Principles of Genetics

By SEID E.
6.Extension and application of Mendelian genetics (gene
interaction and the influence of environment)
 genes are not merely separate elements producing distinct individual
effects, but they could interact with each other to give new phenotypes
(phenotypes arise from developmental processes, which are controlled
by gene products)
 genes action refers to which genes control the phenotypic expression of
various characters in an organism.
 Alleles of a gene may interact with one another in a number of ways to produce
variability in their phenotypic expression is called gene interaction.
 Two types of gene interaction are;
1. Intra-allelic gene interaction; are interaction between alleles of the same gene.
E.g. Aa, Bb, Cc
2. Inter-allelic gene interaction; are interaction between alleles of the different
gene. E.g. AaBb, DdEe
A. Dominance relationships b/n alleles (Intra-allelic /allelic
interactions)
-this is the relation (interaction) b/n the allele of the same gene (alleles of a
locus).
 Intra-allelic interactions are;
I. Based on dominance effect (relation)
1. Complete dominance; when the phenotype in heterozygous is identical to
that homozygous dominant for a concerned dominant allele.
E.g. tall x dwarf in human being →TT X tt →Tt (tall) and phenotypic ratio
3:1
2. In-complete dominance;
the heterozygote’s phenotype is b/n the phenotypes of the two
homozygotes.
 the intensity of phenotype in heterozygous is less than phenotype in
homozygous for concerned dominant allele.
E.g. red x white flower in O clock plant →RR X rr →Rr (pink color) and
phenotypic ratio 1:2:1
Red x white in cattle →RR X rr →Rr (roan color)
3. Co-dominance; both alleles of a gene express themselves in heterozygous.
E.g. Blood A X B in human →AA X BB→ AB (blood AB), In this case, the
IA and IB alleles are codominant to each other
 It is called heterozygous advantage. E.g. Horse x donkey →HH X hh→Hh
(mule)
4. Over dominance; the intensity of phenotype in heterozygous is
greater phenotype in the two concerned homozygous for concerned
dominant allele.
E.g. white eye gene x red eye gene (low concentration gene in
both)→WW X ww →Ww (high eye pigment concentration)
the heterozygote’s phenotype exceeds the phenotypic
measurements of homozygous parents. Eg. In humans,
heterozygotes for sickle cell anemia have superior
resistance to malaria.

