Chapter 7: linkage, recombination, and eukaryotic gene mapping

Principle of Segregation

During meiosis, chromosome pairs separate into different gametes such that each of the two alleles for a given trait appears in a different gamete.

Principle of independent assortment

genes for different traits can segregate independently during the formation of gametes (don't influence each other)

Genes stick together

In reality, many gene pairs do not assort independently
We know that each chromosome hosts thousands of genes
For humans around 20,000 protein genes distributed on 2023 chromosomes

4 situations for two genes

Unlinked: genes on a separate chromosome
Unlinked: genes on the same chromosome
Linked: on the same chromosome
Completely linked: on the same chromosome

Unlinked-genes on a separate chromosome

Located on different chromosomes and separate independently during meiosis

Unlinked- genes on the same chromosome

Far apart on the same chromosome as if two different chromosomes, crossover, and separate independently during meiosis

Linked genes-on the same chromosome

They are close to each other on the same chromosome, but can separate from each other by occasional crossing over with alleles on homologous chromosomes during meiosis

Recombinant

An offspring whose phenotype differs from that of the parents; also called recombinant type.

non-recombinant

An offspring whose combination of traits has not changed from the parental generation.

Completely linked- on the same chromosome

Genes are too close to each other on the same chromosome (tightly linked) cannot separate from each other by crossing over during meiosis

How do you know the two genes are linked?

Look at the % recombinant gametes
50% is unlinked
Less than 50% is linked
0% is completely linked

two configurations for linked genes

Coupling or cis
A B
a b

Repulsion or trans
A b
a B

For unlinked write as: AaBb
For linked : AB/ab or Ab/aB

Determination of the present of recombinant gametes

For example, if you have 50 meiosis events and only one crossing over occurs between two genes
-50 meiotic cells produce 200 gametes (50•4=200)
Linked

2% of meiotic cells (1/50) had a single crossover
One% of recombinant gametes (2/200)
-0.5% Ab; 0.5% aB (1/200=0.5)

Therefore, percent of two recombinant gametes is always half of the percent of meiosis with a single crossover

Linked genes

With linked genes and some crossing over, non-recombinant progeny predominate

Recombinant frequency

# every recombinant progeny/ total # of progeny

Genetic Map Units

1 map unit (m.u.) for every 1% of meiosis that is recombinant
The maximum recombination frequency is 50% or (cM=50)
If 0% or cM=0, cannot distinguish two genes on the same chromosome

double crossover

Double exchanges of genetic material
Used to determine distance between three linked genes
Genes must be heterozygous for two alleles
We cannot distinguish double crossover progeny from no crossover progeny as it underestimates the gene distance

Centimorgan (cM)

A unit of distance between genes on chromosomes.

Double crossover conclusion

Recombinant chromosomes, resulting from the double crossover have only the middle gene altered

Three-point test cross

A test cross where one parent is heterozygous for 3 genes. Used in linkage analysis and gene mapping.

Mapping distance of three genes

Add single crossover and double crossover frequencies to get map distance

Goal of mapping

To localize mutant genes causing disease