, giving the AB
phenotype. of the possible genotypes and phenotypes of children given genotypes and phenotypes of their mother (rows) and father (columns) shaded by phenotype Blood groups are inherited from both parents. The ABO blood type is controlled by a single
gene (the
ABO gene) with three types of
alleles inferred from
classical genetics:
i,
IA, and
IB. The
I designation stands for
isoagglutinogen, another term for
antigen. The gene encodes a
glycosyltransferase—that is, an
enzyme that modifies the
carbohydrate content of the
red blood cell antigens. The gene is located on the long arm of the
ninth chromosome (9q34). The
IA allele gives type A,
IB gives type B, and
i gives type O. As both
IA and
IB are dominant over
i, only
ii people have type O blood. Individuals with
IAIA or
IAi have type A blood, and individuals with
IBIB or
IBi have type B.
IAIB people have both
phenotypes, because A and B express a special dominance relationship:
codominance, which means that type A and B parents can have an AB child. A couple with type A and type B can also have a type O child if they are both heterozygous (
IBi and
IAi). The
cis-AB phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A1 or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group. Individuals with the rare
Bombay phenotype (hh) produce antibodies against the A, B, and O groups and can only receive transfusions from other hh individuals. The table above summarizes the various blood groups that children may inherit from their parents. Genotypes are shown in the second column and in small print for the offspring: AO and AA both test as type A; BO and BB test as type B. The four possibilities represent the combinations obtained when one allele is taken from each parent; each has a 25% chance, but some occur more than once. The text above them summarizes the outcomes. Historically, ABO blood tests were used in
paternity testing, but in 1957 only 50% of American men falsely accused were able to use them as evidence against paternity. Occasionally, the blood types of children are not consistent with expectations—for example, a type O child can be born to an AB parent—due to rare situations, such as
Bombay phenotype and
cis AB.
Subgroups The A blood type contains about 20 subgroups, of which A1 and A2 are the most common (over 99%). A1 makes up about 80% of all A-type blood, with A2 making up almost all of the rest. These two subgroups are not always interchangeable as far as transfusion is concerned, as some A2 individuals produce antibodies against the A1 antigen. Complications can sometimes arise in rare cases when typing the blood. The same study also identified 18 rare alleles, which generally have a weaker glycosylation activity. People with weak alleles of A can sometimes express anti-A antibodies, though these are usually not clinically significant as they do not stably interact with the antigen at body temperature.
Cis AB is another rare variant, in which A and B antigens are transmitted together from a single parent.
Distribution and evolutionary history The distribution of the blood groups A, B, O and AB varies across the world according to the population. There are also variations in blood type distribution within human subpopulations. In the UK, the distribution of blood type frequencies through the population still shows some correlation to the distribution of
placenames and to the successive invasions and migrations including
Celts,
Norsemen,
Danes,
Anglo-Saxons, and
Normans who contributed the
morphemes to the placenames and the
genes to the population. The native Celts tended to have more type O blood, while the other populations tended to have more type A. The two common O alleles, O01 and O02, share their first 261
nucleotides with the group A allele A01. However, unlike the group A allele, a
guanosine base is subsequently deleted. A premature
stop codon results from this
frame-shift mutation. This variant is found worldwide, and likely predates human migration from
Africa. The O01 allele is considered to predate the O02 allele. Some evolutionary biologists theorize that there are four main lineages of the ABO gene and that mutations creating type O have occurred at least three times in humans. From oldest to youngest, these lineages comprise the following alleles:
A101/A201/O09,
B101,
O02 and
O01. The continued presence of the O alleles is hypothesized to be the result of
balancing selection. However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by the immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals. == Clinical relevance ==