5. Pseudo-dominance; the phenotypic expression in recessive allele

of a gene in the hemizygous state due to sex linkage or chromosomal
deletion.
E.g. TT X tt →Tt(ll) but by deletion or linkage → T(li)
(Hemizygous)
II. Based on lethal effect;
 Some genes affect the survival of zygotes or individuals are called
lethal gene.
 The lethal gene causes death of all individual carrying lethal
genotype before reach in adult stage (most in homozygous state).
1. Dominant lethal; a dominant allele of a gene affects the organism.
E.g. the dominant allele ’Y’ is lethal and cause death of homozygous
‘YY’ embryos at early stage of development in mice.
 Yellow female x gray male in mice →YY x yy →Yy (yellow, not
die because it is heterozygous), but Yy x Yy → 1YY (yellow,
die):2carrir yellow (not die):1gray
2. Recessive lethal; allele of a homozygous recessive show the
expression in its genotype’
E.g. albino seedling character in rice and barley is governed by a
recessive alleles, because a recessive alleles totally devoid of
chlorophyll.
 Green x non-green→ GG x gg→ Gg x Gg→1GG (green): 2Gg (carrier
green) : 1 gg (albino and die)
Penetrance; is the ability of a gene to express itself in all individuals,
which carry in the appropriate genotype and produce a phenotypic
effect.
 Types of penetrance are;
1. Complete penetrance; when all individuals that carry a particular
gene exhibit its phenotypic effect.
 All dominant individual will exhibit one phenotype and all
homozygous recessive individual will exhibit another phenotype.
 Recessive allele has no penetrance in heterozygous condition.
E.g. TT (100%) X tt (100%) →Tt (‘T’ exhibit 100%, while ‘t’ has 0%
penetrance)
2. In-complete penetrance; a specific gene does not express their
effect in all individuals, which carry in appropriate genotype.
E.g. polydactyl in humans (it is inheritance for the dominant allele ‘P’), a trait that is
characterized by extra toes and/or fingers.
Expressivity is a degree of phenotypic expression of a gene in
different individuals and influenced by environmental conditions.
 Two types of expressivity are;
1. Uniform expressivity; when the phenotypic expression of a gene
is identical/ similar in all individuals.
E.g. height in human ‘tt’ is dwarf and TT/Tt is tall
2. Variable expressivity; when the phenotypic expression differs in
different carriers of a gene.
E.g. recessive genes in lima bean produce chlorophyll deficiency.
 when P allele(polydactyl in humans) is present, it expresses
variable expressivity
 Inter-allelic interactions are:
I. Based on epistasis gene interaction; two different genes which control the same
character, out of which one masks the expression of other gene, is epistasis.
 the homozygous presence of a recessive allele may prevent or predominate the expression
of other alleles at a second locus (or other loci).
 the alleles at the first locus are said to be epistatic to those at the second locus, and the
alleles at the second locus are hypostatic to those at the first locus.
1. Dominant epistasis (12:3:1)
When out of two genes, the dominant allele (e.g., A) of one gene masked the activity of
alleles
of another gene (e.g., B) and expressed itself phenotypically,
from the classical F2 phenotypic relation of 9:3:3:1 (ABb xAaBb).
 The presence of first dominant allele of one gene masks the genotype of other gene. A-B-
and A-bb =12, aaB-=3 and aabb=1
E.g. BBAA X bbaa (if allele ‘A’ determines black and allele ‘B’ for gray color) →AaBb x AaBb
→ A-B- and A-bb (black)= 12, aaB-(gray)=3 and aabb (white)=1
2. Duplicate dominant epistasis (15:1)
the dominant alleles of both gene loci produce the same phenotype without cumulative effect, the
9 : 3 : 3 : 1 ratio is modified into a 15 : 1 ratio
 Two genes in dominant form is epistasis to the others and can achieve the same result, but
only the double recessive gene will produce a recessive phenotype.
E.g. kernel color in wheat (kernel color (AABB) X white color (aabb)→AaBb xAaBb→ A-B-
(9), A-bb (3), aaB-(3) are kernel colored =15 and aabb (1) is white .
 ecessive/supplementary epistasis (9:3:4)
ometimes the recessive alleles of one gene locus (aa) mask the action
enotypic expression of alleles of another gene locus (BB, Bb or bb
les)
The presence of first recessive allele of one gene masks the genotype of other
gene.
mouse coat color (‘A’ for agouti, ‘C’ produce pigment, ‘aa’ are black and ‘cc’
no white). AACC x aacc →AaCc x AaCc→A-C- (agouti)= 9, A-cc
ino)=3, aaC- and aacc (black)=4
uplicate recessive/Complementary epistasis (9:7)
oth gene loci have homozygous recessive alleles and both of them
duce identical phenotypes, the F2 ratio 9: 3: 3 : 1 would become 9 : 7. In
h case, the genotypes aa BB, aa Bb, AA bb, Aa bb, and aa bb produce
phenotype Both dominant alleles when present together, complement
h other and are called complementary genes and produce a different
notype. A case of such complemental inheritance, resulting from the
mbined action of complemental genes is known in sweet peas.
Two genes in recessive form is epistasis to the others and can achieve the same
esult.
anthocyanin pigment synthesis in sweat pea plants (only the double dominant
- phenotype produces need enzyme to synthesize the pigment). CcPp x CcPp →
- =9, C-pp=3, ccP-=3, ccpp=1 (not produce enzyme).
5. Dominant suppression/ inhibitory epistasis (13:3)
Sometimes, the dominant alleles of one gene locus (A) in homozygous (AA) and
heterozygous
(Aa) condition and the homozygous recessive alleles (bb) of another gene locus (B)
produce the same phenotype, the F2 phenotypic ratio becomes 13 : 3 instead of 9 :
3 : 3 : 1. In such case, the genotype AA BB, AABb, Aa BB, Aa Bb, AA bb and Aa bb
produce same phenotype and the genotype aa BB, aa Bb and aa bb produce
another but same phenotype
 The dominant allele at one of the genetic loci suppresses expression of the other locus.
E.g. feather color in chickens (‘C-’colored, ‘cc’ white and an inhibitor locus ‘I’ block all
expression of feather color, when the dominant allele ‘I-’ is expressed, but no effect recessive
‘ii’
I- (3/4) = 9 white
C- (3/4) colored ii (1/4) = 3 colored, b/s no effect in recessive allele.
I- (3/4) =3 white
cc (1/4) white ii (1/4) = 1 white
6. Additive epistasis (9:6:1)
Certain phenotypic traits (e.g., coat colouration) depend on the dominant alleles of
two gene loci. When the dominant condition (homozygous or heterozygous) at either
locus (but not both) produces the same phenotype, the F2 ratio becomes 9: 6: 1.
 The dominant allele of one gene could be epistasis to the other.
• E.g. red cattle x white cattle (if allele ‘R’ determines red and allele ‘B’ for white color
→RRBB x rrbb→RrBb xRrBb→R-B- (red)=9, A-bb and aaB- (roan)=6 and aabb=1
(white color).
Effect of internal environment on gene expression:
not all effects of the internal environment have been described at molecular
evel.
two of the internal stimuli are age and sex:
Age: the age of an organism reflects internal environmental changes that can
ffect gene function. E.g. pattern baldness in human.
Sex: the expression of a particular gene may be influenced by the sex of the
ndividual.
n some cases, the autosomal genes (on autosomal chromosomes) affect a
articular character that appears in one sex but not in the other sex; such
raits are called sex-limited. E.g. breast development and facial hair in
uman.
Effect of external environment on gene expression:
many factors in the external environment such as temperature, nutrition, light, chemicals,
nfectious agents, etc influence gene expression.
Temperature: some alleles of an enzyme-coding gene may give rise to an enzyme that is
emperature sensitive.
xample: 1. Gene expression of fur color in Himalayan rabbits.
when this rabbit is reared:
at > 30 oc, it becomes white at extremities (ear, nose, paws)
at 25 oc, it becomes normal Himalayan (black extremities)
. Flower color in primrose:
Multiple-Allelism
-Multiple allelism is a condition where several forms of a gene (alleles) exist in a
population.
-many genes with multiple alleles are known in different organisms including
human beings.
-Examples: -ABO-blood group systems in human (3 alleles)
-coat color in rabbits (4 alleles)
-self incompatibility genes (prevent self fertilization) in brassica (>45 alleles)
CHARACTERS OF MULITIPLES
The most important and distinguishing features of multiple alleles are
summarized below :
1. Multiple alleles of a series always occupy the same locus in the chromosome.
2. Because, all the alleles of multiple series occupy same locus in chromosome,
therefore, no crossing-over occurs within the alleles of a same multiple allele
series.
3. Multiple alleles always influence the same character.
4. The wild type allele is nearly always dominant, while the other mutant alleles in
the series may show dominance or there may be an intermediate phenotypic
effect.
5. When any two of the mutant multiple alleles are crossed, the phenotype is
mutant type and not
The wild type.
5.1. Number of different gametes, genotypes & phenotypes possible in a
population for a locus
-The number of d/t types of gametes and genotypes possible in a population
The number of d/t types of possible phenotypes in a population depends on the
number of alleles for the locus and the type of dominance relationship among the
alleles.
(a). If there is serial dominance (a1>a2> a3>--- >an), then the number of possible
phenotypes equals the number of alleles.
-this type of allelic gene interaction is seen in rabbit’s fur color as indicated below:
C+ (wild type-silvery gray) >Cch (chinchilla-white gray) > Ch (Himalayan-white with
black extremities) > C (albino).
(b). If there is codominance or incomplete dominance among all the alleles,
then the number of possible phenotypes equals the number of genotypes. i.e., each
genotype corresponds to its own particular phenotype.
(c) If the types of dominance relationships are not the same for all allelic pairs,
predicting the number of possible phenotypes in the population becomes
complicated.
-A simple example is the ABO-blood group system (3 alleles): A>O, B>O and A&B
are co dominant. Thus, there are 4 phenotypes: A-, B-, AB, and OO.
Blood group systems in human (ABO, MN and Rh blood group inheritances)
-There are many blood group systems including ABO, MN, and Rh systems in
humans.
ABO blood group system
-Four blood group phenotypes exist in the ABO system: A, B, AB, & O.
-The four phenotypes are represented by six genotypes produced by three alleles: I A (A),
IB (B), & iO (O)
-The genetics of the system follows basic Mendelian principles.
-The blood group alleles specify cellular antigens (antibody generating substances) that
are attached to the outer surface of red blood cells (RBC). (Antigens are also called
isoagglutinogens).
The analysis of blood group inheritance and blood typing are used in legal
medicine in cases of disputed parentage or baby identification in hospitals.
-Antibodies against an antigen agglutinate or clump any red blood cell, which has
the antigen on it.
-In case of blood transfusion, the blood type of the donor and that of the recipient
must be compatible.
-The recipient’s blood should not possess antibodies against the donor’s blood.
MN blood group system
-Two codominant alleles (M and N) are involved in this system.
-The M allele produces M antigen and the N allele produces N antigen
(glycoproteins).
-Unlike the ABO system, there are no naturally occurring antibodies against these
antigens in the serum.
Rh Factor
The surface of erythrocytes (RBC) of some individuals contain one more
type of antigen called Rh factor besides the A and B antigens. It is
named after the Macaca rhesus monkey in which Rh factor was first
discovered by Landsteiner and Wiener in 1940. Human beings are
found to contain eight different types of Rh antigens.
The production of Rh antigen (Rh blood phenotype) depends on three
closely set autosomal genes (pseudoallels). If any one of them is
dominant, a Rh antigen is produced, but if all of them are recessive, no
Rh antigen is formed. The individuals possessing the Rh antigen are
called Rh-positive (Rh+) and those lacking it are Rh-negative (Rh–).
Both of these types of persons are normal and none has natural anti-Rh
antibodies in their blood plasma. However, a Rh-negative person can
develop these antibodies on receiving Rh antigens through transfusion
of Rh-positive blood. Such a blood transfusion will be safe only when
the recipient had never been exposed to Rh-positive blood earlier .
If already exposed, the previously developed anti-Rh antibodies will
agglutinate the donor’s RBC. In fact, the degree of RBC agglutination
depends upon the amount of anti-Rh antibodies present. The high
concentration of anti-Rh causes severe agglutination of RBC which
sometimes proves fatal.
Erythroblastosis fetalis. The incompatibility of Rh-positive and Rh-
negative bloods may also be noticed in death of the child before or soon
after birth. If a Rh-negative women marries a Rh positive man and bears
a Rh-positive foetus, sometime due to some placental defect, some of
the foetal RBC carrying Rh antigens may pass into her own blood stream
and cause the production of anti-Rh antibodies. The concentration of
anti-Rh antibodies is gradually built up in the mother and she, thus,
becomes sensitized only at or just before birth of her first Rh-positive
child. In a second or subsequent pregnancy involving a Rhpositive child,
these anti-Rh antibodies may return to the foetus through the placenta
and destroy the Rh antigen carrying RBC of foetus. The child may then
suffer from a disease called erythroblastosis fetalis which is a haemolytic
anaemia often accompanied by jaundice, as liver capillaries become
clogged with the remains of red blood cells and bile is being absorbed by
the blood. Death of the foetus may occur before birth or soon after birth.
Multiple alleles; are an alternative form of a gene and usually one of
them is dominant over the other.
 The two alleles of a gene determine the two contrasting forms of a
single character. E.g. T(tall), t(dwarf)
 It is several allele of a single gene of a character exist and each
one of them governs a distinct form.
a. ABO blood type in human;
 A single gene controlled the human ABO blood system as ‘I’ and it
has three allele IA, IB, and i.
 Allele IA controls the production of antigen-A & produce
individual genotype IAIA and IAi of blood group A.
 Allele IB controls the production of antigen-B & produce
individual genotype IBIB and IBi of blood group B.
 Allele ‘i does not produce any antigen and individuals with
genotype ii is blood group O.
 Individuals with IAIB produce both antigen A and B are classified
as blood group AB.
b. Rh blood type in human;
 Rh system was named after rhesus monkey in which Rh factor was first
discovered by Landsteiner and Wiener in 1940.
 Rh factor is a protein that is either present or absent on the surface of
persons RBCs (the present of Rh factor is Rh+ , while the absent of Rh
factor is Rh-)
 There are different Rh factor antigens (D, C, c, E), but antigen D is the
most immunogenic (Rh+ has antigen-D , while Rh- has antigen ‘d’)
 The Rh factor is inherited from parent to child.
E.g. if the mother is Rh- and father is Rh+ , the fetus can inherited the Rh
gene from his father.
• If the child is Rh+ is incompatibility.
• For first time the Rh- women become pregnant (not incompatibility), but
the second and further more child will be incompatibility and suffer
Hemolytic disease of the new born (HDN)
• Its treatment is after checking of the blood type use injection of Rh
immune globulin (RhIg) anti-D, before she could be pregnant.
 Unit-8. Linkage, crossing-over, recombination and gene mapping
 All genes located in same chromosome would move to same pole
during cell-division.
 Such genes will fail to show independent segregation to inherited
together to the progeny is called linkage.
 Linked refers to the two or more gene located in same chromosome,
so Mendel’s law of independent assortment is not applicable.
 It involves those genes which are located close to each other.
 Strength of linkage depends on the distance between the linked
genes.
 The presence of linkage leads to higher frequency of parental
types than recombinant in test cross.
-If the genes on the same chromosome are always inherited together
(no crossing over), they are said to exhibit complete linkage.
Genes (alleles) at all loci of one chromosome, however, do not necessarily
inherited together because in many instances crossing over (reciprocal
exchange of chromosome segments) may take place during prophase I,
which results in the recombination of alleles between the homologous
chromosomes.
  Genes that are located in the same chromosome and that do
not show independent assortment are said to be linked.
 The alleles of linked genes that are present together in the
same chromosome tend to be inherited as a group.
 Crossing-over between homologous chromosomes results in
recombination that breaks up combinations of linked alleles.
 A genetic map depicts the relative positions of genes along a
chromosome.
 The map distance between genes in a genetic map is related
to the rate of recombination between the genes.
-In many instances, however, certain genes are inherited
together because they are located on the same chromosome.
-Genes on the same chromosome are said to exhibit linkage
and are called linked genes.
-Genes (alleles) at all loci of one chromosome,
however, do not necessarily inherited together
because in many instances crossing over
(reciprocal exchange of chromosome segments)
may take place during prophase I, which results in
the recombination of alleles between the
homologous chromosomes.
-If such occasional separation of two genes on the
same chromosome by crossing over takes place,
the genes are said to exhibit incomplete (partial)
linkage.
-If the genes on the same chromosome are always
inherited together (no crossing over), they are said
to exhibit complete linkage.
Types of linkage are;
I. Based on crossing-over (presence or absence of recombinant phenotype)
1. Complete linkage; is a complete absence of recombinant types due to absence of
crossing over, which observed in male Drosophila and female silkworm.
2. Incomplete linkage; some frequency of crossing over occurs between the linked
genes.
 Recombinant types also observed beside parental combination in test cross
progeny, which observed in female Drosophila, maize and pea.
II. Based on gene involve (either all/some dominant and recessive alleles are linked
together)
1. Coupling phase; all dominant alleles are present in same chromosome or all
recessive alleles are present in same chromosome.
E.g. A B or a b
2.Repulsion phase; some dominant alleles of same genes are linked with some
recessive alleles of other genes on same chromosome.
E.g. a B or A b

