Lecture 14 - Transposon Insertions and Chromosome Abnormalities

What are the four types of change in DNA?

1) Base substitution/point mutation

2) Deletion

3) Insertion

4) Changes to chromosomes

What are three types of insertion?

1) Simple insertion

2) Triplet expansion

3) Transposable element insertion

What are transposable elements/transposons?

Mobile genetic elements found in the genomes of prokaryotes, archaea, and eukaryotes

What is the process of transposition?

Sequences of DNA that can jump around within the genome of a single cell

What happens if a transposable element inserts into an open reading frame or upstream of a gene?

They can alter gene function and cause a mutant phenotype

What enzyme do transposons carry? What does it do?

Transposons carry the enzyme transposase, which facilitates their movement by cutting and pasting them in new locations within the genome.

What was the reason for colorless kernels to have small purple areas?

This mutation was due to an insertion of an unstable element (Ds) into the C gene, which could later ‘jump’ out of the C gene in some cells, which would restore the wild type C gene function resulting in purple pigmentation.

What happens after the transposon ‘jumps’ in and disrupts the C gene?

The transposon later ‘jumps’ out and the gene function is restored - but only in those cells where it occurred and the descendants of those cells → leading to leftover purple spots

What two types of transposable elements are in bacteria?

Simple and complex

What is an insertion sequence (IS)?

1) Have terminal inverted repeats (IR) at ends

2) Carry one gene for transposase

What is a transposon (Tn)?

Contains other genes; often have a gene for antibiotic resistance

What do the antibiotic resistance genes do?

Gives the bacteria that contain the transposon a selective advantage in the presence of the antibiotic which allows to keep the transposon in the bacterial genome

What are the steps for transposable element integration?

1) Transposase cuts DNA at target site

2) Transposable element inserts

3) Gaps are repaired

What are the two transposition mechanisms? What do they do?

1) Cut and paste - moves from one site to another in the genome

2) Copy and paste - leads to duplication of the transposon at a new site

What do both transposition mechanisms lead to?

Disruptions of gene function (mutation) if they insert into an open reading frame

How did Mendel’s wrinkled seed phenotype come about?

Due to the insertion of a transposable element that disrupts gene function causing a recessive phenotype because the presence of one wild type copy of the gene can provide enough protein function to allow a wild type phenotype

How did the dark moth phenotype come about?

Due to the insertion of a transposable element that leads to increased expression of melanin causing a dominant phenotype because the presence of one wild type copy of the gene is enough to cause excess melanin production

What are the two types of transposable elements? What do they do?

1) DNA transposable elements (prokaryotes and eukaryotes): encode a transpose enzyme that allows them to ‘jump’

2) Retrotransposons (eukaryotes): transpose through an RNA intermediate such as a retrovirus

Do cells have a repair mechanism to get rid of transposable element insertions?

No - they just accumulate in the genome over evolutionary time

What are the two types of human chromosomal abnormalities?

1) Structural defects

2) Numerical defects

What are the four types of structural defects?

1) Deletions, 2) Duplications, 3) Inversions, 4) Translocations

What are the two types of numerical defects?

1) An incorrect # for 1 chromosome

2) An incorrect # for ALL chromosomes

How can a chromosomal abnormality of a deletion occur?

Occurs when breaks are induced in chromosomes by: viruses, chemicals, radiation, transposable elements, and errors in recombination

What is Cri-du-chat Syndrome?

Affected children have severe intellectual disability, and suffer from physical abnormalities; terminal deletion in the short arm of chromosome 5; occurs in heterozygous condition

What does the chromosomal abnormality of a duplication do?

The duplication can move genes next to other gene regulatory regions that they are not normally next to, resulting in abnormal gene expression and phenotypes

What are the three types of chromosomal duplications? What do they do?

1) Tandem - duplicate normally

2) Reverse Tandem - duplicate and flip

3) Terminal Tandem - duplicate but delete a segment

What does the chromosomal abnormality of an inversion do?

Part of a chromosome is broken and reinserted in the opposite orientation

What are the two types of inversions? What do they do?

1) Pericentric Inversion - includes the centromere

2) Paracentric Inversion - does not include the centromere

What happens when the inversion is heterozygous?

The recombination can screw up between homologous chromosomes leading to gametes with defective chromosomes

What does the chromosomal abnormality of a translocation do?

Part of a chromosome is moved to a new region

What are the three types of translocations? What do they do?

1) Intrachromosomal - a region moves elsewhere on the SAME chromosome

2) Interchromosomal - a regions moves elsewhere on a DIFFERENT chromsome

3) Reciprocal - two chromosomes swap pieces

What happens when the translocation is heterozygous?

Screw up recombination between homologous chromosomes leading to gametes with defective chromosomes

What is a euploid?

Having the correct chromosome number

What is a polyploid?

Having an incorrect number of chromosome sets

How many chromosomes does a human diploid have?

2N - 46 chromosomes

How many chromosomes does a triploid have?

3N - 69 chromosomes

How many chromosomes does a tetraploid have?

4N - 92 chromosomes

What is an aneuploid?

Having an incorrect number of chromosomes

What is trisomic?

A diploid genome with three copies of one chromosome - 47 chromosomes (2N+1)

What is monosomic?

A diploid genome with one copy of one chromosome - 45 chromosomes (2N-1)

How does aneuploidy happen?

Occurs due to nondisjunction during meiosis I/II

May happen when spindle fibers from one pole attach to both copies of a chromosome or chromosome pair

What is nondisjunction?

When homologous chromosomes or sister chromosomes do not separate during meiosis

How many gametes are affected if nondisjunction occurs during meiosis 1?

Four

How many gametes are affected if nondisjunction occurs during meiosis 2?

Two; other two are unaffected

How many trisomies are seen in live human birth?

Three main types (13, 18, 21) - all other trisomic and monosomic conditions are presumed to be lethal events in utero

What is trisomy 21?

Down Syndrome

What is Down Syndrome?

Intellectual disability (often mild), delayed skeletal development, poor muscle tone and characteristic facial features including a flat facial profile and slanted eyes.

What is TripleX Syndrome?

X inactivation results in only one active X chromosome in mammalian cells

What is a dosage compensation?

Females have two X chromosomes, one X chromosome is randomly inactivated to equal the one X chromosome that males have

What is a Barr body?

The inactive X chromosome in females

What happens when a female is heterozygous for a gene on the X chromosome?

Some cells express one allele only and in another cells the other allele only

What is an example of dosage compensation?

Calico cats have their characteristic fur coloring due to this effect; one allele is expressed in dark patches and the other allele is expressed in orange patches