Recombination and Linkage Analysis Overview

Introduction

• Recombination: Exchange of genetic material between homologous chromosomes during meiosis, leads to genetic diversity.
• Linkage Analysis: Technique to map gene locations on a chromosome based on recombination frequency.

Learning Aims and Outcomes

• Understand recombination processes and molecular mechanisms.
• Comprehend linkage analysis procedure and application in gene mapping.
• Explain recombination frequencies, parental and recombinant classes, and effects of multiple crossovers.
• Map gene locations based on recombination frequencies.

Historical Context

Alfred Henry Sturtevant

• Proposed genes are fixed in a line along chromosomes.
• Created a linkage map using fruit flies based on recombination frequencies.
• Linkage maps show relative gene positions; distant genes recombine more frequently.

Linkage Symbolism and Terminology

• Linkage Symbolism: Notation for gene arrangement on chromosomes.
  • Alleles on different chromosomes are separated by a semicolon.
  • Alleles on the same homolog: in coupling/cis conformation.
  • Alleles on alternate homologs: uncoupled/trans confirmation.

Importance of Recombination

• Increases genetic diversity.
• Separates favorable/unfavorable mutations.
• Prevents fixation of mutations in specific alleles.
• Occurs with precise DNA fragment exchange, no genetic loss/gain.

Genetic Test Crosses

Two-Point Test Cross

• Determines linkage between two genes.
• Involves a heterozygous and a homozygous recessive individual.
• Typical Genotypes and Recombinants:
  • AB/ab: Wild type, 10%
  • Ab/aB: Wild type, 10%
  • AB/AB: Wild type, 0%
  • ab/ab: Mutant, 0%

Three-Point Test Cross

• Determines linkage between three genes.
• Involves a heterozygous and a homozygous recessive individual.
• Typical Genotypes and Recombinants:
  • ABC/abc: Wild type, 5%
  • AbC/aBc: Wild type, 5%
  • ABc/abC: Wild type, 5%
  • abc/abc: Mutant, 0%

Map Distances

• Map Distance: Distance between two genes, measured in centimorgans (cM).
• Determined by crossover frequency.
• Example Distances:
  • Gene A and B: 10 cM
  • Gene B and C: 5 cM
  • Gene A and C: 15 cM

Application of Genetic Linkage Analysis

• Gene Mapping: Locate genes on chromosomes.
• Trait Mapping: Identify genes for specific traits.
• Disease Mapping: Identify genes for specific diseases.
• Forensic Analysis: Use DNA evidence to solve crimes.