Mitosis And Meiosis

Question 1

During mitosis, chromosomes attach themselves to microtubules that propagate from centrosomes.

What are these microtubules made of?

Answer 1

Tubulin

Question 2

Examining a histological section, a pathologist sees a cell undergoing mitosis. The chromosomes are moving towards opposite poles of the cell and there are no nuclear membranes.

Which phase of mitosis is this?

Answer 2

Anaphase

Question 3

Where is DNA inside the cell?

Answer 3

Nucleus

Mitochondria

Question 4

Structure of DNA

Answer 4

• Double helix

•Complimentary base pairs:
•A T (two bonds)
•G C (three bonds)

•Coils around nucleosomes
•Coils again into supercoils
•And again into chromosomes

Question 5

DNA structure and organisation: chromosomes

Answer 5

• There are 46 chromosomes in the human genome (22 autosomal pairs + sex chromosomes (XY))

• Each human chromosome contains a continuous DNA duplex of ~107 bp and contain several hundred genes

• Each has a long arm (q) and a short arm (p) separated by the centromere

Question 6

Staining of chromosomes

Answer 6

• Chromosomes can be characteristically stained for identification and analysis with dyes (Giemsa: G banding, Quinacrine: Q banding)

• G banding gives ~ 400-500 bands/haploid human chromosome set

• Each band ~6-8 Mbp

Question 7

What is mitosis for?

Answer 7

•Producing two daughter cells

•Genetically identical to parent cell

•Growth

•Replace dead cells

Question 8

The steps of mitosis

Answer 8

•Cell must be in cell cycle – interphase

•In S-phase:
•DNA replication
•Centrosome replication

Question 9

Prophase

Answer 9

•Chromatin condenses into chromosomes

•Centrosomes nucleate microtubles and move to opposite poles of nucleus

Question 10

Prometaphase

Answer 10

• Nuclear membrane breaks down

•Microtubules invade nuclear space

•Chromatids attach to microtubules

• Cell no longer has a nucleus

Question 11

Metaphase

Answer 11

Chromosomes line up along equatorial plane (metaphase plate)

Question 12

Anaphase

Answer 12

•Sister chromatids separate and are pushed to opposite poles of the cell, centromere first, as spindle fibres contract

Question 13

Telophase

Answer 13

•Nuclear membranes reform

•Chromosomes unfold into chromatin

•Cytokinesis begins

• To remember mitosis: I Prefer Milk And Tea (Interphase, Prophase, Metaphase, Anaphase and Telophase)

Question 14

Clinical relevance

Answer 14

Categorising tumours as benign or malignant

Grading malignant tumours

• In histology can tell if cell undergoing mitosis if its nucleus is dark (i.e. chromatin has condensed to chromosomes) and if the nuclei are not the same size
• Something is defined as malignant if there are too many mitotic figure i.e. lots of dark nuclei of different sizes
• Number of mitotic figures determine how bad cancer is, the more there are, the worse it is

Downs syndrome, 1 extra chromosome at 21 [trisomy 21]

Question 15

Drugs for prevention of cells replication

Answer 15

Prevent/slow down/stop certain parts of mitosis

Question 16

Mitotic spindle

Answer 16

• Taxol
• Vinca alkaloids – vinblastine, vincristine

Question 17

Anaphase

Answer 17

Colchicine-like drugs

Question 18

Spindle poles

Answer 18

Ispinesib

Question 19

Meiosis

Answer 19

Similar to mitosis but key differences:
• Only in gametes
• Recombination of genetic material generates diversity
• Two cell divisions
• 4 haploid daughter cells (HALF number of chromosomes i.e. 23) cells produced, which are genetically distinct from each other and the parent cell
• MEIOSIS IS NOT A CYCLE

Question 20

Cross over

Answer 20

In prophase 1

In prophase 2

Question 21

Sperm production (gametogenesis)

Answer 21

•Primordial germ cells → lots of mitoses →Spermatogonia (mature sperm)

•Meiotic divisions commence at puberty and continues throughout life
• Some mitosis occurs in embryonic stages to produce primary spermatocytes present at birth

•The cytoplasm divides evenly

•After meiosis II four equal gametes

•Millions of mature sperm continuously produced
•Process takes 60-65 days
•100-200 million sperm/ejaculate

Question 22

Eggs (gametogenesis)

