S6 BIOLOGY(GENETICS- GENE INTERACTIONS AND MUTATION 18.JAN.

2024

GENE INTERACTIONS.
This is where a single characteristic or trait is controlled by the alleles of two or more different
genes interacting with one another. A characteristic which is controlled by more than one gene is
known as polygenic character and its transmission is called polygenic inheritance. These include,
• Gene complex/simple gene interactions/ complementary genes.
• Epistasis.
• Pleiotropy

There are other many situations when genes or alleles interact to control phenotypic
characteristics of organisms they include,
• Incomplete dominance.
• Codominance.
• Multiple alleles.
• Lethal genes.

GENE COMPLEX/ COMPLEMENTARY GENES.

This is a condition where a single characteristic is controlled by the interaction of two or more
genes occupying different gene loci on different chromosomes. It is also referred to as simple
gene interaction. Example of gene complex is the inheritance of shapes of the comb in poultry
(Domestic fowl).
There are two genes located at different gene loci on different chromosomes. One gene has a
dominant allele P and a recessive allele p. whereas the other gene has a dominant allele R and
a recessive allele r. The two genes interact and give rise to four distinct phenotypes (comb shapes
in poultry) and these,
- Pea comb.
- Rose comb.
- Walnut.
- A single.
• Pea comb is determined when atleast its one dominant allele P is present, in absence
of the dominant allele R, other alleles being recessive in the genotype. Possible
genotypes for pea comb, PPrr or Pprr.

• Rose comb arises when atleast its dominant allele R is present, in absence of the other
dominant allele P, other alleles being recessive in the genotype. Possible genotypes for
the Rose comb, ppRR, or ppRr.

• Walnut comb is determined if atleast both dominant alleles P and R are present in the
genotype. Possible genotype for the walnut comb, PPRR, PpRR, PPRr or PpRr.

• A single comb is determined only when both alleles exist in their homozygous
recessive state. A possible genotype for the single comb type is, pprr.

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Let,

R and r represent alleles for rose type comb.

P and p represent the alleles for pea type comb.

SELFING FI OFFSPRINGS.

Random fertilization of the F1 gametes as shown by the punnet square below.

Male gametes

RP Rp rP rp

RP RRPP RRPp RrPP RrPp

Female Gametes walnut walnut walnut walnut

Rp RRPp RRpp RrPp Rrpp

walnut Rose comb walnut Rose

rP RrPP RRPp rrPP rrPp

walnut Walnut pea comb pea comb

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 rp RrPp Rrpp rrPp rrpp

walnut Rose comb pea comb Single

The F2 phenotypes;
9 walnut type combs (R - P)
3 rose type comb (R – pp)
3 pea type comb (rr – P)
1 single (rrpp)

EPISTASIS
This is a condition where a character or trait is controlled by two genes where the presence of
one gene suppresses the effect of another gene at another gene locus. The term “epi” means
over, while “hypo” means under.

Epistatic genes are the ones suppressing the effects of others and also called inhibiting genes.
While the gene, whose effects are suppressed is called hypostatic genes. In addition, epistatic
and hypostatic genes occur at different gene loci on homologous chromosomes. Epistatsis may
create entirely new features. It can also result into variety of phenotypic ratios depending on the
genotype of the mating pairs.

EXPLANATION OF EPISTASIS.
Epistasis arises when different genes control production of different enzymes that catalyse series
of bio-chemical reactions that determine expression of a single character in an individual.
Production of each enzyme depends on specific gene. For example, consider the gene pathway
shown below for the synthesis of sweet pea plant pigment.

Production of enzyme-1, enzyme-2 and enzyme-3 are controlled by specific gene-1, gene-2 and
gene-3 respectively. Compounds L and M are white intermediate compounds. Compound N is a
coloured end product pigment.

Gene-1 initiates production of enzyme-1 which catalyses conversion of precursor molecule to the
intermediate compound L while gene-2 stimulates production of enzyme-2 which catalyses
production of enzyme-2 which catalyses conversion of L to another intermediate compound M.

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Then finally enzyme-3 catalyses convertion of M to to final coloured pigment N. Production of
enzyme-3 is controlled by gene-3.

If gene-2 mutates or fail to stimulate production of enzyme-2, compound M would not be formed
and final coloured pigment N will not be formed. Intermediate compound L will accumulate and
gene-3 will have no effect on the phenotype. In this case gene-2 is epistatic while gene-3 is the
hypostatic.

Epistasis may arise in different ways, and these include,

►A particular gene may have no effect on a phenotype on their own but do so in combination
with another different gene. This is supplementary gene interactions. For example in the
inheritance of fur colour in mice.

