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Assignment – 01
Pharmacogentics-Genomics in
relation to molecular Diagnosis -
Molecular Therapeutic technologies
By
Narra ...
Interrelation between the pharmacogenomics
and Genetics
• Both are nearly same but the study range is variying
• Pharmacog...
Pharmacogenomics - Genetics
• genome-wide approaches
• more than 1,000,000
polymorphisms
• Study of polymorphisms
• Exampl...
Why the study is needed
• Due the genomic variation
• Due to the environmental factors - Ecogenetics
• Example :- ethanol ...
Molecular Therapeutic technologies
Personalised medicine
• Personalized medicine is a broad health care that is informed by each
person’s unique clinical, ge...
Therapeutic principles
• All drug effects vary from person to person and all drug effects are influenced by
genes.
• Most ...
• Genetic polymorphisms of drug targets and drug transporters are increasingly
recognized (receptors, ion channels, growth...
The main principle involved is
Genetic Polymorphisms in Drug Metabolism and
Disposition
• Genetic Polymorphisms in Drug Targets
• Genetic Polymorphisms i...
Example :- selection and dosing of chemotherapy
for a patient with acute lymphoblastic leukemia
(ALL)
• Genetic polymorphi...
Examples for the drug metabolism
Molecular Diagnosis
Diagnosis
• Next generation sequencing.
• DNA chip.
• Transcriptome profiling.
References:-
• Genomic and personalized medicine: foundations and applications GEOFFREY S.
GINSBURG et al., Translational ...
 pharmocogenomics and genetics in relation with molecular therapeutics and diagnosis
 pharmocogenomics and genetics in relation with molecular therapeutics and diagnosis
 pharmocogenomics and genetics in relation with molecular therapeutics and diagnosis
 pharmocogenomics and genetics in relation with molecular therapeutics and diagnosis
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pharmocogenomics and genetics in relation with molecular therapeutics and diagnosis

  1. 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
  2. 2. 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.
  3. 3. 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
  4. 4. 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
  5. 5. Molecular Therapeutic technologies
  6. 6. 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
  7. 7. 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.
  8. 8. • 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.
  9. 9. The main principle involved is
  10. 10. Genetic Polymorphisms in Drug Metabolism and Disposition • Genetic Polymorphisms in Drug Targets • Genetic Polymorphisms in Drug Transporters
  11. 11. 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.
  12. 12. Examples for the drug metabolism
  13. 13. Molecular Diagnosis
  14. 14. Diagnosis • Next generation sequencing. • DNA chip. • Transcriptome profiling.
  15. 15. 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
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    Feb. 15, 2015

Pharmacogentics-Genomics in relation to molecular Diagnosis -Molecular Therapeutic technologies

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