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In domestic cats, the  AB  blood group system consists of the three types  A ,  B , and  C  (usually called  AB ), which vary in frequency among breeds and geographic regions. Mismatches cause acute hemolytic transfusion reactions and hemolysis of the newborn due to the presence of naturally occurring  anti-A  alloantibodies. Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) converts N-acetylneuraminic acid (type  B ) to N-glycolylneuraminic acid (type  A ), and type  C  erythrocytes express both antigens. We examined the feline  CMAH  coding regions and genotyped cats to characterize type  A ,  B , and  C  animals. Of 421 phenotypically typed cats, 60% were  A , 35%  B  and 5%  C . Among the 70 cats for which the  CMAH  coding region was sequenced, 13 new variants were identified in addition to 16 of the previously reported 18 variants. The  CMAH  variant c.268T>A is seen in type  B  cats of most breeds, and the variant c.179G>T results in type  B  in Turkish breeds. The variants c.1322delT and c.933delA cause frameshifts with early stop codons and thereby type  B  in some Ragdolls and domestic shorthair cats, respectively. Protein modeling with PROVEAN affirmed their deleterious effects. No type  A  and  C  cats had more than one allele with one of the above variants. Variant analysis of three SNVs (c.142G>A, c.268T>A and Δ-53) and blood typing of an additional 351 typed cats showed complete phenotype-genotype concordance. In conclusion, the three  CMAH  variants c.179G>T, c.268T>A and c.1322delT are the main reasons for the defective NeuGc synthesis causing blood type  B  in domestic purebred and non-pedigreed cats. Together with the variant c.364C>T for type  C  in Ragdolls they offer a molecular screening scheme for clinical diagnostics to assure blood type compatibility.

Molecular characterization of blood type A, B, and C (AB) in domestic cats and a CMAH genotyping scheme