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

POLYMORPHISM

• Polymorphism is a generic term that means 'many shapes‘

• It is the ability to appear in different form

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

• 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

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)

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.

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

TYPES OF SNPFollowing are the types of SNP

• Non-coding region

• Coding region • Synonymous • Non synonymous

• Missense

• Nonsense

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

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.

EFFECT OF SNP

Silent

Alter the function of the protein

• Directly : alter an amino acid sequence • indirectly : alter the function of the regulatory sequence

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.

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

METHODS OF IDENTIFICATION SNPS

A) Detection of known SNPs

B) Identification of new SNPs

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.

DETECTION OF KNOWN SNPSb) Non-Gel-based High throughput Genotyping Technologies

1- hybridization using fluorescence resonance energy transfer detection (TaqMan genotyping, Molecular beacons).

2- High-density chip array.

B)IDENTIFICATION OF NEW SNPS

It involves two steps:

1- Conformation-based mutation scanning.

2-Direct DNA sequencing.

CONFORMATION-BASED MUTATION 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.

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

SNP APPLICATIONS

•Gene discovery and mapping

•Association-based candidate polymorphism testing

•Diagnostics/risk profiling

•Response prediction

•Homogeneity testing/study design

•Gene function identification

CHALLENGES TO THE GROWTH AND EXPANSION

Education of various healthcare providers regarding pharmacogenomics.

Potentially smaller and more specialized drug markets.

Resistance to genetic testing.

Ethical & Legal issues.

Expense.

PHARMACOGENOMICS

OVERVIEWP

harmacogenomics

Single nucleotide polymorphism

Importance of pharmacogenomics

Examples of altered drug reponse

Benefits of pharmacogenomics

Pharmacogenomic drugs

Ethical concerns

Challenges to the growth and expansion

PHARMACOGENOMICS

Pharmacology + Genomics = pharmacogenomics

PHARMACOGENOMICSI

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.

It is an approach to PERSONALIZED MEDICINE.

SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS)

A Single Nucleotide Polymorphism (SNP) are DNA sequence variation that occurs when a single nucleotide in the genome sequence is altered.

…

CTAGATACGAACTGCATC……

CTAGATACGGACTGCATC…O

ccur in atleast 1% of the population and make up about 90% of all human genetic variation•

Frequency: 1: 300 to 500 Nucleotides

PERSONALIZED MEDICINE

It 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.

SIMPLE DEFINITION

CORELATION

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

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.

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