Lecture 1 - Higher Eukaryotic Chromosomes

Question 1

What is a Telomere?

Answer 1

Area of repetitive DNA and end of chromosomes

Question 2

Are telomere stable?

Answer 2

Yes and they do not fuse with other chromosomes

Question 3

What is a centomere?

Answer 3

Region or kinetocore where the cells spindle fibres attach

Question 4

What are sister chromatids?

Answer 4

Identical copies formed in DNA replication - both copies are joined together by the centromere

Question 5

How is DNA packaged into a nucleus?

Answer 5

DNA is wrapped to make ball like structures they then form chromatin fiber to form metaphase chromosome

Question 6

What grooves open up when the DNA wraps around the nucleosome?

Answer 6

Minor groove

Question 7

What makes the DNA relaxed?

Answer 7

The longer the linker DNA

Question 8

What is found near the centromere?

Answer 8

Heterochromatin

Question 9

What happens to telomeres with age?

Answer 9

Shorten

Question 10

What is it called when the centromere is in the centre of the chromosome?

Answer 10

Metacentric chromosome

Question 11

Where is the centromere in a submetacentric chromosome?

Answer 11

Top of the chromosome, makes a smaller short arm than long arm

Question 12

What is it called when the centromere is at the very top of the chromosomes?

Answer 12

Acrocentric

Question 13

What are satellites?

Answer 13

Secondary constriction site with small chromosomal segment

Question 14

What does a secondary constriction site on a chromosome act as?

Answer 14

Acts as a nuclear organisation region (NOR)

Question 15

What chromosomes do we find Satellites on?

Answer 15

13, 14, 15, 21 and 22

Question 16

What is the stain used to distinguish between similar chromosomes?

Answer 16

Giemsa staining (g-banding)

Question 17

When using giemsa staining what regions stain darker and why?

Answer 17

Heterochromatic regions (AT-rich) and are gene poor

Question 18

When using giemsa staining why are some bands stained light?

Answer 18

GC rich and more active

Question 19

What stops the protein from holding DNA together before giemsa can stain?

Answer 19

Trypsin

Question 20

What is the international system of human cytogenetic nomenclature (ISCN)?

Answer 20

Database showing all the chromosome bands allowing us to locate specific regions and find abnormalities

Question 21

Why do we have the international system of human cytogenetic nomenclature (ISCN)?

Answer 21

Good for accurate and consistent description of genomic changes as identified by karyotyping

Question 22

What is the short arm labelled as?

Answer 22

XP

Question 23

What is the king arm labelled as?

Answer 23

XQ

Question 24

How do you accurately locate positions for specific genes?

Answer 24

FISH

Question 25

How do you do fish?

Answer 25

Isolate metaphase chromosomes and spread in glass slide. Meanwhile clone a gene of interest and make a DNA probe by adding it to a plasmid - fluorescent it label this. Then add dye to the DNA (direct labelling) or add biotin then later the dye by adding streptavidin with dye on it which will react with biotin (indirect labelling). Denature chromosomes and probe and the gene of interest will hybridise to the chromosome. You can now see the gene of interests location

Question 26

Can you do FISH for more than one gene?

Answer 26

Yes - multicolour FIsH

Question 27

How does digital karyotyping work?

Answer 27

Uses short sequence tags taken from specific genomic loci ti provide a quantitative and high-resolution view of copy number changes in a genome wide scale

Question 28

How can Digital karyotyping help you see abnormalities and how does it work?

Answer 28

Genome fragmented into small pieces and labelled Once labelled it’s hybridised too an array of DNA probes which span the wholes gene A computer will then see the amount of fluorescence and you can see if there is any abnormalities

Question 29

What is polyploidy?

Answer 29

One or more additional chromosomes sets e.g triploidy is 3 copies of the haploid chromosome

Question 30

What is aneuploidy?

Answer 30

Loss or gain of genetic material from a single chromosome

Question 31

In aneuploidy what is a monosomy?

Answer 31

Loss of one chromosome

Question 32

In aneuploidy what is a trisomy?

Answer 32

Gain of one chromosome

Question 33

What is the most common cause of aneuploidy?

Answer 33

Nondisjunction in meiosis

Question 34

What are some structural abnormalities?

Answer 34

Deletions, duplications, inversions and translocations

Question 35

What is nondisjunction?

Answer 35

Failure of the chromosomes to unjoin resulting in them going into the same daughter cells

Question 36

What happens if nondisjunction happens in the first division?

Answer 36

One daughter cell gets both sets of chromosomes

Question 37

What happens if nondisjunction happens in the 2nd meitotic division?

Answer 37

The Nondisjunction would leas ti one daughter cell having 2 chromosomes and one having non. However the 3rd and 4th could be normal depending on if only one daughter cell suffered the nondisjunction

Question 38

What is Turner syndrome?

Answer 38

One copy of X chromosomes due to aneuploidy

Question 39

What is Klinefelter syndrome?

Answer 39

Males have one extra X chromosome (XXY)

Question 40

What happens in trisomy X

Answer 40

Females have an extra X chromosomes (XXX) And makes get an extra y (XYY).