• In the Inheritance of fur colour in mice. There are three possible phenotypes, Agouti (grey), Black
fur and Albino (white fur). They are controlled by a pair of genes occupying different loci. The
Epistatic gene determines the presence of colour and has two alleles, the dominant allele
determines coloured (C) and its recessive allele c, that controls white colour (albino). The
hypostatic gene that controls the nature of the colour, has a dominant allele (A) that controls grey
colour or agouti and the recessive allele that controls black colour.

The dominant allele (A) for grey (Agouti) colour or recessive allele (a) for black color only express
them selves when they are accompanied by the dominant allele (C) that controls coloured fur in
the genotype.

Albino conditions appear in mice when the alleles controlling coloured fur are homozygous
recessive even when the alleles controlling agouti and black fur are present in the genotype.

Phenotypes.Possible Genotypes.

(i) Agouti (grey) AaCc, AACc or AaCC.

(ii) Black aaCc or aaCC.
(ii) Albino AAcc, Aacc or aacc.

Using the above ways in which the above alleles of the two genes interact,

(a) Determine the phenotype ratios of the following crosses

(i) AaCc X AaCc. (ii) AaCc X Aacc.
Assuming no linkage.

• Another example of such epistasis is provided by colour differences in onion bulb, fur colour in
mice. Skin pigmentation in humans (albinism) and comb shape in poultry.

In onion bulbs, the red colour is obtained if atleast both dominant allele C and R are present in
the genotype. The colour is yellow if dominant allele C is only present without the dominant allele
R in the genotype and white colour obtained if recessive allele c is present in homozygous

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recessive condition without its dominant allele C, either allele R or r being present in the genotype.
This indicates that the dominant allele C and recessive allele c are epistatic.

PHENOTYPES AND SOME POSSIBLE GENOTYPES OF THE ONION BULB

Phenotypes: Possible genotypes:

Red CCRR , CCRr , CCRR or CcRr
Yellow. CCrr or Ccrr
White ccRR, ccRr, ccrr.

► Presence of one gene affects another gene at another gene locus in such away that when
atleast dominant alleles of each gene is present in the genotype, they interact and produce a
single identical and specific phenotype and in absence of dominant allele of alteast one gene, its
alleles being homozygous recessive, the phenotype is inhibited. This is complementary gene
epistasis.

For example, flower colour in sweet pea plant is determined by two genes with their dominant and
recessive alleles (R, r and W, w). If atleast one dominant allele of one gene is present in the
genotype, it determines purple colour of the flower while homozygous recessive state of alleles
of any one gene determines white colour in flowers.

Consider two plants producing purple flowers, each having the genotype RrWw are crossed. What
will be phenotype ratio of the resulting offsprings. Assuming that each allele is located on its own
chromosome.

Parent,s phenotype : Heterozygous Purple X Heterozygous purple flower

flower producing plant producing plant.
,
Parent, Genotype : RrWw RrWw.

Meiosis.

Gametes : all RW , Rw , rW , rw

Random fusion of gametes shown by the punett square.

Female
Gametes. Male gametes
RW Rw rW rw
RRWW RRWw RrWW RrWw
RW
Purple Purple Purple Purple.

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 Rw RRWw RRww RrWw Rrww

Purple White Purple White.

rW RrWW RrWw rrWW rrWw

Purple Purple. White. White.

rw RrWw Rrww rrWw Rrww

Purple. White. White. White.

Phenotype ratio of the offsprings;

Purple flowers producing plants = 9.
White flowers producing Plants. = 7
9 purple : 7 white flowers = 9 : 7.

►In dominant gene epistasis, the presence of atleast two dominant genes at different gene loci,
will inhibit production of the phenotype while in a homozygous recessive state of one of the genes,
a specific phenotype is produced. The dominant gene is epistatic while the recessive one is
hypostatic.
For example, In white leghorn fowl, plumage colour is controlled by two sets of genes including
the following, W (white) dominant over w (coloured) B (black) dominant over b (brown). The
Heterozygous F1 genotype WwBb is white while wwBB, wwBb are black and wwbb is brown.

PLEIOTROPY.
This is the condition in which a single gene controls two or more unrelated characteristics. It arises
when the gene codes for an enzyme which affects more than one phenotype. In pleiotropy a
single gene affects several phenotypic traits. If it affects a vital function of the body it may become
lethal.
Examples of pleiotropy include,
- A mutation in certain gene for chloride ion secretion in epithelial cells gives rise to
phenotype known as cystic fibrosis. The patients have problems with breathing and
digestion.
- Sickle cell anaemia.
- Coat colour in mice.

