tradeoffs pharmacogenome

1. TRADE-OFFS :
• Is a situation that involves losing one quality or aspect in return for gaining another
quality of aspect.
• In simple word when one think increases some other think decreases.
• In evolutionary content in which case natural selection & sexual selection act as the
ultimate decision makers.
• tradeoffs involves their role in biodiversity

2. POLYMORPHISM
• Polymorphism is a generic term that means 'many shapes‘
• It is the ability to appear in different form

3. SINGLE NUCLEOTIDE POLYMORPHISM
•Single nucleotide polymorphisms or SNP
(pronounced “snips”), are the most common type
of genetic variation among peoples.
•Each SNP represents a difference in a single DNA
building block, called a nucleotide

4. •It is a DNA sequence variation
occurring when a single nucleotide
A, T, C, or G in the genome
differs between members of a
species
•For example, two sequenced DNA
fragments from different
individuals, AAGCCTA to
AAGCTTA, contain a difference
in a single nucleotide

6. SOME FACTS
• In human beings, 99.9 percent bases are same.
• Remaining 0.1 percent makes a person unique.
• Different attributes / characteristics / traits
• how a person looks,
• diseases he or she develops.
• These variations can be:
• Harmless (change in phenotype)
• Harmful (diabetes, cancer, heart disease, Huntington's
disease, and hemophilia )
• Latent (variations found in coding and regulatory
regions, are not harmful on their own, and the change
in each gene only becomes apparent under certain
conditions e.g. susceptibility to lung cancer)

7. SNPS FACTS
• SNPs are found in
• coding and (mostly) non coding regions.
• Occur with a very high frequency
• about 1 in 1000 bases to 1 in 100 to 300 bases.
• The abundance of SNPs and the ease with which they
can be measured make these genetic variations
significant.
• SNPs close to particular gene acts as a marker for that
gene.
• SNPs in coding regions may alter the protein structure
made by that coding region.

8. SNP MAPPING
• Sequence genomes of a large number of people
• Compare the base sequences to discover SNPs.
• Generate a single map of the human genome
containing all possible SNPs

9. TYPES OF SNP
Following are the types of SNP
• Non-coding region
• Coding region
• Synonymous
• Non synonymous
• Missense
•
Nonsense

10. NON-CODING REGION
A segment of DNA that does comprise a gene
and thus does not code for a protein .
CODING REGION
Regions of DNA/RNA sequences that code for proteins

11. Synonymous
A SNP in which both forms lead to the same polypeptide sequence is
termed synonymous (sometimes called a silent mutation).
Non synonymous
If a different polypeptide sequence is produced they are non synonymous . A
non synonymous change may either be missense or nonsense, where a
missense change results in a different amino acid, while a nonsense
change results in a premature stop codon.

12. EFFECT OF SNP
Silent
Alter the function of the protein
• Directly : alter an amino acid sequence
• indirectly : alter the function of the
regulatory sequence

13. ROLE OF SNPS IN DISEASE
PREDISPOSITION
•The Common disease are multifactorial
•The Genetic differences between human
populations make one population more
susceptible to particular disease.

14. SNPS AND CANCER
• SNPs in genes involved in DNA repair and drug
metabolizing enzymes which responsible for
metabolism & detoxification of Carcinogens can
act as cancer susceptibility genes
Through
• Increase activation of chemical carcinogens
• Decrease ability of cells to detoxify & repair
mutagenic damage

15. METHODS OF IDENTIFICATION
SNPS
A) Detection of known SNPs
B) Identification of new SNPs

16. DETECTION OF KNOWN SNPS
a) Gel-Based genotyping methods
1-PCR with restriction enzyme coupled analysis.
2-Amplification refractory mutation system (ARMS).
3-Oligonucleotide ligation assay.
4-Minisequencing.

17. DETECTION OF KNOWN SNPS
b) Non-Gel-based High throughput
Genotyping Technologies
1- hybridization using fluorescence resonance
energy transfer detection (TaqMan
genotyping, Molecular beacons).
2- High-density chip array.

18. B)IDENTIFICATION OF NEW
SNPS
It involves two steps:
1- Conformation-based mutation scanning.
2-Direct DNA sequencing.

19. SCANNING
• Single-strand conformation polymorphism (SSCP).
• most widely used methods.
Principle:
Single strand DNA tend to fold into complex
structure which determines the mobility of the
DNA strand in non denaturating gel.

20. USE AND IMPORTANCE OF SNPS
•Variations in the DNA sequences of humans
can affect how humans develop diseases and
respond to pathogens, chemicals, drugs,
vaccines, and other agents.
•SNPs are also thought to be key enablers in
realizing the concept of personalized medicine

21. SNP APPLICATIONS
•Gene discovery and mapping
•Association-based candidate polymorphism
testing
•Diagnostics/risk profiling
•Response prediction
•Homogeneity testing/study design
•Gene function identification

22. CHALLENGES TO THE GROWTH
AND EXPANSION
ducation of various healthcare providers regarding pharmacogenomics.
otentially smaller and more specialized drug markets.
esistance to genetic testing.
thical & Legal issues.
xpense.

23. PHARMACOGENOMICS

24. OVERVIEW
harmacogenomics
ingle nucleotide polymorphism
mportance of pharmacogenomics
xamples of altered drug reponse
enefits of pharmacogenomics

25. PHARMACOGENOMICS
harmacology + Genomics =
pharmacogenomics

26. PHARMACOGENOMICS
T IS THE BRANCH OF PHARMACOLOGY WHICH DEALS WITH THE
INFLUENCE OF GENETIC VARIATION ON DRUG RESPONSE BY
CO-RELATING GENE EXPRESSION OR SINGLE NUCLEOTIDE
POLYMORPHISM WITH A DRUG’S EFFICACY OR TOXICITY.
t is an approach to PERSONALIZED MEDICINE.

27. SINGLE NUCLEOTIDE
POLYMORPHISMS (SNPS)
Single Nucleotide Polymorphism (SNP) are DNA sequence variation that occurs
when a single nucleotide in the genome sequence is altered.
CTAGATACGAACTGCATC…
CTAGATACGGACTGCATC…
ccur in atleast 1% of the population and make up about 90% of all human genetic
variation
Frequency: 1: 300 to 500 Nucleotides

28. PERSONALIZED MEDICINE
t refers to an approach of clinical
practice where a particular treatment is
not chosen based on the ‘average
pateint’ but on characteristic of an
individual pateint.

29. SIMPLE DEFINITION

30. CORELATION

31. IMPORTANCE OF
PHARMACOGENOMICS
ONE SIZE FITS ALL” Only work for about60 percent
of the population at the best. And the other 40 percent
of the population increase their risks of adverse drug
reaction because their genes do not do what is intended
of them

32. ONE SIZE DOES NOT FIT ALL
A 1998 study of hospitalized patients published in the Journal
of the American Medical Association reported that in 1994, adverse
drug reactions accounted for more than 2.2 million serious
cases and over 100,000 deaths, making adverse drug
reactions (ADRs) one of the leading causes of
hospitalization and death in the United States.

33. EXAMPLES OF ALTERED DRUG
RESPONSE
ENZYME/DISEASES GENE
GLUCOSE -6 -PHOSPHATE
DEHYDROGENASE DEFICIENCY
G6PD
THIOPURINE S-METHYL TRANSFERASE TPMT
CYTOCHROME P450 ENJYME AND
-DRUG METABOLISM
CYP2D6
WARFARIN AND COAGULATION CYP2C9 VKORC1