Exam3Lec2DNArecombination Flashcards
What are the functions and effects of meiosis and meiotic DNA Recombination
- Gene re-assortment (Independent of recombination) and homolog recombination
- Gene conversion/mutation (consequence of recomb b/w homologs)
- Tri-nucleotide repeat expansions (Case w/ Huntingtons)
- Gene duplications (Rare and bad) and deletions (Even worse than duplication)
What are the 2 MECH OF MEIOSIS LEADING TO DIVERSITY IN OFFSPRING, BETTER CHANCE FOR SURVIVAL?
Gene re-assortment (Independent of recombination) and homolog recombination
Diploid to 2 Diploid
Mitosis
Diploid to 4 Haploid
Meiosis
Pairing and crossing over of duplicated homologs and segragation of homologs occurs in what
MEOSIS not mitosis
Separation of homologs occurs in what stage of meiosis?
where do homologs sep?
Anaphase 1
reduction division to one homolog ( 2 sis chromatids)
Segregation of sister chromatids occurs in what stage of meiosis?
Anaphase 2
gives you 4 haploid daughter cells
sis chromatidsn sep so games have one copy of the chromosome
In meiosis we have a paternal and maternal homolog that goes thru DNA replication and sister chromatids are made. They line up where and what occurs?
They line up at the bivariant and this is where the homolog recombination occurs (putting SNPs that never been together) This essentially means that mom and dad come together and snps/ alleles swap.
What is the kinetichore?
Centromere + proteins that link to the spindle apparatus for separation
Explain indepenndent assortment of maternal and paternal homologs
This occurs during meiosis one and there is a 50/50 chance of getting mom or dad chromosome that when separation occurs, we will see which chromosome will be together. This leads to diversity in offspring. You can get all mom or all dad chromosomes and you can get for exampel chromosme 1 from mom, chromosome 2 from dad, etc. These are now tied together forever due to independent assortment.
which chromosome are you going to get
Explain recombination with independent assortment
This is crossing over. So for ex you get a chromosome from the maternal BUT you also get little pieces from paternal and this leads to more diversity. This occurs during propahse one.
swapping snps
What is this picture?
Recombination (bvivalent=crossing over=recombination)
There are 2 sis chromatids on replicated paternal homolog
There are 2 sis chromatids on replicated maternal homolog
Homologs recombine, sister chromatids do not, why?
Sister chromatids are identical
Both homologs and sister chromatids recombine, but sister chromatids recombination does not matter because they are identical so if they switch alleles it does not matter bc they are the same alleles
Which of the following helps meiosis lead to offspring diversity?
-sister chromatid recombination
-homologous recombination
-both
-neither
homologous recombination
Does recombination occur in one place along the homolog?
NO, it occurs multiple times along the length of the homolog, so there are multiple synapses and participation of both sister chromatids
Explain this picture
Independent assortment of homologs. You ahve 23 pairs of (red) maternal and 23 pairs or (blue) paternal, which one do you get? This is random and variability arises due to independent assortment of the chromosomes on the metaphase plate
To create sperm cells and oocytes you go from diploid to haploid
Explain this photo
Each homolog is not exactly the same as the parents anymore, the alleles/SNP have never traveled like this before, you get pieces added.
Explain recombination of homologous DS DNA in meiosis.
This is not a perfect junction. Recombination does not occur at the same exact spot for both strands. When you go through recombination and triple helix is formed, you have Rad51 and BRCA2. But bc its not the exact same spot, you create heteroduplex.
Explain the resolution of the heteroduplex
- Chew back
- One strand attacks (invasion)
- Extension
- Using opposite homolog, you insert sequence that you want
During strand invasion, there is some mismatch
This occurs because the maternal and paternal chromosomes are not identical; just homologous due to allelic variation
Repaired molecules are not like the starting materials because
There is allelic variants b/w mom and dad homologs
What is gene conversion?
This can occur with or without “crossover”, meaning sometimes synapse fails to produce a recombined chromosome.
What is gene conversion without crossover?
You started process of inserting opposite alleles and backed out. So mom alles are still there.
backed out
Strand coming in and changing its mind, going back. Moms’ alleles on either side but dads nuc in the middle
What is gene conversion WITH crossover?
Swapped and recombination occured but you get heteroduplex. With this becuase its not an exact match, specific sequences wont wcbp so heteroduplex needs to be repaired. So you need to chew it back and repair it with something will wcbp
What is the problem with repairing heteroduplex’s?
It will take whatver will wcbp whether its the mom or dad alleles and this leads to gene conversion.
