7

Multiple Alleles (Contd.)

(Blood Groups in Mann)

ABO BLOOD GROUPS

Blood from an individual cannot always be safely mixed with that of
another without leading to some disastrous result. This fact became
evident with the introduction of blood transfusions which sometimes
cured and sometimes killed the patients. This is due to the fact that
blood proteins of one individual differ from those of others. Extensive
studies have shown that there are two types of substances in the blood
known as antigens or agglutinogens and antibodies or agglutinins. These
are designated by the English alphabets A and B. The antigens are
located in R.B.Cs and antibodies in plasma. Normally, if a person
occur
has an antigen is his R.B.Cs his
plasma has natural antibodies against the
other antigen. A person
having antigen-A in R.B.Cs has antibody b in his
plasma. The agglutination occurs on account of the reaction between
antigen and antibody. Recent chemical investigations have shown that
antigens A and B are not proteins but mucopolysaccharides
amino acids) having a molecular (sugars +
of weight 300,000.
PLASMA OF BLOOD GRoUP O (RECIPIENT)

B-ANTIGEN

/ TRANSFUSION OF
ANTIGEN-ANTIBODY
COMPLEX FORMED
L AGGLUTINATION

B-BLOOD (DONOR)
Fig. 7.1. Diagram showing agglutination
response between
blood of recipient (0)
and of donor
(B) blood groups.
Depending upon the presence and absence of antigens and antibodies,
ur blood groups have been differentiated. These are
AD and
0 blood designated as A, D
groups. The persons belonging to blood
group A have
118
b (Rnti-b) n ater the diovery
cells and antuhody he neivvrsal aiyent are
t onger applionble
A their red blood take and gine their bkod to thoir own
Antigen in
B have the
antigen-B n
blooc
ther red bia
od G r o n s A ani
Bran
Persons of blood group
Fersons d group
AE hare an:
in addition they can guve
blai to petsus f roup AR and
in the piasma
antibody a (anti-a)
but o
a n t i h a d v s im the plasnA D See T'able 2 bekow
Bn the red biaod corpuscies bsve doth Possible etects of transtusion of bood
bkood cedls but Talbe 7.2.
have no antigen in red
group O The foliouring table tenre Remerk
antibodies present in the pasmR Receplents Aggt Can be g e n Can recelve
in perscoTS of bood groupe
ditereut blood n
ninates the
blood of blod from
Antigens and antibodies present
antibodies in man
ther antigens and
Table 7.1. Blood groups,
o A BAB
present in the Antibody present in O AB AB Unversal
Blood groups donr
RBC plesma
ant-6 or bor A& AB a A

anb-A or a ora B& AB o. 8

B B
O. AB AB Unversat
NO AB
AB A and ecipent

O ND rt-A and ant or a anc

or a and5

GROUPO

Ara B
anfiody

A-anelgen R
GROUPA
AtA
anbody
B-antige

GROUP B
oAt-A Art-B
AB artibodies
AB antigen

t A anc A-B GROUPAB

xtbodes both
esent o blood groups
Noandgen individuais with different types
Possdle genotypes of
Rg. 7.3
Fig. 7.2. Blood groups in ma.
Inheritance of ABO Blood Groups
It will be noticed that blood oorpuscles trom the inheritance of different bload
jindividuals of blood discovered that
Berntstein (1925) allelie series. There
group O. since they lack antigen, are not clunped by the serum of an determined by a number of multiple
groups in man is of auy
blood group, so that person of group O can gve blood ta alI but can ake determination of blood group
are alleles concerned with the
only from his own group. Hence these are called ena donors. The
serum from individuals of blood group As does not auee person
corpuscles of any group Hence they can take blood r o the
dumpina of
or
all the blood groups. So they are knwon as universal r PETSons
give blood only to the persons of their own group. The te
 120 Gere Mulrple Alleles (Contd) 121

genotypes
of parent..
and the
Table 7.3. Blood
groups
Tmethod of repreeiting these genes and the zenotypes is
and ofisprings
Offsprings andd1
Blood g r o u p A LALA
Parents blood group B
(phenotype)
Genotype Blood group
AB
LL
No Blood group Genotype Blood g r o u p