III. Based on chromosome involved (location of genes on the chromosome)

1. Autosomal linkage; is linkage of genes, which are located on the autosomes.
2. Allosomal/ sex/ x-chromosomal linkage; is linkage of genes, which are
located in sex chromosome, eitherBy‘x’ orS.‘y’, but generally ‘x’.
aynias
-Progeny that show parental combination of alleles are
referred as parentals, and those that show non-parental
combination of alleles are referred as recombinants or non-
parentals or cross over products.
Example: Assume there is partial linkage and the distance
allows only single cross over b/n the two genes.
Detection of linkages is;

 Test cross is the most common method of detecting the linkage.

 In test cross, the F1 heterozygous at two loci (AB/ab) is crossed to a double recessive parent (ab/ab) and
phenotypic ratio of 1:1:1:1 parental and recombinant types, it indicates the absence of linkage.

A B x a b

A B ↓ a b

A B A B. F1 heterozygous
a b a b

F1 hybrid x double recessive parental

A B x a b

a b ↓ a b
Gametes; A B A B. Parental a B. Recombinant

A b x a b a b a b

a B → A b. Recombinant a b. Parental

a b a b a b
Crossing over

The incomplete linkage takes place due to the occurrence of

new combinations or recombination of linked genes. The
recombination in its turn is accomplished through a process
known as crossing over in which the non-sister chromatids
of homologous chromosomes exchange the chromosomal
parts or segments. In another words
“The crossing over is a process that produces new
combinations (recombination) of genes by interchanging of
corresponding segments between non-sister chromatids of
homologous chromosomes”. The chromatins resulting from
such interchanges of chromosomal parts are known as
cross over. The term crossing over was coined by
Morgan.
 Crossing-over;
 It is the exchange of homologous segments between non-sister chromatids
of homologous pairs.
 It occurs through the process of breakage and re-union of chromatids.
 Each events of crossing over produce recombinant and parental types.
I. Types of crossing overs based on № of crosses/chiasma are;
1.Single crossing over; is a formation of single chiasma between non-sister
chromatids of homologous chromosome in prophase.
 Half of the product having parental combination and other half having
recombinant combination
 It involved two linked genes.
2. Double crossing over; is the formation of two chiasma/ cross between two
non-sister chromatids of homologous chromosome.
 It involves three linked genes, but produce only non-recombinant or
parental types.
3. Multiple crossing over; is the formation more than two chiasma between
non-sister chromatids of homologous chromosome.
Frequency of crossing over= (№ of recombinant progeny/ total № of
progeny) 100
Kinds of Crossing Over
According to the number of chiasma following types of crossing
over have been described.
1. Single crossing over. When the chiasma occurs only at one
point of the chromosome pair then the crossing over is known as
single crossing over. The single crossing over produces two
cross over chromatids and two non-cross over chromatids.
2. Double crossing over. When the chiasmata occur at two points
in the same chromosome, the phenomenon is known as double
crossing over. In the double crossing over, the formation of each
chiasma is independent of the other and in it four possible classes
of recombination occur.
3. Multiple crossing overs. When crossing over takes place at
more than two places in the same chromosome pair then such
crossing over is known as multiple crossing overs. The multiple
crossing over occurs rarely.
-There are two types of test cross methods to construct genetic
map: two point test cross and three point test cross.
Characteristics of Crossing Over
1. Crossing over or recombination occurs at two levels
(i) at gross chromosomal level, called chromosomal crossing over and
(ii) at DNA level, called genetic recombination.
2. A reciprocal exchange of material between homologous
chromosomes in heterozygotes is reflected in crossing over.
3. The crossing over results basically from an exchange of genetic
material between non-sister chromatids by break-and-exchange
following replication.
4. The frequency of crossing over appears to be closely related to
physical distance between genes on chromosome and serves as a tool
in constructing genetic maps of chromosomes.
Factors affecting crossing overs are;
1.Distance b/n genes; crossing over b/n two genes would increase with
an increase in distance b/n them.
2.Sex; the heterogametic sex shows relatively lower recombination
frequencies than the homogametic sex of the same species.
Eg: No crossing over occurs between linked genes in Drosophila
males and females of silkworm.
 heterogametic sex shows lower crossing over than homogametic
sex.
3.Temperature; in Drosophila females, crossing over increase in both
lower & higher temperature than 22 oc.
4. Nutrition; The frequency of crossing over in Drosophila is affected
by the presence of metallic ions.
Eg: Ca+2 and Mg+2 in its food.
 Higher the amount, lower will be the crossing over frequency.
 Gene mapping /Chromosome mapping