ADVANTGES OF STUYDYING GENETICS

(i) Enable humans to choose partners with good characteristics for reproduction.
(ii) Used in legal profession to determine the paternity of a child.
(iii)enables elimination of harmful and fatal characteristics diseases from human population
(iv) Enables farmers to produced crops and breed animals with desired qualities such as
increased crop yields, diseases resistance and drought resistance.
used in techniques of artificial insemination or artificial breeding where the closely related
varieties of organisms are crossed so that their characteristics become combined in one individual

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EXERCISE.

1. Flower colour in sweet pea plant is determined by two allelomorphic pairs of genes (R, r and
W, w). If atleast one dominant gene from each allelomorphic pair is present, it determines purple
colour of the flowers, all other genotypes where atleast one dominant allele is absent determine
white colour in flowers.

(a) Explain each one of the following results,

(i) A cross between white flower producing plants, produced all offsprings with purple flowers.
(ii) A cross between a white flower producing plant and purple flower producing plant, produced
offsprings producing white and purple flowers in the ration of 1 : 1.

(b)If two plants producing purple flowers, each having the genotype RrWw are crossed. State
the phenotype ratio of the resulting offsprings, assuming the genes are linked.

2. In white leghorn fowl, plumage colour is controlled by two sets of genes including the
following,

W (white) dominant over w (coloured)

B (black) dominant over b (brown).

The Heterozygous F1 genotype WwBb is white. Account for this type of gene interaction and show
the phenotypic ratio of the F2 generation when the heterozygous white F1 offsprings are selfed.
Assuming no linkage.

3. The banding pattern of the snail Cepea nemoralis is controlled by two unlinked genes. The
dominant allele B gives unbanded shells while the allele b gives banded shell. The dominant allele
M gives midibanded shells while the allele m gives fine banded shells.

(a)(i) State the type of interaction shown by the genes.

(ii) How does allele B affect the gene M or m.
(b)How does allele B affect the genes M or m.
(c)A snail with an unbanded shell of the genotype BBMM was mated with one having a fine
banded shell. Using genetic symbols show the phenotypic ratio of the F2 generation.

4. (a) List down any four features of epistasis.

(b) In an animal species, individuals that are homozygous for gene A or its allele die. Another
independent gene B in the homozygous state, blocks this lethal effect, otherwise gene B
has no other effect on the organism.
Work out the expected phenotypic ratio of the viable offsprings in a cross of individuals of AaBb
and AaBB genotypes.

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MUTATION.

Mutation is the sudden change in the amount or the structure of the DNA on the chromosome of
an organism.

Mutations produces a change in the genotype of the daughter cells and may result in the change
of the phenotype or in appearance of new characteristics of organism in a population, mutations
which occur in gamete cells are inherited whereas as those occurring in somatic cells can not be
inherited but appear in daughter cells produced by mitosis.

GENERAL EFFECTS OF MUTATION.

- Genetic variation.
- Emergence of new characteristics.
- Retarded growth.
- Mental retardation.
- Body deformities/Abnormal development of body parts and organs.
- Sterility.
- Hybrid vigour.
- Errors in metabolism.
- Diseases.

GENERAL PROPERTIES (CHARACTERISTICS) OF MUTATION.

i. It is spontaneous, occurs on its own

ii. Most mutations are disadvantageous to organism but some are advantagious.
iii. There occurrence is not common but when it occurs, it becomes persistent
iv. They occur gradually.
v. Their occurrence is very sudden
vi. They occur randomly in nature
vii. Environment has less influence over them.

CAUSES OF MUTATION.
Any agent which causes mutation is called a mutagen. Muatagens alter structure of a DNA or its
amount by causing some chromosomal changes. The causes of mutation include,

▪ Most forms of high energy radiations such as ultra–violet light, x–rays and gamma rays.

▪ High energy particles and neutrons are even more dangerous mutagens.

▪ A number of chemicals such as colchicines, formaldehydes, nitrous acid and mustard gas,
cause mutations. Colchicine inhibits spindle formation and so causes polyploidy.

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A natural mutation rate is greatly increased, in species of organisms with shorter life cycle and
therefore has more frequent Meiosis. And the chance of occurrence of mutation is increased
during gamete formation.

TYPES OF MUTATIONS.
Mutations are of two categories.

(i) Chromosome mutation: Is the sudden change in the amount or arrangement of DNA on
the chromosome.

(ii) Gene mutation ( point mutation)

Is a change in the structure of DNA at a single locus on a chromosome.

CHROMOSOME MUTATION
A change in the amount or arrangement of DNA on the chromosome can arise due to
changes in the number or structure of chromosomes. These changes may involve the
following aspects:
• Changes in the whole sets of chromosomes (Polyploidy)
• changes in the number of the chromosomes (Aneuploidy)
• Changes in the chromosome structure.