(Phenotype) Blood g r o u p

(1) Ox Oo W+X +/+ GENOTYPES AND BLOOD GROUP OF

++xA/A
+A BLOOD GROUP INHERITANCE OF GENES OFFSPANGS
OF PARENTS
(2) Ox A
A ++, +/A
+4x +A
(3) OxA BB B B/+
(4) 0x B A and B

(5) Ox B +/B o&B +l +/B

t/+xAB +iA, +/B
(6) OxAB
AVA x AVA A AA
7)AxA
(8) |AxA A+x A+ A &O AWA, A+,
AAxAV+ A/A, A+ AS B.A and O
(9) AxA A and B

JA x B/B AB A/B
(10) AxB
(11) AxB AVA x B/+ A, AB A/+, AB
(12) Ax B + x B/B 8, AB B/+, AB
A, B, AB &O +HA, B/+, A/B& +l+
(13) AxB A/4 x B/+
A and B AB ard B

(14) A AB AA x A/B , AB A'A, A/B

(15)Ax AB +/A x B A, B, AB AVA, +/B & A/B

(16) BxB B/B x B/B B B/B
(17) BxB B x B/B B +/B, B/B
AB and A
A and B
(18) BxB +/B x +/B 0, 8 4 , B, B/B
(19) B xAB B/BxAB AB, B A/B, B/B
(20) BxAB +B x AB A, B, AB +WA, +/B, AB, B/B
(21) AB x AB AB x AB A, B, AB
AJA, B/B, AB
For convenience group O is A and O
are said to
regarded as normal and alleles A and BB
represent two dominant mutations which have occurred on the
same locus. These
represent codominant alleles. If normal gene is
represented by +, the three genes will be +,A and B. Since
individuals of group O will have a + is
recessive
individuals of blood genotype +/+; gene A is dominant.
groups A might have a
A/A and genotype either +/A or L A and O
similarly individuals of group B might have A and O

individuals of group AB will have a +/ Bor B/ Band

results of crosses between the genetic composition A /B. The
in the Table 7.3. individuals of different
genotypes are shown to show inheritance of ABO blood groups
Flg. 7.4. Diagram
122
in the sinsl
Genete Multiple Alleles (Contd)
123

inherited
therefore, le Meni
a n d the occurrence and reactivity of A, , A3 and A4
are,
These blood groups of blood grou»ups can be
the four lypes
common

fashion. Offsprings of all

between heterozygous
male and
female for blood
prodr
oups Aa
ore ch of the A subgroups is determined by a separate
dually diminishes. Eac
these genes are alleles. The genes A,,A and A4 usually
from a cross
gene and all
s
B (Fig. 7.5) Male heterozygous for with A, as
combination

4A'Aj
dominant over
Female heterozygous for in
blood group - B occur is and so on.
blood group -A to
A2 ,A3 A4. A2
dominant
LA Homozygous
A/Aare very common, whereas homozygous A2 A2 or

very
rare.
are

Gametes Ag Ag basis of blood group is its reaction with

subdivisions of A
The
nd to contain two types of
which is found antibodies a and a, The
B-serum
react and remove both the antibodies
corpuscles of blood group B,
the corpuscles of group combine only with a
A,
LAg8 LA a and a,
While
antibodies in the B-serum (fig 7.6).
Gametes
Group AB Group A antibodíes, thus leaving a,
person
In a blood group
of A, A,
AB, there might be , Aq or A, ,
GroupGroup B Group O
subgroups and hence AB blood group can be divided into subgroups
is some evidence that the B group is also
Fig. 7.5. Mechanism of iheritance of blood groups in man. A.B, A,B, A,B, A4 There established so far.
into subgroups but it has not been
divided
Subdivisions of Blood Group A of ABO Series
Medico-Legal Aspects
On the basis of difference in the degree of behaviour, the blood on in solving
Knowledge of ABO blood groups is very much helpful
cases
has been separated into
A ,A2, Ag and A Subgroups. Of themgroup A
4 A of parentage and settle the cases of illegitimacy.
disputed
cases of mix
1. Solution of Disputed Parentage theseAlthough
in
up

parentage are hospitals,

rare in the but may happen r a r e cases

taken
-TEST TUBE and have occurred in the past. In past, two sets of parents had
home from a particular hospit al at about the same time. Both the
babies
families discovered it but family 2 was not ready for the exchange. Blood
tests in that case demonstrated the possibility of exchange
and the
exchange theie upon satisfied both the families.

