Genetics 8 - Further Mapping and Human Haplotypes

Learning Outcomes

  • Ability to describe different methods used to map complex genetic traits.

  • Understanding variations in haplotypes among different human populations using real examples.

Key Concepts

Haplotype Definition

  • Haplotype: A group of alleles inherited together from a single parent.

  • Often discussed in the context of tightly linked Single Nucleotide Polymorphisms (SNPs).

  • This is because SNPs are unique markers and are often inherited together. They contribute to a trait which allow scientists to track the inheritance of such genetic trait.

SNP Mapping

  • Historical Context: The International HapMap Project aimed to locate about 3 million human SNPs before DNA sequencing became cheap and fast.

  • Current Status: Approximately 10 million SNPs identified in the human genome.

  • Principle of Mapping: Closely linked SNPs are passed on together.

Genome-Wide Association Study (GWAS)

  • GWAS Definition: A method utilizing genomes from two groups: one with a specific trait (e.g., high blood pressure) and a control group.

  • Purpose: To identify genetic variants associated with specific traits by comparing the allele frequencies.

  • Outputs: Manhattan Plots for a certain trait where:

    • X-axis: SNP locations in chromosome order.

    • Y-axis: Probability of SNP being associated with the trait; higher probability, higher allele frequency among individuals with the trait.

    • ‘Peaks’ indicate regions of genetic association (e.g., diseases like Systemic lupus erythematosus, Schizophrenia, type-2 diabetes).

Advances in Genomics

  • 100,000 Genome Project (2018): Aimed to improve understanding of rare diseases among NHS patients.

  • 5 Million Genome Project: Ongoing initiative to expand genomic research in the UK.

Haplotypes and Human Evolution

Sickle Cell Haplotype Variations

  • Sickle cell mutation: Identical mutation with variations in SNP combinations, resulting in five distinct haplotypes, indicative of independent origins:

    1. Benin

    2. Cameroon

    3. Central African Republic

    4. Saudi Arabia

    5. India and Senegal.

  • Natural selection favored this mutation due to its malaria resistance, further illustrating the impact of migration on allele frequency in populations (notably in Portugal).

DDT Resistance Example

  • In house flies, a haplotype providing resistance to DDT emerged due to selective pressure, indicating how specific environmental factors can shape genetic diversity.

Human Skin Color Haplotype Variants

  • Color Pigment: Melanin production is influenced by natural selection, leading to diverse skin colors globally:

    • Darker skin evolved near the equator as protection from UV radiation; reduces skin cancer risk.

    • Lighter skin in extreme latitudes allows for better vitamin D production due to lower UV absorption.

  • Vitamin D deficiency: Associated with several health issues, disproportionately affecting darker-skinned individuals in high UV environments.

  • Genetic Variants:

    • SLC24A5 gene: First identified in zebrafish, with human variants A/G correlated with skin color.

    • The A variant is prevalent in Europe (whiter skin), while the ancestral G variant is common in Africa (darker skin).

    • Asian populations also have G variant but with modifications.