This document discusses genetics and epigenetics. It covers DNA organization including histones and DNA-protein complexes. It describes DNA replication, transcription, and translation. It discusses different DNA polymerases and their functions. It also covers Mendelian inheritance patterns and defines genetics concepts like genes, alleles, and loci. The document then defines epigenetics as heritable changes in gene expression that do not involve changes to DNA sequence. It discusses the main epigenetic mechanisms of DNA methylation, histone modification, and non-coding RNAs. It also mentions applications of polymerase chain reaction and how epigenetics may play a role in sepsis.

1. GENETICS
DR SATHUL HAK

2. • Basic genetics
• PCR
• Genetics and sepsis

3. DNA ORGANISATION

4. • Telomerase – elongated end of DNA
• Histones – positive charge amino acid
rich in lysine and arginine
• Types
1. H1
2. H2A
3. H2B
4. H3
5. H4

6. DNA and OCTOMER
• Alteration
1. Acetylation
2. Methyalation
3. ADP ribosilation
4. Covalant linkage
5. Phosphorlation

7. • DNA loose – Euchromatic
• DNA tight – hetrochromatic

8. • Replication – DNA-DNA
• Transcription –DNA-RNA
• Translation –RNA-PEPTIDES

9. Semi conservative

10. • Replication fork – DNA opener – enz-helixases
• Super coiles –remove end part of DNA

12. Topoisomerase 1 and 2

13. • Drugs like
• quinolones and anti cancer drug like
etoposides and teniposides

14. • DNA dependent DNA polymerase
Function
• Read DNA sequence
• Polymerazation
• Repair mechanism

16. • Alpha polymerase –
1. Primase
2. Short DNA
• Beta polymerase –DNA repair
• Gamma polymerase –replecation DNA in
mitrochondria
• Delta polymerase –elongated leading stand and
making okashaki fragment
• epsilon polymerase-DNA polymerase

17. • DNA polymerase –
1. Mis match repair
2. Base excision repair
• Eg heretetary non polyposis colon carcinoma

19. • Reading towards replication fork-leading stand
• Away from the replication fork –lagging stand
• Oka zaki fragment –multiple short strecth of
newly formed DNA

20. DNA base

21. • Drug alter sugar bases
1. Inosyine- Didanosine
2. Adenine- vidarabine
3. Guanine-acyclovir
4. Cytocyine-cytarabine
5. Thymine - zidovudine

22. DNS transcription

23. Factor regulating expression of gene
• Catabolic gene activator protein
• Promotor site
• Operator region
• Operon- structural and regulatory gene

25. In eukaryotic
• Chromatin –inactive (gene not expressed)
• hetrochromatic
• active( expressed gene)
• euchromatic
• Conversion of euchromatic into hetro
chromatic is called chromatic remodelling

26. Mendelian inheritance
• Classical pattern
• Non classical pattern
• Classical pattern
1. Autosomal dominant
2. Autosomal recessive
• Sex chromosome
1. Autosomal dominat
2. Autosomal recessive

27. • Non classical pathway
1. Mitochondrial inhertiance pattern
2. Tri nucleotide expression

28. • Gene – sequence of nucleotide in DNA with
specific RNA
• Phenotype –expression of gene
• Genotye – genetic information present in
specific locus of homologus chromosome
• Allele- different version of gene which present
in homologus chromosome

29. • Locus – specific position of gne
• Homologus- similar set of gene
• Allelic hetrogenicity – mutation in same allele
produce different type of mutation

30. Dominant

31. Recessive

32. • Autosomal dominant – mutation with gain of
function
• Autosomal recessive – mutation with loss of
function

33. EPIGENETICS

34. Change in phenotype without
change in genotype

35. DEFINITION
• Regulatory control of gene expression, are capable
of overriding information encoded in the DNA
sequence to increase or decrease the risk of a
disease.
• Heritable change in gene expression that does not
effect underlying DNA sequence .

36. DEFINITION
• Epigenetics (epi: above, upon; genetic, DNA sequence)
• Implies that information encoded in the DNA sequence
may be modifiable in some way by higher-order
information that regulates the levels of activity of
specific genes
• Refers to external modification to DNA that turns genes
“on “ or “ off”
• These medication do not change DNA sequence

37. • Epigenetic changes are natural and regular
• But can be influenced by several factors
 Lifestyle
 Disease state
 Age

38. MECHANISM OF EPIGENETICS
1. DNA methylation
2. Histone modification
3. Non – coding RNA associated gene

39. MECHANISM OF EPIGENETICS
1. DNA methylation
2. Histone modification
3. Non – coding RNA associated gene

40. DNA METHYLATION
• DNA methylation is biological process by which =
methyl group are added to DNA
• It changes activity of DNA
• Does not change the sequence of DNA
• Typically represses the “Gene Transcription”

41. METHYLATION SPECIFIC PCR
• Methylation specific PCR is used for analysis of DNA
methylation patterns CpG Ilands.
• DNA is modified and PCR performed with two primer
pairs
• Which are detectable as methylated and unmethylated
DNA respectively
• MSP is rapid method of assessing methylation status in
CpG ilands

42. ADVANTAGE-
Excessive methylation of CpG dinucleotides in
promoter represses the gene expression
In cancer gene silencing is occurred through
aberrant methylation in promoter of tumor
suppressor gene

43. MECHANISM OF EPIGENETICS
1. DNA methylation
2. Histone modification
3. Non – coding RNA associated gene

44. HISTONE MODIFICATION
• Subjected to variety of posttranslational
modifications
• Such as
Lysine acetylation
Arginine methylation
Threonine phosphorylation
Lysine ubiquitination

45. • Affects the chromosome functions atleast by two
mechanisms:
1.Mechanism
Either by changing the electrostatic charge of
histone
Results in structural change in histone/or their
binding DNA

46. 2. Mechanism
These modifications are modifications in binding
sites for protein recognition modules
That recognizes acylated lysines /methylated lysines

47. MECHANISM OF EPIGENETICS
1. DNA methylation
2. Histone modification
3. Non – coding RNA associated gene

48. NON –CODING RNA ASSOCIATED
GENE
• Represents small RNA molecules encoded in genomes
• Regulates the expressions of genes by binding to the 3’-
untranslated regions of specific mRNA
• Play major role in cell differentiation and growth ,
mobility and apoptosis
• Dysregulation of which results in diseases such as
cancer

49. POLYMERASE CHAIN REACTION
Kary Mullis

50. Defenition
• PCR is an in vitro method of synthesis of
nucleic acid wherein a specific DNA segment is
amplified rapidly without concomitant
replication of the rest of the DNA molecule.

51. Reaction tube
• Test DNA
• Primer pair
• dNTPs
• Mg
• DNA polymerase

52. Procedure
1. Denaturation
2. Annealing
3. Primer extension

53. APPLICATION OF PCR

54. TECHNIQUE

55. • DNA FINGERPRINTING
• GENE CHIP

56. EPIGENETICS ROLE IN SEPSIS

60. REFERENCE
1. Nelson

61. THANK YOU