Molecular Genetics and Pathology

Question 1

What is less stable; RNA or DNA?

Answer 1

RNA is less stable.

-hydroxyl (OH) group on C2&raquo_space; neutrophilic attack&raquo_space; breaks chain

Question 2

What direction are DNA and RNA synthesised in?

Answer 2

5’ to 3’ direction.

Question 3

What strand is normally written in DNA shorthand?

Answer 3

The ‘sense’ strand.

-strand that ends up as mRNA

Question 4

How many base pairs are present in a human haploid genome?

Answer 4

~3,000 Mbp.

chr 1 = 263, chr 22 = 39

Question 5

What proportion of DNA is non-coding?

Answer 5

> 90%.

Question 6

How many protein-coding genes are there?

Answer 6

~20,000.

Question 7

What is the average size of a gene (kb)?

Answer 7

50-100 kb.

Question 8

What are the classes of genome sequences? (2)

Answer 8

• Single copy sequences (non-repetitive)

- Repetitive sequences

Question 9

What is transcription?

Answer 9

DNA&raquo_space; mRNA.

• by RNA polymerase
• 1st step of gene expression

Question 10

What is translation?

Answer 10

mRNA&raquo_space; proteins.

-at ribosomes

Question 11

What are regulatory sequences?

Answer 11

Components of genes.

• promoters
• enhancers
• locus control regions

Question 12

What is the general process of gene production?

Answer 12

(NUCLEUS)
>>transcription
>>cleavage and polyadenation
>>splicing
>>(CYTOPLASM)
>>translation
>>postranslational modifications

Question 13

What is alternative splicing?

Answer 13

Exon skipping.

-large variation; single gene can code for multiple proteins

Question 14

What are pseudogenes?

Answer 14

DNA sequences that resemble protein-coding genes, but are non-functional due to mutations.
-cannot be translated

Question 15

What are processed genes?

Answer 15

Intronless copies of other genes.

-occasionally remain functional (e.g. PGK2)

Question 16

What causes processed genes?

Answer 16

Spliced RNA copy genes being reverse transcribed&raquo_space; DNA and re-entering genome.
-e.g HIV

Question 17

What are the main types of repetitive sequences?

Answer 17

• ‘Satellite’ DNA

- Interspersed repeat

Question 18

What is satellite DNA?

Answer 18

Large repetitive DNA sequences at centromeres and heterochromatic chromosomal regions.
-various sizes (polymorphic)

Question 19

What is alphoid DNA an example of?

Answer 19

Satellite DNA.

• 171 bp unit
• at centromeres, required for assembly
• particularly repetitive

Question 20

How is alphoid DNA used to identify individual chromosomes?

Answer 20

It’s chromosome specific.

Question 21

What are interspersed repeats?

Answer 21

Repeats scattered around the genome.

-may form part of gene structure

Question 22

Give an example of an interspersed repeat (most widely distributed).

Answer 22

Alu repeat.

• 500,000 copies
• 5% of genome
• dispersed by retrotransposition

Question 23

What problem can occur during meiosis 1 (crossing over)?

Answer 23

Misalignment of chromosomes due to interspersed repeats.
»unbalanced ‘hybrid’ chromosomes
-1 deletion, 1 duplication

Question 24

What size deletion is most likely to remain functional?

Answer 24

3bp deletion.

-doesn’t cause a frameshift mutation

Question 25

Why can large deletions / insertions be hard to detect?

Answer 25

Sequence either side remains the same.

Question 26

What type of mutation causes Duchenne muscular dystrophy?

Answer 26

Deletions.

Question 27

What type of mutation causes Charcot-Marie-Tooth disease?

Answer 27

Duplication.

Question 28

What mutation causes Haemophilia A?

Answer 28

``` F8C mutation (x-linked). >> FVIII deficiency -recombination and inversion of F8C gene ```

Question 29

Why is the F8C mutation hard to detect in haemophilia A?

Answer 29

Exons are still present.

Question 30

What are the types of point mutation? (3)

Answer 30

- Silent - Missense - Nonsense

Question 31

What is a silent point mutation?

Answer 31

Mutation codes for the same AA. | -if >1% of chromosomes = polymorphism

Question 32

What is a missense point mutation?

Answer 32

Codes for another AA. | -conservative if small functional change (e.g. Asp >> Glu)

Question 33

What is a nonsense mutation?

Answer 33

Truncated protein formed. | -often >> stop codon

Question 34

What DNA sequence is particularly susceptible to mutation (1/3 of mutations)?

Answer 34

CG >> TG. | -position of methylation

Question 35

How can mutation outside the coding frame cause disease?

Answer 35

Due to splicing. - begins at wrong point - always GT >> AT

Question 36

What us the nomenclature for mutation?

Answer 36

TYPE - genomic DNA = g. - cDNA =c. - protein = p. POSITION from codon (e.g. 128) MUTATION - e.g. A>G, del.T, dup.

Question 37

Examples of mutation nomenclature.

Answer 37

c. 658delG | c. 122+1G>A

Question 38

What type of inheritance do loss of function mutations normally have?

Answer 38

Recessive. | -50% gene function adequate

Question 39

What type of mutation does dominant inheritance normally result from?

Answer 39

Gain / alteration of function. | e.g. achondroplasia

Question 40

What mutation causes achondroplasia?

Answer 40

FGFR3 G380R. | -glycine >> arginine

Question 41

What are trinucleotide repeat expansions?

Answer 41

3 nucleotides tandomly repeated. | -e.g. polyglutamine (CAG) repeats

Question 42

What disorder does polyglutamine (CAG) repeats have an association with?

Answer 42

Huntington's disease.

Question 43

What trinucleotide repeat is associated with Fragile X syndrome?

Answer 43

CGG repeat expansion. | -in non-coding area >> DNA alteration