14/5 - Human Variation and Genetics

Craig Maritz is the co-convener of the course.
Exam is on May 29th.
Scripts for parasitology mini conferences are due at 2PM on the day of the conference.

Human variation underpins genetics, medicine, and human health.
Variation is shaped by evolution and natural selection driven by pathogens and parasites.
Direct connection between previous lectures on pathogens/parasites and current topic.

Focus is on normal human variation (height, gender, skin color) rather than just genetic diseases.

What is genetic variation in human populations, within populations, and between populations?
How do we define a human population?
How has this variation arisen and been shaped by our evolutionary past?
How do differences in our genotype translate into differences in our traits (phenotypes)?
How can our understanding of variation and genomic tools be used to inform treatment of disease and assess disease risk?

Simple genetic traits (Mendelian traits) controlled by a single gene or a few genes.
Most traits (sporting prowess, height, color) are determined by many genes acting together.
The effect of genotype at one gene can be influenced by the genotype at a second gene.
- Gene A determines a protein product.
- Gene B controls expression of Gene A.

Eye color involves pigments expressed during eye development. Genes also affect skin and hair color.
OCA2 Gene: Determines melanin production.
HERC2 Gene: Controls expression of OCA2.
Lack of OCA2 leads to albinism.
Brown eyes are dominant over blue eyes.
- Blue phenotype requires two copies of the recessive allele.
Multiple alleles can have the same effect on phenotype.

Codominance: Heterozygous alleles result in a distinct phenotype.
ABO blood types are determined by variations in a single gene that codes for antigens on red blood cells.
- A allele: Produces A antigen.
- B allele: Produces B antigen.
- O allele: No antigens.
Each of A and B are dominant over O.
If both A and B are present, both antigens are produced (AB blood type, co-dominance).
Blood type variation is maintained by selective advantage, particularly to rare types in a population. This is influenced by interactions with diseases, bacteria and viruses that shape our immune system.

X chromosome carries many genes, including those for color vision.
Color vision is controlled by opsins or light detectors on cone cells in the retina.
Variations in ability to perceive colors are linked to these opsins.
Two of the opsin genes are on the X chromosome.
Genes can recombine, leading to different variants.
Red-green color blindness is more common in males than females because men only have one X chromosome, there is nothing to mask the color-blindness recessive allele.
- Approximately 8% of males from European descent are red-green color blind, 1% of females.
Females can be carriers of the allele without expressing the phenotype. The allele to be expressed would need to be present on both X chromosomes.

Most human variation is caused by many genes interacting across the genome plus environmental effects.
Example: Human height.
Polygenic Inheritance: Variation due to many genes.
Environmental factors, such as nutrition, also affect height, nutrition during puberty is a significant determining factor of height.
Example: average male height is directly correlated to protein intake. The more protein consumed during puberty, the taller the average male.

P = G + E
- Where:
  - P is the total phenotypic variation.
  - G is the genetic variation.
  - E is the environmental effect.
Genetic and environmental interactions can be complex