POLYPLOIDY (EUPLOIDY)
This is a condition where a diploid cell of an organism has an additional whole sets of
chromosomes. The cell contains multiples of the haploid number of chromosomes such cells are
termed as polyploids. Polyploidy can be where three sets of chromosomes are present in a cell
called triploid (3n), with four whole sets of chromosomes present in a cell it is tetraploid (4n), five
whole sets presnt, these are pentaploids (5n), etc.

It results into great increase in composition of DNA molecules in the cell, resulting into
chromosome mutation.

It arises commonly in plants, sometimes fish and Amphibians. It is associated with many
advantageous features, though it often results into sterility in some organisms.

CAUSES OF POLYPLOIDY/HOW POLYPLOIDY ARISES.

● Non-disjunction where all homologous pairs of chromosomes fail to be separated during
anaphase I of meiosis. This occurs due to failure of spindle fibres to form during prophase I of
meiosis. This can be induced by a chemical colchicines. Diploid gametes are formed, usually an
ovum, and when this gamete fuses with another normal haploid one usually the sperm, a tetraploid
(3n) is formed. Self fertilization of diploid gametes form a tetraploid (4n).

● During cell divison by mitosis, chromosome duplication and DNA replication during interphase
results into a tetraploid (4n) cell. These cells remain tetraploid if no nuclear and cytoplasm
divisions subsequently followed. The tetraploid cell then undergoes normal mitotic division to

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produce tetraploid (4n) daughter cells. These tetraploid will have larger size because of increased
size of their nucleus and cytoplasm.

● Doubling of chromosomes of a hybrid zygote after fertilization. Hybrid zygote is formed when
mating take place between two genetically unrelated species. A fertile tetraploid individual may
develope which only reproduces when selfed.

● Polyploidy can also occur when whole set of chromosome double after fertilization.

Tetraploid organisms (4n) have two complete sets of homologous chromosomes and the
organism is fertile. In the other hand, a triploid (3n) does not have two complete sets of
chromosomes and cannot form complete homologous pairing during the gamete formation by
meiosis and such organisms are sterile.

Polyploidy is much more common in plants than in animals. This is because a lot of errors occur
during gamete formation by meiosis. However most plants are capable of propagating themselves
vegetatively (Asexual reproducing). In animals polyploidy is also associated with sterility but in
plants it is associated with hybrid vigour like increased yields, resistance to diseases and drought
where as the polyploid plants can be propagated vegetatively unlike the animals.

So, Polyploidy in plants is often associated with advantageous features such as :

Increased size, hardness and resistance to diseases. This is called hybrid vigor. Most domestic
plants are polyploids, producing large fruits, large storage organs, flowers and leaves, triploid
tomatoes, produce more vitamin C. Polyploidy plants include most angiosperms, wheat, coffee,
banana, sugar cane, apples e.t.c

There are 2 types of polyploidy

• autopolyploidy
• allopolyploidy

Autopolyploidy is the type of polyploidy where by the whole sets of chromosomes added in the
cell arises from sets of chromosomes of organisms of the same species. The number of
chromosomes in an autopolyploidy is always an exact multiple of its haploid number.

Allopolploidy is where the whole sets of chromosomes added in the cell arise from sets of
chromosomes from more than one different species of organisms.

ANEUPLOIDY
Is a condition in which a diploid cell (2n) contain an extra chromosome (2n+1) or one chromosome
missing (2n-1). It is a more common condition that occurs among mammals like humans.
It leads to slight increase or decrease in the composition of DNA molecules in the cell, resulting
into chromosomes mutation.

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CAUSE OF ANEUPLOIDY.
Aneuploidy is caused by non-disjunction where one of the homologous pairs of chromosomes fail
to be separated (segregated) during anaphase I of meiosis. Gametes formed contain either one
extra chromosome (n+1) or one chromosome missing (n-1). And during fertilization, when a
haploid gamete containing one extra chromosome (n +1) fuses with another normal haploid
gametes (n) produces a diploid individual with an extra one chromosome (2n + 1), and when a
haploid gamete with one chromosome missing (n-1) fuses with another normal haploid gametes
(n) during fertilization, produces a diploid individual with one chromosome missing (2n - 1).

A child born with one extra chromosome in one of the homologous pairs results into the diploid
cells containing three similar chromosmes a condition called Trisomy, while diploid cells with one
chromosome missing resulting into only one chromosome present of a certain pair, a condition
called monosomy. In children and adults Trisomy or monosomy results into complications and
these include,

• Down’s syndrome (Mongolism).

