Recombination and Linkage Analysis Overview

Introduction

• Recombination and linkage analysis are essential in genetics.
  • Recombination: Exchange of genetic material between homologous chromosomes during meiosis, increasing genetic diversity.
  • Linkage Analysis: Maps gene locations on chromosomes based on recombination frequency.

Learning Aims and Outcomes

• Appreciate recombination and its molecular mechanisms.
• Understand linkage analysis in gene mapping.
• Explain linkage analysis details, including:
  • Recombination frequencies.
  • Parental and recombinant classes.
  • Consequences of multiple crossovers.
• Understand mapping locations of linked genes based on recombination frequencies.

The First Linkage Map: Alfred Henry Sturtevant

• Sturtevant's proposition:
  • Genes are fixed linearly along chromosomes.
  • Used Morgan's fruit flies for linkage mapping.
  • Map based on observed recombination frequencies.
• Linkage map shows relative gene positions:
  • Distant genes have higher recombination likelihood.

Linkage Symbolism and Terminology

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

Importance of Recombination

• Essential for genetic diversity and separating mutations.
• Without it, chromosome content would be fixed.
• Occurs during exchange of DNA fragments between chromatids.

Two-Point Test Cross

• Used to determine linkage between two genes.
• Involves heterozygous and homozygous recessive individuals.
• 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 heterozygous and homozygous recessive individuals.
• Genotypes and recombinants:
  • ABC/abc (Wild type): 5%
  • AbC/aBc (Wild type): 5%
  • ABc/abC (Wild type): 5%
  • abc/abc (Mutant): 0%

Map Distances

• Refers to gene distance on a chromosome, measured in centimorgans (cM).
• Determined by crossover frequency.
• Example Map Distances:
  • A to B: 10 cM
  • B to C: 5 cM
  • A to C: 15 cM

Application of Genetic Linkage Analysis

• Gene Mapping: Locating genes on chromosomes.
• Trait Mapping: Identifying genes for specific traits.
• Disease Mapping: Identifying genes causing diseases.
• Forensic Analysis: Using DNA evidence in crime-solving.