Lecture 18

Question 1

Non-disjunction

Answer 1

• Causes genome structure changes
• is the failure of chromosomes and sister chromatids to properly
  separate during cell division
• Cause dosage imbalance

Question 2

NDJ in germline cells

Answer 2

Meiosis 1/2

Question 3

Somatic Cell

Answer 3

Mitosis (if not caught by a checkpoint, can lead to mosaicism where some cells have a diff number of chromosomes than others), can also do a apoptosis

Question 4

Gene dosage

Answer 4

• Humans are enormously sensitive to changes in gene dosage
• Dosage imbalance generally more severe fitness effects in animals, (bc don’t have good mechanisms to deal with extra autosomes, have them for sex chromosomes and can compensate for them using things like barr bodies), than in plants
• Of all aneuploidies that are possible, only three of them produce viable offspring, which the exception of 13, 18, and 21
• Theoretically, there are
  potentially 24 different
  kinds of trisomy in
  humans, one for each
  autosome and one each
  for X and Y
• Yet only autosomal
  trisomy of chr.13, 18 and
  21 are seen with any
  measurable frequency

Question 5

Aneuploidy

Answer 5

Monosomy and trisomy and polyploidy

Question 6

Polyploidization

Answer 6

≥ 3 sets of chromosomes in the nucleus of an organism

Question 7

Autopolyploidy

Answer 7

Duplication of original genome

Question 8

Meiotic whole genome ndj

Answer 8

• Diploid gamete
• Example: 2n (egg) + n (haploid) (pollen) = 3n plant (triploid)
• Example: 2n (egg) + 2n (pollen) = 4n plant (tetraploid

Question 9

Mitotic whole-genome ndj

Answer 9

• Example: 2n cell ND = 4n cell, fail to separate any homologs at all

Question 10

Mitotic and meiotic nondisjunction can also combine

Answer 10

Example: MEIOTIC → 2n (egg) + n (pollen) = 3n MITOTIC → 6n

Question 11

Allopolyploidy

Answer 11

Combining the chromosome sets of different species through hybridization, can either create a new species or sum w a unique chromosome set map

Question 12

Example of autopolyploidy and allopolyploidy

Answer 12

• Strawberry with 8N is much larger than 2N strawberry
• Can artifically engineer in lab to disrupt spindle fibres and therefore disjunction and strawberries grow bigger

Question 13

HYBRIDIZATION +
GENOME DOUBLING

Answer 13

• ~12,000 y ago: AA (T.
  urartu) × B-genome wild
  grass → AABB
  allotetraploid emmer
  wheat (4n=28)
• ~8,000–7,000 y ago:
  AABB × DD (T. tauschii) →
  AABBDD allohexaploid
  wheat (6n=42)
• Modern species: bread
  wheat (T. aestivum) and
  spelt (T. spelta) =
  AABBDD

Can end up w an odd number of chromosomes that not meiosis friendly, and plants handle this by participating in genome doubling and salvage their sex cells

Question 14

What kind of benefits can we obtain from
polyploidization?

Answer 14

• Bigger with larger fruits
• Fertility is decreased, particularly in odd numbered polyploids (3n, 5n, etc).
• Seedless grapes, watermelon, etc.
• Hybrid vigor in allopolyploids → Hybrids may sometimes outcompete
  ancestral strains, higher fitness than ancestral contributors
• Polyploidization as a mechanism for rapid
  speciation (up to 40% of flowering plant species are hypothesised to have originated from hybridization

Question 15

Cause of chromosome structure changes #1: Chromosome breakage

Answer 15

Due to missed ligation or duplicated ligation

• loss of whole (part of) chromosomes can produce several abnormalities

Question 16

Missed ligation

Answer 16

Loss of chromosome segments-> deletion

some fragment didn’t get ligated and therefore is missed

Question 17

Duplicated ligation

Answer 17

Gain of chromosome segments -> duplication

2 homologous chromosomes both of them r broken up, and a section from one homolog gets ligated to the other

Question 18

Terminal Deletions

Answer 18

• The loss of a chromosome
  segment that includes the
  telomeric region.
• If a single break occurs and fragment can’t repair itself and it don’t have a cetromere it will be lost cos spindl fibres can’t connect to a kinetochore and pull it apart

Question 19

Interstitial
deletion

Answer 19

• The loss of a portion of a
  chromosome from within one arm.
• 2 break points and breaks fuse together but the fragment in the middle gets lost, either degrades or can’t go to either of the poles

Question 20

Cause 2: Unequal crossover during meiosis

Answer 20

Consequence:

• Partial deletion heterozygote: Williams-Beuren syndrome
  (neurodevelopmental disorder)
• Partial duplication heterozygote: Normal
• Some regions of the chromosome have high similarity and it makes a mistake have partial deletions and partial mistakes

Question 21

How to detect duplication and deletion?

