“Glycosidic exclusion” does not include the Oh or Bombay Type

The molecular biological relationship between human fertility and the ABO(H) blood group phenotype formation becomes visible through special cell surface structures and immunoglobulin M specificities arising in people with the rare Oh or <i>Bombay</i> blood type, whom Charles Darwin would, by the history of his own family, the “<i>Darwin/Wedgewood Dynasty”</i>, have analyzed to result from reduced fertility in consanguinities. The classical type is characterized by the lack of expression of any ABO(H) epitope and instead shows the development of high isoagglutinin levels, additionally exerting strong binding of complement to anti-H agglutinin. The red cell surface presents with the naked structure Gal-β1-R, which has not been completed for the H-receptor (Fuc-α1-2-Gal-β1-R), thereby representing the structural fundament for ABOH epitopes. In its native form, the <i>Bombay</i> type occurs in individuals with the extremely rare genotype (h/h;se/se). This molecular biological phenomenon is explained by point mutations at the H- and Se genes on chromosome 19 such that the fucosyltransferases FUT1 and FUT2 are not encoded. FUT1 and FUT2 are epistatically connected with the A and B allelic glycotransferase functions encoded on chromosome 9, and fucosyl residues provide the functional-structural basis of the formation of any ABOH phenotype on the cell surface or in secretions and plasma proteins. Moreover, through developmental varying of the positions of the fucosyl residues between the cell surfaces and the heavy chains of immunoglobulins, they appear to augment or reduce antibody-mediated cellular cytotoxicity. This involves the regulation of growth processes and control over physiological autoreactivity in embryonic stem cell to germ cell transformation, where the predominantly <i>O</i>-glycosylations become in <i>Bombay type</i> individuals consequently exposed to metabolic competition with multiple glycosidic sites of extremely glycan depleted immunoglobulins.

人类生育能力与ABO(H)血型表型形成之间的分子生物学关联，可通过罕见的Oh型或孟买型（Bombay）血型个体所特有的细胞表面结构与免疫球蛋白M（immunoglobulin M）特异性得以显现。查尔斯·达尔文曾基于其家族——“达尔文/韦奇伍德家族（Darwin/Wedgewood Dynasty）”的历史，分析得出这类个体的生育能力下降源于近亲婚配。经典孟买型的特征为完全不表达任何ABO(H)表位，同时会产生高滴度的同种凝集素，还能介导补体与抗-H凝集素的强力结合。红细胞表面存在裸露的Gal-β1-R结构，该结构尚未完成H受体（Fuc-α1-2-Gal-β1-R）的修饰合成，而这正是ABOH表位形成的结构基础。天然状态下的孟买型仅见于基因型为(h/h;se/se)的极罕见个体。这一分子生物学现象可由19号染色体上H基因与Se基因的点突变解释：此类突变导致岩藻糖基转移酶FUT1与FUT2无法正常编码合成。FUT1与FUT2与9号染色体上编码的A、B等位基因糖基转移酶功能存在上位性相互作用；岩藻糖残基则是细胞表面、分泌物及血浆蛋白中任一ABOH表型形成的功能结构基础。此外，岩藻糖残基在细胞表面与免疫球蛋白重链之间的发育性位置变化，似乎可调控抗体介导的细胞毒性作用的强弱。这一过程涉及胚胎干细胞向生殖细胞转化过程中的生长调控与生理自身反应性控制：在孟买型个体中，以O-糖基化（O-glycosylations）为主的糖基化位点，会与聚糖极度缺失的免疫球蛋白的多个糖苷位点产生代谢竞争。