Lecture 1: Higher Eukaryotic Organisms Flashcards
How are metaphase chromosome structures formed?
Nucleosomes condense into chromatic fibre, which condense further into metaphase chromosomes
How are nucleosomes formed?
Chromosomes consist of thread like DNA molecule which wraps histone octamers, forming nucleosomes
What is the centromere?
Constructed region or kinetochore where spindle attaches to
What are telomeres?
Highly stable regions of repetitive DNA at the ends of chromosomes
How many chromosome pairs are in the human karyotype?
23 pairs: 22 autosomal pairs, 1 sexually dimorphic pair
What are acrocentric chromosomes?
Centromere is at far from end, one arm is very short/nearly absent
What are submetacentric chromosomes?
Chromosomes with the centromere positioned so one arm is shorter than the other
What are metacentric chromosomes?
Centromere is central so both p and q arms are equal
What other features can chromosomes contain?
- Secondary constriction that can act as nucleolar organisation regions (NORs)
- Small chromosomal segments called satellites
What chromosomes are satellites associated with?
Chromosomes 13, 14, 15, 21 & 22
How does G-banding work to determine chromosomes?
Giemsa staining forms light and dark bands characteristic to each chromosome
What do dark bands mean in G-banding?
Heterochromatic regions which are A-T rich and gene poor
What do light bands mean in G-banding?
DNA is G-C rich, gene rich, and transcriptionally active
What is ISCN?
International System of Human Cytogenic Nomenclature
Used to distinguish and identify chromosomes, up to 600 bands can be seen in metaphase chromosomes
What is FISH and what’s it used for?
Fluorescent in situ hybridisation is used for mapping genes on chromosomal regions
What steps are involved in the FISH process?
- isolate metaphase chromosomes from cell and spread them on glass slide
- gene of interest is cloned and replicated inside large plasmid
- DNA plasmid is labelled with fluorescence
- single stranded DNA is produced by denaturing, so can hybridise
- gene A will specifically hybridise into the region that’s homologous in the chromosome
- genome DNA shows geneA location as its complementary to the chromosome
What is digital karyotyping used for?
Uses short sequence tags derived from specific genomic loci to provide quantitative view of copy number changes
What steps are used in digital karyotyping?
- genome is fragmented into small pieces and labelled with fluorophore
- fragments are hybridized to an array of DNA probes
- amount of detected fluorescence helps identify regions of the genome that have more DNA than others
What are the 6 types of chromosomal abnormalities?
Numerical abnormalities: aneuploidy, polyploidy
Structural abnormalities: duplications, deletions, translocations and inversions
What is polyploidy?
One or more additional chromosome sets
What is aneuploidy?
Loss or gain of genetic material from a single chromosome
What are 3 examples of conditions caused by aneuploidy in sex chromosomes?
Turner syndrome
Klinefelter syndrome
Trisomy x
What are 3 examples of conditions caused by aneuploidy in autosomes?
Down syndrome - 21
Edward’s syndrome - 18
Patau syndrome - 13
What structural abnormalities lead to an unbalanced genome?
Inversion and duplication
What structural abnormalities can lead to balanced genome?
Inversions
How can a gene be disrupted?
If an arrangement occurs within a gene that’s important, it can produce a phenotype that will affect the individual
Paracentric vs pericentric inversions
Paracentric: occurs in arm of chromosome, centromeres preserved
Pericentric: happens across centromere, changes gene order and centromere position
What causes structural abnormalities?
DNA breakage & non-allelic homologous recombination (NAHR)
What causes double stranded break of DNA?
Can occur naturally, but more frequently after mutagen exposure
How can recombination occur between non-allelic chromosomes?
NAHR causes recombination as they contain segments of DNA similar in sequence
What are the outcomes of different segregations?
Alternate segregation: balanced, viable
Adjacent-1: unbalanced, not viable
Adjacent-2: unbalanced, not viable
What is robertonsian translocation?
Balanced fusion of 2 acrocentric chromosomes
Ends break, fusion forms large chromosome
What is the Philadelphia chromosome?
Translocation exchange between 9q and 22q
What are CNVs?
Copy number variants, where duplications are in tandem
What are the 2 CNV groups?
Long repeats and short repeats
What is fixed segmental duplication?
Where redundant genes are generated and are free to evolve
What is synteny?
A situation in which genes are arranged in similar blocks in different species
Conservation of blocks between species
What are synthetic genes?
Genes on the same chromosome
