Gene mutations can occur in several ways: 1) Substitutions exchange one DNA base for another and may alter the resulting protein. Sickle cell anemia is caused by a substitution. 2) Insertions add extra DNA bases. Huntington's disease results from repetitive CAG insertions. 3) Deletions remove sections of DNA. Cystic fibrosis stems from a deletion in the CFTR gene. 4) Frameshifts alter gene parsing and produce truncated proteins. Tay-Sachs disease arises from a frameshift mutation in the HEXA gene.

1. Gene mutation
Lecture 6
Prepared by
Samira Fattah
Assis. Lec.
College of health sciences-HMU

2. What is gene
• A gene is the basic physical and functional unit of
heredity.
• Genes, which are made up of DNA, act as instructions
to make molecules called proteins.
• In humans, genes vary in size from a few hundred DNA
bases to more than 2 million bases.
• The Human Genome Project has estimated that
humans have between 20000 and 25000 genes.

3. • Every person has two copies of each gene, one inherited
from each parent.
• Most genes are the same in all people, but a small number
of genes (less than 1 percent of the total) are slightly
different between people.
• Alleles are forms of the same gene with small differences
in their sequence of DNA bases.
• These small differences contribute to each person’s unique
physical features.

4. • Mendel while explaining the results of his
monohybrid and dihybrid crosses, first of all
conceived of the genes as particulate units and
referred them by various names such as hereditary
factors or hereditary elements.

5. The Discovery of DNA
• DNA was first identified in 1869 by Friedrich
Miescher, a Swiss biologist, removed the nuclei of
pus cells and found that they contained a chemical
material , he called nuclein, which , he separated the
substance into a basic part (which we now know is
DNA) and an acidic part (a class of acidic proteins
that bind to basic DNA).
• Later the scientists realized that there are two types
of nucleic acids : DNA (deoxyribonucleic acid ) and
RNA (ribonucleic acid )

6. Nucleic Acids
• Deoxyribonucleic Acid (DNA) is the genetic
material found in the cells of all living organisms.
• Nearly every cell (with a nucleus) in a person's
body has the same DNA.
• Most DNA is located in the cell nucleus (where it
is called nuclear DNA),
• but DNA can also be found in the mitochondria
(where it is called mitochondrial DNA or mtDNA).

7. • DNA and its close relative RNA are perhaps the most
important molecules in biology.
• They contains the instructions that make every single
living organism on the planet, and yet it is only in the
past 50 years that we have begun to understand them.
• and they are called nucleic acids because they are
weak acids, first found in the nuclei of cells.
• They are polymers, composed of monomers called
nucleotides.

8. Nucleotide parts
• Nucleotides have three parts to
them:
1-a phosphate group:
which is negatively charged, and
gives nucleic acids their acidic
properties.
2-a pentose sugar, which has 5
carbon atoms in it.
- the carbon atoms are numbered as
shown to distinguish them from the
carbon atoms in the base.

9. Nucleotide parts
• If carbon 2 has a hydroxyl group attached then the sugar is
ribose, found in RNA.
• If the carbon 2 just has a hydrogen atom attached instead,
then the sugar is deoxyribose, found in DNA.

10. 3-a nitrogenous base.
• There are five different bases, but they all contain
the elements carbon, hydrogen, oxygen and
nitrogen.
• The base thymine is found in DNA only and the base
uracil is found in RNA only, so there are only four
different bases present at a time in one nucleic acid
molecule.

11. Nitrogen Bases are:
• Adenine (A)
• Guanine (G)
• Cytosine (C )
• Uracil (U)
• Thymine (T)

12. Nucleotide Polymerisation
• Nucleotides polymerise by forming bonds between
carbon 3 of the sugar and an oxygen atom of the
phosphate.
• The bases do not take part in the polymerisation, so
there is a sugar-phosphate backbone with the bases
extending off it.
• This means that the nucleotides can join together in
any order along the chain.

14. Structure of DNA
• The three-dimensional structure of DNA was
discovered in the 1950's by Watson and Crick.
• The main features of the structure are:
• DNA is double-stranded, so there are two
polynucleotide stands alongside each other.

15. • The strands are antiparallel,
i.e. they run in opposite
directions.
• The two strands are wound
round each other to form a
double helix.
•The two strands are joined
together by hydrogen bonds
between the bases.
• The bases therefore form
base pairs, which are like
rungs of a ladder.

