ABO phenotype protected reproduction based on human specific 1,2 fucosylations as explained by the Bombay type formation

Peter Arend
2017 Figshare  
The molecular biological relations between the formation of the ABO(H) blood group phenotype and human fertility is evident in the rare (Oh) or Bombay blood type, which Charles Darwin would have interpreted as resulting from reduced male fertility in consanguinities, based on the history of his own family, the Darwin/Wedgewood Dynasty. The classic Bombay type occurs with the extremely rare and human specific genotype (h/h; se/se), which does not produce the fucosyltransferases FUT1and FUT2
more » ... s FUT1and FUT2 encoded on chromosome 19 due to point mutations, and does not synthesize the fucosyl residues or H receptor, which in epistatic connection with the A- and B-allelic glycotransferases, encoded on chromosome 9, provides the structural basis for ABO(H) phenotype formation on the cell surfaces, secretions and functional plasma proteins. The innate isoagglutinins instead show extremely elevated levels of anti-H-reactive IgM, assumed to reflect the identical non-fucosylation of plasma proteins, and acting over a wide range of temperatures with an amplitude at 370C. The FUT1/FUT2-based ABO(H) plasma reactivity, which is strictly expressed according to the ABO(H) phenotype by A2M, shows the lowest levels in Bombay type individuals. In general, antibody avidity appears to be inversely proportional to the degree of glycosylation, and phenotypic glycosylation regulates the physiological anti-self reactivity of the germline-encoded IgM molecule. In contrast, the total lack of somatic phenotypic glycosylation will maintain the natural polyreactivity of this molecule, which while arising from the germline, in the Bombay type individual remains exposed to the non-somatic developmental glycosylation-deglycosylation processes during ESC-to-GC transformation, involving aberrant glycosylations.
doi:10.6084/m9.figshare.1409398.v411 fatcat:o42vrtgegra4xbovxsojdutk4a