• Klinefelter,s syndrome.
• Turner’s syndrome.

DOWN,S SYNDROME (MONGOLISM), TRISOMY 21.

This is the condition where a child is born with the diploid cells containing one extra chromosome
on 21st pair of chromosomes. One extra chromosome in the 21st pair of the homologous
chromosomes is trisomy 21, in humans the individual will possess 47 chromosomes (2n+1).

The cause of this condition is the non-disjunction that occurs at the 21st pair of chromosomes
during gamete formation by meiosis. The Down ’s syndrome in children has certain characteristic
features, which include:
 protruding tongue.
 Flattened face.
 Short neck.
 Small ears.
 Small hands and feet.
 A single line across the palm of the hand.
 Heart defects.
 Coarse, straight hair.
 Tiny white spots on the iris of the eyes.
 Severe mental retardation.
 Congenital hearing abnormalities.
 Low IQ.
 Poor muscle tone.
 A Short life expectancy.
 Intestinal problems and leukaemia are common.

They have risks to certain diseases, such as,

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  Heart defects.
 Leukemia (cancer of the blood).
 Ear and respiratory infections.
 Hypothyroidism.
 Intestinal problems.
 Reduced resistance to infections.

Non – disjunction that occurs in other pairs of chromosomes, normally result in foetus aborting or
the child dying soon after birth.

KLINEFELTER,S SYNDROME (TRISOMY 23)

This is a condition where a child is born with one or more extra sex chromosome. There will be
an extra sex chromosome in the 23rd pair (trisomy 23.

The extra chromosome arises due to non-disjunction on the 23rd pair of chromosomes during
meiosis called sex chromosomes. This can occur during spermatogenesis or oogenesis. Upon
fertilisation, zygotes or individuals with the following genotypes can arise,

• XXX.
-These are females.
- Slightly taller than the ordinary woman.
- Behavioural abnormalities and learning difficulties occur.
- Promiscuity is evident.

• XXY and XXXY.

- These are males.
- Are sterile.
- They show some female secondary sexual characteristics.
- Mentally retarded.
- Little breasts may develop.
- Little facial hair/lack beards.
- Higher than normal secretion of FSH.

• XYY.
- These are males.
- Are fertile males.
- May have a high propensity for violence.
- Relative taller than average.

TURNER’S SYNDROME (MONOSOMY 23)

This is a condition where a child is born with diploid cells having one sex chromosome missing,
the sex chromosmes is X and Y chromosomes. The individuals are 2n-1 such individuals do not
survive birth but when born they are mainly females.

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It occurs due to non-disjunction of the homologous pair of sex chromosomes in the 23rd pair.This
can occur during spermatogenesis or oogenesis. Upon fertilisation, zygotes or individuals with the
following genotypes can arise,

• YO.
- Zygote do not develop because many genes are missing.

• X0.

- are phenotypically females,

- Have wide or web like necks.
- Finger nails and toe nails are narrow and turn upwards.
- sexually immature,
- physically very short,
- Their nipples are closer together.
- Small uterus.
- Sterile.
- The hair line at the back of the head is lower than normal.
- Retarded growth.
- Puffy hands and fingers at birth.
- Arms that turn outwards at elbows.

CHANGES IN CHROMOSOME STRUCTURE

Several mistakes may occur during the crossing over in prophase I of meiosis. This lead to
chromosome mutations, the changes in the chromosome structure occurs by anyone of the
following ways.
- Deletion.
- Inversion.
- Translocation.
- Duplication.

Deletion.
A portion of the chromosome is broken and lost, resulting into shortening of chromosome and
loss of genes. This condition is often lethal.

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Inversion.
A portion of a chromosome becomes deleted, but becomes re-attached on the same chromosome
in an inverted position. The sequence of genes (nucleotide base sequence) is reversed, the
genotypes remain the same but the phenotypes may be altered.

Translocation.
A portion of chromosome becomes deleted and rejoins at a different point on the same
chromosome or with a different chromosome.

Duplication
A portion of chromosome is doubled, resulting in repetition of a gene sequence a different genetic
constitution from the rest results, this is called a genetic mosaic.

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GENE MUTATION.
Is the sudden change in the structure of DNA which occurs at a single locus on a chromosome.
It is also called point mutation. The change in the structure of the DNA involves change in the
nucleotide base sequence of the DNA, this can take place during DNA Replication.

The structure of a DNA molecule can change resulting into gene mutation in one or more of the
following ways,

♦ Duplication.
An extra portion of nucleotide base sequence may be added in the nucleotide chain of the DNA.
A portion of a nucleotide chain of a DNA may become repeated .