Answer 22

• Primordial germ cell → 30 mitoses → oogonia
•Oogonia enter prophase of meiosis I by 8th month of intrauterine life

•Process suspended
•Cells enter ovulation 10-50 years later
•Cytoplasm divides unequally – 1 egg and 3 polar bodies (that apoptose- go onto die)

•Meiosis I is completed at ovulation
(then cells remain in suspended animation) - at this point there is 1 big cell, 1 small cell each with diploid DNA. Then go on to divide again each (after fertilisation) to form 1 big cell (egg) and 3 small cells (polar bodies)

•Meiosis II only completed if fertilisation occurs

Question 23

Non-disjunction

Answer 23

Failure of chromosome pairs to separate in Meiosis I or sister chromatids to separate properly in meiosis II

Question 24

Down syndrome

Answer 24

Most cases result from regular trisomy 21

~75% maternal meiosis I
~25% maternal meiosis II
~3-5% paternal non disjunction

likelihood of this happening increases with age of both men and females

Question 25

Gonadal mosaicism

Answer 25

•Occurs when precursor germline cells to ova or spermatozoa are a mixture of two or more genetically different cell lines (due to errors in mitosis) •One cell line is normal, the other mutated •Incidence increases with advancing paternalage •Parent is healthy (since genetic change is only in the germline so all the other cells are unaffected - have usual genetic components), but the fetus may have a genetic disease

Question 26

Where can Gonadal mosaicism be observed?

Answer 26

Can be observed with any inheritance pattern, but most commonly autosomal dominant and X-linked Observed in a number of conditions, including osteogenesis imperfecta and Duchenne muscular dystrophy More common in males

Question 27

Summary

Answer 27

•Mitosis allows faithful cell replication and the production of 2 daughter cells •Meiosis produces 4 genetically different daughter cells •The structure of DNA is essential to successful mitosis and meiosis •Mitosis and meiosis are clinically relevant, in terms of disease causation, diagnosis and treatment!

Question 28

Autosomes

Answer 28

Anything that isn’t sex determining

Question 29

Karyotype

Answer 29

Number and appearance of an individual’s complete set og chromosomes in a cell. Spreads are arranged in size order, biggest is pair 1 and smallest is pair 22, sex pair is 23

Question 30

Chromosome structure

Answer 30

- Each chromosome contains a continuous DNA duplex of roughly 107 base pairs and contain several hundred genes - we have around 30,000 genes - Each chromosome has a long arm (q) and a short arm (p - can remember p as petit) separated by a centromere - 22,000 genes in humans

Question 31

Chromatin

Answer 31

Chromosomes when the Cell is not in replication DNA associated with his tone proteins

Question 32

Chromosomes

Answer 32

Referred to chromosomes DURING cell replication When the DNA is short and condensed

Question 33

Chromatids

Answer 33

Chromosomes are called chromatids after cells have replicated Diffuse and uncondensed form of chromosomes

Question 34

For a cell to undergo mitosis…

Answer 34

The cell must be in the cell cycle interphase

Question 35

Interphase

Answer 35

Longest phase G1, S, G2

Question 36

G1

Answer 36

no visible activity but the following occurs • Rapid growth • Normal metabolic function • New organelles produced • Protein synthesis of proteins involved in spindle formation

Question 37

S (synthesis)

Answer 37

• DNA doubles through DNA replication • Histone proteins double through protein synthesis ( 2 x as much DNA at end of S) • Centrosome replication

Question 38

G2

Answer 38

• Energy stores accumulate • Mitochondria and centrioles double

Question 39

CYTOKINESIS

Answer 39

• Cell organelle become evenly distributed around each nucleus • Cell divides into two daughter cells with a nucleus in each and 46 chromosomes

Question 40

Meiosis 1

Answer 40

• Chromosome number is halved • In Prophase 1, crossing over occurs between non-sister chromatids [genes sort independently thus if 1 gene switches over, doesn't mean another one will], resulting in genetic diversity • In Metaphase 1, random assortment occurs on the metaphase plate - also resulting in genetic diversity

Question 41

Meiosis 2

Answer 41

• Sister chromatids separate • Haploid cells produced

Question 42

GAMETOGENESIS

Answer 42

• The first stage is the proliferation of primordial (undifferentiated) germ cells (developing gametes) by mitosis • The timing of mitosis in germ cells differs greatly in males and females