The use of genetic crosses to determine the relative locations of genes on

chromosomes is known as genetic mapping.
-Before beginning to construct a genetic map of genes on a chromosome,
one must show that the genes under consideration are linked.
-Therefore, the way to test for linkage is to analyze the results of crosses
and see whether the data deviate significantly from those expected in
independently assorting genes (Mendelian ratios).
-percentage of recombinants could be used as a quantitative measure of
the genetic distance between two linked genes.
distance is measured in map units (mu) or centimorgan (cM).
-By carrying out two-point testcrosses, we can determine the relative
number of parental and recombinant classes in the progeny.
-Two-point test cross should yield a pair of parental types that occurs with
about equal frequencies, and a pair of recombinants that also occurs with
about equal frequencies.
-To get the percentage of recombinant types, the following formula is used
Percetage Recombinants = Number of recombinants X 100
Total number of progeny

The value for percentage recombinant is directly converted

into map units. For example, 10.2% recombinants indicate
that the two genes are 10.2 mu (cM) apart.
NB. Map units cannot be greater than 50, because for any
test cross the percentage of recombinants cannot exceed
50%.
 Recombination;
 It is a separation of linked gene for the formation of new gene
combination as a result of crossing over.
 It is used to calculate the percentage recombinant progeny
produced in a cross
Recombinant frequency =
(№ of recombinant progeny/ total № of progeny) 100
I. Types of recombination are;
1. Inter chromosomal recombination; recombination occurs in
different chromosome of genes.
2. Intra chromosomal recombination; recombination occurs in
same chromosome of genes.
Progeny that show parental combination of alleles are
referred as parentals, and those that show non-parental
combination of alleles are referred as recombinants or
non-parentals or cross over products.
 Map-distance;
• It is the distance b/n two linked genes on the chromosome, which is
the average cross-over between them
• The map unit is called centi-morgan (cM) named by Morgan, who
first constructed the linkage map in Drosophila and measured in
map unit (mu). 1mu= 1cM
Coincidence;
 It is refers to the occurrence of two or more crossing over at the
same time in the same region of a pair of homologous chromosome.
Coefficient of coincidence(c)= observed / expected frequency of
double crossover
 Interference;
 It is the occurrence of crossing over in one region of a
chromosome interferes with its occurrence in the neighboring
segment.
 The term interference was coined by Muller. It defined as the
tendency of one crossing over to prevent another crossing over
from occurring in its vicinity.
 It ranges from 0 to 1.
 When interference close to 1 and was strong, which implies that
the cross over occurred with interfering of each other.
Interference= 1-c
To get the percentage of recombinant types, the following formula is
used
Based on the coefficient of coincidence interference can
be described to range from absolute (no double
crossovers) to partial (doubles less frequent than
expected), none (doubles equal to expected frequency) or
negative (doubles more frequent than expected).

Coefficient of coincidence = Observed DCO frequency

Expected DCO frequency

Interference = 1 - Coefficient of coincidence

Interference and Coincidence
-Once a crossing over event has occurred in one part of the meiotic
tetrad, the probability of another crossing over event occurring nearby is
reduced. This phenomenon is called chiasma interference.
-The usual way to express the extent of interference is as a coefficient
of coincidence; The coefficient of coincidence is equal to the ratio of the
observed percentage of double crossovers to the expected percentage
of double crossovers. The extent of interference is different between
different pairs of genes. The value of coincidence falls and the value of
interference rises when the distance between genes decreases. Based
on the coefficient of coincidence interference can be described to range
from absolute (no double crossovers) to partial (doubles less frequent
than expected), none (doubles equal to expected frequency) or negative
(doubles more frequent than expected).

Coefficient of coincidence = Observed DCO frequency

Expected DCO frequency

Interference = 1 - Coefficient of coincidence

Example: Assume there is partial linkage between the two genes and the
following data were obtained from the test cross AB/ab x ab/ab:
AB/ab = 35…parental
Ab/ab = 15…recombinant
aB/ab = 15…recombinant
ab/ab = 35….parental
Total = 100
-What is the distance between the two genes?
-To find the distance b/n the genes, we should first calculate percentage of
recombinants;
Percentage recombinant = 15+15 x 100
100
= 30%
Thus, the distance b/n the two genes (A & B or a & b) is 30 mu (cM).
A_______30mu_______B
-Note that when the distance b/n two genes is large, the chances of
occurrence of multiple crossover b/n them increases. As a result, it becomes
difficult to obtain an accurate measure of map distance.
a) Distance b/n Y & D: all crossovers (single and double) occurred in the region must
be added to calculate percentage recombinants.
-Percentage recombinants = SCO recombinants + DCO recombinants x 100
Total progeny
= (52+46) + (4+2) x 100
500
= 20.8% Therefore, the distance b/n Y and D is 20.8 mu.
b) Distance b/n D & E: all crossovers (single and double) occurred in the region must
be added to calculate percentage recombinants.
-Percentage recombinants = SCO recombinants + DCO recombinants x 100
Total progeny
= (22+22) + (4+2) x 100
500
= 10.0% Therefore, the distance b/n D and E is 10.0 mu.
c) Distance b/n Y & E: can be found simply by adding the two map distances, i.e., the
distances b/n the middle gene (D) and the two genes (Y and E).
-Therefore, the distance b/n Y and E is 10.0 mu + 20.8 mu = 30.8 mu.
OR, it can also be found using the above formula as follows:
-Percentage recombinants = (52+46) + (4+2) + (22+22) + (4+2) x 100
500
= 30.8% Thus, the distance is 30.8 mu.
30.8mu
Y____________20.8mu_________D _____ 10.0mu_______E
 Unit-9. Sex determination and inheritance of related to
sex (genetic linkage change in chromosome №)
• Sex refers to the contrasting features of male and female
individuals of the same species.
• Sex determination is a process of sex differentiation of a
particular individual will develop into male or female.
• In higher organisms, the № of sexes has been reduced to
two, but some are possess more than two sexes.
• An animal possessing both male and female sex organ
called Hermaphrodite, which is relatively unimportant.
 Various mechanisms of sex determinations are;
A. Chromosomal sex determination
B. Environmental factors
A. Chromosomal basis of sex determination;
 Chromosomes are differing in morphology, size and № in male
and female sex and contain genes responsible for the
determinations of sex are called allosomes.
Allosome chromosomal sex determination types are;
a. Heterogametic male
b. Heterogametic female
c. Male haploidy (haplodiploidy)
 Sex Determination and Inheritances Related to Sex
Chromosomal Sex Determination

