Chromosomes and abnormalities Flashcards
1
Q
Basic structure of chromosomes
A
- Linear chromosomes
- Telomere
- Centromere
- Chromatin
- Extragenic sequences
2
Q
Telomere
A
- Bits at end
- Repetitive nucleotide sequences at end which protect chromosome from deterioration or from fusion with neighbouring chromosomes
3
Q
Centromere
A
- Bit in middle
- Constricted region that links sister chromatids. Held together by cohesion
- Has repetitive DNA sequences such as satellited DNA
- Side of kinetochore, core where there is microtubule attachment from spindles
- Protein complex that binds to microtubules
4
Q
Chromatin
A
- DNA packaged with histone proteins into units called nucleosomes
- Histones have +ve change
- Heterochromatin
- Euchromatin
5
Q
How DNA is packaged
A
- Nucleosome -> chromatin fibre -> fibre-scaffold complex -> chromsome
- Negatively charged DNA neutralised by positively changed histone proteins
- DNA takes up less space
- Inactive DNA can be folded into inaccessible locations until required
6
Q
Chromosome structure
A
- 2 sisters
- q (longer) arm and p (shorter) arm
- Banding can define each chromosome
7
Q
Metacentric
A
Far away from centre
8
Q
Submetacentric
A
Closer to centre
9
Q
Acrocentric
A
Petit arm is entirely occupied by heterochromatin
10
Q
Extragenic sequences
A
- Tandemly repeated DNA sequences: satellite and mini-satellite
- Both non-coding DNA
11
Q
Satellite DNA
A
- at centromeres and telomeres
- A-T rich DNA, separates in a different place
12
Q
Minisatellite DNA
A
- DNA used for DNA fingerprinting
13
Q
Cell cycle and cell division
A
G1, gap phase, cell grows
S, replication of DNA
G2, gap phase, cell prepares to divide
Mitosis
14
Q
Stages of mitosis
A
- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis
15
Q
Prophase
A
- Chromosomes condense
- Nuclear membrane disappears
- Spindle fibre form from the centriole
16
Q
Metaphase
A
- Chromosomes aligned at the equator of the cell
- Attached by fibre to each centriole
- Maximum condensation of chromosome
17
Q
Anaphase
A
- Sister chromatids separate at centromere
- Separate longitudinally
- Move to opposite ends of cells
18
Q
Telophase
A
- New nuclear membranes form
- Each cell contains 46 chromosomes (diploid)
19
Q
Cytokinesis
A
- Cytoplasm separates
- 2 new daughter cells, receive complete and precise copies of genomes
20
Q
Meisosis
A
- Cell divisions in germ cells
- Diploid cells divide to form haploid cells
- Chromosomes are passed on as rearranged copies: creats genetic diversity, recombination between homologs is defining event in sexual reproduction
21
Q
Gametogenesis. Male vs. female
A
- Female: happens for years from early embryotic life
- Male: takes a matter of days
22
Q
How to chromosome analysis
A
- Blood sample
- Separate off red cells
- Add culture medium to white cell suspension
- Incubate
- Colchicine-microtubule inhibitor added
- Cells assemble in mitosis, increases population of cells
- Hypotonic saline added
- Cells fixed and stained
- Karyotyped (meta, sub-meta and acrocentric. Chromosomes are numbered in size order)
23
Q
FISH
A
- Fluorescent in situ hybridisation
- For looking at a sequence of specific interest
- Take a fragment of DNA sequence you’re interested in and labelled using fluorescent dye
- Denature and hybridise the DNA to find the DNA you’re interested in
24
Q
Types of FISH
A
- Unique sequence probes
- Centromeric probes: useful for chromosome number
- Telomeric probes: useful for detecting subtelomeric rearrangements, useful for children with unexplained mental retardation
- Whole chromosome probes: cocktail of probes covering different parts, translocations and rearrangments
25
3 basic types of chromosomal abnormalities
- Numerical
- Structural
- Mutational
26
Numerical chromosomal abnormalities
- Trisomy, 3 of the same chromosomes
| - Monosomy, only one X chromosome
27
Trisomy examples
Autosomal aneuploidy syndrome: trisomy 13: Patau, dysmorphic, mental retardation. Trisomy 18: Edwards, severe developmental.
Sex chromosomes aneuploidy syndromes: 47, XXY. Male but infertile, small testes
28
Monosomy example
- Only one X chromosome.
| - 45,X Females of short stature, infertile. Inteligent. Normal life span
29
Structural chromosomal abnormalities
- Wrong arrangement
- Balanced or unbalanced translocations
- Deletions
- Insertions
- Inversions
30
Balanced translocations
- All genetic information is still present
| - 2 chromosomes of different size translocate
31
Reciprocal translocation
- Breaks in 2 chromosomes with formation of 2 new derivative chromosomes
- If a reciprocal translocation carrier is fertilised by a normal gamete 1/4 chance normal, 1/4 chance balanced and 1/2 chance unbalanced
- Unbalanced means partial trisomy and monosomy
32
Robertsonian translocation
- fusion of 2 acrocentric chromosomes
| - 2 chromosomes are fused but no genetic info is lost, 2 short arms are lost
33
Deletions
Break in the chromosome and there is genetic material deleted
34
Inversions
- Paracentric inversion: break in the chromosome and there is an inversion of the centromere and reinserted
35
Origin of chromosome abnormalities
- Non-disjunction
- Meiosis I
- Meiosis II
- Abnormalities are most common from maternal meiotic as eggs sit for decades in meiosis I phase and the disjunction process becomes less accureate
