L5 Gene Mapping 24-25

Lecture Overview

  • Course: Genes, Evolution and Development (BIOL10521)

  • Instructor: Dr. Samina Naseeb

  • Email: Samina.naseeb@manchester.ac.uk

Contents of Today's Lecture

  • Different types of gene maps

  • Importance of gene mapping

  • Overview of linkage mapping

Gene Maps: Definition

  • Each chromosome contains many genes.

  • Gene map:

    • Illustrates the relative order of genes on a chromosome.

    • Displays the distance between genes.

Importance of Gene Maps

  • Helps identify genes linked to diseases or traits through positional cloning.

  • Aids in studying gene function.

  • Supports plant and animal breeding programs.

  • Facilitates comparison of genome structures across species (conserved/shared synteny).

Types of Gene Maps

  1. Genetic/Linkage Map

  2. Cytogenetic Map

  3. Physical Map

    • 1 centiMorgan (cM) is approximately equal to 1 Megabase (Mb) in humans.

    • 1 Megabase (Mb) = 1 million base pairs.

Physical Map Example

  • CFTR gene: Mutated in cystic fibrosis.

  • Construction Methods:

    • Initial physical maps were developed using restriction enzymes that cut DNA at specific sites.

    • The Human Genome Project provided a comprehensive physical map with complete DNA sequence information.

Human Cytogenetic Maps

  • Utilizes G-banding after mild proteolytic digestion and staining with Giemsa.

  • About 850 G-dark bands identified across 23 human chromosomes.

  • Genes are assigned based on location: short arm (p) or long arm (q), specific regions, bands, and sub-bands. Example: CF gene position is 7q31.2.

Linkage Maps of Drosophila melanogaster

  • Illustrates various traits with distances between linked genes on Chromosome 1(X), showing significant genetic markers and their distances.

Genetic Linkage Principles

  • Alleles of genes on the same chromosome usually segregate together in gametes unless affected by crossing-over during meiosis.

  • Crossing-over can occur randomly.

  • Frequency of crossing-over is proportional to the physical distance between genes on the chromosome.

Measuring Crossing-Over Frequency

  • Frequency of recombinant gametes can give an estimate of the distance between genes.

Genetic Consequences of Crossing-Over

  • If no crossover occurs, parental gametes are produced.

  • More frequent crossing-over leads to a higher proportion of recombinant gametes.

Recombination Frequencies vs Distance

  • Recombination Frequency (RF): Calculated as

    • RF = (Number of recombinant gametes / Total gametes) x 100

  • Implications for mapping:

    • Close genes < 50% RF = linked.

    • Genes on different chromosomes or further apart have 50% RF.

Testcross for Linkage Mapping

  • Design crosses to determine gamete genotypes based on phenotypes of offspring, known as testcross.

  • Method steps:

    • Create double heterozygote.

    • Use testcross to determine parental vs recombinant gametes.

Linkage Mapping Calculation

  • Use the formula for RF to determine genetic distance:

    • Units in centiMorgans (cM); e.g., 10% RF = 10 cM.

Two-Point Mapping Experiment

  • Example: Calculate RF using crosses to determine genetic distances between traits.

  • Importance of identifying parental vs recombinant types in analyzing traits and phenotypes.

Combining Map Distances

  • Genetic distances are used to construct linkage maps with associated traits.

  • Note: Genetic distances are approximately linear, but may not be precisely additive due to multiple crossover events or interactions.

Summary of Linkage Mapping Principles

  • Frequency of crossing-over is inversely related to distance between genes.

  • RF < 50% indicates linkage.

  • Distances are measured in centiMorgans (cM) but not perfectly additive over long distances.

Practice Problems

  1. Classify offspring from eye color distributions in fruit flies to determine parental types, gamete genotypes, and map distances.

  2. Calculate expected percentages in progeny based on known genetic distances between traits on the same chromosome.

Future Topics

  • Upcoming lectures on Human Genetics.

Learning Outcomes

  • Understand differences among linkage maps, physical maps, and cytogenetic maps.

  • Identify various progeny types in two-point crosses, calculate map distances, and construct linkage maps from two-point cross data.

Recommended Readings

  • Biology Textbook (10/11e), Chapter 15 (15.3)

  • iGenetics 3e by PJ Russell, pages 405-410.