Differentiation between sex and autosomal chromosomes

Autosomes: The chromosomes, which have no relation with the sex and
contain genes, which determine the somatic characters of the individual,
are known as autosomal chromosomes.
Sex chromosomes: The chromosomes, which are responsible for the
determination of sex; X and Y-chromosomes. Most of our attention in this
chapter will be focused on specific chromosomal determinants. The sex
chromosomes are highly specialized chromosomes. They are rod-shaped
X-chromosome and hook-shaped Y-chromosome. The sex chromosomes
are an exception to the general rule that homologous chromosomes are
identical in all appearance, and for certain portion of the segments they are
not identical and referred as homologous. The sex chromosomes non-
similar part is called the differential segment, and in the chromosomes (X
or Y) the differential segment appears in single dose and they are
hemizygous for these genes. The differential segment is the cause for the
sex-linked inheritance.
a. Heterogametic male; is that the female sex has two ’xx’ and male
sex has only a single ‘x’ chromosome.
• As the male lakes ‘x’ chromosome during meiosis, produce two
different gametes interims of sex chromosome called
heterogametic sex.
• The female sex during meiosis, produce similar gametes is called
homogametic sex.
1.XX-XY; the female possess two ‘xx’ called homogametic, while
male possessing only one ’x’ and one ‘y’ called heterogametic.
E.g. in hunan being, some plants, insects (Drosophila), reptile …
2.XX-XO the female has two ‘xx’ called homogametic and male has
only one ‘xo’ called heterogametic.
E.g. in cockroaches, grasshoppers, spiders, nematode …..
b. heterogametic female; is when the male possess two
homogametic sex chromosome. While the female possess either a
single ‘z, o’ or ‘z, w’ chromosome called heterogametic.
1.ZZ-ZO; the female possess one ‘z’ chromosome called
heterogametic, while male possess two ‘zz’ are homogametic.
E.g. in moths, better fly …
2.ZZ-ZW; the female possess one ‘z’ and one ‘w’ called
heterogametic, while male possess two ‘zz’ called homogametic.
E.g. in insects and vertebrates (fish, some reptile and birds).
Chromosomal basis of sex determination (mammals, grasshoppers, birds,
etc)
A. Male Heterogametic: -In this type, the female has two X-
chromosomes and the male one X-chromosome. The sex of offspring is
determined by the male gamete. The heterogametic males may be of the
following types:
1. XO-XX type: The female has two XX chromosomes and the maleness
is determined by one chromosome only. Organisms with such type:
cockroaches, grasshoppers, beetles, spiders and nematodes; the
male produces sperms with X or without X chromosome.
2. XX-XY type: In mammals, and certain insects two X-chromosomes without Y-
chromosome determine femaleness and XY chromosomes determine maleness.
So the sex of embryo depends on the kind of sperm. An egg fertilized by X
bearing sperm produces female, but, if fertilized by a Y bearing sperm, a male is
produced. Y-linked genes determine maleness and strong enough to overcome
those on X-chromosomes. Alleles that are recessive in a female are automatically
expressed in a male (because there is no second allele to overshadow the
recessive one). This system of sex determination is seen in human and other
placental mammals.
-The females have a homomorphic pair of chromosomes (XX) while males have
a heteromorphic pair of chromosomes (XY).
-The Y-chromosome is active in determining the sex of an individual.
Individuals carrying the Y-chromosome are genetically male, while individuals
lacking Y-chromosome are genetically female.
-If Y-chromosome is present, the primordial gonads develop into testis otherwise
into ovaries.
-In humans, a gene called SRY (Sex-determining Region Y) has been identified
on the Y-chromosome.
B. Female Heterogametic: -The femaleness can be determined in either of the
following types:
1. ZO-ZZ type: The male has two Z-chromosomes and femaleness is determined
by having one Z-chromosome. The female produce two gametes, one with Z-
chromosome and the other without Z-chromosome and the male produces one
type of gamete with Z-chromosome, hence, the eggs determine femaleness such
organisms as, moths and butterflies.
2. ZW-ZZ type: This type of sex determination occurs in certain insects and
vertebrates such as fishes, reptiles, and birds. Here, the female sex has one Z
and one W-chromosome and produce two type of eggs that carry the Z-
chromosome or W chromosome. The male produces one type of sperm that
carry Z chromosome. The egg determines femaleness; the Z carrying egg
becomes male and W caring become female after being fertilized by the Z
carrying sperm.
c. Male-haploidy (haplo-diploidy); in honey bees, queens usually
mates only once during its life time and the sex ratio of offspring is
under control of queen.
• The fertilized eggs become diploid female are called queen and
unfertilized eggs develop a haploid male called drones.
• During meiosis females are produce all haploid cells, but crossing
over and reduction divisions fails to occur in haploid nature of
male.
• Most of eggs laid in the hive will be fertilized and developed into
worker females.
E.g. honeybee, ants and wasps (Hymenoptera) …
• All eggs become X-bearing through differential maturation, and all
sperms contain only a set of autosomes.
• Two sets of autosomes + X determine femaleness, and one set of
autosomes + X determines maleness.
C. Haplodiploidy Type of Sex Determination (The Honey Bee
Method)
This is common in insects; hymenoptera, such as bees,
wasps and ants which have membranous wings. In this type,
the fertilized egg becomes diploid female and the unfertilized
develop into haploid male, and sex is determined by ploidy
level of the genome; monoploidy maleness and diploidy
femaleness. The development of male from unfertilized
female egg is called parthenogenesis. The male develops
parthenogenetically and produces gametes without reduction
of chromosomes (meiosis without reduction).
D. X-chromosome to autosomal chromosome balance
system
-This system of sex determination is seen in Drosophila and
nematode.
-Sex of Drosophila is determined by the ratio of the number
of X-chromosomes to the number of autosomal sets.
B. Environmental sex determination;
• Sex is determined by fully or partially through environmental
factor in a № of organisms.
E.g. in reptile.
• In turtle species, female are produced at high temperature (30-
35oc), while males are produce at low temperature (20-30 oc) and
in alligator is the reverse to the turtles.
 Environmental influence on sex-determination (e.g. reptiles)
-Environment plays a major role in sex determination of many organisms.
Examples:
-Temperature is one of the environmental factors that play a role in sex
determination.
e.g. In certain turtles, eggs incubated above 32 0C produce females, while eggs
incubated below 28 0C produce males, but eggs incubated in between these
temperatures produce mixture of male and female.
-In the marine worm Bonellia, if the free-swimming larval form settles alone, it
develops into female, but if the larva attaches to the body of the adult female, it
develops into a male worm.
Inheritances related to sex (sex-linked, sex-limited, and sex-influenced)
A) Sex-linked inheritance in humans
-Traits due to genes located on the sex chromosomes are referred as sex-linked traits.
Inheritances of related to sex are;
a. Sex-linked inheritance;
 Sex linked genes are genes found in the deferential region of ‘sex’
chromosome.
 In human beings, colorblindness and hemophilia (bleeder’s
disease) are related to sex-linked genes.
 Colorblind is a recessive sex linked disease and genes present in
the homologous parts of ‘xx’ chromosome and hemophilia is
also recessive sex linked disease and genes present in non-
homologous region of ‘y’ chromosome and pass directly from
parent to child's.
 The allele for colorblindness (c) is found on ‘x’ chromosome of
females chromosome (XcXc), while in male the ‘x’ chromosome
carries a wild type (+), but the ‘y’ chromosome lacks both the ‘+’
or ‘c’.
E.g. a marriage between color blind female and normal man gives
rise to all normal daughter and colorblind sons.
X-linked recessive inheritance:
-A trait due to a recessive mutant allele carried on the X-chromosome is called X-
linked recessive trait.
-In X-linked recessive traits, the female usually must be homozygous for the
recessive allele in order to express the mutant trait.
-The trait is expressed in the male who possesses one copy of the mutant allele on
the X-chromosome.
-Generally, the characteristic of the traits are summarized as follows:
Most affected individuals are males.
Affected males have carrier or affected mothers,
Affected females come from affected fathers and carrier/affected mothers
Affected female's sons must be affected
Approximately half the sons of carrier females should be affected
No male-to-male transmission in the pedigree
-Color blindness is another example of this inheritance.