♦ Insertion (addition)
A portion of a nucleotide base sequence becomes inserted in the nucleotide chain of the DNA.

♦ Deletion
A portion of a nucleotide base sequence in the DNA nucleotide chain may be broken and lost.

♦ Inversion
A nucleotide base sequence in the DNA becomes separated from the chain. It rejoins in its original
position only inverted. The nucleotide sequence of this portion is then reversed.

♦ Substitution
One nucleotide base in the nucleotide chain of the DNA may be replaced (substituted) by another
nucleotide carrying a different nitrogenous base.

THE EFFECTS / CONSEQUENCES OF GENE MUTATIONS.

When these errors occur, the new DNA is not an exact copy of the original. Such changes in the
structure of the DNA is called gene mutation.

When a gene mutates, the changes in the sequence of the base in the DNA causes a
complementary changes in the sequence in codons of messenger RNA. The altered codon when
translated will cause the following errors,

▪ Synthesis of a polypeptide chain with one or more amino acids missing (Non-sense
translation).

▪ Synthesis of polypeptide chain where in the amino acid sequence, one aminoacid is substituted
or replaced with a nother different one or some amino acids simply added to the polypeptide chain
(Mis-sense Translation).

▪ The polypeptide chains formed with such errors are usually defective and can results into the
following,

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 - Formation of abnormal protein molecules which are defective and can not efficiently
perform their functions.

- Non-production of certain particular essential protein molecules required for normal

physiological functions.

- Production of certain protein molecules which may attain toxic properties.

- Inborn error of metabolism leading into in-ability to synthesise specific enzymes or

sythesise enzymes which can not catalyse certain essential metabolic reactions.

Non-production of certain proteins, or production of proteins which are non-functional or defective

or attain toxic properties and the inborn errors of metabolism leads to genetic diseases.

GENETIC DISEASES.
There are a number of genetic disorders arising from the consequences of gene mutations
causing production of abnormal proteins, non-production of certain important protein molecules,
or in-ability to synthesize specific enzymes or synthesis of enzymes that do not catalyse any
essential metabolic reactions and such genetic diseases include,

- Haemophilia.
- Red-green colour blindness.
- Duchene muscular dystrophy.
- Sickle cell anaemia.
- Cystic fibrosis.
- Huntington’s chorea.
- Phenylketonuria.
- Alkaptonuria.
- Galactosaemia.

HAEMOPHILIA.
Is caused by mutation of the genes in a DNA that provide instructions for production of clotting
factor VIII or IX proteins called antihaemophiliac globulin, this gene mutation leads to none
production of these clotting factor VIII or IX proteins or prevent them from working normally. This
causes a bleeding disorder that slows or prevents the process of blood clotting. It often results
into excessive bleeding both internally and externally in times of injuries which may cause death.

The gene for factor VIII is carried on the X chromosome. So, Haemophilia is a sex linked (X linked)
character caused by the mutant recessive allele, the normal allele is the dominant.

Haemophilia is more common among males than the females in a population.

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RED-GREEN COLOUR BLINDNESS.
Is caused by genetic mutation of genes responsible for production of proteins leading to Red
pigment , green pigment and blue pigment proteins in the retina of the eyes, leading to production
of defective red cones and green cones in the retina of the eye which can not properly work
causing red-green colour blindness.

Red-green colour blindness is controlled by sex linked mutant recessive alleles.The dominant
allele controls the normal condition. The person cannot distinguish between red and green shades
of colours. This condition is more common in males than females in a population.

DUCHENE MUSCULAR DYSTROPHY (DMD).

Is caused by mutation of Duchene muscular dystrophy gene that codes for production of the
proteins dystrophins which keep muscles intact and strong. This gene mutation prevents
production of the protein dystrophins in muscles. Muscles without the protein dystrophins are
more sensitive to damage, resulting in progressive loss of muscle tissues and function.

It is a severe progressive muscle wasting disease that leads to difficulty in movement and
eventually cardiac and respiratory failures occur resulting into death.

THE SICKLE CELL ANAEMIA.

Is caused by base substitution gene mutation of a gene that determines production of normal
haemoglobins in red blood cells. This gene mutation leads to production of abnormal
haemoglobins called haemoglobins S in red blood cells resulting into red blood cells attaining
sickle shaped structures causing conditions of sickle cell anaemia. Sickle cell anaemia is
associated with the following conditions, symptoms, consequences ,

- Anaemia, low Red blood cells count.

- Oxygen deficiency.
- Poor blood circulation.
- Enlargement of the spleen.

NOTE :
Sickle cell anaemia affects mainly the African, Americans, the people of Mediterranean countries
and northern Africa.

