Meiosis Flashcards
What is the biochemical cause of Down’s syndrome
Aneuploidy
Define homologous chromosomes, sister chromatids, bivalents, centromeres and kinetochore
Homologous chromosomes are chromosomes that are similar in structure but differ in parental orgins. Sister chromatids are identical chromosomes that have been made by DNA replication Bivalents are structures formed by the association of homologous chromosomes Centromere is a structure at the center of the chromosome which has kinetochore attached to it whereas the kinetochore is the protein structure that attaches the centromere to the spindles
What is N and C
N is number of chromosomes, C is number of chromatids
What happens to N and C after Meiosis 1
Initially we have 2N, we go down to 1N and for C we have 4C at the beginning, after meiosis 1 we go down to 2C. The 4C form bivalents
What happens in meiosis II
Sister chromatids separate, very similar to mitosis
3 processes that happens during Prophase 1
- Homologous chromosomes pairing 2. Synaptonemal complex formation 3. Crossing over, also called recombination
What are the different stages of prophase 1
LZPD 1. Leptotene 2. Zygotene 3. Pachytene 4. Diplotene
The DNA is extremely long. How does the chromosome identify their homologous pairs and adjacent positions
The telomeres cluster around the nuclear envelope forming a chromosome bouquet. It is associated with rapid chromosome movement. Know that there are chromosomal attachment proteins that bind to the dyenins and help with this movement of chromosomes so that they can align themselves
What happens after the chromsomes have aligned themselves
There is the formation of synaptonemal complex. It is a tripartite structure that functions as a glue to hold the chromsomes together. It consists of several different proteins
What are the functions of synaptonemal complex
- It organizes the chromtids 2. Mediates synapses via protein-protein interactins 3. It aids in the assembly of recombination complexes
How does the synaptonemal complex look like
What happens during homologous recombination
- There is programmed double stranded breaks along the length of the DNA at locations called ‘hot spots’
- Exonucleic resection of the strand at 5’ end - this basically mean that the small length of one chromatid breaks off
- Strand invasion
- repair of the double stranded breaks by Homologous recombination
Cross over leads to the formation of chiasmata
What happens if there is not even 1 cross over event in the chromsomes during Meiosis
If there is not even a single cross over event then it will lead to aneuploidy
How many cross over events usually occur in 1 meiotic division
Around 23
How does meiosis introduce genetic diversity
There are 2 ways:
- Independent assortment of the chromsomes - this basically means that the matenal and paternal homologs are aligned such that they are mixed up
- Crossing over
What happens at the first stage of the prophase 1
At the liptotene stage we have:
- Chromosome bouquet formation
- The synaptonemal complex proteins start to polymerize to align the chromsomes
- There are programmed double stranded breaks at the hot spots
What happens next
At the zygotene stage we have:
- Chromsomal pairing ends
- Synapses begins
(Think of this stage as zipping up of the homologs)
What happens next
At the Pachytene stage we have:
- Completion of synapses
- Maturation of recombination sites into cross overs
What happens at the last stage of prophase 1
At the diplotene stage we have:
- Chromsomes undergo desynapsis
- Homologs are held together by cross overs
- Further chromosomal condensation occurs
What is chaismata
It is the point where 2 homologs non sister chromatids exchnage genetic information. It is visible only during (and after) the diplotene stage
How does the sister homologs seperate in meiosis 1
What is the significance of the position and number of cross overs
Chiasmata is the physical manifestation of the cross over that binds the 2 homologs together. If there is no cross over or if the cross over is far away from the centromere, which is called a distal cross over, this can lead to non disjunction.
This is the cause of seveal trisomies.
Name the different trisomies and their associated pathologies
- Trisomy 21: Down’s syndrome
- Trisomy 18: Edward’s syndrome
- Trisomy 13: Patau’s Syndrome
When is cohesion made around he new DNA
During the pre mieotic S phase
What is the structure of cohesion and what breaks down this structure
It has a ring like structure, it is broken do seperase during anaphase
What are the functions of cohesion during meiosis
Stabilizes the chiasmata formed by homologous recombination and it established the geometry for kinetochore-microtubule interactions
Where is cohesion present
It said on the slides that it is present at the centromere and at the chromosomal arms but on the diagram the cohesion rings were missing from the centromere
What are the consequences of non disjunction
- Loss of autosomes are lethal
- Can lead to trismoies which also can be lethal excpet for 21, 18 and 13 (know their names)
- Sex chromosome aneuploidies are most common in live birth
What is Sex Dimorphism
A phenotype that varries between male and female
Describe the process of spermatogenesis
- Spermatogonia proliferate by mitosis
- Primary spermatocytes enter meiosis 1
- Secondary spermatocytes enter meiosis 2
- These then mature into late spermatids
Describe the process of oogenesis
- Meosis starts at 11 to 12 weeks in gastrulation
- At birth all oocytes are arrested at meiosis 1 at diplotene stage
- Meiosis 1 is completed during ovulation and Meiosis II is completed during fertilization
It is important to know that women are born with a finite number of oocytes
How many mature haploid gametes are produced in the male and female
In males 4 are made however in female only 1 mature egg is made while the other form first and second polar body
Polar bodies are the by product of meiosis I and II
What do we seperate in first and second meiosis
Homologous chromsomes and sister chromatids respectively
Where does the majority of the aneuploidies come from
From the mom since meiosis I is frozen for such a long time
Compare oogenesis and spermatogenesis in terms of mieotic errors
Oogenesis is more robust, meaning it will power through and result in mature egg even where there have been some meiotic errors whereas spermatogenesis may result in no production in sperm at all if there are any errors
Checkpoint mechanisms in the male are more stringent
What are the factors that lead to trisomies at a late maternal age
- Recombination errors (errors in frequency and location of recombination)
- Faulty DNA repair
- Low sensitivity to cell cycle checkpoints
- Spindle formation abnormalities
- Change in chromsome structure
- Deterioration of cohesion
Why is cohesion deterioration related to trisomies
Cohesion is loaded on the chromosomes at S phase that happens during fetal development. At later age it is the same cohesion that is in the chromosomes so it deteriorates over time, leading to trisomies 13, 18 and 21
What is the underlying biochemical cause of cohesion related to trisomies
In a young women, cohesion is wrapped around the entire chromosome, that allows the sister chromatids to act as a unit and leads to proper segregation of the chrosomes by AMPHITELIC attachment of the kinetochore with the microtubules
However in older women, cohesion has been lost form the arms and from the center of the chromosomes. Now the chromatids cant function as a single unit and the kinetochore can attach to 2 spindles, which causes improper segregation of the chromsomes during meiosis I (and then in Meiosis II). This attachment is called Merotellic
What is the loss of cohesion exacerbated by
Improper crossing over, which happens far away from the centromere. This increases the liklihood of premature chromsomal segregation leading to trisomies
What happen when BPA is administered to replicating cells
Spindle fibers cant align properly, anaphase is haphazard and doesnt execute properly