X-linked dominant inheritance:
-A trait due to a dominant mutant allele carried on the X-
chromosome is called X-linked dominant trait.
-The X-linked dominant traits follow the same sort of inheritance
rules as X-linked recessive traits, except that heterozygous
females express the trait.
-Generally, X-linked dominant inheritance is summarized as
follows:
The trait does not skip generation.
Affects either sex, but more females than males.
Affected males must come from affected mothers.
All the daughters, but none of the sons of an affected father are
affected.
Approximately half of an affected female's sons and daughters are
affected (assuming unaffected father and heterozygous mother).
-Vitamin-D resistance rickets that results in low-level blood
phosphorus and faulty enamel traits are examples of X-linked
dominant inheritance.
Y-linked inheritance:
-A trait due to a mutant gene carried on the Y chromosome but with no counterpart on the X
is called Y-linked (holandric inheritance = ‘’wholly male’’) trait.
-No females ever show Y-linked traits.
-Generally, Y-linked inheritance shows the following features:
Affects only males
Affected males always have an affected father, i.e., the trait is always passed from father to
son.
All sons of an affected male are affected
-Hairy ear rims is an example.
X-linked genes: - are represented twice in the female and once in male because male has
one X-chromosome. The recessive genes on X-chromosomes to be expressed phenotypically
in the female both alleles should be recessive but in the male since there is only one allele
(X-chromosome) it is expressed whether it is dominant or recessive.

2) Z-Linked inheritance in chicken: - Z-linked genes determine the color of feathers in

