Lecture 1: Higher Eukaryotic Organisms

Question 1

How are metaphase chromosome structures formed?

Answer 1

Nucleosomes condense into chromatic fibre, which condense further into metaphase chromosomes

Question 2

How are nucleosomes formed?

Answer 2

Chromosomes consist of thread like DNA molecule which wraps histone octamers, forming nucleosomes

Question 3

What is the centromere?

Answer 3

Constructed region or kinetochore where spindle attaches to

Question 4

What are telomeres?

Answer 4

Highly stable regions of repetitive DNA at the ends of chromosomes

Question 5

How many chromosome pairs are in the human karyotype?

Answer 5

23 pairs: 22 autosomal pairs, 1 sexually dimorphic pair

Question 6

What are acrocentric chromosomes?

Answer 6

Centromere is at far from end, one arm is very short/nearly absent

Question 7

What are submetacentric chromosomes?

Answer 7

Chromosomes with the centromere positioned so one arm is shorter than the other

Question 8

What are metacentric chromosomes?

Answer 8

Centromere is central so both p and q arms are equal

Question 9

What other features can chromosomes contain?

Answer 9

• Secondary constriction that can act as nucleolar organisation regions (NORs)
• Small chromosomal segments called satellites

Question 10

What chromosomes are satellites associated with?

Answer 10

Chromosomes 13, 14, 15, 21 & 22

Question 11

How does G-banding work to determine chromosomes?

Answer 11

Giemsa staining forms light and dark bands characteristic to each chromosome

Question 12

What do dark bands mean in G-banding?

Answer 12

Heterochromatic regions which are A-T rich and gene poor

Question 13

What do light bands mean in G-banding?

Answer 13

DNA is G-C rich, gene rich, and transcriptionally active

Question 14

What is ISCN?

Answer 14

International System of Human Cytogenic Nomenclature

Used to distinguish and identify chromosomes, up to 600 bands can be seen in metaphase chromosomes

Question 15

What is FISH and what’s it used for?

Answer 15

Fluorescent in situ hybridisation is used for mapping genes on chromosomal regions

Question 16

What steps are involved in the FISH process?

Answer 16

• 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

Question 17

What is digital karyotyping used for?

Answer 17

Uses short sequence tags derived from specific genomic loci to provide quantitative view of copy number changes

Question 18

What steps are used in digital karyotyping?

Answer 18

• 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

Question 19

What are the 6 types of chromosomal abnormalities?

Answer 19

Numerical abnormalities: aneuploidy, polyploidy
Structural abnormalities: duplications, deletions, translocations and inversions

Question 20

What is polyploidy?

Answer 20

One or more additional chromosome sets

Question 21

What is aneuploidy?

Answer 21

Loss or gain of genetic material from a single chromosome

Question 22

What are 3 examples of conditions caused by aneuploidy in sex chromosomes?

Answer 22

Turner syndrome
Klinefelter syndrome
Trisomy x

Question 23

What are 3 examples of conditions caused by aneuploidy in autosomes?

Answer 23

Down syndrome - 21
Edward’s syndrome - 18
Patau syndrome - 13

Question 24

What structural abnormalities lead to an unbalanced genome?

Answer 24

Inversion and duplication

Question 25

What structural abnormalities can lead to balanced genome?

Answer 25

Inversions

Question 26

How can a gene be disrupted?

Answer 26

If an arrangement occurs within a gene that’s important, it can produce a phenotype that will affect the individual

Question 27

Paracentric vs pericentric inversions

Answer 27

Paracentric: occurs in arm of chromosome, centromeres preserved
Pericentric: happens across centromere, changes gene order and centromere position

Question 28

What causes structural abnormalities?

Answer 28

DNA breakage & non-allelic homologous recombination (NAHR)

Question 29

What causes double stranded break of DNA?

Answer 29

Can occur naturally, but more frequently after mutagen exposure

Question 30

How can recombination occur between non-allelic chromosomes?

Answer 30

NAHR causes recombination as they contain segments of DNA similar in sequence

Question 31

What are the outcomes of different segregations?

Answer 31

Alternate segregation: balanced, viable
Adjacent-1: unbalanced, not viable
Adjacent-2: unbalanced, not viable

Question 32

What is robertonsian translocation?

Answer 32

Balanced fusion of 2 acrocentric chromosomes

Ends break, fusion forms large chromosome

Question 33

What is the Philadelphia chromosome?

Answer 33

Translocation exchange between 9q and 22q

Question 34

What are CNVs?

Answer 34

Copy number variants, where duplications are in tandem

Question 35

What are the 2 CNV groups?

Answer 35

Long repeats and short repeats

Question 36

What is fixed segmental duplication?

Answer 36

Where redundant genes are generated and are free to evolve

Question 37

What is synteny?

Answer 37

A situation in which genes are arranged in similar blocks in different species

Conservation of blocks between species

Question 38

What are synthetic genes?

Answer 38

Genes on the same chromosome