Topic 1 - Introduction to Genetic Analysis

Genetics

Analysis of the relationship between genotype and phenotype

Genotype

Genetic constitution of an organism, with respect to one or a few genes under consideration

-Denoted via references to alleles

-Two alleles of a gene that are the same are “Homozygous”, two alleles of a gene that are different are “Heterozygous”

-When denoting phenotypes, alleles involved must use the same symbol

Phenotype

Observable characteristics of an individual which are a result of interactions between genotype and the environment

Allelic Heterogeneity

Occurs when a similar phenotype (along a spectrum) is produced by different mutations (alleles) of the same gene

-Example: Fruitfly eye colours being white (w), light orange (wa), dark orange (wco) and red (we)

Phenotypic Heterogeneity

Occurs when a different phenotype is produced by different mutations of the same gene

Determining Phenotype

-Visual inspection (microscopy, staining

-Biochemical/chemical assays

-Behavioural assays

Genetic Analysis

Field of study in which properties of genes are used as an approach to solving/dissecting complex biological problems/process

-Manipulating genotypes/genes

-Analyzing phenotypes

-Drawing conclusion of the relationship

Approaches to Genetic Analysis

Forward Genetics - “What gene causes this phenotype?”

Reverse Genetics - “What phenotype does this gene cause”

Forward Genetic Approach

-Select biological process

-Generate mutants

-Screen and select for mutants with desired phenotype

-Map and clone the gene responsible for the phenotype

-Determine molecular/cellular function of the isolated gene

Reverse Genetic Approach

-Select gene of interest

-Generate mutations to the sequence

-Introduce sequences into the host

-Screen transformants

-Analyze phenotype of the mutants

Forward Genetics Advantages

1. Time tested approach used with much success

2. Doesn’t require prior knowledge of the “system” (truly unbiased)

3. Works well for phenotypes that can be distinguished quickly/easily

4. Stable mutant lines generated

Forward Genetics Disadvantages

1. Phenotypes that are hard to evaluate make approach tedious

2. Only one trait is examined

3. Some genes may be missed

Reverse Genetics Advantages

-Targeted approach (individual gene or group of genes)

-Can apply a high-throughput approach

-Often know molecular function of the gene — insight into phenotype

Reverse Genetics Disadvantages

-Requires a known gene sequence

-With some methods, may not achieve “null” mutation

-Require transformation method (most model organisms have such)

-May have off-target effects with some methods