Parental blood groups Blood group of childd

B
SERUM- taken homne
Family Ax AB
B-serum containing B-serum with
a-and a-antibodies Az Corpuscles
B-serum with Family I OxO 8
a- antibody
2. Solution of Cases of legitimacy A widely known movie star in
Only California was accused by a former starlet protege of being the fat her of
her young daughter. The physician made blood tests of the alleged father.
the mother and the baby with these results

NO ANTIBODIES Blood Group

Alleged tather
Mother A

Daughter B

The blood tests showed that the defendent could not be the father
The real father would have belonged either to blood group B or AB.
Fig.7.6. Basis for the 3. Disputed Cases of Claimants Blood tests can be used to solve
subdivisions of A blood
group. Cnes of claimants to est ates or in
certain
kinds of criminal proceedings
 124

M-N BLOOD GROUPS Genena Multiple Alleles (Contd) 125

Rh Postive
In the course of their investigations of hunan blood The Rh fnctor hns great ignuficance in child-birth Rh Negativ
Landsteiner and Levine in 1927 discovered M and N antigens, Wh found that n. Rh-egative wonan married

injected into rabbits or guinea pigs, stimulated antib

tibody produ hich wle It
has
en
Rh-positive man, becomes Bensitized Bimply by
withy child within her body. Some of
the serum of the experimental animals Human populati ation can be Rh-positive
mix into her
blood
into blood group M, blood group N MN depending
or blood group MI
the presence of these antigens, but their serum does no
divpided the ells
m
from the
during
embryo may
development.The first child of the
own

back-ground in nearly always

antibodies. If human blood is injected into rabbit, the rabbit i ts with this genetic is
Ordinarily, at lest one pregnaney required
parents
to
antibodies in its serum. These antibodies are found to be antagon nal. But in the sond pregnancy the
RR
different antigens. Landsteiner and Levine in 1927 found that t 9ensitize a
mother.
the blood strenn of the nother, pas
population can be divided into three categories (groups) on the h a bodies in
nnd c a u s e damage to the red cells
O0
their reaction which antibodies developed in rabbit. These categories through the placenta
This c a u s e s the diseue known s
are the foetus.
of the
by
foetalis, hich is charncterie
Table 7.4. Blood groupsM,thelrganotype, antibodies andantigensIn mae
man
hroblastosis
mia due to
hemolysis (breakdown of the rerd blood/
Blood Red Blood Cells reaction with Antlbodles Serum and consequent jaundice ns the blood Rr Rr R
Group ells) in the foetus RR
Genotype Anti-M Anti-N Cellular
Antgens
Antibodie vessels in the liver
become clogged with the broken cells
disnse may be
Flg. 7.7. Rh blood
absorbed by the blood. The group and its
M M/M M and bile is
to cause death of foetus
betoje
None DR or birt inheritance in man
MN MN few days after the birth)
neonatal death (denth within a
M/N
None
N NN
N None A. First Rh Pregnancy
In MN allelic series, no recessive alleles are known for the
absence of either Immunisation to
antigen The pedigree analysis of M and N individuals presents the existence of
,Rh' Red blood cells
1:2:1 F, phenotypic ratio, showing
phenomenon of codominance.
Ss Antigens Rh (Antibodies for med)
In 1947 another pair of antigens
M and N series. The
S/s were found to be associated with
genes for S and s antigens (MS and Ns) are not
allelic to the MN genes. Race and
Sanger (1968) have described these
genes as codominant and closely liuked and
The different gene combinations inter-related with MN genes.
of MN and Ss series can be MS, Ms,
NS, Ns, MNSS, MNSs or MNss.
First Rh' Child
RH FACTOR Woman
normal
The Rh factor was discovered in 1940
from rabbits immunised with the blood of aby Landsteiner and A.S. Wiener B.Succeeding Rh Pregnancles
blood from a rhesus monkey was monkey, Macaca rhesus. When
the guinea pig produced antibodies
injected into guinea pig it was found that
which ald Antibody Responee
of all rhesus monkeys. This agglutinate the red cells
this species contain a indicates that the red
cella of all monkeysof Rh' Foetus Rh antbodies
particular
human blood was tested by this antigen, which was
designated
Reac: with Rh antigen