CAUSES OF SICKLE CELL ANAEMIA (HOW SICKLE CELL ANAEMIA ARISE)

Sickle cell anaemia is caused by base substitution gene mutation. It occurs on one of the triplet
nucleotide bases i.e Cytocine, thymine, cytocine in a DNA located on the 11th pair of
chromosomes that carry genetic information for the production of beta polypeptide chain,
determining formation of haemoglobin molecule.

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During this base substitution gene mutation, the nucleotide base, Adenine replaces thymine in
the DNA nucleotide triplet code i.e cytocine, thymine, cytocine (CTC), forming a wrong DNA triplet
nucleotide base sequence i.e Cytocine, Adenine, Cytocine (CAC).

During transcription, messenger RNA copies complementary DNA nucleotide base sequence
which will include the codon Guanine, Uracil, Guanine (GUG) as a result of the base substitution,
instead of the Guanine, Adenine, Guanine (GAG). This causes a mistake to occur on the 6 th
aminoacid in the beta polypeptide which is 146 amino acids long, where the amino acid valine
replaces the aminoacid glutamic acid.

The presence of valine instead of glutamic acid in the beta polypeptide leads to production of
abnormal haemoglobin called haemoglobin S. This is because the messenger RNA codon GAG
codes for aminoacid glutamic acid while GUG codes for amino acid valine.

Glutamic acid carries a negative charge and is polar where as valine is non-polar and
hydrophobic. So, abnormal haemoglobin S is much less soluble than normal haemoglobin and it
begins to crystallize when the oxygen concentration falls as it does in the capillaries of body
tissues, resulting into the red blood cells normally biconcave disc shaped to assume the shape of
a crescent or become sickle shaped, this reduces their surface area for absorption of oxygen and
there fore, With their abnormal haemoglobins, the sickle shaped red blood cells are far less
efficient at carrying oxygen in blood.

OCCURRENCE AND DISTRIBUTION OF THE SICKLE CELL ANAEMIA IN A POPULATION.

Is a genetic disorder or disease caused by the base substitution gene mutation occurring in DNA.

The genes controlling sickle cell anaemia show codominance in some cases but sometimes
described as recessive autosomal genes showing complete dominance. Homozygous recessive
individuals possess both recessive allele(HbsHbs) and suffer sickle cell anaemia and may die at
an early age.

It shows codominance because heterozygous individuals possess both the dominant allele (HbA)
and the recessive allele (Hbs) with a genotype (HbAHbs). The red blood cells of this individual
contain about half of normal haemoglobin and about half of the abnormal haemoglobin S. In this
case The Alleles HbA and Hbs are codominant but it shows complete dominance in some other
cases this is because the heterozygous individuals (HbAHbS) are described as showing sickle cell
traits and the individuals do not suffer from the conditions of the sickle cell anaemia.

Heterozygous individuals are only affected at unusually very low oxygen concentrations like
climbing at high altitudes. So some the haemoglobin can crystallize causing some few red blood
cells to attain sickle shapes.

The sickle cell condition shows some advantages. It is widely distributed in a population in and
remain persistent. The frequency of the recessive alleles for abnormal haemoglobin S is high in
malarial infected areas. This is because individuals carrying the recessive alleles do not suffer

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from malaria (are less susceptible to malarial infections) since the plasmodium parasites do not
multiply in the red blood cells containing abnormal haemoglobins S, sickle celled red blood cells
have reduced surface area and cannot absorb sufficient oxygen. Lack of enough oxygen in the
red blood cells prevents adequate aerobic respirations to occur and many physiological processes
can not take place in the plasmodium and may be destroyed inside the sickle shaped red blood
cells, so its life cycle is not completed and many other red blood cells can not be infected. So,
heterozygous individuals have a selective advantage over non-carriers and are more likely to
survive and continue to pass the recessive alleles for abnormal haemoglobin in the next
generations. The final frequency of the genes in the population is determined by the levels of
malarial infections in the population. This is an example of balanced polymorphism.

CYSTIC FIBROSIS.
Is caused by deletion of three nucleotide bases in a gene called cystic fibrosis transmembrane
conductance regulator (CFCR) gene. This mutation leads to production of defective proteins in
the plasma membranes called cystic fibrosis transmembrane regulators that work as chloride
channels in the cells that produce mucus, sweat and digestive enzymes.

In persons suffering from cystic fibrosis, the cystic fibrosis transmembrane regulators do not
function. Thus mucus lining the cell surfaces become thick and sticky. This affects mostly the
lungs, pancreas and the liver where unusually thick mucus clogs lungs, liver and pancreas.

