Complex Diseases & Personalised Medicine

A set of flashcards covering key concepts in complex diseases and personalised medicine.

How are animal models generated?

By gene transfer and tools for gene targeting.

What does genomic engineering utilize?

Programmable nucleases and homologous recombination.

What is CRISPR/Cas?

A highly flexible system for various applications in DNA and RNA engineering.

What technologies analyze whole human genomes?

High-throughput sequencing technologies.

What is pharmacogenomics focused on?

Applications of personalised medicine.

What are the major differences between monogenic and complex diseases?

Monogenic diseases are caused by a single variant, while complex diseases involve combinations of multiple genetic factors.

What is high-throughput sequencing?

A method that allows for the sequencing of DNA quickly and on a larger scale.

How is DNA immobilized during high-throughput sequencing?

By base pairing to attached standard oligonucleotides.

What method is commonly used in second-generation sequencing?

Sequencing-by-synthesis.

What is the advantage of the reversible terminator sequencing method?

It allows for parallel short-read sequencing.

What do the images recorded during sequencing represent?

Each image corresponds to a sequencing cycle; colors indicate specific nucleotides.

What is single-molecule real-time sequencing?

A sequencing method where a single molecule of DNA is sequenced in real-time.

What is the purpose of a ZMW in single-molecule sequencing?

To reduce the detection volume and enhance signal detection.

How does nanopore sequencing work?

A DNA molecule passes through a nanopore, altering ion flow to determine base sequence.

What do we mean by drug disposition?

The process by which a drug is absorbed, distributed, metabolized, and excreted.

What does ADME stand for in drug disposition?

Absorption, Distribution, Metabolism, and Excretion.

What are the two main phases of drug metabolism?

Phase 1 (catabolic) and Phase 2 (anabolic) reactions.

What role do cytochrome P450 enzymes play in drug metabolism?

They are key players in phase 1 reactions.

What are the common types of reactions in Phase 2 drug metabolism?

Acetylation, glucuronidation, sulfation, and methylation.

What kind of response characterizes Type A adverse drug reactions?

An exaggerated response to a standard dose.

What characterizes Type B adverse drug reactions?

An unexpected response unrelated to the drug's normal action.

What is the most common adverse drug reaction?

Gastrointestinal bleeding.

How can genetic variation influence drug metabolism?

Variations can affect drug uptake, distribution, and how the body processes the drug.

What is pharmacokinetics?

The study of how drugs are absorbed, distributed, metabolized, and excreted.

What is pharmacodynamics?

The study of how drugs affect the body and their mechanisms of action.

What is a common example of pharmacogenomics?

The dosage of warfarin based on individual genetic makeup.

What is the significance of VKORC1 and CYP2C9 in warfarin therapy?

They modulate the pharmacokinetic and pharmacodynamic variations of warfarin.

What is a polygenic trait?

A trait influenced by multiple genes.

What role do twin studies play in understanding genetic factors in diseases?

They help estimate heritability and familial risk in complex diseases.

What defines a liability threshold in complex diseases?

A genetic burden that must be exceeded for disease manifestation.

How are complex traits different from Mendelian diseases?

Complex traits have multiple genetic influences and often late onset, while Mendelian diseases have a single genetic cause and early onset.

What are genome-wide association studies (GWAS)?

Studies that identify genetic variants associated with diseases.

What does the odds ratio indicate in genetic association studies?

The likelihood of disease occurrence in individuals with a specific genetic marker versus those without.

What is the role of polygenic risk scores in disease prediction?

To estimate the relative risk of developing a complex disease based on multiple genetic markers.

What are some common ethical issues related to high-throughput DNA sequencing?

Incidental findings, confidentiality, genetic discrimination, and genetic manipulation.

How does the 100,000 Genomes Project relate to personalized medicine?

It aims to advance the implementation of genomic medicine in healthcare.

What is continuous trait variation?

Variation in traits that can be measured along a continuum, like height or body mass.

How can variants influence the pharmacodynamic response to drugs?

Genetic differences can alter the response of drug targets.

What factors can affect an individual's drug response aside from genetics?

Drug interactions, age, and disease status.

What does GWAS data visualisation typically include?

Quantile-quantile plots and Manhattan plots to show the significance of associations.

In terms of genetic studies, what is linkage disequilibrium (LD)?

The tendency of alleles at different loci to be inherited together.

What is the importance of achieving large sample sizes in genetic studies?

To accurately identify loci associated with complex diseases.

What are some limitations of current genetic association studies?

Limited diversity in population studies and challenges in clinical application.

What must be considered when determining the clinical use of polygenic risk scores?

The ancestry of the population in the underlying genetic studies.