1.

Introduction(Def and importance)

Genome is a total genetic library which contains chromosome
pairs spreading over 20,000-25,000 protein coding genes.
Haploid genome-3.2 x 109 nucleotides
Diploid genome-9.6 x 109 nucleotides
Suggestion -> approximately 3.2 x 109 nucleotides over
24 different chromosomes
Genome is redundant most of the time. Only 2% of the
genome actively functions.

Importance of Genomic Stability

● Individual’s health and survival
● Prevention of mutations
● Genetic diversity for the adaptation and evolution of
species
● Proper reproduction

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2. Causes of genomic instability (Mutagens)

Endogenous Factors
● ROS
● Telomere shortening

● DNA
● DNA replication errors
● DNA Repair Defect

Exogenous Factors
● Ionizing Radiations (UV & X rays)
● Chemical Mutagens
● Viral Infections (HIV, HSV-8)

Others
● Dysregulated tumor suppressor genes functions
● Damage to chromosome
● Chromosome abnormalities
(unequal segregation during M phase

sample

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3. Maintenance of genomic stability

Checkpoints
● G1-S restriction checkpoint
● G2-M checkpoint ( For DNA damage)
● Spindle assembly checkpoint ( Metaphase to anaphase
transition)
 ● DNA polymerase( proofreading)

Suggested simple diagram for DNA polymerase

● Oncosuppressor genes ( RB & p53)
● P21 ( CDKI )
● DNA repair mechanisms
● Cyclin-CDK complexes
● Growth Factors ( G0 to G1 )

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4. Effects or consequences of genomic instability

● Single gene disorder - sickle cell anemia, G6PD
deficiency, cystic fibrosis
● Multifactorial - DM, hypertension, Alzheimer’s ds, Cancer
● Chromosomal disorder - Down syndrome, CML
● Mitochondrial disorder
 ● Drug resistance

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5.Clinical Importance
Dx for inherited and congenital diseases
Cancer screening
Clinical trials and vaccines
Genetic variations that increase risk of specific ds

Apoptosis
Extrinsic pathway induced by Fas receptor ligation
Intrinsic pathway induced by upregulation or activation of
BH-3 only family members
● Ataxia-telangiectasia

● Xeroderma pigmentosum
● Huntington's disease
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(Cell Cycle Diagram with checkpoints and CDK, Cyclin

on the boundary)
(Diagram ?.?)
(Arrangement Sketch on draft paper …)

Suggestion of Images to use are shown below ::

https://www.mdpi.com/ijms/ijms-19-03219/artijjcle_deploy/html/i
mages/ijms-19-03219-g001.png

Apoptosis
Extrinsic pathway induced by Fas receptor ligation. Intrinsic
pathway induced by upregulation or activation of BH-3 only family
members.

If p53 dependent,
DNA damage too severe>>p53 increases>>over induced
p21>>apoptosis (with cell shrinkage)