Linkage, recombination and gene mapping

What does Mendel’s Law of Independent Assortment assume?

All allele combinations are equally likely (genes assort independently)

When does independent assortment occur?

When genes are on different chromosomes or far apart on the same chromosome

What is genetic linkage?

The tendency of genes close together on the same chromosome to be inherited together

What happens when genes are linked?

They do not assort independently and are inherited together more often than expected

What is recombination?

The exchange of DNA between homologous chromosomes during meiosis

What are recombinant chromosomes?

Chromosomes with new allele combinations different from the parents

What are nonrecombinant (parental) chromosomes?

Chromosomes that retain the original allele combinations

What is recombination frequency (Rf)?

The percentage of recombinant offspring produced in a cross

What is the formula for recombination frequency?

(number of recombinant offspring / total offspring) × 100

What is the maximum recombination frequency?

50%

What does an Rf of 50% indicate?

Genes are unlinked or very far apart

What does an Rf close to 0-50 indicate?

Genes are very close together (tightly linked)

How does distance between genes affect recombination?

The farther apart genes are, the higher the recombination frequency

The smaller the distance, the smaller the frequency

What causes does recombination breakpoint to fall either above or below the two genes (yielding no gametes with chromsomes) and what occurs from this?

Genes are too close to recombine, 0% RF

Where does recombination occur more frequently on chromosomes?

Near telomeres more than centromeres (decrease in recombination)

What factors influence recombination?

1) gene proximity near the telomere

2) the different chromosomes genes lie on

3) Gender

4) Ethnic group

What is a genetic map?

A map showing distances between genes based on recombination frequencies

What is a map unit (centiMorgan)?

A unit of genetic distance equal to 1% recombination (1cM)

Why is observed recombination frequency sometimes underestimated?

Double crossovers can cancel out and go undetected

What is a dihybrid testcross?

A cross between a heterozygote (AaBb) and a homozygous recessive (aabb)

What is the expected ratio in a dihybrid cross if genes are unlinked?

9.3.3.1 phenotypic ratio

Why does linkage distort Mendelian ratios?

Linked genes are inherited together more often, reducing recombinant types

What is coupling (cis configuration)?

Both dominant alleles are on one chromosome and both recessive on the other (AB / ab)

What is repulsion (trans configuration)?

Each chromosome has one dominant and one recessive allele (Ab / aB)

if the recombinant genes are like p+b and pb+ is it cis or trans?

Cis

If the recombinant genes are p+b+ and pb is it cis or trans?

trans

How do you calculate recombination frequency from offspring data?

Count recombinant offspring and divide by total offspring

What is a two-point testcross?

A cross used to measure recombination between two genes

What is a three-point testcross?

A cross used to determine gene order and distances between three genes

In a three-point cross, which offspring are most common?

Nonrecombinant (parental) types

In a three-point cross, which offspring are least common?

Double recombinants

How do you identify the middle gene in a three-point cross?

Compare double recombinants to parentals—the gene that changes is in the middle

What is a single crossover?

Recombination between two genes resulting in two recombinant gametes

What is a double crossover?

Two recombination events that can restore parental allele combinations

How do you calculate map distance between two genes?

Add single crossover and double crossover frequencies

How do you calculate distance between outer genes?

Add distances between inner gene pairs

What is interference?

The phenomenon where one crossover reduces the likelihood of another nearby

What is coefficient of coincidence?

Observed double crossovers / expected double crossovers

How do you calculate interference?

1 − coefficient of coincidence

What does positive interference mean?

Fewer double crossovers than expected

What is linkage analysis?

A method to locate disease genes by tracking inheritance of markers in families

What is a genetic marker?

A known DNA sequence used to track inheritance

How do you identify a disease-linked marker?

It is consistently inherited with the disease phenotype

How do recombinants help in linkage analysis?

They help narrow down the region where the mutation is located

What is a LOD score?

Logarithm of odds comparing likelihood of linkage vs no linkage

What does a LOD score > 3 indicate?

Strong evidence for linkage

What does a LOD score < 0 indicate?

No linkage

Why are LOD scores used?

Human families are small, so statistical support is needed

What is the probability of recombination if genes are unlinked?

50%

What is an association study?

A study comparing allele frequencies between affected and unaffected individuals

What is a GWAS (genome-wide association study)?

A study scanning the entire genome for disease-associated markers

What indicates a risk allele in an association study?

It appears more frequently in affected individuals

What indicates a protective allele?

It appears more frequently in unaffected individuals

What is the difference between linkage analysis and GWAS?

Linkage uses families; GWAS uses populations

What is the key assumption of genetic mapping?

Closer genes have lower recombination frequencies