Multiple alleles
Multiple Alleles
• Alleles can be defined as genes that are members of the same gene
pair, each kind of allele affecting a particular character somewhat
differently than the others.
• In Mendel's experiments there were two possible kinds of alleles in a
gene pair, i.e, smooth or wrinkled (S,s) yellow or green (Y, y)
• There are more than only two possible kinds of alleles in a gene;
hundreds or perhaps thousands of possibilities exist.
• The grouping of all different alleles that may be present in a gene pair
is defined as a system of multiple alleles.
Multiple
Alleles
• Dominance in this series appears to be
incomplete, although it would be difficult to
make such a decision without this type of
refined analysis.
• Alleles of this type which act within the same
phenotypic range of each other have been
termed isoalleles.
• Some of these alleles has also been discovered
in abnormal character, mutant isoalleles and
some within the phenotypic range of wild type,
normal isoalleles.
• A multiple allele system may therefore be quite
complex, including within it various subsidiary
isoallelic systems.
Multiple allelic blood group systems
MultipleAllelic BloodGroup
Systems.
• In animals, tissues that are removed from
one individual and grafted onto another are
frequently sloughed off or rejected because
of incompatibility between the introduced
material and that of host.
• In 1947, Walsh and Montgomery found that
a certain portion of human blood serum
could be used to distinguish new varieties of
MN blood system.
• There appear to be four codominant alleles
LMS, LMs, LNS, LNs, (or MS, Ms, Ns, NS) which
would give nine different phenotypic
combinations.
MultipleAllelic
BloodGroup
Systems
The first case of multiple alleles demonstrated in
man was really that of another blood group system
which has been discovered by Landsteiner and his
students in early 1900s.
This system called ABO was shown by Bernstein in
1925 to consist of three alleles of a single gene, IA,
IB and IO forming four different phenotypic groups:
A(IAIA or IAIO), B(IBIB or IBIO), AB(IAIB) and O(IoIo).
In this case, the blood serum of man himself
manufactured the antibodies that reacted with the
blood-cell antigens of other individuals.
Multiple-Allelic Blood-Group
Systems
• According to Kabat, Watkins and others it is the terminal
sugars of these compounds which differ between the A
and B antigens.
• The A substance bears an N-acetyl group at the number
2position of the galactose sugar; the B substance carries
a hydroxyl group at this position and the O substance
lacks the terminal galactose sugar entirely.
• The distinction between the A and B substances thus
arise from the distinctive difference in the kinds of
terminal galactose sugars transferred to a precursor
substance by the action of the a and B alleles; each allele
produce transferase enzyme but one function as an Nacetyl galactosaminyl transferase(A) and other as
galactosyl transferase(B).
• In case of O, no terminal transferase enzyme appears to
be produced and it can therefore be called a null allele.
MultipleAllelic
BloodGroup
Systems
• In respect to A and B, we can see the antigenic
differences, although small, are nevertheless
significant, so that antibodies can discriminate
between one antigen and the other.
• In fact, additional multiple alleles at the ABO
locus have recently been found (A2, A3, Ax and
Am) which probably differ in even more minor
respects.
• According to Stormont, the number of different
alleles for a particular blood type gene called B
reached more than 300.
RH and ABO
incompatibility
The agglutination reaction that occurs when red blood
cells are clumped by serum antibodies may also occur in
the circulation of the mammalian embryo having a
blood type antigenically different from its mother.
RH and ABO
incompatibility
The first instance of such compatibility was noted in
checking the blood types of children born with serious
anemia (erythroblastosis fetalis or hemolytic disease of
the newborn) caused by the breakdown (hemolysis) of
their normal red blood cells.
Before 1940, this disease was present in about one out
of 200 births.
As determined by Levine and others, these children had a blood
type, Rh positive, inherited from their fathers, but antigenically
different from their Rh-negative mothers.
RH and ABO
incompatibility
This Rh factor, first detected in the red blood cells of Rhesus
monkeys, was initially thought to be caused by a gene with only
two alleles, R and r.
The events leading to erythroblastosis thus arose from the Rhnegative genotype of the mother (rr) producing antiserum
against the antigens of the Rh-positive offspring(Rr)
Since the R allele acted as a dominant to r, Rh positive males
married to Rh negative females could have either all or half their
offspring phenotypically Rh positive depending on parent's
genetic constitution was respectively homozygous (RR) or
heterozygous (Rr).
Anti D Injection
• Brief detail about anti D injection
RH and ABO incompatibility
• The Rh blood group is only one of the systems which may cause mother-offspring
incompatibilities.
• Other blood group antigens may also travel across the placenta and produce
maternal antisera.
• Rh incompatibility is estimated to occur in about 10 percent of all pregnancies;
nevertheless, only 1/20 to 1/50 of these incompatible offspring turn out to be
affected by hemolytic anemia.
• This diffusion not seem to occur very frequently and even when it occurs the
amount of diffused antigen may be low enough so that the amount of maternal
antibody production is not very high.
• Although Rh incompatibility may exist
between mother and offspring, ABO
incompatibility may prevent anti-Rh serum
from developing.
RH and ABO
incompatibility
• Incidence of Rh hemolytic disease occur when
mother and offspring are compatible for the
ABO blood groups.
• When they are incompatible, and the diffusing
fetal cells can be destroyed by maternal ABO
antibodies, the frequency of Rh hemolytic
disease decreases.