Meiosis Flashcards
Meiosis - Overview 1
Diploid organism has two version of each chromosome (homologues)
Homologues are either maternal or paternal
Only one homologue for each chromosome packaged into a gamete
Meiosis resembles mitosis except there are extra steps that segregate homologous chromosomes
Pairing homologues before segregation allows for crossing over (homologous recombination)
Two stages of meiosis: Meiosis 1 and meiosis 2
Meiosis 1 - Crossing over and segregation
Centrioles+ chromosomes are replicated (just like mitosis)
Maternal + paternal homologs pair up
Genetic diversity generated by recombination between homologous chromosomes
One complete chromosome (2 chromatids) pulled to separate poles
Crossing-over takes place when homologues pair up
Note that sex chromosomes behave like homologues during sperm formation due to small regions of homology
Homologous chromosomes line up next to each other in centre cell
Meiosis 2 - resembled mitosis
Main difference is that cells are haploid instead of diploid
Meiotic prophase 1 is when homologues pair up
Pairing is facilitated by synaptonemal complex (proteins) as well as DNA base pairing between homologues
Serves 2 purposes:
- It aligns chromosomes up ready for anaphase, along with formation synaptonemal complex
- Allows for genetic recombination between paternal and maternal DNA on same chromosome
Multiple chiasma can occur down one bivalent and is what causes genetic diversity
Chiasma are extended strand exchange
Synaptonemal complex - found only in mitotic cells and is complex that stitches chromosomes together to allow dDNA variation to occur
Chromosomes homologs pairing up leads to formation synaptonemal complex
Paired homologs brought to 400 nm apart
Possibly recombination complex (which recognises ds breaks) helps bind homologs together
Axial core (proteins that bind the chromatin via cohesion) are cross-linked by transverse filaments to form the Synaptonemal complex
This is what allows for strand exchange
Synaptonemal complex - details
This tight bringing together of sister chromatids by synaptonemal complex aligns the two chromosomes and helps in homologous recombination
Homolog segregation depends on several unique features of meiosis 1
Fundamental difference:
- Mitosis - sister chromatids separate
- Meiosis - Homologs separate
What allows difference?
1. Both kinetochores attach to same spindle pole
- This avoidance is done by protein complex that is removed after meiosis 1
2. Crossing over = physical linkage between homologs
3. Cohesion is only removed from the arms
Cell cohesion bridge removed completely in mitosis, but not completely removed in meiosis 1 as stays between kinetochores in the chromatids
Crossing over in meiosis is highly regulated
There’s at least one crossing over per bivalent but no more than 4
They form at DS breaks
Breaks tend to form in open chromatin
Regulation not well understood:
- Ensures at least 1 crossover forms
- Crossover interference - once one forms it inhibits others close by
Thus number per arms is limited
Meiosis frequently goes wrong
Generally two categories of chromosome abnormalities:
1. Abnormalities in chromosome number
2. Chromosome structural rearrangements
Chromosomes carry hundreds of genes therefore even small rearrangements can have severe effects
Aneuploidy
Either through mitosis or meiosis followed by fertilisation have to maintain diploid chromosome number
There are two types of aneuploidy:
- Monosomy - 1 copy of a chromosome
- Trisomy - 3 copies of a chromosome
Can get whole extra sets of chromosomes called polyploidy
Aneuploidy is a disorders of chromosome number caused by chromosome nondisjunction
Either in:
- Homologous chromosomes
- Sister chromatids
Fail to separate in;
- Meiosis 1
- Meiosis 2
- Mitosis
SKY (spectral karyotyping) of colorectal carcinoma cell line
Probed chromosomes with different colours then run on computer software that’s able to tell you what chromosomes you have and if you are missing any, also allows you to see if some chromosomes have been mixed up
What are the consequences of numerical chromosomal abnormalitites
Polyploidy
- Triploid (e.g. 69, XXX, XXY, XYY)
- Embryonic lethal
Aneuploidy (autosomes)
- Nullisomy (missing a pair of chromosomes) - pre-implantation lethal
- Monosomy (missing one chromosome) - Embryonic lethal
- Trisomy (One extra chromosome) - Usually lethal (but some exceptions)
Aneuploidy (Sex chromosomes)
- Additional sex chromosome - 47, XXX; 47, XXY; 47, XYY - minor problems relatively normal lifespan
- Lacking a sex chromosome - 45,X; Turners, 99% abort, rest normal but infertile. 45, Y; not visible
Person known as mosaic when have 2 or more genetically different sets of cells in their body
Not always lethal because defects in creating body tissue, biggest problem caused is in placental development
Syndromes arising from nondisjunction - autosomal trisomy
Trisomy 22
- Undeveloped face (midface hypoplasia)
- Malformed ears
- Wide-spaced eyes (hypertelorism)
- Microcephaly
- Congenital heart disease
- Rare in live born (usually die shortly after birth) is found in miscarried foetuses
Trisomy 18 (Edwards syndrome)
- Severe intellectual disability
- Low birth weight
- A small, abnormally shaped head
- A small jaw and mouth
- Clenched fists with overlapping fingers
- Congenital heart defects
- Various abnormalities of other organs
- Death before birth or within 1st month of life
- Rare survival to teenage years
Syndromes arising from nondisjunction - monosomy
45, XO turners syndrome
- Complete or partial absence of a second sex chromosome in phenotypic females
- Common diagnostic factors
- Poor growth
- Short stature
- Delayed/absent pubertal development
- Congenital heart defects
- Skeletal abnormalities
- Only 1% survive to term with 50% mosaic
- UK: 1 in 2000 females at birth
Why do we see lethality? the two explination
Haploinsufficiency - pseudo autosomal genes expressed from both alleles and does matters
Imprinted genes on X - i.e. monoallelic expression which is lost (imprinting only applies to certain genes)
Urbach and Benvenisty suggest abnormal placental differentiation caused by haploinsufficiency of X-linked, pseudo autosomal genes
