14/5 - Human Variation and Genetics

Introduction to Human Variation

• 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.

Understanding Human Variation

• 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.

Course Overview

• Introduction to human variation.

• The human genome and its functions.

• Causes of variation: mutation, recombination, genetic mixing.

• Selection and its impact on human variation.

• Modern genetic and evolutionary medicine and its ethical considerations.

Shifting Focus

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

Key Questions

• 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?

Essential Terminology

• The course is about variation, not a formal deep dive into genetics.

• Recommended prerequisite reading provided online to explain key terms.

Basic Concepts:

• Cells and Genetic Material: DNA, chromosomes.

• DNA Expression: DNA -> RNA -> proteins.

• Chromosomes: Located within the nucleus.

• Human genome is organized into two sets of 23 chromosomes.

  • Diploid (2n): normal body cells.

  • Haploid (n): eggs and sperm.

  • 22 autosomes (shared by males and females).

  • 1 sex chromosome (X and Y).

    • Females: XX

    • Males: XY

• Gene: Part of the genome that determines a function.

• Alleles: Variants of a gene.

• Homozygous: Two identical alleles.

• Heterozygous: Two different alleles.

• Dominance/Recessive: How alleles are expressed.

• X-linkage: Genes located on the X chromosome.

Types of Variation

• Physical attributes: height, skin color, hair color.

• Metabolic traits: metabolic rate, temperature regulation, blood pressure.

• Brain function and immune function.

Phenotype vs. Genotype:

• Phenotype: Visible and physiological characteristics.

• Genotype: DNA sequence and how genes are expressed.

Other Types of Variation:

• Linguistic variation.

• Cultural variation: value systems, ethics, religions, beliefs.

Genetic Variation

• 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 Example

• 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.

Pedigree Analysis:

• Recessive traits (blue eyes) can skip generations.

• Depends on whether offspring are heterozygous or homozygous.

Geographic Variation:

• Different alleles for blue eyes are more common in certain populations.

• Hypotheses: sexual preference, adaptation related to skin color.

Gene Interaction:

• HERC2 controls OCA2 expression.

• Epistasis: Outcome of alleles at one gene depends on another.

Blood Groups Example

• 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-Linkage with Color Blindness

• 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.

Polygenic Inheritance and Environmental Effects

• 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.

Equation for Variation

• 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