What is Bombay Blood Group ?Rare Blood Group “Bombay (Oh) Phenotype : RareBloodGroups.Org

Of the hereditary conditions of blood, theblood group serology plays an important role inthe transfusion medicine. The discovery of a rareblood group, “Bombay phenotype” in threeunrelated individuals in Mumbai (formerlyBombay) by Bhende et al. (1952) was importantin the field of immunohematology. The discoverylater helped Watkins and Morgan (1959) andGerard et al. (1982) to elucidate biosyntheticpathway for ABH and Lewis (Le) antigens,suggesting that secretor (Se) and H are closelylinked structural genes. Recently, moleculargenetics studies were carried out to determinethe role of the H, Se, and Le genes in theexpression of H antigen in secretions and Lewisblood group antigen on erythrocytes (Kanekoet al. 1997; Oriol et al. 2000).It is important to be cautious in predictingthe ABO blood type of children based on thephenotypes of their parents. This is due to thefact that a third antigen (H) on the surface of redcells can prevent the expected ABO blood typefrom occurring. Normally, if an A blood typemother has an O type child, the father is expectedto be type O or at least to carry the O allele (OO,AO, or BO genotype). The child has inherited anO allele from both parents. However, an O bloodtype child can also be born to parents who donot have the O allele if a recessive form of theallele for the H antigen also is inherited from bothparents.