chicken. In Plymouth Rock chicken, the gene for barred feathers is dominant (Z B) and the
gene for black or red unbarred feathers is recessive (Z b). The male is homogametic (ZZ) and
female is heterogametic (ZW), hence; male are carriers of sex-linked characters.
Sex-influenced inheritance;
 Sex influenced genes are the autosomal genes present in
both male and female, whose phenotypic expression is
different in different sexes and they act as dominant in one
sex and recessive in another.
E.g. baldness in humans
 Baldness is autosomal dominant traits or genetically inherited
conditions, where the allele for baldness ‘B’ is dominant in
male and recessive in female and is non-bald.
E.g. a marriage between baldness men with non-bald women
Phenotype: baldness men x non-bald female
Genotype: (BB or Bb) x (Bb or bb)
Sex-Influenced Genes
traits appear in both sexes but more one sex than another.
-Pattern of baldness in male humans is an example.
The male hormone testosterone is needed for full expression of
baldness.
Due to this hormone d/ce, the allele for baldness acts as dominant in
males, but as recessive in females.
In case of the women, it is usually expressed as a thinning of hair rather
than balding.
c. Sex-limited inheritance
 Sex limited genes are autosomal genes, whose phenotypic
expression is limited to one sex only, and their phenotypic
expression is influenced by the sex hormones.
 Sex limited genes are mainly responsible for secondary sexual
characters in human being and cattle.
E.g. milk production in female, beard (facial hair) development in
male …
UNIT 10: CYTOPLASMIC INHERITANCE AND
MATERNAL EFFECT (Assignment)
UNIT 11: THE GENETIC MATERIAL
11.1. Nucleic acid are large polymers composed of monomer units
called nucleotides.
A. DNA (deoxy ribose nucleic acids)
B. RNA (ribose nucleic acids)
A. DNA structure composition and replication mechanism ;
 It is genetic materials that encode all the information to make a bacteria or
a human being.
 It is found in the chromosome of the nucleus.
 It is double stranded (helix) consists of two long chains of sub units
(nucleotides) twisted together (Watson and Crick).
 Each nucleotide consists of pentose sugar, nitrogenous base and
phosphate group, but a combination of nitrogenous base and sugar without
phosphate group is called nucleosides.
 DNA contains four bases that A, G, C, T.
 The phosphate group is attached to the 5’ carbon in sugar and nitrogenous
base is attached to the 1’ carbon in sugar.
 Associated of each sugar with nitrogenous base of one or two carbon-
nitrogen rings;
 Bases containing one carbon-nitrogen ring called pyrimidine.
 The common pyrimidine present in DNA are T and C, while in RNA are U
and C.
 Bases containing two carbon-nitrogen rings called purine.
 The common purine in both RNA and DNA nucleic acids are A and G.
 № of pyrimidine base (T +C) = № of purine base (A+G) or ratio of pyrimidine to
purine is constant and close to one (T+C/A+G =1), because A is complement to T
(A=T) and C is complement with G (C= G).
 The two twisted strand of DNA molecules are oriented anti-parallel to each other
(the 5’ end of one strand is located with the 3’ end of the other strand at the same end
of a DNA molecules).
 The one strand extends to meet the other strand through base pairs are called
complementary base pairs.
 ‘A’ present in one strand of DNA linked by two hydrogen bond with ‘T’ present in
opposite strands.
 ‘C’ present in one strand of DNA linked by three hydrogen bond with ’G’ present in
opposite strands
In the DNA molecule, each of the bases adenine, thymine, guanine, & cytosine is
covalently bonded to the sugar.
The 5’ → 3' phosphodiester bridges link the sugars together.
It goes from the 5' carbon of one sugar to the 3' carbon of the next sugar. The double
helix is formed because of hydrogen bonds between the nitrogenous bases. Adenine &
thymine are held together by 2 relatively weak hydrogen bonds Guanine and cytosine
are held together by 3 relatively weak hydrogen bonds. If duplex DNA is heated to near
100 OC, the hydrogen bonds will break apart & the two strands will pull apart. This
process is called Denaturation.
5'-3' phosphodiester bridges link nucleotides together to form polynucleotide chains.
The "central dogma" of molecular biology describes the transcription of
genetic information from a DNA nucleotide triplet code to an RNA triplet
code, followed by translation to specific amino acid sequences in protein.
DNA-templated RNA synthesis is achieved by a process that is
superficially quite similar to leading strand synthesis in DNA replication.
1. Messenger RNA (mRNA):
Comprised only 5% of total cellular RNA.
Function:_Carry genetic information from DNA in the nucleus to
ribosomes (in cystol) where it is used as template for protein biosynthesis.
A copy of the gene that is being expressed. Groups of three bases in
mRNA, called “codons” code for each individual amino acid in the protein
made by that gene.
In eukaryotes, the initial RNA copy of the gene is referred as the “primary
transcript”, which is modified to form matured mRNA.
2. Ribosomal RNA (rRNA): 80 % of total RNA in the cells are rRNA.
rRNA are found in combination with several proteins ( about 82 proteins)
as component of the ribosome which is the site of protein
3. Transfer RNA (tRNA): tRNA represents 15% of total RNA in the cell.
Structure:
1- amino acid attachment site or amino acid acceptor: which terminates with the triplet
CCA.
2- Anticodon loop or anticodon triplet.
3- D loop & T loop: contain unusual bases e.g. dihydrouracil,ribothymidine or methyl
guanine
Functions of tRNA:
Transport amino acids to ribosome for protein synthesis. Each tRNA carry only one
amino acid. The specific amino acid is attached enzymatically to 3' end of tRNA.
Recognize the specified codon on mRNA to ensure the insertion of the correct amino
acid in the growing polypeptide chain. This function is due to anticodon triplet which
binds to codon on mRNA by base pairing.
NB: Three nucleotide bases on mRNA form a codon which is then translated into specific
amino acid. DNA polymerases always add new nucleotides to the 3' end of a growing
DNA strand. Thus, synthesis always proceeds in the 5' to 3' direction. All of these
polymerases can remove nucleotides from the 3' end, and are considered to have
exonuclease activity.
DNA polymerase I: - primarily used for filling small segments during replication and
repair.
DNA polymerase II: - alternative repair enzyme.
As the DNA helix is uncoiled, there are two strands, one is called
the leading strand and the other is the lagging strand. On the
leading strand, DNA synthesis proceeds non-stop in the 5' to 3'
direction as DNA polymerase III reads the original strand of DNA,
which is oriented in the 3' to 5' direction. On the lagging strand,
DNA synthesis is discontinuous because the orientation of the
original strand of DNA is in the 5' to 3' direction and synthesis
cannot go in the 3' to 5' direction, thus DNA synthesis proceeds in
blocks called Okasaki fragments.
The replication begins, when Helicase unwinds and opens the
DNA at the replication fork. Single-strand binding proteins serve
to keep the two strands of DNA apart until DNA synthesis can
begin.
 Flow of Genetic Information: DNA→RNA→Protein.
 The composition of the DNA is the same in all cells within an organism
Variation among different cells is achieved by reading the DNA differently.
 In some viruses the genetic material is RNA.
 Bases carry the genetic information while the phosphate backbone is
structural.
 Genetic information is transferred from parent to progeny organisms by a
faithful replication of the parental molecules.
 Usually the information resides in one or more double-stranded DNA
molecules.
 There are three models of replication: Semi-conservative, Conservative and
Dispersive.
 To elongate the other strand, polymerase must work in the direction away
from the replication fork. This is the lagging strand or Okazaki fragment.
DNA ligase: joins Okazaki fragments to make a single DNA strand.
polynucleotides will contain a 5' phosphate and 3' hydroxyl terminal
groups. The common representation of polynucleotides is as an arrow
with the 5' end at the left and the 3' end at the right.
B. RNA structure, transcription process;
 RNA, like DNA, is a polymer consisting of nucleotides joined
together by phosphodiester bonds.
 RNA nucleotides have ribose sugars.
 T, one of the two pyrimidines found in DNA, is replaced by uracil in
RNA.
 RNA is usually single stranded, consisting of a single polynucleotide
strand.
 It is a genetic material in most plants and viruses and also needed for
protein synthesis.
 It is mostly found in ribosome in the cytoplasm.
RNA has three main types;
A. Messenger (mRNA); is a single stranded base and a complementary
cope of one of DNA strands of a gene.
 It provides for the formation of amino acid sequence.
B. Ribosomal (rRNA); is used to bind mRNA with tRNA in ribosome.
C. Transfer (tRNA); is also called soluble (sRNA).
 It is used to carry № of amino acids and attach them to mRNA
template for protein synthesis.
 tRNA has specific anti-codon base pairs with the appropriate mRNA
codon.
E.g. 5’ATGCTATAA3’ in single stranded DNA
3’TACGATATT5’ complementary base pair of DNA
5’AUGCUAUAA3’ in mRNA.
AUG is start and UAA is stop codon, and Amino acids (CUA, leusine)
RNA processes:
A. Transcription: is the synthesis of RNA using DNA as a template, the
process by which RNA molecules are initiated, elongated and terminated.
 Two aspects of transcription must be considered.
 Enzymology is the enzymatic synthesis of RNA using RNA polymerase).
 The signals determine where a DNA molecule transcription begins and
stops.
B. Translation (protein biosynthesis); is the process by which the nucleotide
sequence in mRNA specifies the amino acid sequence of a protein.
 Translation takes place on ribosomes; indeed, ribosomes can be thought of
as moving protein-synthesizing machines.
 Protein synthesis can be conveniently divided into four stages:
The binding of amino acids to the tRNAs;
1. Initiation, in which the components necessary for translation are
assembled at the ribosome;
2. Elongation, in which amino acids are joined, one at a time, to the growing
polypeptide chain; and
3. Termination, in which protein synthesis halts at the termination codon
and the translation components released from the ribosome.
Post-transcriptional Changes
Molecular organization of eukaryotic genes: We have already seen that a typical
eukaryotic gene has an upstream promoter sequence, as well as various enhancer
and silencer sequences associated with it. The region that is transcribed is also
quite complex, consisting of far more than a simple protein coding sequence. The
messenger RNA that is derived from the transcript always begins with a 5'-
