Chromosome Biology 2

Question 1

What types of chromosomal abnormalities can arise?

Answer 1

• Numerical
• Structural
• Mutational

Question 2

What stages have the highest percentage incidence of abnormalities?

Answer 2

First trimester abnormalities - 50%

Children with mental retardation - 35-40%

Question 3

Name two numerical abnormalities

Answer 3

• Trisomy (extra chromosome)

- Monosomy (loss of chromosome)

Question 4

Name three trisomy conditions and the abnormality

Answer 4

• Patau: 47,XX+13
• Edwards: 47,XY+18
• Down: 47,XX+21
• Klinefelter: 47,XXY

Question 5

Name a monosomy condition and the abnormality

Answer 5

Turner: 45,X

Question 6

What does 46,XX+13 indicate?

Answer 6

• 46 chromosomes
• XX - the extra chromosome
• 13 - at which chromosome

Question 7

What problems arise in non-disjunction?

Answer 7

• 1st stage: homologous pair not separated

- 2nd: sister chomatids fail to separate - one cell is disomy (2 copies)

Question 8

What is an example of an autosomal aneuploidy syndrome?

Answer 8

-Trisomy 21 (down)

Question 9

What does non-dysjunction cause?

Answer 9

Autosomal aneuploidy syndromes - Down, Patau, Edwards (only ones that survivable)

Question 10

Examples of sex chromosomes aneuploidy syndromes?

Answer 10

• Turner

- Klinefelter

Question 11

Examples of structural abnormalities

Answer 11

• Balanced/unbalanced rearrangements
• Translocations
• Deletions
• Insertions
• Inversions

Question 12

Describe balanced translocations

Answer 12

Two non-homologous undergo reorganisation - retains same amount of DNA so no severe effects

Question 13

Describe unbalanced translocations

Answer 13

Reorganistion leads to:
-Partial trisomy (extra chromosome)
-Partial monosomy (chromosome missing)
of each chromatid

Question 14

Describe Robertsonian translocation

Answer 14

Translocation where two acrocentric chromosomes are fused but no DNA is lost

Question 15

What happens in R translocation?

Answer 15

Two Q arms join, and two P arms join (usually lost)

-Unbalanced trans. leads to trisomy and monosomy

Question 16

What is an acrocentric chromosome?

Answer 16

Centromere located near one end of the chromosome

Question 17

Describe deletion mutations

Answer 17

Interstitial break in chromosome leading to deleted genetic material

Question 18

Describe inversion mutations

Answer 18

Interstitial break in chromosome and inverted - no loss of DNA (balanced)

Question 19

Name and describe the two types of inversion mutations

Answer 19

• Paracentric - on the arms

- Pericentric - around centromere

Question 20

Examples of genetic mutations

Answer 20

• Germline or somatic
• Gene disruption
• Polymorphism

Question 21

Types of genetic mutations

Answer 21

• Non coding

- Coding

Question 22

Give examples of coding mutations

Answer 22

• Silent - no change to AA
• Missense - change of AA
• Nonsense - stop codon leading to truncated protein
• Frameshift -deletion/insertion

Question 23

Cys64Arg

Answer 23

AA 64 changed from cys to arg

Question 24

M252X

Answer 24

AA 252 codes sor stop codon

Question 25

1294del40

Answer 25

At AA 1294 theres a deletion of 40 nucleotides

Question 26

662-42C>T

Answer 26

42 nucleotides BEFORE 662 change from C to T

Question 27

IVS2+12insG

Answer 27

12 nucleotides into exon theres an insertion of G

Question 28

Methods of detecting mutations

Answer 28

- PCR - Gel electrophoresis - RFLP - ARMS - DNA sequencing

Question 29

What is PCR used for

Answer 29

Amplifying small segments of DNA

Question 30

What is required for PCR?

Answer 30

- Oligonucleotide primers - DNA sample - DNA polymerase (heat resistant)

Question 31

What are the step in PCR?

Answer 31

1. Denaturing: DNA heated into 2 strands (break H bonds) 2. Annealing: temp lowered so DNA primer attached to template DNA 3. Extending: temp increase and DNA polymerase enzyme forms new strand

Question 32

What is the principle of gel electrophoresis?

Answer 32

Separating DNA fragments by size

Question 33

Mechanism of gel electrophoresis

Answer 33

1. Apply an electric field 2. DNA negatively charged due to -ve phosphate backbone and so moves towards +ve electrode 3. Separate through agarose gel matrix 4. Visualise DNA fragments

Question 34

PCR and gel electrophoresis

Answer 34

Gel used to visualised the results of PCR

Question 35

PCR applications

Answer 35

- DNA cloning/sequencing - Gene identification - Mutation detection

Question 36

What is the use of ARMs?

Answer 36

To differentiate between wild type (normal) and mutant alleles

Question 37

Normal primer + wild type allele

Answer 37

Amplification

Question 38

Normal primer + mutant allele

Answer 38

No amplification

Question 39

Mutant primer + wild type allele

Answer 39

No amplification

Question 40

Mutant primer + mutant allele

Answer 40

Amplification

Question 41

What can ARMs be used in combination with?

Answer 41

PCR and Gel electrophoresis

Question 42

What is a disadvantage of PCR?

Answer 42

Primer design is critical - need to know what mutation codes for condition

Question 43

What are restriction endonucleases?

Answer 43

They're enzymes from bacterial cell that degrade the DNA of invading viruses and recognise specific DNA sequences

Question 44

What is RFLP analysis?

Answer 44

Use of restriction endonuclease to cut specific section of DNA and run through gel electrophoresis

Question 45

What can RFLP analysis diagnose?

Answer 45

Sickle cell anaemia - use mutant primer in PCR to show mutant base

Question 46

What is DNA sequencing?

Answer 46

Chain termination method using dideoxynucelotides - from 5' to 3' end