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Flashcards in Chromosomes and abnormalities Deck (35):
1

Basic structure of chromosomes

- Linear chromosomes
- Telomere
- Centromere
- Chromatin
- Extragenic sequences

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Telomere

- Bits at end
- Repetitive nucleotide sequences at end which protect chromosome from deterioration or from fusion with neighbouring chromosomes

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Centromere

- 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

Chromatin

- DNA packaged with histone proteins into units called nucleosomes
- Histones have +ve change
- Heterochromatin
- Euchromatin

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How DNA is packaged

- 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

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Chromosome structure

- 2 sisters
- q (longer) arm and p (shorter) arm
- Banding can define each chromosome

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Metacentric

Far away from centre

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Submetacentric

Closer to centre

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Acrocentric

Petit arm is entirely occupied by heterochromatin

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Extragenic sequences

- Tandemly repeated DNA sequences: satellite and mini-satellite
- Both non-coding DNA

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Satellite DNA

- at centromeres and telomeres
- A-T rich DNA, separates in a different place

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Minisatellite DNA

- DNA used for DNA fingerprinting

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Cell cycle and cell division

G1, gap phase, cell grows
S, replication of DNA
G2, gap phase, cell prepares to divide
Mitosis

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Stages of mitosis

- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis

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Prophase

- Chromosomes condense
- Nuclear membrane disappears
- Spindle fibre form from the centriole

16

Metaphase

- Chromosomes aligned at the equator of the cell
- Attached by fibre to each centriole
- Maximum condensation of chromosome

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Anaphase

- Sister chromatids separate at centromere
- Separate longitudinally
- Move to opposite ends of cells

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Telophase

- New nuclear membranes form
- Each cell contains 46 chromosomes (diploid)

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Cytokinesis

- Cytoplasm separates
- 2 new daughter cells, receive complete and precise copies of genomes

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Meisosis

- 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

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Gametogenesis. Male vs. female

- Female: happens for years from early embryotic life
- Male: takes a matter of days

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How to chromosome analysis

- 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

FISH

- 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

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Types of FISH

- 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

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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

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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

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Balanced translocations

- All genetic information is still present
- 2 chromosomes of different size translocate

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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

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Deletions

Break in the chromosome and there is genetic material deleted

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Inversions

- Paracentric inversion: break in the chromosome and there is an inversion of the centromere and reinserted

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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