Answer 21

• If duplications are large, can use g banding
• If small can use fish

ex. Wild type (normal) chromosome has A B + C

if theres a deletion u won’t see B if theres a duplication you’ll see 2 B’s

• for an unpaired loop at synapsis, if theres extra genes, the chromosome makes a loop to make sure it can align properly, bulge in chromosome

Question 22

Unequal crossing over meiosis example

Answer 22

• PMSA and PMSB
• Separated by 17 diff genes

-High level of sequence similarity causes PMSa and PMSA to align by looping

Question 23

Chromosome inversion

Answer 23

A structural alteration of a chromosome in which a
segment breaks away from the chromosome and subsequently reattaches
after 180° rotation

Question 24

Chromosome translocation

Answer 24

The relocation of a chromosome or chromosome segment to a non homologous chromosome

Question 25

How are inversions and translocations generated?

Answer 25

- Caused by chromosome breakage and incorrect reattachment - If no critical gene or regulatory region is broken or in the inverted/ translocated regions, there may be no phenotypic consequences - However, in germline cells, they can affect chromosome segregation and reduce fertility during meiosis

Question 26

Two types of chromosome inversion

Answer 26

Paracentric inversion, and pericentric, - Inversion heterozygotes have one normal and one inverted homolog

Question 27

Paracentric

Answer 27

Centromere outside of inverted region (not included in inversion) - Theres a bit without a centromere and gets lost, both outer chromosome on on pair and third inner chromosome on other pair stay the same. The outer on second chromosome and inner on first chromosome recombine. 2 viable chromosomes and 2 non-viable chromosomes.

Question 28

Acentric

Answer 28

Result of paracentric division and lacks a centromere

Question 29

Pericentric

Answer 29

Centromere within inverted regions (included in inversion) - The chromosomees are duplicated - The inverted part of the chromosome loops over in order to better align with its counterpart on the homologous chromosome. - then they recombine and the outer chromosome stays the same, the innee ron one chromosome is longer and recombined, thee other inner is shorter, and the last one has the recombination and is shorter

Question 30

How does a pericentric inversion influence crossing over and fertility during meiosis?

Answer 30

- Forms inversion loop at synapsis - Crossing over that occurs within a pericentric inversion results in both duplicated and deleted regions in both of the recombinant products - Recombination event yields two viable gametes (from the non-crossover chromatids) and two non-viable gametes (from the crossover chromatids) - Crossing over that occurs outside the inverted regions takes place normally

Question 31

What does crossing over within inverted regions do?

Answer 31

Results in duplications and deletions in the recombinant chromosomes: a dicentric chromosome (2 centromeres → nonviable) and an acentric fragment (no centromere → lost in subsequent division)

Question 32

Observations and implications of recombination in inversion heterozygotes

Answer 32

1) The probability of crossover within the inversion loop is linked to the size of the inversion loop, smaller loop has lower chances of recombination 2) Inversion suppresses the production of recombinant chromosomes 3) Fertility may be altered based on inversion size (small inversions may not experience a loss in fertility, while a large inversion that spans nearly an entire chromosome will result in loss of approx. half of the gametes)

Question 33

Translocation

Answer 33

Broken ends of non-homologous chromosomes are re-attached * Translocation heterozygotes may experience semi-sterility due to segregation abnormalities

Question 34

3 types of translocation

Answer 34

1) Unbalanced translocation 2) Reciprocal balanced translocation 3) Robertsonian translocation (chromosome fusion)

Question 35

Unbalanced translocation

Answer 35

Segment breaks and attacthes to another non-homologous chromosome and only occurs bw one pair

Question 36

Balanced translocation

Answer 36

2 breakages and swap places

Question 37

Robertsonian translocation

Answer 37

Chromosome fusion, one chromosome has a centromere located towards the end of the chromosome so most of the gene products are on the long arm, can have a fusion event around the centromere where all of the gene products from the long arm that fused to another chromosome, the small arm is lost

Question 38

What are the consequences of balanced reciprocal translocation?

Answer 38

* Somatic cells → Usually no observable effect * Germline cells → ½ viable gametes and ½ inviable gametes * Alternate segregation and adjacent-1 segregation each occurs in approx. 50% of meiotic divisions At anaphase I in alternate segregation, chromosomes I and V move to one cell pole and chromosomes II and III move the opposite → ALL GAMETES VIABLE RARE → At anaphase I in adjacent-2 segregation, chromosomes I and II migrate to one pole and III and IV to the other. Because this does not separate homologous chromosomes, none of the gametes are viable

Question 40

Balanced Reciprocal Translocation in Somatic cells

Answer 40

- Usually no observable effect