Chromosomes and abnormalities Flashcards
Basic structure of chromosomes
- Linear chromosomes
- Telomere
- Centromere
- Chromatin
- Extragenic sequences
Telomere
- Bits at end
- Repetitive nucleotide sequences at end which protect chromosome from deterioration or from fusion with neighbouring chromosomes
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
Chromatin
- DNA packaged with histone proteins into units called nucleosomes
- Histones have +ve change
- Heterochromatin
- Euchromatin
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
Chromosome structure
- 2 sisters
- q (longer) arm and p (shorter) arm
- Banding can define each chromosome
Metacentric
Far away from centre
Submetacentric
Closer to centre
Acrocentric
Petit arm is entirely occupied by heterochromatin
Extragenic sequences
- Tandemly repeated DNA sequences: satellite and mini-satellite
- Both non-coding DNA
Satellite DNA
- at centromeres and telomeres
- A-T rich DNA, separates in a different place
Minisatellite DNA
- DNA used for DNA fingerprinting
Cell cycle and cell division
G1, gap phase, cell grows
S, replication of DNA
G2, gap phase, cell prepares to divide
Mitosis
Stages of mitosis
- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis
Prophase
- Chromosomes condense
- Nuclear membrane disappears
- Spindle fibre form from the centriole
Metaphase
- Chromosomes aligned at the equator of the cell
- Attached by fibre to each centriole
- Maximum condensation of chromosome
Anaphase
- Sister chromatids separate at centromere
- Separate longitudinally
- Move to opposite ends of cells
Telophase
- New nuclear membranes form
- Each cell contains 46 chromosomes (diploid)
Cytokinesis
- Cytoplasm separates
- 2 new daughter cells, receive complete and precise copies of genomes
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
Gametogenesis. Male vs. female
- Female: happens for years from early embryotic life
- Male: takes a matter of days
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)
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
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
3 basic types of chromosomal abnormalities
- Numerical
- Structural
- Mutational
Numerical chromosomal abnormalities
- Trisomy, 3 of the same chromosomes
- Monosomy, only one X chromosome
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
Monosomy example
- Only one X chromosome.
- 45,X Females of short stature, infertile. Inteligent. Normal life span
Structural chromosomal abnormalities
- Wrong arrangement
- Balanced or unbalanced translocations
- Deletions
- Insertions
- Inversions
Balanced translocations
- All genetic information is still present
- 2 chromosomes of different size translocate
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
Robertsonian translocation
- fusion of 2 acrocentric chromosomes
- 2 chromosomes are fused but no genetic info is lost, 2 short arms are lost
Deletions
Break in the chromosome and there is genetic material deleted
Inversions
- Paracentric inversion: break in the chromosome and there is an inversion of the centromere and reinserted
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
