Chromosomes Abnormalities

Question 1

What are Chromosomes territories and where are gene rich/poor placed

Answer 1

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

Question 2

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)

Answer 2

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

Question 3

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?

Answer 3

• Least condensed state is a 10-nm fiber.
• Described as “beads on a string”
  ○ Beads = nucleosome
  ○ String = linker DNA

Question 4

Define chromosome scaffold and what its function is and its nm fiber length

Answer 4

• composed of nonhistone proteins that form an infrastructures that anchors DNA loops and gives chromosomes their shape
  ○ 30-nm fibers used

Question 5

Match nm fibers to structures/ terms

Answer 5

~ 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

Question 6

Does chromosome number correlate with the genome size and the number of genes of the species?

Answer 6

no

Question 7

True or false? In mammals, the number of chromosomes is proportional to the amount of DNA.

Answer 7

False

Question 8

Recorded maximum/minimum # of chromosomes identified and species/common name associated with it.

Answer 8

• Ophioglossum reticulatum (a fern)
  ▪ 2n = 1262
  ▪ 631 pairs
  ○
• Red vizcacha rat
  ▪ Mammal record holder
  ▪ 2n = 102

Question 9

identify the different chromosome staining techniques

Answer 9

• Fluorescence in situ hybridization (FISH)
• C-banding
• G-banding (Giemsa)
• ZOO-FISH

Question 10

What is chromosomal nondisjunction and how does it affect ploidy?

Answer 10

failure of chromosomes and sister chromatids to properly
separate during cell division
○ Resulting in abnormalities in chromosome number

Question 11

aneuploidy vs polyploidy

Answer 11

~ 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.

Question 12

What is the difference between chromosomal disjunction errors during meiosis I and meiosis II and how does each affect gametes?

Answer 12

• 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

Question 13

True or false? a. Trisomy for many different chromosomes is routinely observed in spontaneous abortions. b. Monosomy

Answer 13

a. true
b. false, autosomal monosomics die in utero

Question 14

Why is autosomal trisomy more tolerated when it happens in small chromosomes than when it happens in large chromosomes?

Answer 14

Larger chromosome contain more genetic content, making any abnormalities more likely to be lethal.

Question 15

What are the three human chromosomes that can be trisomic in liveborns? Which is the most common among the three?

Answer 15

• 13, 18, and 21
  
  • Trisomy 21 is the most common (Down syndrome)

Question 16

Name the main categories of structural aberrations that can occur in mammalian chromosomes.

Answer 16

Deletions, duplications, inversions, translocations

Question 17

fertility is decreased with odd or even polyploidy and this can lead to seedless varieties?

Answer 17

Decreased fertility in odd numbered polyploids (3n, 5n, 7n, etc.)

Question 18

What is the definition of acentric and how does it occur after a chromosome break and terminal deletion?

Answer 18

lacks a centromere
- Chromosome breaks, the detachment of an entire chromosome arm could result in terminal deletion and could be acentric

Question 19

What is an inversion and are there any consequences?

Answer 19

linear order of a segment is inverted 180 degrees, no change in the overall amount of genetic material (2 normal and 2 abnormal gametes)

Question 20

What inversion leads to the tobiano coat color in horses?

Answer 20

Inversion of 3q

Question 21

What is a deletion and what are the consequences of this aberration?

Answer 21

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

Question 22

What was the syndrome we used as an example of a deletion? Where was the deletion?

Answer 22

Cri-du-chat syndrome has a segmental deletion of chromosome 5p.

Question 23

Name the two main types of translocations.

Answer 23

• Nonreciprocal translocations- a piece of one chromosome is translocated to a nonhomolog
• Reciprocal balanced translocations - two nonhomologs switch places

Question 24

What type of translocations has generated the Philadelphia chromosome?

Answer 24

• 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

Question 25

describe the human Philadelphia chromosome and its homolog in dogs

Answer 25

reciprocal translocation

Question 26

What are the possible consequences of translocations for reproduction/gametes?

Answer 26

Can result in genetically unbalanced gametes.
○ Familial down syndrome

Question 27

What is the definition of duplications? How can they affect the genome?

Answer 27

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

Question 28

What gene is involved in Charcot-Marie-Tooth syndrome?

Answer 28

PMP22 gene

Question 29

What is a fragile site, can they be common, and can they be associated with diseases all the time?

Answer 29

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.

Question 30

Give an example of a human genetic disorder associated with fragile sites. Explain its mechanism

Answer 30

Fragile X syndrome
○ Involves strand slippage
○ Expansion of trinucleotide repeats in FMR1 gene

Question 31

Sex chromosome disorders: Klinefelter Syndrome, Turner Syndrome. XXX/XYY condition

Answer 31

45,X (Turner syndrome)
47,XXY (Klinefelter syndrome)
47,XYY (XYY syndrome) 47,XXX

Question 32

Nucleosome core particles

Answer 32

fundamental units of histone protein organization with two molecules each histone (octamer)

Question 33

Fluorescence in situ hybridization (FISH)

Answer 33

• 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

Question 34

C-banding

Answer 34

Staining of only the centromeres

Question 35

G-banding (Giemsa)

Answer 35

Differential staining along the length of each chromosome

Question 36

ZOO-FISH

Answer 36

Uses another species form comparative chromosome painting, shows conserved synteny (similarities between the two species) and the chromosomes unique to the species

Question 37

Two type of inversions and result products

Answer 37

• 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