For example:Repaired in Favor of the dads alleles
But if 1 nucleotide repaired one way,
Another nucleotide repaired the other way,
Can create a premature stop codon
With recombination you switch mom and dad allele form a heteroduplex that wcbp and try to fix it with mismatch repair, you can have gene conversion or you can completely converte gene and loose it
What are the mechanisms of diversity for meisosis?
Independent Assortment
Recombination
Gene Conversion
Strand Slippage
What is strand slippage?
When you have a lot of repeats nucleotides are added because one of them became undone, so you still continue to do it and it comes back so you have an extra nucleotiede
in this pic, number two slipped out, we went and added number 2, and number 2 came back so there is an extra dinucleotide.
Slippage causes insertion; it’s a source of di-nucleotide and tri-nucleotide repeats
What is huntington’s disease?
Strand slippage adds more and enough to get HD
Its a repeat of CAG, but you need specific number of repeats (40) to get neurological issues. Since there is a repeat we can wcbp anywhere and cause a loop out.
What can occur with repeated added nucleotide?
Misalignment
Large and unequal relatively rapid increases in the number of repeats as a result of “unequal” crossing over This can lead to misalignment of the chromosomes when chromosomes are meant to recombine Can lead to unequal homolog exchange; the repeats do not line up in a way that exactly represents the correct numbers of repetition
Misalignment can lead to what of genes?
Homologs and sisterchromatids are uneven, so when trying to recombinine they are misaligned that can lead to addition or deletion of genes
this is misalignent at the bivalent stage
What are the two sources of adding repeats in meiosis?
2 sources of adding repeats in Meiosis:
Strand slippage
Misalignment and unequal Recombination/cross over
for both homologs and sister chromatids
Explain this picture
Misalignment of homologs. You can add a gene to one and delete a gene for another
duplicate genes on one homolog, no genes on other homolog
Repeats like SINEs and LINES line up the homolog for recombination but they can misalign
What are some examples of diseases that occur due to gene loss and unequal crossing over.
Thalassemia, mild anemia, HbH disease, hydrobs fetalis
Because misaligned, you lost specific genes that you needed leading to disease
Which of the following is a medical issue that is traceable to unequal crossing over?
Tri nuc repeat expansion
-Loss of a gene
-both
-neither
both
What is an example of gene gain due to “environmental response”, by unequal crossing over.?
Having a high starch diet leads to environmental effect and misalignement, and you added more copies of amylase gene so you can digest starch
Other groups w/ low starch have less copies
Basically, individuals with more AMY1A repeats often tend to eat more starch
The tally of diversity mechanisms for meiosis:
____ of homologs with respect to each other –>Some gametes get the paternal homolog for any given chromosome “number”, and some gametes get the maternal homolog.
Independent assortment
The tally of diversity mechanisms for meiosis:
Essentially random ____ between maternal and paternal homologs –>new combos of alleles on one homolog.
recombination
The tally of diversity mechanisms for meiosis:
DNA replication slippage causes
tri-nucleotide expansions
The tally of diversity mechanisms for meiosis:
Unequal crossing over causes
tri-nucleotide expansions and gene deletion or duplication
What is the impact of single-nucleotide polymorphisms (SNPs) in OGG1 and XPC on the age at onset of Huntington disease.
CAG with huntingtonds disease. It is a trinucleotide repeat that codes for glutamine, Lots of glutamine causes neurological issues. OGG1 & XPC are DNA Repair Genes , bc we had issues with these genes and could not repair it, we get more cag repeats, leading to huntingtons. Increase of CAG repeat causes decrease of DNA Repair. Where did this happen? Variants in the 3’UTR resulted in altered protein levels via allele-specific mIR binding (MicroRNA inhibits translation of XPC).
HD: Trinucleotide repeat of CAG, which codes for glutamine. Lots of Glutamine causes neurological problems
OGG1 & XPC = DNA Repair Genes , CAG repeats are expanding bc of lack of DNA repair
Increase CAG repeat= Decrease of DNA Repair
What is an indicator for huntingtons disease?
SNPs in OGG1 and XPC
What famous bond does OGG1 hydrolyze?
N-Glycosidic bond
What amino acid is repeated in HD and why does the repeat of this amino acid lead to neurological damage?
Glutamine, makes Huntington protein toxic
What is a “haplotype”?
Set of DNA Variations/Polymorphisms that tend to be inherited together
How do the SNPs help establish the result of the case? In other words, how are the SNPs “used”?
Used as markers for disease presentation
Normal ___________ recombination leads to mixing of maternal and paternal DNA strands, termed strand invasion and _________ formation, and to “mismatch repair”, with the possibility of gene conversion
homologus, heteroduplex
Unequal crossing over and unequal sister __________ exchange can expand tri-nucleotide repeats and lead to duplicated genes or the loss of whole genes.
chromatid