Question 41

What is seen in spontaneous abortions?

Answer 41

Every possible trisomy

Question 42

Example of trisomy?

Answer 42

Down syndrome

Question 43

Examples of lethal trisomy’s?

Answer 43

Patau syndrome and Edward syndrome

Question 44

What are the 4 ways chromosomes can be rearranged ti cause structural abnormalities?

Answer 44

Duplication, deletion, inversion and translocation

Question 45

What happens in a duplication?

Answer 45

Prices of genome duplicated

Question 46

What happens in a deletion?

Answer 46

Chromosome fragment lost

Question 47

What happens in inversion?

Answer 47

DNA fragment reversed

Question 48

What happens in translocation?

Answer 48

Chromosome fragment moved to different strand

Question 49

What is reciprocal translocation?

Answer 49

Two DBA fragments have changed their position

Question 50

What are Consequences if rearranged chromosomes?

Answer 50

Change in gene dosage in deletion and duplication leading to unbalanced genes

Question 51

Why are inversions easier ti tolerate than duplication and deletions?

Answer 51

The gene dosage remains the same so no unbalanced chromosomes

Question 52

What is a Paracentric inversion?

Answer 52

Centromeres are parallel which conserves location if centromeres

Question 53

What does pericentric mean with inversion?

Answer 53

The centromeres aren’t parallel which changes the order of genes and the location of centromeres This affects meiosis and next generation

Question 54

Where are low copy repeats found and what does non-allergic homologous recombination (NAHR) between two LCR’s lead ti?

Answer 54

These are interspersed throughout the genome and a NAHR between 2 LCRs can lead ti deletion or tandem duplications of the flanking area of the genome

Question 55

Can you get crossover between homologous but non-alleic LCR?

Answer 55

Yes

Question 56

What are low copy repeats?

Answer 56

DNA sequences which appear the same in lots of different places in the genome

Question 57

In a duplication how many copies of a gene will you get?

Answer 57

3

Question 58

In a deletion how many copies of a gene is there?

Answer 58

1 copy deleted in one allele and one normal in the other allele

Question 59

Where are LCR’s found?

Answer 59

In hotspots

Question 60

What are balanced reciprocal translocations?

Answer 60

When a gene translocated with another gene and this doesn’t create a duplication or a deletion.

Question 61

What happens to carriers of balanced reciprocal translocations?

Answer 61

They are healthy and fertile but can transmit the unbalanced form to offspring.

Question 62

What would happen if the 4 chromosome reciprocal translocation structure was split adjacent 2 (vertically)?

Answer 62

It would be unbalanced

Question 63

What would happen to the 4 chromosomal structure reciprocal translocation is it was split horizontally (adjacent)?

Answer 63

Unbalanced

Question 64

What would happen if the 4 chromosomal reciprocal translocation structure was split alternatively?

Answer 64

It would be balanced

Question 65

What determines whether or not reciprocal translocations would lead to unbalanced or balanced segregation?

Answer 65

Depends of how they are segregated

Question 66

What are robertsonian translocations?

Answer 66

Centric fusion of two Acrocentric chromosomes

Question 67

How do robertsonian translocations work?

Answer 67

The long arm fuses with another arm of a different chromosomes when the DNA breaks.

Question 68

What arm has more genes?

Answer 68

Long arm.

Question 69

In robertsonian translocation what product is lost and why?

Answer 69

Short arm as there is no essential genea

Question 70

Is the robertsonian translocation balanced?

Answer 70

Yes

Question 71

What disease is caused by robertsonian translocation?

Answer 71

Down syndrome

Question 72

What is an example of a reciprocal translocation and how is it done and what does it cause?

Answer 72

Philadelphian chromosome where long arm of chromosome 9 fuses with chromosome 22. This can cause leukaemia.

Question 73

How do you diagnose the Philadelphia chromosome?

Answer 73

FISH

Question 74

What are copy number variations?

Answer 74

Small variations only seen through genome sequencing and causes human variation

Question 75

Are CNV’s lethal or neutral?

Answer 75

Both

Question 76

Do duplications of CNV’s go in tandem?

Answer 76

Yes

Question 77

What are the two CNV groups?

Answer 77

Long and short repeats

Question 78

Example of segmental duplication and evolution: AMY-1

Answer 78

People adapted to get more energy from starch food

Question 79

What do fixed segmental duplications generate?

Answer 79

Redundant genes free to evolve and can generate de novo rearrangements

Question 80

What do karyotypes need to evolve?

Answer 80

They need to be fixed and passed through the germ line through meiosis

Question 81

Do chromosomes from different species have the same ancesterol chromosome?

Answer 81

Yea

Question 82

If something is described as being syntenic what does this mean?

Answer 82

A situation in which genes are arranged in similar blocks in different species and the conserved order of genes between species

Question 83

When looking at blocks how can you tell how close the evolution is?

Answer 83

The smaller the number of blocks

Question 84

When looking at syntenic blocks between 2 species what does more conserved syntenic blocks mean?

Answer 84

There is more evolutionary rearrangement and they are close in evolution