In the pancreas fibrous patches called cysts develop and in the lungs, when the thick mucus dries
up, it causes blockage of air ways of the lungs, and branches of pancreatic ducts and the bile
duct from liver into the gut. This leads to repeated lung infections , difficulty in breathing and
digestive problems. Male and female infertility occurs, the individual may also show other
symptoms which include,
- Production of very salty sweat.
- Persistent coughing at times with phlegm.
- Frequent lung infections including pneumonia or bronchitis.
- Poor growth.
- Nasal polyps. These are soft, painless, non-cancerous growths on the lining of your nasal
passages or sinuses.

Note:
- Cyst is a growth or swellings containing liquids that form on the body of a person.
- Cystic fibrosis is a recessive gene mutation very common in Europe.

HUNTINGTON,S DISEASE (CHOREA).

Is a progressive brain disorder that causes uncontrolled movements, emotional problems and
loss of thinking ability(cognition).

Huntington,s chorea is caused by the mutation of the huntingtins gene located on chromosome 4
where nucleotide base sequence CAG on DNA is duplicated or repeated 40 to 60 times.

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The mutant gene is an autosomal dominant allele, meaning that only one mutant gene of the two
copies of the gene in the cell is sufficient to cause the disease.

The normal Huntingtons gene provides instructions for making a protein called huntingtins.
Huntingtins is a soluble protein found in many of the body,s tissues with the highest levels in the
brain and the testes. Within cells the protein huntingtins seem to be involved in, chemical
signaling, transporting materials, binding to proteins and other structures and protecting the cells
from self destruction.

The mutation of the huntingtons gene by nucleotide base sequence CAG repeat, causes
alteration of the nature of the huntingtins protein which attain toxic properties (a toxic gain of
function phenotype). This results in neuro-degeneration and break down of the neurons in the
part of the brain responsible for coordination of habit and emotional memories and voluntary
movements, resulting into,
- Deterioration of brain cells, resulting into loss of intellectual ability.
- Involuntary muscular movements or loss of control of voluntary muscles by motor
neurones. This results into uncontrollable shaking and dance (chorea) like movements.
- Hallucinations, mood and personality changes.

Genetic counseling and gene cloning techniques can be applied to diagnose the disease and
prevent frequency of its occurrences.

PHENYLKETONURIA.
Phenylketonuria (PKU) is caused by gene mutation of the gene for production of the enzyme
phenylalanine hydroxylase (PAH) found on chromosome 12. It is an autosomal recessive disorder
resulting from the essential amino acids phenylalanine accumulating the in the blood, causing
brain damage.

It Is a rare genetic disorder 0r disease where the individual can not synthesize the active form of
an enzyme phenylalanine hydroxylase which catalyze conversion of excess essential amino acid
phenylalanine to tyrosine in the liver or the enzyme produced is less efficient. Deficiency or
absence of the enzyme causes the amino acids phenylalanine to accumulate and become in
excess in the blood. The excess phenylalanine is converted to toxins. This will prevent the child.s
brain from absorbing sufficient amounts of other essential amino acids from the the blood, as a
result the brain, other organs and tissues such as muscles and cartilage fail to grow and develop
normally, leading into the,
- Mental retardation.
- Organ damage.
- Child can not walk properly and will have awkward posture during walking.
- Females with high concentration of phenylalanine in their blood, would have the risk of the
brain of their developing fetus getting damaged.
- Convulsions.

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ALKAPTONURIA (THE BLACK URINE DISEASE).
Is a defect in the gene resulting into in-ability to synthesize certain enzymes needed for the proper
metaboilism of aminoacids tyrosine and phenylalanine. This leads into poor breakdown of the
amino acids tyrosine and phenylalanine in the body. The excess aminoacids tyrosine is converted
to acids called alkapton (homogentisic acids).
The alkapton(homogentisic acids) build up in the skin and other connective tissue like the
cartilage. The acids leave the body through the urine and if treatment delays, it will lead to severe
deformity of joints, spines and organ dysfunction.

The urine of people with alkaptonuria turns black when exposed to light due to high concentration
of the acids alkapton. When alkapton get deposited in the cartilage, it causes the tip of the nose
to turn black. It can also lead to severe joint pains.

GALACTOSAEMIA.
Is caused by mutations of a gene that results into deficiency or in-ability to synthesize the enzyme
needed for conversion of the sugar galactose to glucose. Accumulation of the sugar galactose in
blood causes cataracts, damage of the liver or the kidney.

Children with galactosaemia are often normal when they are born but within weeks they begin to
vomit much of the milk they drink and fail to undergo normal processes of growth and
development. If the conditions are not dealt with quickly the child may become blind and mentally
retarded.

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