untranslated sequence, which, among other things, provides sequences needed for
ribosomal attachment in preparation for translation. This is followed by the actual
coding sequence and a relative long 3'-untranslated region, which may contain
specific signal sequences related to such things as message stability. The initial
transcript and the DNA that it is transcribed from also contain numerous intervening
sequences that interrupt not only the coding sequence, but also the 5'- and 3'-
untranslated sequences. These are called introns. The segments of mRNA
sequence located between the introns are called exons. The term hnRNA
(heterogeneous nuclear RNA) is sometimes used to describe the original products
of transcription of eukaryotic genes before they have been processed into
messenger RNA.
Processing of the mRNA precursor: The initial transcript of a typical eukaryotic
gene is not capable of functioning as a messenger RNA. In most cases, both ends
Capping: Addition of a "cap" structure on the 5'-end of the message transcript occurs soon
after transcription has been initiated, when the growing RNA chain is only about 50
nucleotides long. The reaction occurs in two steps. First, a GTP is added to the 5'-end, which
already has a 5'-triphosphate structure left over from the first nucleotide triphosphate (NTP)
that initiated growth of the transcript in a 3'-direction. An unusual linkage is formed in which
the GTP is joined to the first nucleotide of the RNA in a 5'- to 5'- triphosphate bond.. In
addition to protecting the mRNA from degradation, the cap structure is also needed to
initiate ribosomal binding onto the message.
Polyadenylation: Most (but not all) eukaryotic mRNAs have a polyadenylic acid tail of 150
to 250 nucleotides added to their 3'-ends before they are exported to the cytoplasm. This is
done by an enzyme complex that clips off the 3' end of the original transcript slightly
downstream from a specific recognition signal (AAUAAA) and initiates polymerization of
ATP to generate the poly (A) tail. Although polyadenylation is a very important
phenomenon, please be aware that a subset of mRNAs, including those for the histones, do
not have poly (A) tails. Also, please be fully aware that the poly (A) tail is generated by a
simple polymerization process that does not require a template. Removal of introns: Nearly
all of eukaryotic protein-coding genes contain introns that must be removed to generate a
functional messenger RNA that is capable of being translated. There are specific recognition
signals at the beginning and end of each intron that allow an enzyme complex in the nucleus
to recognize the presence of an intron and to remove it, coupling the exons on either side
with sufficient precision so that the codons (nucleotide triplets coding for individual amino
acids) continue to be read correctly.
Translation is a polymerization process in which amino acids are joined together
by means of peptide bonds to form proteins. The amino acid sequence of each
protein is determined by the sequence of ribonucleotides in messenger RNA
(mRNA) that in most cases has previously been transcribed from DNA. The
amino acid sequence is specified by a nucleotide triplet code in the mRNA.
The mRNA code is read by anticodons on transfer RNA (tRNA) molecules.
Specific types of tRNA molecules are charged with specific amino acids by
animoacyl tRNA synthetase molecules, which are the only "bilingual" component
of the translation process. If a tRNA is charged with the wrong amino acid, that
amino acid will be inserted into the protein in place of the amino acid that should
have been on the tRNA. The joining of tRNAs to their respective amino acids is
an energy-requiring process driven by hydrolysis of ATP, with an aminoacyl-AMP
intermediate.
Translation occurs on ribosomes, which are assembled from subunits each time a
new translation event is initiated. Hydrolysis of GTP is required for the binding of
each charged aminoacyl-tRNA to the ribosome, and hydrolysis of a second GTP is
required for a translocation process that prepares the ribosome to accept the next
aminoacyl-tRNA. Termination of peptide chain growth occurs at specific stop
codons in the message and also requires hydrolysis of GTP.
Genetic code;
 There are 20 natural occurring amino acids involved in protein synthesis by
only four bases in the DNA.
 The sequence of bases in mRNA specifying an amino acid is called codon,
while the set of base in tRNA is a complementary base pair with codon of
mRNA called anti-codon.
 Sequence of base in codon is exactly the opposite in the anti-codon.
 Codon and anti-codon segment runs anti-parallel to each other, when the
base pair of codon is written in 5’→3’ direction, while anti-codon usually in
3’→5’ direction.
 The set of all codon specify 20 amino acids are called genetic code, which
is a triple (sequence of three nucleotides in mRNA code) for amino acid
synthesis.
 № of total codons are 64 (43), 61 code for 20 amino acids, while 3 code are
stop and non- sense codons.
 3 codons UAA, UAG& UGA do not code for any amino acid and called
non-sense/stop/termination codon.
 1 codon, AUG is called methionine or start/ initiation codons, & it starts the
synthesis of polypeptide chain.
Characteristics of genetic code are;
 Triplet; sequence of three nucleotides. E.g. AUGUGA
 Universal; applicable to all forms of organisms.
 Comma less; written without comma or break, which is continuous.
E.g. AUGGGGUCG
 Non-overlapping; three base codes for only one amino acid. E.g.
AUG= met, CUU= leu ….
 Degenerate; several codons for the same amino acids. E.g. CUU,
CUG, CUA, CUC, UUA, UUG= leu
Inborn error of metabolism
A group of natural disorder caused by an inherited detect in a single
specific protein that result in abnormality.
A. Phenylketonuria (PKN) is an inherited disorder cause of an
amino acid (phenylalanine) to build up in your body by mutation.
B. Alkaptonuria is an inherited disorder and people with
alkaptonuria cannot metabolize phenylalanine (UUU & UUC)
and tyrosine (UAU & UAC), which are used to produce hormone,
pigments and neurotransmitter.
C. Albinism is an inborn disorder, characterized by complete/partial
absence of melanin pigment in skin, hair and eye due to the absence
of tyrosine (UAU & UAC).
 Unit12. Gene and chromosomal mutation
12.1. Mutation;
 It is a sudden heritable change in the character of an organism due to segregation
or recombination can be passed on the next generation
 It is a permanent change in the DNA sequence of genes.
E.g. heart disease, diabetes, stroke (HBP) …
 It also acquired on some environmental agents, such as radiation using nuclear
disasters.
E.g. Hiroshima and Nagasaki
 An organism that inhibits anoxic phenotype resulting from mutation is called
mutant.
 Types of mutations are;
I. Based on direction
1. Forward mutation; any change from wild type to mutant allele.
2. Back ward/reverse mutation; any change from mutant allele to wild type allele.
II. Based on source/ cause
1. Spontaneous mutation; mutation occurs naturally, due to errors of DNA
replication.
2. Induced mutation; mutation occurs in response to mutagenic treatments.
III. Based on origin
1. Somatic mutation; mutation occurs in somatic cells.
2. Germinal mutation; mutation occurs in reproductive/sex cells.
IV. Based on trait/character effect
1. Morphological mutation; mutations that alter the morphological features
of an organism.
2. Biological mutation; mutations that alter bio-chemical functions of an
organism.
V. Based on site of mutation
1. Gene/point mutation; mutation occurs by alternations in base sequence
of genes.
• It can be classified as;
a. Substitution; is an exchange b/n two base in genes that alter the amino
acids.
E.g. normal RBCs sickle cell anemia
GAG GTG
CTC CAC
GAG (glu) GUG (val)
 Substitution can be classified as;
1. Silent mutation; substitution may not affect the protein structure. E.g.
arg(GGU) →U replace by G→GGG (arg)
2. Non-sense mutation; substitution changes amino-acid coding code to stop
codon. E.g. UAU (try)→ U replaced by A →UAA (stop codon)
3. Mis-sense mutation; substitution changes amino-acid sequence that
results non-functional proteins.
b. Insertion; is an extra base pairs are inserted/ added into a new replace in
DNA.
E.g. AUGGCA (met, ala)→if G inserted b/n G &C→AUGGGCA (Met, Gly)
c. Deletions; is a section of DNA is lost/ loss or some base pair of the genes
are deleted.
E.g. GCAGAG (ala, glu)→if G b/n A &A is deleted →GCAAG (ala, AG)
• The insertion and deletion of some base pairs can be completely change a
coding code of protein synthesis and is called frame shift mutation.
2. Chromosomal mutation; mutations associated with the change in
chromosome № or structure.
 Types of chromosomal mutations are;
a. Structural mutation; is variation in chromosome structure.
• Mutation due to change of gene, but not change in chromosome №.
• It can be classified as;
i. Deletion/deficiency/ of gene; is loss of parts of chromosome/ segment.
E.g. cri-du-chat syndrome (deletion on short arm of 5)
Prader-willi syndrome (deletion on long arm of 15)
ii. Duplication/ repeats/; is doubling of a chromosome segment.
E.g. evolution of multi-gene mutation
iii. Inversion; a segment of chromosome is oriented in reverse direction.
• It has two types based on whether the centromere involved or not in the
inversion;
A. Para-centric inversion; the inverted segment does not include the
centromere
B. Peri-centric inversion; the inverted segment include the centromere
IV. Translocation; is an exchange segments of chromosome with non-
homologous pairs.
b. Numerical mutation; is variation in chromosome №.
• Ploidy refers to a № of sets of chromosome that an individuals have
and is variation chromosome №.
• It can be classified as;
1. Haploid; individuals with a single set of chromosome № (n) and can
be;
 Monohaploidy; are individuals that arise from normal diploid
species. E.g. maize 2n=20, n=10
 Polyhaploidy; are individuals that arise from polyploidy species and
denoted by ‘x’.
E.g. bread wheat. 2n=6x=42 and n=3x=21
2. Diploid; individuals with two sets of chromosome (2n). E.g. human
being. 2n=46 and n=23
3. Polyploidy; individuals that possess many sets of chromosome like
triploidy (3n), tetraploidy (4n), pentaploidy (5n) …
• Euploidy; an organism that gain or lose the whole (complete) sets
of chromosome.
• Aneuploidy; an organism loss or gain of few sets of chromosome,
but not the whole.
1. Monosomy (2n-1). E.g. Turner syndrome (monosomy, 45x or
44+x )
• Is trisomy x syndrome in female
2.Nullisomy (2n-2).
3. Trisomy (2n+1).
 Down syndrome (trisomy21,47 or 45+xx/xy )
 Edward syndrome (trisomy18 or 45+xx/xy)
 patan syndrome or D trisomy (trisomy13,47 or 45+xx/xy )
 klinefter syndrome (trisomy,47xxy or 44+xxy)
4.Tetrasomy (2n+2).
THE END!!!