Meiosis and mendelian inheritence Flashcards
Define ploidy: What impact does meiosis have on ploidy?
Number of sets of chromosomes. (e.g. diploid) Meoisis halves number of chromosome sets. (it is reductional)
Describe Mitosis in terms of ploidy level and number of gene copies?
2N, 2C at G1 stage (a chromosome from each parent, one chromatid). S stage DNA replication creates sister chromatids. 2N, 4C. (2 homologous chromosomes, each with sister chromatids) Chromosomes align on metaphase plate with NO homologous pairing. Sister chromatids separate! Pulled to either end by spindle fibres attached to kinetochores on centromere. Identical 2N 2C daughter cells.
Key differences in meiotic cycle that differ from mitosis?
After DNA replication, homologous chromosomes pair! (recombination occurs) In the ‘reductional division’ meiosis I, homologous chromosomes are segregated. leaving haploid cells 1N 2C cells (with 2 sister chromatids) (mendels first law, of segregation) with either a maternal or paternal copy of each chromosome. In meiosis 2, sister chromatids separate. leaving 1N 1C haploid cells. (4 total)
What are mendels laws?
First law, of segregation: each daughter cell gets only one randomly selected allele for each gene. Second law: of independent assortment of alleles. (each gene’s alleles independent of other genes, assuming no linkage)
How are sister chromatids kept together during meiosis 1?
By MONOPOLAR sister kinetochore orientation, and by the maintenance of COHESIN between sisters until meiosis II (step-wise loss of cohesin)
How do homologous chromosomes pair before meiosis I? (forming bivalent structure)
Aligned by changes in nuclear architecture: Rabl centromere clustering and then bouquet telomere clustering align homologous chromosomes.
The pairing itself is mediated by HOMOLOGOUS/MEIOTIC RECOMBINATION (based on sequence homology)!
Synaptonemal complex is a protein complex that zip up homologous chromosomes together after telomere clustering and meiotic recombination.
What is a chiasma?
Cytological manifestation of crossing over process in meiotic/homologous recombination. (between homologous chromosomes in bivalent structure)
What could be causing the increase in aneuploidy (chromosome misssegregation) in aging women?
Decrease in integrity of cohesin and so decrease in integrity of Bivalent structures. (and decrease in chiasmata)
What is monopolin complex?
A complex found in yeast!
which binds sister kinetochores together, facilitating the monopolar sister kinetochore orientation, as the sister chromatids’ fused kinetochores then act as one.
What is the purpose of the step-wise loss of cohesin?
Cohesin loss starts at arms of chromatids, facilitating the separation of bivalent structure at anaphase 1 (in meiosis.
But centromeric cohesin must be maintained to keep sister chromatids together!
Centromeric cohesin removed at anaphase 2.
(removal of cohesin catalysed by Separase enzyme, tethered to Securin until needed)
Mendels second law: of segregation (law governing mendelian inheritance). What is the mechanism behind it?
Random alignment and then segregation/assortment of homologous chromosomes at anaphase 1 occurs independently for each chromosome.
Assuming genes aren’t linked (by being on the same chromosome) they are therefore independently assorted from one another, leading to a predictable pattern of inheritance of genotypes of multiple genes)
What is linkage disequilibrium?
When genes are not assorted independently of each other because they are linked on the same chromosome, so you get more of a certain genotype (with linked alleles occurring together more frequently together in an offspring population than would be expected) AB much more than Ab for example.
(linkage can be advantageous)
How can you assess mendelian segregation?
Assessing the gametes directly (typically genotype, via PCR)
Or assess phenotype or genotype of F1 (next) generation.
Stages of prophase 1:
defined by chromosome architecture
Leptotene (thin), chromosomes condense into visible threads
Zygotene (“paired threads”, homologous chromosomes align with Rabl and bouquet clustering, synaptonemal complex forms),
Pachytene (“thick threads” crossing over occurs at this stage)
Diplotene (2 threads, still connected at chiasmata but synaptonemal complex degenerated)
Role of Spo11?
Causes double strand breaks at highly regulated sites during meiosis 1 prophase 1 pachytene stage.
Initiates meiotic recombination at these sites.
They are non-random initiation sites so small chromosomes like Y chromosome get at least 1 chiasma (for homologous pairing)
What happens to the double strand breaks in DNA, so that crossing over occurs?
single strand resection leaving overhanging single strands.
These are guided to interact with homologous non-sister chromosome.
D-loop forms in other chromosome so broken ss can integrate.
If second end of broken strand is captured then 2 holiday junctions are formed and in their resolution, crossing over occurs!!
When determining the type of mis-segregation by allele specific PCR, how do you identify the difference between disomic gamete produced by meiosis 2 non-disjunction and other disomic gametes?
Meisosi 2 non-disjunction (failure of sister chromatids separating) produces 1 disomic gamete with 2 sister chromatids present.