The H antigen is a precursor to the Aand B antigens. For instance, the B allele must bepresent to produce the B enzyme that modifiesthe H antigen to become the B antigen. It is alsotrue for the A allele. However, if only recessivealleles for the H antigen are inherited (hh), the Hantigen will not be produced. Subsequently, theA and B antigens also will not be produced. Theresult is an O phenotype by default since thelack of A and B antigens is the O type. Thisimpossible phenotype has been referred to as aBombay (Oh) phenotype.The present study was designed with thefollowing objectives: i). To detect and identifythe rare blood groups like Bombay (Oh)phenotype, if any in the tribes of Orissa; ii).Todiscuss the data on Bombay phenotype in thelight of earlier studies from India.BOMBAY PHENOTYPEThe gene interactions come across instanceswhere a novel phenotype does not appear butan effect caused by one gene pair interferes withor hides an effect caused by another gene pair.This type of interaction is called epistasis andmay be considered the counterpart of dominancerelations between alleles (when one allelemodifies or hides the effect of another allele atthe same gene pair). Epistasis may be caused bythe presence of homozygous recessives at onegene pair. This pattern of epistatic interactioncan also be seen in humans, where theappearance of detectable ABO blood typeantigens has been shown to depend upon thepresence of H gene. The ABO gene is located onchromosome 9(9q34.1). The other traitsassociated with genes on chromosome 9 aregalactosemia, nail-patella syndrome, andxeroderma pigmentosa. An individual who ishomozygous for the very rare recessive h allele,shows no such antigens and is phenotypicallyof blood type O (Bombay phenotype). The Hgene is responsible for the attachment of certainsubterminal sugars to those polysaccharidesupon which the terminal sugars attach themselvesas specified by the ABO genes. Thus, homo-zygous (hh) individuals lack the polysaccharideorganisation for terminal sugar attachment and,therefore, appear to lack ABO blood typeantigens, although they do not lack ABO genes(Strickberger 1999).The existence of a human H/h geneticpolymorphism was first established by thediscovery in India (Bombay) of an individualdevoid of the H antigen on red cells, who hadantibodies in plasma reacting with all the cellsexhibiting the normal red cell ABO phenotypes(Bhende et al. 1952). However, this H deficient orBombay phenotype was rare, since it occurred inabout one in 10,000 individuals in India and oneper one million individuals in Europe. Morerecently, a large series of H deficient individuals(~1:1000) was found in a small French Island 800kmeast of Madagascar, in the Indian Ocean, calledReunion Island (Le Pendu et al. 1983). Two distinctphenotypes were found, the classical Bombayphenotype among Tamoul Indian immigrantfamilies and a new, partially deficient phenotype,called the “Reunion” phenotype. The twophenotypes resulted from products, or lack ofproducts, of two different alleles of FUT1 andFUT2 genes (Le Pendu et al. 1983 ); the same andalso additional alleles of both FUT1 and FUT2were documented in other populations,particularly, in Japan, where the incidence ofBombay and para-Bombay individuals wasshown to be 1-2 in 300,000 (Kaneko et al. 1997).In Taiwan, para-Bombay phenotype has afrequency of 1:8000 (Yu et al. 1997).The mutational analysis has revealed that theBombay phenotype fails to express the ABHantigens of ABO blood group system on redblood cells and in secretions because of a lack inactivities of the H gene (FUT1)- and Secretorgene (FUT2)-encoded alpha (1,2) fucosyl-transferases (Koda et al. 1997). In this study, theyexamined the FUT1 and the FUT2 from threeunrelated Indian individuals with the Bombayphenotype and found to be homozygous for aT725G mutation in the coding region of the FUT1,which inactivated the enzyme activity. Further,they could not detect any hybridized bandcorresponding to the FUT2 by Southern blotanalysis using the catalytic domain of the FUT2as probe, indicating that the three individualswere homozygous for a gene deletion in the FUT2.These results suggested that the T725G mutationof FUT1 and the gene deletion of FUT2 areresponsible for the classical Indian Bombayphenotype. Later studies (Fernandez-Mateos etal. 1998) have pointed out that the Indian red cellH null Bombay phenotype depends on a newmutation of the FUT1 gene, i.e. T725G changingLeu242→Arg. Their salivary nonsecretorphenotype is secondary to a complete deletionof the FUT2 gene. The red cell H weak Reunionphenotype depends on another new mutation ofFUT1, C349→T, which induces a change ofHis117→Tyr. Their salivary nonsecretorphenotype is due to the known Caucasianinactivating mutation G428→A (Fernandez-Mateos et al. 1998).There is the possibility of linkage disequili-brium of FUT1 and FUT2 genes. The two geneslie in close proximity on chromosome 19q13.3.There is co-existence of unique sets of mutationsin FUT1 and FUT2, each set occurring inindividuals of a certain ethnic group. Thus inIndia, the FUT1 mutation 725T>G travels almostalways (one exception) with a total deletion ofFUT2; in Reunion Island (Caucasian), the majorinactivating mutation of FUT1 or 349C>T, travelsalmost always with the inactivating mutation ofFUT2 or 428G>A; and the main Orientalinactivating mutations of FUT1 travel almostalways with the wild type FUT2 (Fernandez-Mateos et al. 1998).After the first report of Oh phenotype fromMumbai (formerly Bombay) in 1952 by Bhendeand coworkers, several other workers detectedthis peculiar phenotype in India (Simmons andD’senna 1955; Roy et al. 1957) and also in theEuropean countries (Alosia et al. 1961; Aust etal. 1962). Later on, it was found that many of theEuropean cases, which were initially labelled astypical Bombay phenotypes, turned out to bepara Bombay phenotypes after absorption elution
The most striking finding of the present studywas the detection of two unrelated cases ofBombay (Oh) phenotype in the primitive tribe,Kutia Kondh from the Belghar area of Phulbanidistrict in Orissa. No case of Bombay phenotypehas ever been reported among the primitive tribesfrom the state of Orissa and this is the first suchreport from Central East part of India. Thedifficulty in Bombay phenotype is that theindividual having blood group of Bombayphenotype (Oh) can only receive blood from anindividual of Bombay phenotype and no otherblood will match in case of an emergency forblood transfusion.The present study shows an incidence ofBombay phenotype 1 in 33 among the KutiaKondh tribe, 1 in 127 among Kondh tribe and 1 in1,244 among the tribal populations of Orissa.Since the population size of Kutia Kondh tribewas relatively small (around 5000 individuals) andthe practice of endogamy is strictly followed,therefore, the inbreeding and consanguinityamongst them is not ruled out which may be oneof the major factors for the combination ofrecessive rare alleles like Bombay phenotypeamong the Kutia Kondh tribe. Bhatia and Sanghvi(1962) calculated the incidence of this phenotypeFig.1. Map of India showing different statesas 1 in 13000 individuals in Mumbai. Later on,Bhatia and Sathe (1974) found its incidence as 1in 7600 after screening a large number of samplesin Mumbai. Gorakshakar et al. (1987) aftersystematic screening of the rural population fromRatnagiri and Sindhudurg districts ofMaharashtra reported the incidence of Bombayphenotype as 1 in 4500 in that region, whileMoores (1980) found its incidence as 1 in 18404amongst Indians settled in South Africa.Regarding the distribution and spread ofBombay phenotype in different states of India,the Oh phenotype is more common in state ofWestern and Southern parts of India as comparedto other states (Fig. 1). Of the 179 cases reportedby Sathe et al. (1988) from the Institute ofImmunohematology (formerly Blood GroupReference Centre, Bombay), Mumbai, 112 (62.6%)cases belonged to the state of Maharashtra alone.The frequency was also high in Karnataka (14cases), Andhra Pradesh (8 cases), Goa (6 cases),Gujarat (5 cases), Uttar Pradesh (5 cases) and soon in the decreasing order.The incidence ofBombay phenotype is high in those states ofIndia where the consanguineous marriages aremore prevalent, i.e. Andhra Pradesh, Tamil Nadu,Karnataka, Maharashtra, Gujarat, etc. than theother states The Bombay phenotypes were also detectedin Japan (Okubo 1980; Kaneko et al. 1997),Malaysia (Lopez, 1972), Thailand (Sringarm et al.1977) and Sri Lanka (De Zoysa 1985). Yunis et al.(1969) found seven individuals of Oh phenotypein two generations in an Indian family settled inthe USA. They were the natives of Orissa state.Similarly, Moores (1980) found 24 cases of Ohphenotypes in eleven unrelated Indian familiessettled in Natal, South Africa. Most of thesefamilies were either Tamil or Telugu speaking.Therefore, their origin presumed to be AndhraPradesh or Tamil Nadu. This indicates that theBombay phenotype is mostly confined to South-East Asian countries.Further molecular and mutational research isrequired on Bombay phenotype regarding theevolutionary significance and the operation ofnatural selection among the Kutia Kondhprimitive tribe of India.

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