Genetics Lecture 9: Linkage & Chromosome Structure

Using a linkage analysis, geneticists discovered male pattern baldness was associated with

SNPs on the p-arm of the X chromosome

What are linkage groups?

Groups of genes that are physically connected, They can have different alleles and crossing over breaks up linkage groups

Linked genes far apart vs linked genes close together

Genes far apart appear to segregate independently whereas genes close to each other will not assort independently

Who discovered two genes that did not assort independently?

William Bateson and Reginald Punnett

Who were the scientists involved in the race to prove recombinations?

Harriet Creighton and Barbara McClintock vs Curt Stern

What is the purpose of genetic mapping?

To determine the linear order of linked genes along chromosomes. Each gene has its own unique locus

What is the purpose of genetic maps?

Estimates the relative distance between linked genes.

Why is the distance between genes important?

Recombination frequencies are correlated with the distance between genes.

Far apart genes=Many recombinant offspring

Close Genes=Very few recombinant offspring

One map unit is equivalent to

1% recombination frequency

Genetic mapping experiments are typically accomplished by a test cross. What is a test cross?

Mating between an individual that is heterozygous for multiple genes and one that is homozygous recessive for the same genes

A test cross is expected to yield a maximum of only 50% recombinant offspring, Why?

1.If genes exhibit 50% recombination, the most that can be said is they belong to different linkage groups

2.Distance between genes far apart on the same chromosome tend to be underestimated because of double cross over events

Construct a genetic map based on the following data

Answer

What is coupling?

Where one chromosomes contains both wild-type alleles or both mutant alleles

What is repulsion?

Wild type alleles are found on opposite chromosomes

Double recombinant only have which gene altered?

The middle gene

What is interference?

Crossovers are not independent events because one crossover inhibits the other

What is positive interference?

The first crossover decreases the possibility that a double crossover event will happen nearby

Levels of recombination among species

There is 2x more recombination in humans than rodents

Levels of recombination among chromosomes do a single species

Chromosomes 21 and 22 have highest recombination rates; 2 and 4 have lowest

Recombination hot spots

Appear to be associated with trinucleotide repeats

In humans, tend to be near, but not in, active genes

Areas near centromeres often have reduced rates

Levels of recombination among sexes

Female tend to have higher recombination than males

What is synteny?

Refers to genes that are physically located on the same chromosome

What are syntenic blocks?

Refers to the evolutionary conservation of syntenic genes (genes that have remained together during evolution)

When recombination rate is high, linkage blocks will be

Short

When recombination rate is low, linkage blocks will be

Long

What are deletions?

The loss of a chromosomal segment

What are duplications?

The repetition of a chromosomal segment compared to the normal parent chromosome

What are inversions?

A change in the direction of part of the genetic material along a single chromosome

What are translocations?

A segment of one chromosome becomes attached to a different chromosome

What are effects of deletions?

1.If deletion includes centromere, chromosomes will not attach to microtubules and will be lost.

2.deletions are lethal in the homozygous state

3.individual heterozygous for a deletion causes an imbalance in gene dosage (pseudodominance can occur)

4.Haploinsufficiency

What is pseudodominance?

Expression of a normally recessive gene

What is haploinsufficiency

When the single copy of a gene is not enough to produce wild-type phenotype

How do duplications form?

Abnormal events during recombination, by repetitive sequences or misaligned crossovers

What is a pericentric inversion?

Inversion involving the centromere

What is a paracentric inversion?

Inversion that does not involve the centromere

What is the break point effect?

An inversion break point occurs in a vital gene

What is the position effect

A gene is repositioned in a way that alters its gene expression

What is a reciprocal translocation?

A two-way exchange of segments

What is simple translocation?

Genetic material moves from one chromosome to another without trading

What is a robertsonian translocation?

Long arm of two acrocentirc chromosomes become joined, creating chromosome with two long arms and one with two short arms.

How often does a robertsonian translocation occur?

1 in 900 births