1. Gene mutations are alterations in DNA sequences that can change the genetic code and potentially cause genetic diseases. 2. The most common type of gene mutation is point mutations, which change a single DNA nucleotide and can be silent, missense, or nonsense. 3. Examples of diseases caused by gene mutations include sickle cell anemia from a missense mutation, various cancers from oncogene and tumor suppressor gene mutations, cystic fibrosis from a deletion mutation, and myotonic dystrophy and fragile X syndrome from trinucleotide repeat expansions.

1. GENE MUTATION
Genetics
By: Jaycris C. Agnes

2. The genetic code is the set of rules by
which information encoded within
genetic material
(DNA or mRNA sequences)
is translated into proteins (amino
acid sequences) by living cells.
Genetic Code
•Introduction:

3. • The Codons in mRNA are
nucleotide bases, “read” in blocks
of three.
• There are 64 codons, 61 of these
base triplets correspond to specific
amino acids. Three other serve as
signal to stop translation.
Codons

5. A gene mutation is defined as an
alteration in the sequence of
nucleotides in DNA a polymer of
nucleotides joined together.
Gene Mutation

6. • During protein synthesis, DNA
is transcribed into RNA and
then translated to produce proteins.
• Altering nucleotide sequences most
often results in nonfunctioning proteins.
• Mutations cause changes in the genetic
code that lead to genetic variation and
the potential to develop disease.

7. Kinds of Gene Mutation

8. Point mutations are the most common type of
gene mutation. Also called a base-pair
substitution, this type of mutation changes a
single nucleotide base pair. Point mutations can
be categorized into three types:
1. Point Mutation
SILENT MISSENSE
NONSENSE

9. SILENT MUTATION
Although a change in the DNA sequence
occurs, this type of mutation does not change
the protein that is to be produced.

10. MISSENSE MUTATION

11. TYPES OF MISSENSE MUTATION
Conservative
Non-conservative
Result in an amino acid change. However,
the properties of the amino acid remain the
same (e.g., hydrophobic, hydrophilic, etc).
Result in an amino acid change that has
different properties than the wild type. The
protein may lose its function, which can
result in a disease in the organism.

12. DNA sequence Amino acid sequence
Type of
mutation
ATG CAG GTG ACC TCA GTG M Q V T S V None
ATG CAG CTG ACC TCA GTG M Q L T S V Conservative
ATG CCG GTG ACC TCA GTG M P V T S V
Non-
conservative
Conservative vs. Non-conservative

13. Non-conservative Mutation
Diseases
• Sickle Cell Anemia (loss-of-function)
Sequence for normal hemoglobin
ATG GTG CAC CTG ACT CCT GAG GAG AAG TCT GCC GTT ACT
START Val His Leu Thr Pro Glu Glu Lys Ser Ala Val Thr
Sequence for Sickle Cell Anemia
ATG GTG CAC CTG ACT CCT GTG GAG AAG TCT GCC GTT ACT
START Val His Leu Thr Pro Val Glu Lys Ser Ala Val Thr

14. • Cancer
Valine Glutamic Acid
Mutation changing a valine to glutamic acid in
the braf gene; this leads to an activation of the
RAF protein which causes unlimited proliferative
signalling in cancer cells.

15. All cancers derive from
single cells that have
acquired the
characteristics of
continually dividing in an
unrestrained manner
and invading
surrounding tissues.
•What is cancer?
Human melanoma cell
undergoing cell division
Credit: Paul Smith & Rachel Errington, Wellcome
Images

16. • Cancer cells behave in this
abnormal manner because of
changes in the DNA sequence of
key genes, which are known as
cancer genes. Therefore all
cancers are genetic diseases.
•What is cancer?

17. Oncogene(gain-of-function)
Cancer
Ras
Genes which normally function to PROMOTE cell
growth/division in a controlled manner

18. Tumour suppressor gene (loss-of-function)
TS
Cancer
These genes normally function to PREVENT
cell growth/division

19. •Importance of somatic DNA
changes in human cancer
Somatic
Inherited
Both
Only 5 –10% of cancer cases have a clear hereditary
component,
e.g. BRCA1 and BRCA2 in breast cancer
Even in those cases where susceptibility is clearly inherited,
somatic changes are required for cancer to develop

20. NONSENSE MUTATION

21. 2. Frameshift Mutation

22. 3. Repeat Expansion Mutation

24. END.

25. 1. Causes thick, sticky mucus and
very salty sweat.
2. Bacteria colonize in the mucus
causing infections.
3. Eventually fatal.
• Cause by Deletion of a base in Phenylalanine
in chromosome number 7. X-Linked recessive.
•Cystic Fibrosis

26. 1. Myotonic dystrophy is
a chronic, slowly
progressing, highly
variable, inherited
multisystemic disease.
2. It is characterized by
wasting of the muscles
(muscular
dystrophy), cataracts,
heart conduction
defects, endocrine ch
anges, and myotonia.
•Myotonic Dystrophy
Caused by trinucleotide repeat of CUG (Leucine).
X-linked Dominant.

27. • Large, protruding ears (one or both)
• Long face (vertical maxillary excess)
• High-arched palate (related to the
above)
• Hyperextensible finger joints
• Hyperextensible ('Double-jointed')
thumbs
• Flat feet
• Soft skin
• Postpubescent macroorchidism (Lar
ge testes in men after puberty)
• Hypotonia (low muscle tone)
• single palm crease (crease goes
across entire palm)
•Fragile X Syndrome
Caused by trinucleotide repeat of CGG(Arginine) in X-
Chromosome. X-linked Dominant.

28. • Autism/ ADHD/ Mental Retardation.
• Strabismus (lazy eye)
• Obsessive-Compulsive Disorder (OCD) [some]
• Speech may be cluttered or nervous.
• Stereotypic movements (e.g., hand-flapping)
and atypical social development, particularly
shyness, limited eye contact, memory
problems, and difficulty with face encoding.
People inflicted by FXS have:
•Fragile X Syndrome

29. • Afflicted person suffered from
severe anemia.
Caused by Nonsense mutation of
CAG(glutamine) to UAG (STOP). Autosomal
Recessive.
•B-Thalassemia