BIOL 2500 - Topic 7 (part 7)

Deletions

It is when both strands of DNA are severed at the chromosome breakpoint, which can lead to the partial deletion of genes on the chromosome

Broken ends of broken chromosomes

1.) They retain their chromatin structure

2.) They can re-adhere to each other, other truncated chromosomes, or to the ends of intact chromosomes

3.) One piece is lost entirely

Two types of deletions

1.) Intragenic deletions

2.) Multigenic deletions

Intragenic deletions

Deletion within a gene, therefore it disrupts gene function (i.e. it is a null mutation, as the protein is no longer functional)

Multigenic deletions

1.) It affects multiple genes. resulting in more severe consequences

2.) If the deletion is homozygous, it is almost lethal

Chromosomal deletions vs. point deletions

Chromosomal deletions can be detected underneath the microscope, based on altered banding patterns

Partial deletion heterozygotes

1.) Deletion only occurs in one homolog, therefore the other homolog is still intact

2.) If this occurs, sometimes it is still viable

Deletions pairing up

Homologs cannot pair up 100% accurately, resulting in the formation of a deletion loop on the unaltered homolog

Pseudodominance

It is when the dominant allele is the one that gets deleted on the dominant homolog, allowing the recessive phenotype to be unmasked and expressed

Deletion example 1

Cri-du-chat syndrome, where a heterozygote terminal deletion occurs on chromosome 5 on the p arm

Terminal deletion

An entire end of one homolog is deleted

Interstitial deletion

It is when we get 2 chromosomal breaks, resulting in the loss of an internal segment, and then internal broken ends are joined back together

Deletion example 2

WARG syndrome, where a multigenic interstitial deletion occurs on chromosome 11 on the p arm, resulting in dosage imbalance

Importance of deletions

1.) Missing segments of chromosomes affects gene dosage

2.) It can be lethal

Lethal deletions

1.) If the centromere is lost, the chromosome cannot complete meiosis

2.) If the segment is deleted from both homologs, it is a homozygous deletion

What is more lethal, duplications or deletions?

Deletions

Duplications

It is when segments of chromosomes are repeated, which can arise from unequal crossing over

Tandem duplication

The duplicated region is right next to the gene

Insertional duplication

The duplicated region is located elsewhere in the genome, far away from the replicated site

Effect of duplications

1.) Individuals with duplication heterozygotes will have 3 copies of the chromosomal region (one normal homolog and then two from the duplication)

2.) It also forms loops during meiosis

Duplications effect on phenotypes

1.) It increases gene dosage

2.) Extra genes can take on new functions or develop into new gene families over evolutionary time

3.) Expression can vary both before and after birth