cells of some persons were guinen pig serum, it was foundRh.thatWhen

the
not affected. It was clumped whereas the blood of other persons was
concluded
(Rh) as found in the blood of
that
8BOme persons have the
rhesus monkeys, while others dosame antigen
Those with the antigen not have it.
without it Rh-negative (Rh were_designated Kh-po8itive
). Rn 1s presumed to(Rh*) and those Red Blood cell
character and Rh is a recessive trait. be
Agglutination Haemolylc
Diseese

7.8. Erythroblastosis in
man.
Flg.
126
lation of Western
Genen Multuple Alleles (Contd.
127
populati«

About 85 per cent of the

Rh-positive
white

nnd about
lb per cent in
p
urope hy donor8
immunised The rhogam forms a cont around foet al
Anmerica is im the genenl htained from
North frequently As a Tesult no Rh-positive antigens are available
occurs loss and probn pRCe in not her's blood
Erythroblastosis

would be expected
on the basis
of gene Ireqiency
occurring from the
asty lity Onl stimulate mother's
cireulation and no antibodies are
formed
proportion of
the frequencies
w o n n n have produced
ngs bel to
rhesius blood groups
Though in the beginning
thought to depend
were

S1all y mptoa and r

and Rh-negative of allcles, R (determining Rh-posit.ive)
Rh postive man
o just a single pair lnter it was found that there were more than
the disense Foetalis determining Rh-negative),
Method of Preventing
Erythroblastosis
Rh blood groups.
These are , R', R°',
R, R2 or
Rx, ,
Rz R, Ry
,

Rhogam blood test after deliver of her Rh wo forward to explain the nature of
in given specinl put
a theories have been
The Rh-inother mother's blo and r. Two
cells nre present in different Rh blood groups
child If fortal Rh preparation of anti-Rh giv
tibody. I This theory was jput forward by Wiener
ne
is a
Allele Theory
1jections of thogam. Rhogam 1. Multiple
According to Wiener the
known ns Wiener's hypothesis.
and is also series of multiple alleles
are determined by a
Foetus various Rh blood groups
(0,+1) designated as R1, R2, R', R°, R,
or
R, R, , R, and r, etc.
,

This theory wns put forward by Fisher.

2. Gene Complex Theory
Mother three pairs of closely linked genes determine the
A,-) According to this theory
Mother (AB-) These genes are so closely linked that they are
end various Rlh blood groups.
Foetus 1/0) block and are called pseudoalleles. These three pairs of
Anl-B uSually inherited as a
which can form folloving eight possible combinations
genes are CDE/cde
have confirmed Fisher's Gene Complex Theory.
Tecent investigations
is inherited together as
Placenta Each haploid combination of these three genes
Foetal CPlls Foetal cells enter gene. Of the 8 combinations,
the most common complexes are
a single
enter at delvery mother's vessels CDEand cde (r).
(R,)
just three. These are CDe (R,),
The dominant genes CDE determine the production of protein C,
reactions with
protein D and protein E. On the basis of agglutination
these proteins four types of antisera have been identified.

Mothers Plasma
develops ant-Rh These are
(1) antisera-D containing ant ibody ngainst protein D anti-D
or A.
antibodhes
(2) antisera-c contains antibody agaiust protein C: anti c or y It
Rhogam antbodes reacts wit h Rh-persons.
Foetus 2(0.) Coat surface of antisera-E contains antibodies agninst protein E.
0' foetal cells (3)
nti-Rh antubodies
enler letal biood (4) antisera-C contains antibodies against protein C and D
Table 7.5. Comparatlive designation of Wiener's and Fisher's symbols of
ditferent Haploid elements of Rh blood
According to gene According to Multiple Phenotype
Complex Theory of Fisher Allele Theory of Wiener
cde Rh
Foelal Cells dump
And lyse cDe Rh
Mother Cde R Ah
Foetus 2 (A-) cdE R Rh'
(0)
CDe Rh
Fig. 7.9. cDE Rh
Diagram showing the effect of
Rh incompatability in later pregnancies Flg. 7.10. Rhogam method ofpreventing CDE Rx or R Rh
a Rh
in erythroblastosis foetalis. CdE Ry Rh
mother.
 129
Genetiu Multiple Alleles (Contd.)

