A double-sided handout was given at the lecture. A summary of the lecture is available on the Virtual Campus here.

Only about 5% of the human DNA codes for genes, therefore genes are separated by intervening DNA. At the beginning of the strand are promoter elements. When mRNA is processed, it gets a polyA tail added, introns are removed, and it is now ready for protein synthesis. ATG always begins the sequence (methionine).

Types of changes that may occur:
a) single base substitutions (point mutations)
b) deletions
c) insertions (or additions)
d) duplications
e) inversions

Classified according to their chemistry - C and T are pyrimidines, A and G are purines. You would therefore expect a transition:transversion ratio of 1:2, but you actually get 2:1 because cytosine is prone to methylation.

1. 5’ methyl cytosine is replicated to adenine instead of guanine
2. adenine is replicated to thymine
3. this results in a C => T transition

1 base pair to several thousand base pairs can occur - see (3) on the handout.

1. insertions (1 base pair to several thousand base pairs)
2. can arise from the movement of (eg) transposable elements, or certain viral genomes
3. duplications - inserted material is identical to adjacent sequence
4. runs of bases of repeated motifs are common sites for duplications as it may predispose to enzyme slippage or recombinant errors

1. silent
2. deletions - may result in a human genetic disorder
3. advantageous

Substitutions in the coding sequence only affect the triplet repeat codon in which they lie (eg: see 6 on handout).

1. silent - new codon encodes the same amino acid as the old; resulting protein is normal
2. missense - the new codon encodes a different amino acid from the old; the resulting protein differs from the normal at that position
3. non-sense - codes for a stop or termination codon

Regulation elements are sites to which regulation proteins bind. They are usually at the 5’ end (upstream) of a gene. They control transcription levels, tissue specificity etc. (see 8 on handout).

Although there is a continuum of deletion sizes, four classes of deletion size can be distinguished by their effect on the gene:

1. very large deletions which remove several genes resulting in a contiguous gene syndrome.
2. large gene deletions which remove an entire gene
3. medium sized deletions which remove a whole exon or several exons
4. small deletions which remove a few base pairs from a single exon

Effect depends on whether the number of base pairs deleted or inserted is divisible by 3. Small rearrangements that disrupt the reading frame (frame shifts) can be more deleterious than large ones that do not (inframe) - see 11 on the handout.

Deletion of exons can:

1. remove or impair functional domains in the protein
2. alter the reading frame of the mRNA: this depends on the number of base pairs in the deleted exon rather than the total amount of DNA deleted. (see 12)