Lecture 3: The human genome

Question 1

What is the central dogma in molecular biology?

Answer 1

Genetic information is transferred from DNA to RNA (by transcription) to produce a functional protein product (through translation).

Question 2

What are the 3 functions of DNA?

Answer 2

1. Encode all info required to make an organism (DNA to RNA to protein)
2. Replicate itself accurately
3. Allow beneficial mutations to be selected

Question 3

Describe the composition of the human genome

Answer 3

The human genome is composed of 3.2 billion bases of DNA but around 20,000 genes; ~50% is high-copy repetitive elements and ~1.5% is actually involved in protein coding.

Question 4

What is the impact of genomics in medicine?

Answer 4

1. Identification of disease mechanisms
2. Targeted therapeutics and gene therapy
3. Greater understanding of human evolution
4. Possibility of preventative medicine
5. Ability to predict disease progresion
6. Use in pharmacogenetics- designing drugs better suited to patients or prescribing drugs which will be more effective

Question 5

Describe the composition of DNA

Answer 5

DNA is composed of a (supercoiled) double helix of nucleic acids which have complimentary strands of nucleotides (A-T, C-G). The sequence of these nucleotide bases code for different proteins; each 3 nucleotides bases (codon) code for 1 amino acid, and each sequence of amino acids code for a protein.

Question 6

How are the nucleotides joined in a strand of DNA?

Answer 6

Each strand of the double helix is held together by weak hydrogen bonds between the complimentary nucleotide bases but strong phosphodiester covalent bonds between the nucleotides within the strand.

Question 7

Describe the supercoiling of the DNA double helix

Answer 7

First level of folding: DNA double helix is wrapped around histone octamer to form “beads-on-a-strong” form of chromatin which packed into nucleosomes.
Second level of folding: Chromatin fibres are folded into loops which requires histone H1.
Third level of folding: Looped chromatin fibres form mitotic chromosome

Question 8

How is DNA condensation regulated?

Answer 8

Regulated by chromatin-remodelling complexes and histone-modifying enzymes ( which add or remove acetyl, phosphate or methyl groups).

Question 9

How does DNA supercoiling effect gene expression?

Answer 9

Supercoiling can cause genes to be switched off if folded into heterochromatin

Question 10

What is epigenetics?

Answer 10

Heritable changes in gene function that cannot be explained by changes in DNA sequence (e.g. methylation).

Question 11

Describe a chromatin disease

Answer 11

Rubinstein-Taybi syndrome (RSTS):
• Affects 1/100,000
• Non-specific symptoms such as intellectual disability, facial abnormalities, broad thumbs and broad great toes
• Caused by mutation in histone acetyl-transferases

Question 12

How many chromosomes does each human cell possess?

Answer 12

22 pairs homologous autosomal chromosomes + 2 sex chromosome (XX or XY) = 46 chromosomes