128 the Four

ANTIGENIc sUBSTANCES IN OTHER
A.
with ORGANISMS
of the Three Maln
Gene Complexes tlsera
Table 7.6.
Reactions

Antl-c
Antl-E Anti-C Antigens have
also been discovered in other animals such as cattle,
Anti-D These antigens are under the control of specific genes.
and chicken.
CDe (R) sheep han 160 different antigenic reponses (phenogroups) have been
with the gene for B blood group in cattle alone. In
cDE (A) found
in
association

are found associated with B-locus and more

cde () the reactious
of all six otypes previ
8enotypes previousy sheep
about 50 phenogroups at the B-locus in chicken. Presumably all
Table 7.7 gives
four known sera. than
20 alleles have been found
inentioned to the the corpuscles of phenogroups
ntrolled
are by separate alleles.
reactions between these
have a substance similar but not
The results of agglutinationknown sera have been summarised in
in t New World Monkeys
and lemurs
different Rh genotypes
and four in man. The A, B and AB blood groups are
entical
ident
with B-antig
Table 7.7. Orangutan and A in Gibbon. Three blood groups have been
Rh blood Groups with Four known Antlser found in
Table 7.7. Reaction of slx Main in cats with
a genetic 3ystem similar to those in man.
Anti-c Anti-E Antl-c found
Antl-D
blood tested by using antisera- Antisera-A,
Genotypes of blood
Human group is
group and anti-Rh or antisera-O.
antisera-B
1. A R (CDe/CDe) Red blood cells added
A B CAB
2 R/Ra (CDe/cDE)
3.
R/r(CDe/cde)
Ra/Ra (cDEJcDE)
Aa/r (CDE/cde)
. r/r (cde/cde) Anti-A
OTHER HUMAN BLOOD GROUPPS plasma

Besides the ABO blood groups of man, eighty-two human blood

Red blood cells added
19O0 to 1965 (P. Spencer, B
group phenotypes have been discovered from CAB
systems of man have been shown in
1966). Some importnt blood-group
thetable 7.8
Some detectable antlgens Basic genes
Blood-group
System
ABO A, B, H L L4.12.Ls, 1C Anti-B
Le, Le Le, le plasma
2. Lewis
M, Mg. M, N, N, S, s, U, Mf.LM, LMg. Ly, LM, LN.S, s, N, Fig. 7.11. Diagram to show testing of human blood group with the aid
3.
MNS Vw. Mu, Hu, He, Vr, Me, Rf. |M,v", Mu, Hn, He, Vr of antisera-A and antisera-B
Sta Mt", Ri, St Antisera-A and antisera-B is taken on slide or in test tube. Add a
P
PPa. Pk R. Pa. P drop of blood in each tube. Stir well and observe.
5. Rh
C, W",c, D, E, See table 7.4. (1) Coagulation in tube A with antisera-A shows that bloud belongs
Lutheran Lu,P Lu, Lu to Blood group-A
kell K, K, Kp, Kp, Js Js, k K, k, Kp, Kp, Js*, Js, K (2) Coagulation in tube-B shows that blood belongs to blood
8.
Duffey Fy,Fy, Fy Fy.Fy,Fy°, Fy group-B
9. Kidd Jk, Jk JK, JkD, Jk (3) No coagulation in either of the tubes shows that blood belongs to
10. Diego DP,Di DA, DP blood-0
11. Auberger Au Au Au
(4) Coagulation in both the tubes shows that blood belongs to blood
12.
13. Xg group-AB
Xg.Xg
14. Combrock Do Do,Do