Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mutations associated with the domestic cat AB blood group

Bighignoli, Barbara; Niini, T.; Grahn, Robert A.; Pedersen, Niels C; Millon, L. V.; Polli, M.; Longeri, M.; Lyons, Leslie A.

doi:10.1186/1471-2156-8-27

Cited by 69 publications

(153 citation statements)

References 33 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…The enzyme responsible for synthesizing this common mammalian glycan, α1-3-galactosyltransferase or Gal-T, has been inactivated in the Old World monkey and hominoid lineage (27,28). There are also resident glycan polymorphisms in humans (blood groups for example) and other mammals (including some species which maintain polymorphism in Neu5Gc itself) (29). We predict that glycan antigens, which remain polymorphic, will have features allowing them to avoid being targeted by the female immune system by interrupting one or more of the above-mentioned three operational requirements of incompatibility by immunity.…”

Section: Discussionmentioning

confidence: 99%

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Ghaderi

Springer

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(−/−) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-offunction alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-offunction allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines.glycan antigen | sialic acid | xeno-antigens

show abstract

Section: Discussionmentioning

confidence: 99%

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Ghaderi

Springer

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Unlike human, CMAH gene has been conserved and is active in species as primitive as echinoderms. Moreover, CMAH gene exhibits highly similarity among mammals [14] .…”

Section: Introductionmentioning

confidence: 99%

“…Also, type B cats possess strong agglutinins against type A cats. A rare blood type in cats is type AB which has both Ne5Ac and Neu5Gc in similar quantities [14] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Türkiye, İzmir Sokak Kedilerinde Neonatal İzoeritrolizisle İlişkili Sitidin Monofosfat-N-Asetilnöraminik Asit Hidroksilaz (CMAH) Geninin Analizi

Can¹,

Şahar²,

Döşkaya³

et al. 2016

Kafkas Univ Vet Fak Derg

View full text Add to dashboard Cite

Neonatal isoerythrolysis is a life threatening disease in new born cats. It occurs when type A or type AB kittens are born from a type B queen (female cat). A homozygous 18 bp insertion located in cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene has been detected in type B cats, causing production of inactive CMAH enzyme. Currently, molecular methods are being used to determine type B blood in female cats, which can help prevent neonatal isoerythrolysis in kittens. These molecular assays target the presence of 18 bp insertion in CMAH gene.

show abstract

“…To further correlate the identified variant with disease, 627 cats were genotyped by direct Sanger‐based sequencing or an allele‐specific assay, as described previously (Bighignoli et al . 2007; Gandolfi et al . 2012) (Table 1, Table S1, Table S3).…”

mentioning

confidence: 99%

COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy

et al. 2015

Self Cite

View full text Add to dashboard Cite

SummarySome Devon Rex and Sphynx cats have a variably progressive myopathy characterized by appendicular and axial muscle weakness, megaesophagus, pharyngeal weakness and fatigability with exercise. Muscle biopsies from affected cats demonstrated variable pathological changes ranging from dystrophic features to minimal abnormalities. Affected cats have exacerbation of weakness following anticholinesterase dosing, a clue that there is an underlying congenital myasthenic syndrome (CMS). A genome‐wide association study and whole‐genome sequencing suggested a causal variant for this entity was a c.1190G>A variant causing a cysteine to tyrosine substitution (p.Cys397Tyr) within the C‐terminal domain of collagen‐like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). Alpha‐dystroglycan expression, which is associated with COLQ anchorage at the motor end‐plate, has been shown to be deficient in affected cats. Eighteen affected cats were identified by genotyping, including cats from the original clinical descriptions in 1993 and subsequent publications. Eight Devon Rex and one Sphynx not associated with the study were identified as carriers, suggesting an allele frequency of ~2.0% in Devon Rex. Over 350 tested cats from other breeds did not have the variant. Characteristic clinical features and variant presence in all affected cats suggest a model for COLQ CMS. The association between the COLQ variant and this CMS affords clinicians the opportunity to confirm diagnosis via genetic testing and permits owners and breeders to identify carriers in the population. Moreover, accurate diagnosis increases available therapeutic options for affected cats based on an understanding of the pathophysiology and experience from human CMS associated with COLQ variants.

show abstract

Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mutations associated with the domestic cat AB blood group

Cited by 69 publications

References 33 publications

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Türkiye, İzmir Sokak Kedilerinde Neonatal İzoeritrolizisle İlişkili Sitidin Monofosfat-N-Asetilnöraminik Asit Hidroksilaz (CMAH) Geninin Analizi

COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy

Contact Info

Product

Resources

About