mutations in Genome Gene mutation chromosomal Mutation

1. •Mutations

2. Definition
• Mutation is basically alteration of one or more
nucleotides in an organism extra
chromosomal DNA, virus or any material
related to gene.
• Mutations occur due to mutagens.

3. Generally:
• Permanent change.
• Vary in size from genome to genome.
• Alteration may be single or large fragment
containing one or more than one gene mutation
is cause of dissimilarities between individuals of
same species and different .
• It may lead to evolution.

4. History:
• Mutations idea extends from Darwin to modern
genetics.
• Since than there have been a lot of changes in
the definition of the term
• Today Mutations are important in order to
differentiate between the individuals.

5. History:
• Prof Sir Mike Stratton :
• He was the first one who gave remarks on the
mutations that occur in embryo.
• Mutations can help in better understanding of
human development.

6. Causes
• DNA fails to copy accurately:
Most mutation is naturally occurring .when cell
devide it makes makes copy of DNA Some time
copy not perfect. Small difference from original
DNA is mutation.
• External influences can create mutations
Mutation can cause by specific chemicals or
radiations. These cause to break DNA. When cell
repair the DNA then it might not be a perfect
job.

7. Types
There are two types of mutations:
• Gene Mutation
• Chromosomal Mutation

8. Gene Mutation
• Point Mutation:
INDELL.
• Frameshift:
Substitution.

9. Gene Mutation
• Gene mutation is describe as any change in the
nucleotides sequence.
• This change occur in single nucleotide base or
large segment.
• Due to this genetic variations occur.
• Some variations may help for better survive.
• Different mutagens which produce mutation.

10. Types
• There are basic types
1. Point mutation
i.) Insertion
ii.) Deletion

11. Point mutation
• Simple type of gene mutation.
• Single base pair altered.
• Mostly occur during DNA replication.
• Caused by mutagens.

13. Insertion
• One or more nucleotide base pair are added into
a sequence of DNA.

14. Deletion
• In which segment of DNA is removed which
consist of one or more nucleotide.

15. • Point mutation on basis of protein structure:
1. Silent Mutation.
2. Missense Mutation.
3. Nonsense Mutation.

16. Frameshift Mutation
• Frameshift mutation- Adding or deleting
nucleotides to a DNA sequence.
• A frameshift mutation is much worse than a point
mutation because it causes the entire DNA
sequence to be shifted over.
Example: DNA: ATTAAACCG
ATAAACCG

17. Frameshift Mutations:
• Insertion: Nucleotide added – Entire DNA
sequence changed
• Deletion: Nucleotide missing – Entire DNA
sequence changed

18. Tay-Sachs Disease:
The absence of a vital enzyme called
Hexosamindase A (Hex-A)
Hex-
A
Accumulation of GM2 in nerve
cells of the brain
Normally
However, in Tay-Sachs, there is no Hex-A so this
process does not occur

19. Gene Location
• Chromosome 15
showing location of
the syndrome

20. Cystic Fibrosis
• Inherited monogenic disorder presenting as a
multisystem disease.
• Typically presents in childhood
▫ 7% of CF patients diagnosed as adults
• Most common life limiting recessive trait among
whites

21. Cystic Fibrosis
• Prognosis improving
▫ 38% of CF patients are older than 18
▫ 13% of CF patients are older than 30
• Median survival:
▫ Males: 32 years
▫ Females: 29 years

22. Genetics of CF
• Autosomal recessive.
• Gene located on chromosome 7.

23. Genetics of CF
• Most common mutation occurs in 70% of CF
chromosomes 3 base pair deletion leading to
absence of phenylalanine at position 508 (DF508)
of the CF transmembrane conductance regulator
(CFTR)
• DF508 mutation leads to improper processing
and intracellular degradation of the CFTR
protein

24. Chromosomal Mutation
• Deletion
• Duplication
• Tranlocation
• Inversion

25. Deletion
• Deletion is the lost of the nucleotides from the
chromosomes the loss could be in larger number
or in smaller number.
• Deletion is actually when a base is deleted from
the sequence.
• Chromosomal fragment are lost due to deletion
of a base.
• There is no specific location for deletion, it can
happens anywhere or everywhere.

26. • Sometimes the one copy of gene is lost from the
organism which have two copies before or
sometimes both the copies from an organism
lost.

27. Duplication
• Duplication is opposite to deletion.
• A part is copied or replicated.
• A sequence is repeated or may be a single base
or two bases are repeated or duplicated.
• This type of chromosome have an extra
information or repeated information.

29. Mechanism of Duplication
• There are following five mechanism of
duplication that are defined below
Ectopic recombination:
• Duplication due to unequal crossing over occurs
during meiosis in misaligned homologous
chromosomes.
• It occurs due to the replication of two elements
of chromosome.

30. Replication Slippage
• It is actually a error in the DNA due to which short
sequences are repeated in the chromosomes.
• DNA polymerases starts copiyng the DNA during
replication process.
• It place the Strand in wrong location and accidently
copy the strand again due to which the duplication
occurs.
• Replication slippage is actually the repetitive
sequences

31. Retrotransposition
• Retrotransposons are genetic elements that
can amplify themselves in a genome.
• These DNA sequences use a "copy-and-paste"
mechanism, whereby they are
first transcribed into RNA, then converted back
into identical DNA sequences using reverse
transcription, and these sequences are then
inserted into the genome at target sites.

32. Polyploid
• Poliploid cells and organisms are those
containing more than two paired (homologous)
sets of chromosomes.
• Most species whose cells have nuclei
(Eukaryotes) are diploid, meaning they have two
sets of chromosomes—one set inherited from
each parent.

