Numerical Chromosomal Abnormalities Flashcards
What are the events in meiosis that produce genetic variability among offspring?
- Crossing over
- Assortment of alleles
- Reduction in genetic material from diploid to haploid
What are the two key differences between mitosis and meiosis?
1 - paternally- & maternally-derived homologous chromosomes pair at the onset of Prophase I (the two homologs segregate independently in mitosis)
What are bivalents and why are they important?
Bivalents are structures in which mat & pat homologous become paired along their entire length
(brought together by the synaptonemal complex)
=> 2-3 crossovers occur on each chromosome
=> genetic reassortment b/w chromosomes
What is the synaptonemal complex?
A proteinaceous structure that promotes inter-homolog interaction (necessary for bivalent structures)
It disassembles at the end of Prophase I
=> bivalents only held together by chiasmata
What is the most frequent mutational mechanism in humans, and during which stage does it occur?
Chromosome Nondisjunction
during Meiosis I (most error-prone step)
What are the three classifications for chromosomes?
- Metacentric = centromere is in the middle, chromosome arms are approx same length
- Submetacentric = centromere slightly removed from center
- Acrocentric = centromere is near one end
How else are chromosomes classified?
Cytogenetically, based on banding patterns observed microscopically
Unique banding patterns => unequivocal identification of each chromosome
What is chromosome nondisjunction?
The missegregation of chromosomes at metaphase (in either mitosis or meiosis) in which daughter cells receive extra or fewer chromosomes
What is aneuploidy?
A condition in which cells contain an abnormal chromosome number
(frequently the result of chromosome nondisjunction)
What type of errors predominate almost all trisomies, and when do they occur?
maternal errors in the first meiotic division
Disturbances in the recombination pathway are associated with abnormalities in chromosome segregation in the first mitotic division. How does the location of chiasmata affect nondisjunction?
Crossvover too near/far from the centromere increase chromosome nondisjunction.
Distal exchanges are less effective in ensuring appropriate spindle attachment and separation of paired homologs in meiosis I
Proximal exchanges, or excessive number of exchanges, lead to entanglement of paired homologs in meiosis I => reductional division
What is the maternal age effect?
The notable increase of aneuploidy in the eggs of women approaching menopause
What is the “two hit” theory for the maternal age effect?
1st Hit = diminished recombination from lack of chiasma or mislocalization -> chromosome more susceptible to possible nondisjunction
2nd Hit = diminished ability of oocytes to successfully complete chromosome segregation in the presence of unfavorable recombination events
What is the function of the cohesion complex in meiosis?
It ensures cohesion b/w sister chromatids and maintains inter-homolog associations distal to the site of crossovers
Degradation of cohesion complexes over the extended meiosis I-arrest (oocytes) results in precocious separation of homologs.
What are the common clinical features of Trisomy 21?
(Down Syndrome) Characteristic facies Short stature Hypotonia Moderate intellectual disabilities
Endocardial cushion defects
Duodenal atresia and other GI anomalies
Hirschprung disease