DPT 756 Lec 1 pt 4 SNPs & epigenetics

Factors that increase likelihood of genetic mutations (2)

Chemical mutagens (ex. pollution, chemical exposures)

Ionizing radiation (ex. X-rays, metal detectors)

What type of mutations do chemical mutagens typically cause? Ionizing radiation?

Chemical mutagens: Point mutations

Ionizing radiation: Large insertions, deletions, translocations

Are all gene mutations deleterious?

No, some can be beneficial, can cause positive adaptations

Define SNPs. Frequency?

Single nucleotide polymorphisms: Most common genetic variation

Difference in one nucleotide

1/1000 nucleotides

How do SNPs affect health outcomes for different people?

Cause diversity in traits

Can be silent or benign, beneficial, or problematic

How do SNPs affect precision medicine and precision rehabilitation?

SNPs can predict health traits about people, which can make it easier to write super personalized health plans for patients

Through evolution, genes are...

Conserved

What percentage of genes are unique to humans? Implication?

Only 1% of genome is unique to humans

Makes it easy to perform animal studies

What does it mean for a species to be "experimentally tractable"?

It's easy to control all the variables about the animal in the experiment

Model organisms that are often used for genetics research (4)

Fly

Mouse

Worm

Rat

What percentage of human genes have been demonstrated/ inferred from orthologous genes in other organisms?

About 1/2 of all human genes

Why is it easier to use animals to study genetics than humans? (3 reasons)

We cannot inbreed or crossbreed humans

Genes and environment interact

Ethical conflict with human genomic testing

How many human diseases have been CURED because of animal testing?

Over 600 diseases!

How does the gene for phenylalanine hydroxylase demonstrate the connection between genes and neural disease?

If the gene for PA is abnormal, patients unable to absorb PKU -> Cognitive impairments

Shows how genes impact neural disease

Describe the multigenic involvement of autism spectrum disorder (ASD). Implication?

ASD involves many many different genes

Psychiatric conditions have complex multigenic origins

Types of traits that genes influence (3)

Psychological traits

Physiological

Cognitive

Inter-individual differences are a result of the interplay of these factors (4)

Genetics

Environment

Chance

Individual choice

Define epigenetics

Changes to gene expression that occur because of environmental factors

Are epigenetic changes potentially heritable?

Yes

Describe how epigenetic changes can affect offspring

Changes to gene expression may occur in offspring, or may not

Describe how methylation causes epigenetic changes

Methylation ("tagging" certain genes) can either promote, enhance, or turn off genes

What area of genes are methylated?

Histones (tails)

Relationship between tightness of histone spools, methylation, and gene expression

Tightly wound histones -> more methylated -> changes whether gene is read or not

Does methylation enhance or impede gene transcription?

Impede gene transcription, turns genes "off"

(Can be good or bad)

Define precision medicine

Medicine that takes into account a patient's genetic makeup, physical and biochemical markers, developmental hx, environment, society

How is precision medicine more precise than one-size-fits-all?

Risk for disease and effectiveness of potential treatments are estimated directly from patient's unique combo of factors

Define BDNF. Function?

Brain derived neurotrophic factor: Powerful, activity dependent neurotrophic factor that enhances neuroplasticity

(Fertilizer for brain)

What is the Vall66Met polymorphism?

SNP that affects how BDNF is trafficked in cells

Which Vall66Met polymorphism has the best BDNF trafficking? Worst? Implication?

Best: val/val

Worst: met/met

People with val/met or met/met need more activity for comparable BDNF activation

Define the apolopoprotein E SNP. Function?

APOE SNP: Regulator of lipid metabolism and transport.

Predicts risk of Alzheimer's disease (AD)

Relationship between E2, E3, E4 APOE alleles and AD

E2/E2: Best outcomes (least likelihood of AD)

E3/E3: Average

E4/E4: Worst outcomes (highest likelihood of AD)

Disadvantageous traits of E4/E4 carriers (2)

Higher risk of AD, death during stroke, motor progression of PD

Poorer outcomes after TBI and falls