Flashcards in Chromosomal Abnormalities (Megee L1) Deck (30)
Cell cycle - Mitosis
Interphase [G1 --> S --> G2] --> Mitotic [M] phase
Within M-phase: Prophase -> Prometaphase -> Metaphase -> Anaphase -> Telophase -> cytokinesis
Two key differences between mitosis and meiosis
1. meiosis: pat. and mat. derived homologs pair at prophase I
mitosis: pat. and mat. derived homologs segregate independently
2. meiosis: reciprocal recombination between mat. and pat. sister chromatids = chiasmata between homologs
mitosis: recombination rare
(also, mitosis 2n --> 4n --> 2n
meiosis 2n-> 4n -> 2n -> n)
What is a chiasma (pl. chiasmata)? How many are there per homolog pair and how do they form?
a physical linkage between homologs that occurs during the onset of meiosis (prophase I) allowing for reciprocal recombination between homologs.
2-3 per homolog pair
each link requires two double-strand breaks in order to form
At what points during cell division do chromosomal abnormalities arise and what are they?
Meiosis: Germ line mutations; genetic reassortment during meiotic crossovers
Mitosis: Somatic and Germ line mutations; mosaicism
What are pseudoauosomal regions?
Regions of sex chromosomes that can cross over during male meiosis. That is, part of the Y chrom. can cross over with part of the X chrom.
Allows for proper alignment and segregation of these two chromosomes
Often appears as an autosomal pattern in a pedigree.
What is a bivalent structure in and what is the structure that holds a bivalent together at the beginning of prophase I?
When mat. and pat. homologs become paired (synapsed) along their entire length.
Held together by synaptonemal complex (proteinaceous structure)
At the end of prophase I what holds the bivalent together?
just the chiasmata since the synaptonemal complex has disassembled.
When does recombination occur?
What is the total estimated variability this can produce?
prophase I of meiosis
What is the difference between sister chromatids and homologous chromosomes?
Sister chromatids are generated when a single chromosome replicates. Now there are two copies
Homologous chromosomes are two different copies of a chromosome (one from mom, one from dad)
In meiosis, when do sister chromatids and homologous chromosomes separate?
Homologous chromosomes: Meiosis I; Anaphase I
Sister chromatids: Meiosis II; Anaphase II
What is nondisjunction?
Abnormal segregation of homologues or sister chromatids.
Metacentric, Submetacentric, Acrocentric?
Meta: centromere in the center
Submeta: centromere slightly off of center
Acro: centromere near one end
Acrocentric is unique. Describe. Which human chromosomes are acrocentrei?
On the small end, they have a small bit of chromatin called a satellite attached to the centromere by a stalk.
13, 14, 15, 21, 22
What is contained in the satellite and the stalk of an acrocentric chromosome?
Satellite region is many bp repeats.
Stalk contains DNA that encodes for rRNA (which, as we know, makes up a large portion of the ribosomal structre) as well as repeats.
What is Giemsa?
Stain used to identify individual chromosomes. Produces an unique banding pattern on a chromosome.
The short and long arms of a chromosome are labeled as what?
p = short arm (petite)
q = long arm
What does "der" stand for?
derivative. when there is translocation we use "der" to designate where a piece of translocated DNA and centromere came from
Aneuploidy and Polyploidy?
Aneuploidy = loss or gain of a particular chromosome (e.g. trisomy 21 or monosomy X)
Polyploidy = extra copies of all chromosomes (e.g. 3n, 4n)
What are the three viable (survive to birth) trisomies and why are they (likely) to be such?
13, 18 and 21. These chromosomes contain the fewest gene-encoding regions of all the chromosomes. Only the Y chromosome has fewer genes located on it.
Discuss the mechanisms that can produce polyploidy.
1. Triploidy: di-spermy or diploid egg or diploid sperm
2. Tetraploidy: DNA duplication but no cell division (endomitosis)
List some factors leading to Aneuploidy.
Meiotic chromosome nondisjunction
* location of recombination too close to centromere or telomere
* reduced frequency of crossover (recombination) events
Maternal age > 35 years
presence of 2 or more genotypes in cells in a tissue derived from a single zygote.
How many mitosis divisions do germ cells undergo before entering the final meiotic division?
about 30 - 50
Two examples of somatic chromosomal errors that occur during development and lead to mosaicism.
1. 47, XX +21 / 46, XX mosaic trisomy 21 (Down's syndrome)
2. 46, XX / 46, XY true hermaphroditism
Somatic chromosomal mosaicism can lead to...
overexpression of oncogenes or loss of tumor suppressor genes
How do the children of mosaic parents fare?
children will be fully affected.
Common cause of mosaicism
nondisjunction in an early post-zygotic mitotic division.
germ line mosaicism can result from...
mitotic nondisjunction in germ cell precursor
Nondisjunction event in meiosis I will lead to...
100% abnormal gametes
2 are N+1 and the other 2 are N-1