Abstract
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.
Highlights
We discovered new variants associated with type A, B, and C, report their predicted effect on the enzyme, and are proposing a simple scheme with single nucleotide variants (SNVs) to accurately screen cats genetically for all three blood types in different breeds
Blood typing results were concordant by immunochromatographic strip and gel column blood typing techniques for all cats studied
When comparing the Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene sequences obtained here from 36 type B cats belonging to nine breeds with the reference genome and the sequences of the 14 type A cats from this study, we found five of 17 nsSNVs/Indels (c.364C>T, c.374C>T, c.376G>A, c.868A>C, c.1342G>A) occurring in type A cats indicating that they are not part of a type B haplotype (Table 2)
Summary
It is speculated that the variant c.364C>T reduces the activity of CMAH leading to the presence of both NeuGc and NeuAc, but no biochemical studies have been performed [10] These prior studies included a limited number of cats with unconfirmed phenotyping results; blood typing is done immunologically in clinics and diagnostic laboratories, and it is recommended to confirm type B and C results with back typing and or crossmatching by a reference laboratory [3, 12,13,14]. We sequenced the exons and regulatory regions of the CMAH gene from 70 purebred and non-pedigreed domestic cats which had been carefully phenotyped as having type A, B, and C blood, assessed the non-synonymous variants by modeling, and genotyped an additional 351 blood typed cats. We discovered new variants associated with type A, B, and C, report their predicted effect on the enzyme, and are proposing a simple scheme with SNVs to accurately screen cats genetically for all three blood types in different breeds
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