Chromosomes Abnormalities Flashcards
What are Chromosomes territories and where are gene rich/poor placed
discrete domains occupied by each chromosome in
interphase
○ Gene poor - edges of the nucleus, HSA18 nuclear periphery
○ Gene rich - near the center of the nucleus, HSA19 nuclear interior
What are chromatin and how does it make up the nucleosome core particle? (what does this consist of, i.e.. Histones and different types and locations)
nucleoprotein structures that eukaryotic chromosomes are complexed into
- Bound into nucleosome with histones
▪ H2A and H2B form dimers, H3 and H4 form dimers
▪ 2 of the H3-H4 dimers form a tetramer
▪ 2 of the H2A-H2B dimers join the tetramer, making an octamer
▪ About 146 bp DNA wraps around each octamer to form a nucleosome
What is the least condensed state of chromatin and what is the morphology described as? (think of how long of a fiber) and what connects the beads?
- Least condensed state is a 10-nm fiber.
- Described as “beads on a string”
○ Beads = nucleosome
○ String = linker DNA
Define chromosome scaffold and what its function is and its nm fiber length
- composed of nonhistone proteins that form an infrastructures that anchors DNA loops and gives chromosomes their shape
○ 30-nm fibers used
Match nm fibers to structures/ terms
~ 10-nm fiber - not observed under normal conditions
~ 30-nm fiber - observed under in vitro conditions
○ Forms when the 10-nm fiber coils into a solenoid structure
~ Chromosome scaffold - composed of nonhistone proteins that form an infrastructures that anchors DNA loops and gives chromosomes their shape
○ 30-nm fibers used
Does chromosome number correlate with the genome size and the number of genes of the species?
no
True or false? In mammals, the number of chromosomes is proportional to the amount of DNA.
False
Recorded maximum/minimum # of chromosomes identified and species/common name associated with it.
- Ophioglossum reticulatum (a fern)
▪ 2n = 1262
▪ 631 pairs
○ - Red vizcacha rat
▪ Mammal record holder
▪ 2n = 102
identify the different chromosome staining techniques
- Fluorescence in situ hybridization (FISH)
- C-banding
- G-banding (Giemsa)
- ZOO-FISH
What is chromosomal nondisjunction and how does it affect ploidy?
failure of chromosomes and sister chromatids to properly
separate during cell division
○ Resulting in abnormalities in chromosome number
aneuploidy vs polyploidy
~ Aneuploidy - abnormal amount of chromosomes, missing or extra
○ A number of chromosome that are NOT euploid (a complete set)
○ 2n ± x chromosomes
~ Polyploidy - presence 3 or more sets of chromosomes
○ 3n, 4n, etc.
What is the difference between chromosomal disjunction errors during meiosis I and meiosis II and how does each affect gametes?
- Meiosis I nondisjunction - failure of homologs to separate
○ Gametes produced are either n+1 or n-1 - Meiosis II nondisjunction - failure of sister chromatids to separate normally
○ 2 gametes will be normal (n), 1 gamete will be n+1, 1 gamete will be n-1
True or false? a. Trisomy for many different chromosomes is routinely observed in spontaneous abortions. b. Monosomy
a. true
b. false, autosomal monosomics die in utero
Why is autosomal trisomy more tolerated when it happens in small chromosomes than when it happens in large chromosomes?
Larger chromosome contain more genetic content, making any abnormalities more likely to be lethal.
What are the three human chromosomes that can be trisomic in liveborns? Which is the most common among the three?
- 13, 18, and 21
- Trisomy 21 is the most common (Down syndrome)
Name the main categories of structural aberrations that can occur in mammalian chromosomes.
Deletions, duplications, inversions, translocations
fertility is decreased with odd or even polyploidy and this can lead to seedless varieties?
Decreased fertility in odd numbered polyploids (3n, 5n, 7n, etc.)
What is the definition of acentric and how does it occur after a chromosome break and terminal deletion?
lacks a centromere
- Chromosome breaks, the detachment of an entire chromosome arm could result in terminal deletion and could be acentric
What is an inversion and are there any consequences?
linear order of a segment is inverted 180 degrees, no change in the overall amount of genetic material (2 normal and 2 abnormal gametes)
What inversion leads to the tobiano coat color in horses?
Inversion of 3q
What is a deletion and what are the consequences of this aberration?
loss of any genetic material, single locus or larger segments
▪ Loss of chromosome segments
▪ Loss of gene(s) and gene products
▪ Problems in meiotic pairing
▪ Changes in phenotype - phenotypic variation, disorders/diseases
What was the syndrome we used as an example of a deletion? Where was the deletion?
Cri-du-chat syndrome has a segmental deletion of chromosome 5p.
Name the two main types of translocations.
- Nonreciprocal translocations- a piece of one chromosome is translocated to a nonhomolog
- Reciprocal balanced translocations - two nonhomologs switch places
What type of translocations has generated the Philadelphia chromosome?
- Marker chromosome in chronic myeloid leukemia.
○ ABL + BCR fusion protein: results in abnormal signal transduction and continuous proliferation of cells - Raleigh chromosome = homolog in dogs
○ Translocation between CFA9 and CFA26
describe the human Philadelphia chromosome and its homolog in dogs
reciprocal translocation
What are the possible consequences of translocations for reproduction/gametes?
Can result in genetically unbalanced gametes.
○ Familial down syndrome
What is the definition of duplications? How can they affect the genome?
any part of the genetic material - single locus or larger - present
more than once
○ Redundancy of genetic material - overdose
○ Problems in meiotic pairing
○ Changes in phenotype - phenotypic variation, disorders/disease
What gene is involved in Charcot-Marie-Tooth syndrome?
PMP22 gene
What is a fragile site, can they be common, and can they be associated with diseases all the time?
heritable loci on chromosomes that are visible as gaps or breaks when cells are expose to specific chemicals
○ Two types: common and rare
* They can be common.
* Can only be associated with disease in rare fragile sites.
Give an example of a human genetic disorder associated with fragile sites. Explain its mechanism
Fragile X syndrome
○ Involves strand slippage
○ Expansion of trinucleotide repeats in FMR1 gene
Sex chromosome disorders: Klinefelter Syndrome, Turner Syndrome. XXX/XYY condition
45,X (Turner syndrome)
47,XXY (Klinefelter syndrome)
47,XYY (XYY syndrome) 47,XXX
Nucleosome core particles
fundamental units of histone protein organization with two molecules each histone (octamer)
Fluorescence in situ hybridization (FISH)
- Uses molecular probes to detect a target sequence, may be gene-specific
- Probes are labeled with fluorescent compounds, can vary by wavelength and be used simultaneously
C-banding
Staining of only the centromeres
G-banding (Giemsa)
Differential staining along the length of each chromosome
ZOO-FISH
Uses another species form comparative chromosome painting, shows conserved synteny (similarities between the two species) and the chromosomes unique to the species
Two type of inversions and result products
- Paracentric inversion: centromere is outside of the inverted region
○ Crossing over results in a dicentric chromosome and an acentric fragment - Pericentric inversion - centromere in within the inverted region
○ Crossing over results in both duplicated and deleted regions of product
