This document discusses the relationship between pharmacogenomics, genetics, and molecular diagnostic and therapeutic technologies in relation to personalized medicine. It explains that pharmacogenomics studies drug response in relation to an individual's entire gene complement, while pharmacogenetics focuses on a smaller number of genes. The study of these fields is important for personalized medicine due to genetic and environmental factors that influence drug metabolism and response. Molecular diagnostic technologies like next generation sequencing and DNA chips can provide genetic information to guide personalized treatment selection and dosing based on a person's genetic profile. The goal of these approaches is to optimize medical care for each individual.

1. Assignment – 01
Pharmacogentics-Genomics in
relation to molecular Diagnosis -
Molecular Therapeutic technologies
By
Narra Naga Pavan Kumar (KVPY Fellow)
1st M.Tech Biotech (14IS1D0301)
Institute of Science & Technology, JNTUK University

3. Interrelation between the pharmacogenomics
and Genetics
• Both are nearly same but the study range is variying
• Pharmacogenomics is the branch of pharmacology that involves the
study of drug response with the entire compliment of genes.
• Pharmacogenetics, refers to study of drug response with a relatively
restricted number of genes.

4. Pharmacogenomics - Genetics
• genome-wide approaches
• more than 1,000,000
polymorphisms
• Study of polymorphisms
• Example :- next generation
Sequenceing
• Gene wide approach
• More then 25, 000 genes
• Study of mutations
• Example :- Microarrays

5. Why the study is needed
• Due the genomic variation
• Due to the environmental factors - Ecogenetics
• Example :- ethanol sensitivity, which is related to acetaldehyde-
dehydrogenase deficiency.
• Due the food we are taking
• Example :- milk intolerance because of lactase deficiency.
• The immune responses of a person
• Toxicogenetics :- Example :- carcinogens
•Results = personalised medicine

7. Molecular Therapeutic technologies

8. Personalised medicine
• Personalized medicine is a broad health care that is informed by each
person’s unique clinical, genetic, genomic, and environmental
information to individualizing patient care across the continuum
(from health to disease).
• Goal :- to optimize medical care and outcomes for each individual, to
include treatments, medication types and dosages, and/or prevention
strategies may differ from person to person

9. Therapeutic principles
• All drug effects vary from person to person and all drug effects are influenced by
genes.
• Most drug responses are multifactorial (that is, many genes and many
environmental factors contribute to them).
• Genetic polymorphisms of single genes, including mutations in coding sequences,
gene duplications, gene deletions and regulatory mutations affect numerous drug-
metabolizing enzymes. Several cytochrome-P450 enzymes (for example, CYP2D6
and CYP2C9), N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT)
and UDPglucuronosyltransferases (UDP-GT) are examples. Individuals that possess
these polymorphisms are at risk of experiencing documented adverse reactions or
inefficacy of drugs at usual doses.

10. • Genetic polymorphisms of drug targets and drug transporters are increasingly
recognized (receptors, ion channels, growth factors) as causing variation in drug
responses.
• Several targets of cancer therapy, for example, the epidermal-growth-factor
receptor, respond to treatment only in subgroups of patients who carry sensitizing
mutations of these targets.
• The frequency of variation of drug effects,whether multifactorial or genetic,
varies considerably in ethnically defined populations (for example, alleles of N-
acetyltransferases).
• Application of response-predictive genetic profiles (for example, genotyping for
polymorphisms in antidepressant or cancer-drug therapy) on clinical outcomes
has, so far, been done mostly in academic centres and has not yet reached clinical
practice.

11. The main principle involved is

12. Genetic Polymorphisms in Drug Metabolism and
Disposition
• Genetic Polymorphisms in Drug Targets
• Genetic Polymorphisms in Drug Transporters

13. Example :- selection and dosing of chemotherapy
for a patient with acute lymphoblastic leukemia
(ALL)
• Genetic polymorphisms in drug-metabolizing enzymes can have a profound effect
on toxicity and efficacy of medications used to treat ALL and that individualizing
drug dosages can improve clinical outcome.
• It has also been established that the genotype of leukemic lymphoblasts is an
important prognostic variable that can be used to guide the intensity of
treatment.
• all these will be placed on a chip called ALL Chip give the results for a selective
therapy. (reference William E. Evans, et al Science 286, 487, 1999) as same as
microarray technology.

14. Examples for the drug metabolism

15. Molecular Diagnosis

16. Diagnosis
• Next generation sequencing.
• DNA chip.
• Transcriptome profiling.

19. References:-
• Genomic and personalized medicine: foundations and applications GEOFFREY S.
GINSBURG et al., Translational Research December 2009;272 – 287.
• Molecular Genetic Markers as A Basis for Personalized Medicine Sonja Pavlovi et
al., J Med Biochem 33: 8–21, 2014.
• Pharmacogenetics: data, concepts and tools to improve drug discovery and drug
treatment Jürgen Brockmöller et al., Eur J Clin Pharmacol (2008) 64:133–157.
• Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics
William E. Evans, et al. Science 286, 487 (1999).
• Pharmacogenetics – five decades of therapeutic lessons from genetic diversity,
Urs A.Meyer, Nature Reviews Genetics September 2004, vol 4, 669 -676