Lecture Notes: Linkage and Chromosome Mapping in Eukaryotes

Instructor: Natalie Prescott

Course: 4BBY1070 Genetics and Molecular Biology

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Key Concepts

• Genetic Linkage: The tendency of genes located close together on a chromosome to be inherited together.
• Linkage Map: A genetic map showing the relative positions of genetic markers along a chromosome based on recombination frequencies.
• Map Unit: A unit for measuring genetic linkage, defined as the distance between chromosome positions (genes) for which the expected average number of intervening chromosomal crossovers in a single generation is 0.01.

Genetic Diversity in Eukaryotes

1. Mechanisms that drive diversity:

   • Independent assortment
   • Homologous recombination during meiosis

2. Independent Assortment:

   • Humans are diploid (23 pairs of chromosomes).
   • Each gamete receives a random set of one chromosome from each pair, resulting in 2^23 possible combinations.

3. Homologous Recombination:

   • Occurs during metaphase I of meiosis when non-sister chromatids exchange genetic material.
   • Leads to new allele combinations on chromatids.
   • Chiasma formation is crucial for recombination.

Genetic Linkage and Recombination

• Recombination Frequency:

  • It is more likely between genes that are far apart on a chromosome.
  • Used to estimate the physical distance between genes (in centimorgans, cM).

• Linked Genes:

  • Genes located close together are less likely to be separated by recombination.
  • This concept helps in constructing linkage maps.

Genetic Mapping Techniques

1. Dihybrid Test Cross:

   • Used to calculate distances between two linked genes.
   • The frequency of recombinants is used to estimate distance in map units (cM).

2. Trihybrid Test Cross:

   • Used for mapping three linked genes and determining their order.
   • Double recombination events (the least frequent) help identify the middle gene.

Application in Drosophila

• Drosophila Mutant Phenotypes:

  • Wild type vs. Mutant for eye, wing, and body color genes.
  • Experimental crosses help in understanding linkage and gene order.

• Thomas Hunt Morgan:

  • Established fruit flies as a model organism.
  • Developed the concept of genetic mapping, using recombination to infer distances.

Human Chromosome Mapping

• Challenges:

  • Fewer progeny, inability to make experimental crosses, complex phenotypes.

• X-linked Traits:

  • Example traits include hemophilia and red-green color blindness.
  • Easier to map due to sex-linked inheritance patterns.

• Linkage Studies:

  • Use polymorphic markers to identify chromosomal regions associated with disease genes.

Advances in Gene Discovery

• Human Genome Project:

  • Provided a complete map of the human genome.
  • Revolutionized disease gene discovery, enabling faster identification using linkage data.

• Whole Genome Sequencing:

  • Allows comprehensive analysis for mutation and linkage regions.

Historical Context

• First Genetic Map:

  • Developed by Alfred Sturtevant using Drosophila.

• Pioneering Studies:

  • Work by JBS Haldane and Julia Bell on X-linked disorders.

Summary

1. Genetic diversity and recombination are key to evolution and species variation.
2. Linkage maps aid in identifying gene locations, crucial for disease research.
3. Modern genomics tools have accelerated discovery and understanding of genetic diseases.

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Questions?

Feel free to ask any questions regarding the lecture materials or the concepts discussed.

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