Genes, Environment and Epidemiology

This isn't technically something I read, but rather a lecture in which I am sitting currently.
The problem is that I am already focused on the long weekend ahead, and I don't think this stuff is on any upcoming exams. Therefore, sharing some of these ideas with you may help them stick in my mind.

Central Dogma
Gene transcribed into mRNA then translated into protein and stuff.

Human Genome
3 billion base pairs
30,000 genes
46 chromosomes

Genetic Variation
a. Mutations include deletions, insertions, gene rearrangements, chromosome translocations, copy number variants
b. Polymorphisms are when alternate forms are present. Single nucleotide polymorphisms (SNPs)

Penetrance = strength of the association between a mutation/allele and risk of disease.
expressed by the proportion of variant carriers who develop phenotypic manifestations.

Genetic Epidemiology Approaches
Hope to figure out relative contributions of genetic and environmental factors.
Example: Down syndrome associated with leukemia or alzheimer's?

Time trends = compare disease rates over time.
sharp increase over time points to environmental factor because genetics don't change very quickly.
Melanoma is an increasing very quickly, but why?

Age of onset can also give clues about etiology.
Germ-line mutations have earlier onsets.
Somatic mutation/environmental exposure take longer to lead to disease state.

Family studies
look in family trees (pedigrees aka genogrames)
a. segregation analysis -- is observed pattern similar to mendelian theories?
b. linkage analysis --can help to identify and localize where the guilty gene is.

Twin studies
a. monozygotic twins share 100% of genes.
b. dizygotic tins share 50% of genes
compare the concordance rate between the two.

Adoption studies
can show if some disease is genetic or environmental
especially interesting with behavioral things

Migrant studies
Comparison of disease rates between people in their home country and the same people once they migrate to a new place.

Genetic Markers
DNA markers
SNPs
RNA markers
Protein markers

When disease process identified, try to think which of the following area is most likely for some malfunction.
Metabolism genes
DNA repair genes
Immune function genes
Cell-cycle control genes

Genome-wide association studies (GWAS)
Simultaneous scanning of markers (SNPs) across complete sets of genomes.
Case-control study design.
New pathways can be identified.
Unfortunately variations identified are likely not causal.

Phenylketonuria (PKU) is a metabolic disorder resulting in mental retardation in children.
Requires genetic mutation and dietary exposure to phenylalanine

Nature vs. Nurture
Genetic factors explain only a small proportion of disease.
Remainder can be attributed to environmental factors.
But really it's the interplay between the genetic and environmental factors.
Gene-environment interaction (GE interaction)
Again can use 2X2 tables to figure out relative risk.
This is effect modification.

This lecture is going way to fast to really catch anything or have a moment to think.
Presenter is literally speaking at double speed.

Pharmacogenomics
Genetic variation can impact whether or not a drug is beneficial or toxic.
Gene expression profiling.