Dit document omvat de samenvatting (info slides + lesnotities) van les 7 van het vak 'genome technology and applications'. Les 4 was gewoon een inleiding van NGS voor de taak. Hierbij moet je in groep een presentatie geven over een bepaalde NGS techniek.
Pharmacogene+cs and genomics
Introduc)on
- The study of the gene/c modifica/ons of variable human responses to
pharmacological agents
- We all differ in all aspect. It is very unlikely that we would react on drugs in the same
way -> we differ on all levels
- If you have a health problem -> you go to the doctor -> diagnosis -> drug
o If this doesn’t work -> back to the doctor -> change diagnosis -> change
treatment
- What we are aiming is to move to personalized medicine
o individual risk for complex diseases
§ Because of gene/c factors
o Individual reac/on to drugs
o Feasible?
§ Need for insights into individual gene/c and environmental risk factors
§ => analysis of genome is feasible
• Clear guidelines for the use and interpreta/on of risk analysis for the
clinicals
- Many drugs only response rate between 25 and 75%
o A large number of the drugs don’t help the pa/ents
- The overall incidence of adverse drug reac/ons is about 5-10%
- Adverse effects lead to 2 million people hospitalized/ year of which 100.000 die
o They get a drug which wasn’t a good drug of them
- These unan/cipated reac/ons to medica/ons are largely gene/cally determined.
➔ Pharmacogene/cs encompasses any gene/cally determined varia/on in response to
drugs
The gesta)on of a new discipline
- Osler: medicine is not really science, more art because pa/ents are so different
- Garrod: if you give a drug some pa/ents will not react and other will overreact
- 1932: biZer taste blindness for phenylthiocarbamide with racial differences
o How we feel the taste of this product is gene/c determined
- World war II: acute hemoly/c crises in 10% of American soldiers (few Caucasian)
treated with an/malarial drug (primaquine)
o Also here the background defined how the soldiers would react
o Ethnic background has an influence
- 1957: “inheritance might explain many individual differences in the efficacy of drugs
and in the occurrence of adverse drug reac/ons” Motulsky
- 1959: “Pharmacogene/cs: the Role of Gene/cs in Drug Response” Friedrich Vogel
Evidence for gene)c determinants for drug effect
- Link between ethnicity and aberrant drug responses
- Link between inheritance and aberrant drug responses
- 1957-1970: Evidence for heritability by family and twin studies
Appearances of “pharmacogene)cs” and “pharmacogenomics” in PUBMED
- In the beginning of the century almost no papers, now we have an increase
, Adminstra)on of drugs
- Give drug to pa/ents
o Plasma concentra/on will increase
o We want to reach a concentra/on that is in the therapeu/c range -> we see the
effect of the drug
§ Below threshold -> therapeu/c failure
§ Over threshold -> toxic levels -> adverse effects
Aims of pharmacogene)cs
- Improving therapeu/c efficacy
- Reducing drug toxicity
- Reducing costs
è “Personalized medicine”
Possible explana)ons for differences in drug response
- There are number of /me points where there can be differences in the reac/on
o The way the drug is given
o Absorp/on of the drug
o Transport of the drug
o Metabolizing steps are involved
o Reach the site of ac/on: there are cells that have a receptor -> varia/on in
receptor can influence how the pa/ent will react
o Excre/on of the metabolites can also be different
- An/ epilep/c drug: Metabolized in the liver -> need to be transported through the
BBB -> effect on some parts of the brain
o On all these places varia/ons can occur
- Gene/c differences in absorp/on and transport of drugs
- Gene/c differences in metabolisa/on of drugs
- Gene/c differences in drug target
o Human growth hormone
o B1 adrenerg receptor: sensi/vity for B-blocking agents
- Differen/a/on between subtypes of a disease
o Biochemical markers
§ Can indicate with what type of disease you are dealing with
o Gene/c markers
§ Cytogene/c abnormali/es in cancer/gene/c polymorphisms
Les avantages d'acheter des résumés chez Stuvia:
Qualité garantie par les avis des clients
Les clients de Stuvia ont évalués plus de 700 000 résumés. C'est comme ça que vous savez que vous achetez les meilleurs documents.
L’achat facile et rapide
Vous pouvez payer rapidement avec iDeal, carte de crédit ou Stuvia-crédit pour les résumés. Il n'y a pas d'adhésion nécessaire.
Focus sur l’essentiel
Vos camarades écrivent eux-mêmes les notes d’étude, c’est pourquoi les documents sont toujours fiables et à jour. Cela garantit que vous arrivez rapidement au coeur du matériel.
Foire aux questions
Qu'est-ce que j'obtiens en achetant ce document ?
Vous obtenez un PDF, disponible immédiatement après votre achat. Le document acheté est accessible à tout moment, n'importe où et indéfiniment via votre profil.
Garantie de remboursement : comment ça marche ?
Notre garantie de satisfaction garantit que vous trouverez toujours un document d'étude qui vous convient. Vous remplissez un formulaire et notre équipe du service client s'occupe du reste.
Auprès de qui est-ce que j'achète ce résumé ?
Stuvia est une place de marché. Alors, vous n'achetez donc pas ce document chez nous, mais auprès du vendeur evagoormans. Stuvia facilite les paiements au vendeur.
Est-ce que j'aurai un abonnement?
Non, vous n'achetez ce résumé que pour €7,16. Vous n'êtes lié à rien après votre achat.