33. Aneuploidy
• Aneuploidy is the presence of an abnormal
number of chromosomes in a cell, for example a
human cell having 45 or 47 chromosomes
instead of the usual 46.
• It does not include a difference of one or more
complete sets of chromosome.

34. Inversions:
• An inversion is a chromosome rearrangement in
which a segment of a chromosome is reversed end to
end.
• Breakage and rearrangement within a chromosome.
• Inversions do not change the overall amount of the
genetic material.
• Show no particular abnormalities at the phenotypic
level.

36. • Inversions usually do not cause any
abnormalities.
• In individuals which are heterozygous for an
inversion, there is an increased production of
abnormal chromatids.
• This leads to lowered fertility due to production
of unbalanced gametes

38. Types:
There are two types of Inversion mutation in
chromosomes:
• Pericentric Inversions.
• Paracentric Inversions.

39. Pericentric Inversions:
• Pericentric inversions include the centromere
and there is a break point in each arm.
• Chromosome can be elongated or shorted after
the inversions have taken place.

40. Paracentric Inversions:
• Paracentric inversions do not include
the centromere and both breaks occur in one
arm of the chromosome.
• A reversal of the normal order of genes in a
chromosome segment involving only the part of
a chromosome at one side of the centromere.

41. Detection:
• Cytogenetic techniques may be able to detect
inversions, or inversions may be inferred
from genetic analysis.
In most species small inversions go undetected.

42. Example:
• The most common inversion seen in humans is
on chromosome 9, at inv(9)(p12q13).
• No harmful effects.
• Suspicion it could lead to an increased risk for
miscarriage or infertility for some affected
individuals.

43. Translocation:
• A chromosome translocation is
a chromosome abnormality caused by
rearrangement of parts between
nonhomologous chromosomes.
• Translocations can
be balanced or unbalanced.

45. Types:
• Balanced:
in an even exchange of material with no genetic
information extra or missing, and ideally full
functionality
• Unbalanced:
Where the exchange of chromosome material is
unequal resulting in extra or missing genes.

46. Diseases Caused:
• Some human diseases caused by translocations are:
• Cancer: Described mainly in leukemia. Translocations
have also been described in solid malignancies such
as Ewing's sarcoma.
• Infertility: If parent is a carrier of balanced then chances
of an offspring being infertile are increased.
• Down syndrome: Caused by Translocation between
chromosome 21 and chromosome 14

47. Harmful Mutation
• In which organism fitness is decreased and
produced a diseases.
• Sickle cell anemia, color blindness etc
Are all mutations harmful?
• Change the codes for protein synthesis.
• Single mutation or more than 10 mutation.

48. Harmful Mutation
Neutral Mutation:
• Also called silent point mutation.
• Eye color.
Germ-Line Mutation:
• Inherited.
• Wilms Tumor.

49. Harmful Mutation
Explanation:
• Most inherited genetic diseases are recessive.
• Some disease caused by one copy of defective
gene.
• Rare (Huntington’s Disease)
• 5-10 deadly mutation in our body

50. Harmful Mutation
Causes:
i. Radiation
(UV Radiation, X-rays)
ii. Chemicals
Also called mutagens.
(Benzoyl peroxide, cigarette smoke)
iii. Infectious Agents.
(Human papillomavirus)

51. Harmful Mutation
Chemicals Contaminations:
• 28 April, 1986
• Chernobyl Disaster
• 985,000 excess cancers occurred between 1986
and 2004. (Russian Publication)
• 1.4 million excess cancers occurred
(2001, European Committee on Radiation Risk)

52. Examples
Sickle cell Anemia:
• Hemoglobin-Beta gene found on chromosome
11.
• Sickle shaped red blood cells.
• Type of point mutation.
• Two copies of the mutated genes cause sickle cell
anemia.

53. Examples
Huntington’s disease:
• Mutation in chromosome number 4.(HD
gene)
• Basal ganglia cells are destroyed.
• 50% chance.
• Symptoms appear between 30 to 50 ages.

54. Examples
Cancer:
• Mutation in p53, BRCA1, BRCA2
• BRCA1 = breast cancer 1
• BRCA2 = Breast cancer 2

55. Beneficial mutation
Beneficial Mutation:
• Which are helpful for humans.
• EXAMPLES
i. Apolipoprotein AL Milano
ii. Increased bone density
iii. Malaria resistance
iv. Tetrachromatic vision

56. Beneficial mutation
Apo lipoprotein:
• All humans have a gene which are said to be
apolipoprotein.
• The function of this gene is to transport
cholesterol via the process of bloodstream.
• It is considered more beneficially due to the
removal of cholestrol from arteries.

57. Beneficial mutation
Increased bone density:
• The gene which caused bone density in human
being are said to be low lipoprotein related to
protein 5 (LRP5).

58. Beneficial mutation
Malaria Resistance:
• These variations occur in humans due to the
hemoglobin variation that make it like sickle
shape
• The missing of one copy of that gene in human
causes 29% chances to get malaria. On the other
hand people with two copies of this gene
respond to 93% of that disease

59. Tetra chromatic vision:
• Different genes present in humans shows
different color vision of light.
• The gene which has one kind of cone show blue
color at chromosome at 7.

60. Beneficial mutation in organisms:
1. Nylonase: nylon bacteria
• Nylonase are the most authentic example of
beneficial mutation in bacteria.
• Nylonase eat the short molecule of nylon 6.

61. Gene mutation: Almond Trees:
• The species which have almond contain
amygdalin.
• Amygdalin is a chemical that convert the cyanide
into human body.