Lecture 6: The Promise of the Human Genome Project

Genetics

The study of individual genes and how they contribute to a trait

Genomics

Understanding the multifactorial modes of inheritance

8, centromeres, telomeric regions, immune system genes, genes for medication reactions

In 2022, 200 million letters of code were added the the HGP making up the last ___% of the genome and including mostly _____ and some _____. Other genes included ______ and ______

Pan Genome

A composite genome developed by sequencing genomes from 47 participants of varying ethnicity

Personalised Medicine

A form of medicine that uses information about a person’s own genes or proteins to prevent, diagnose, or treat disease

P450 cytochrome, enzymatic activity, ¼ of all prescription drugs, metabolise codeine

Up to 10% of individuals have a mutation in CYP2D6, a ________, that limits ______— CYP2D6 metabolises _______ and people deficient can not _______

symptoms of morphine overdose with therapeutic doses of codeine

Those who have hypermorphic CYP2D6 activity can experience…

Warfarin

Anticoagulant that works by decreasing the amount of available vitamin K, which is required for blood clotting

risk of hemorrhage, risk of thrombosis/embolism, 20, Asian

Too high warfarin dosages can increase ______ while too low dosages increase ______. The effective dose of warfarin varies up to _____ times between patients, particularly of ______ heritage

R, CYP1A2 and CYP3A4, L, CYP2C9

The ___ isoform of warfarin is less potent and is metabolised by ______ while the ____ isoform is more potent and is metabolised by _____

genotype does not predict the patient’s full respones

The CDC recommends genotyping before prescribing warfarin but this never happens because…

East Asians, Westerners, Chinese, COX2, ITGA2

Aspirin has an increased risk of gastrointestinal bleeding in ______ compared to _____— aspirin-resistance is more common in ____ populations due to polymorphisms in ____ and ____

Han Chinese, Thai, gout

Some ethnic groups such as ____ and ____ have increased risk of adverse reactions to allopurinol, a medication used to treat _____

MC1R

Gene expressed on the surface of melanocytes and regulates pigment formation— is the gene mutated in people with red hair in which the mutant causes excess pheomelanin production

an individual’s response to a drug is multifactorial (genes, environment, polygenic effects)

Progress in personalised medicine is much slower than previously hoped with the human genome project because…

predict, prevent, participate, personalise

The P4 approach is:

we probably do not know enough for most conditions (yet) and patients will never know enough

Genetics is instrumental in the pillars of P4 medicine but…