16. • The base pairs are specific.
• A only binds to T (and T with A)
• and C only binds to G (and G
• with C).
• These are called complementary
base pairs.
• This means that whatever the
• sequence of bases along one
• strand, the sequence of bases
• on the other strand must be
• complementary to it.

17. Function of DNA
DNA is the genetic material, and genes are made
of DNA. Therefore DNA has two essential
functions:
replication and expression.

18. • Replication means that the
DNA, with all its
genes,must be copied
every time a cell divides.
• Expression means that the
genes on DNA must control
characteristics.

19. • A gene was traditionally defined as a factor
that controls a particular characteristic (such
as flower color).
• but a much more precise definition is that a
gene is a section of DNA that codes for a
particular protein. Characteristics are
controlled by genes through the proteins they
code for.

20. Expression can be split into two parts:
• transcription (making RNA) and translation (making proteins).
• These two functions are summarized in this diagram
(called the central dogma of genetics).

21. RNA
RNA is a nucleic acid like DNA, but
with 4 differences:
1-RNA has the sugar ribose
instead of deoxyribose
2-RNA has the base uracil instead
of thymine
3-RNA is usually single stranded
4-RNA is usually shorter than DNA

23. The Genetic Code
• The sequence of bases on DNA codes for the
sequence of amino acids in proteins.
• But there are 20 different amino acids and only 4
different bases, so the bases are read in groups of 3.
• This gives 43 or 64 combinations, more than enough
to code for 20 amino acids.

24. • A group of three bases coding for an amino acid is called a
codon, and the meaning of each of the 64 codons is called the
genetic code.
• The genetic code can be expressed as either RNA codons or
DNA codons.

27. Mutation
• Mutation is the alteration of DNA sequence.
• whether it be in a small way by the alteration of a single base
pair, or whether it be a gross event such as the gain or loss of
an entire chromosome.
How common are mutations?
• Mutations occurs at a frequency of about 1 in every 1 billion
base pairs
• Everybody has about 6 mutations in each cell in their body!

28. If we have that many mutations, why don’t
we look weird?
• Mutations are not always seen. The affected
gene may still function.
• Mutations may be harmful.
• Mutations may be beneficial.
• Mutations may have no effect on the
organism.

29. How do mutations affect a population
• One consequence may be genetic disease.
• However, although in the short term mutation may
seem to be a BAD THING, in the long term it is
essential to our existence.
• Without mutation there could be no change and
without change life cannot evolve. Some variations
may help population to survive better

30. Somatic or germinal?
• The first point to consider is where is the mutation
occurring?
• Most of our cells are somatic cells and consequently most
mutations are happening in somatic cells.
• Only mutations in gametes (egg & sperm) are passed onto
offspring.
• That is not to say that somatic mutation is unimportant,
cancer occurs as a direct consequence of somatic mutation.

31. Types of mutations
1. Substitution
A substitution is a mutation that exchanges one
base for another (i.e., a change in a single "chemical
letter" such as switching an A to a G). Such a
substitution could change a codon to one that
encodes a different amino acid and cause a small
change in the protein produced.

32. For example, sickle cell anemia is caused by a
substitution in the beta-hemoglobin gene, which
alters a single amino acid in the protein produced.

33. 2. Insertion
Insertions are mutations in which extra base
pairs are inserted into a new place in the DNA.

34. Example :Huntington's Disease (HD) is a brain disorder that
affects a person's ability to think, talk, and move.
-Normally, the coding region of this gene contains the DNA
sequence "CAG" repeated again and again. The number of
times this triplet is repeated varies from person to person,
ranging from 10 to 26 times

35. 3. Deletion
Deletions are mutations in which a section of
DNA is lost, or deleted.

36. Example :Cystic fibrosis is a genetic disorder that affects the
respiratory and digestive systems.
-People with cystic fibrosis inherit a defective gene on
chromosome 7 called CFTR (cystic fibrosis transmembrane
conductance regulator)

37. 4. Frame-shift
insertions and deletions can alter a gene so that its message is
no longer correctly parsed. This usually generates truncated
proteins that are as useless These changes are called
frameshifts.

38. Example :
• Tay–Sachs disease(or hexosaminidase A deficiency)
is a rare autosomal recessive genetic disorder. causes a
progressive deterioration of nerve cells and of mental and
physical abilities that begins around 7 months of age and
usually results in death by the age of four.
• -caused by a genetic mutation in the HEXA gene on
(human) chromosome 15.