic acid hydrolase (CMAH) gene have been associated with types A, B and AB, but the specific functional effects of these variations have not yet been determined (4,5).…”

Neuigkeiten zur praktischen ABC-Blutgruppen-Bestimmung bei Katzen

“…Of course, these estimates may vary greatly locally and among catteries, because breeding regimes may influence the blood type frequencies. Interestingly, type C is extremely rare except in Ragdolls [4][5] [6] [7] [8], Turkish Angoras, and non-purpose-bred cats in England, Israel, and the Iberian Peninsula (albeit typing methods may have affected some results) [9][10] [11].…”

“…This information is needed when breeding cats from breeds with type B and C cats to avoid NI. Although the CMAH gene, which is responsible for the types A, B, and C, was sequenced more than a decade ago [6] [20], genotyping of type B and C cats has proven to be inaccurate until recently.…”

“…While this system has been found to be accurate, it is possible that in the future new genetic variants will be found in different cat populations (e. g. in different breeds as well as non-purpose-bred cats and geographic regions) which can be readily added to the current genotyping scheme. Laboklin's recent geno-and phenotyping surveys [4] [7] showed the superiority of the new genotyping scheme (SNVs c.179 G > T, c.268 T > A, c.364 C > T and c.1322delT) over the original scheme (SNVs c.142 G > A and ∆-53) [6] [20]. Type C cats with the genotypes a c /a c and a c /b can now also be accurately detected.…”

“…The variant at position 179, responsible for type B was found in several purpose-bred and domestic shorthair cats. And the variant at position 364 is the cause of type C and was found in type A (A/a c ) and C Ragdolls and in several other purpose-bred and domestic shorthair cats[4][6]. This is one of the first examples of a complex trait in cats characterized by different variants in the same gene causing different phenotypes(blood type A, B, and C).The feline ABC blood group system is particularly important, because cats have naturally occurring alloantibodies which can be responsible for acute hemolytic transfusion reactions and NI[1][3] [22][23][24][25].…”