DNA and genomics

Question 1

Gene mutation

Answer 1

• a gene mutation is an alteration in the sequence of nucleotides which may change the sequence of amino acids in a polypeptide chain, this may change the 3D shape and hence the function of the protein and subsequently affect phenotype of organism
• substituition, inversion, insertion, deletion

1. frameshift mutation: due to insertion or deletion of nucleotides that is not divisible by 3, the reading frame is disrupted hence different and non-functional polypeptide is synthesised
2. silent mutation: is a point mutation that does not change the amino acid sequence in a polypeptide, due to degeneracy of the genetic code, more than one codon can code for the same amino acid, hence same polypeptide will be synthesised
3. nonsense mutation: point mutation which codes for a premature stop codon, causing polypeptide to be truncated and non-functional
4. missense mutation: point mutation results in a change in codon, hence change in amino acid sequence

Question 2

Sickle cell anaemia

Answer 2

• change in DNA sequence from CTC to CAC, change in mRNA from GAG to GUG, hence change in amino acid from charged, hydrophilic glutamate to non-polar hydrophobic valine
• charged and hydrophilic glutamate replaced by non-polar hydrophobic valine, at low concentrations of oxygen, HbS will lose the oxygen and undergo a conformation change which will cause hydrophobic patches to stick out
• the hydrophobic patches of HbS will polymerise and clump together, resulting in formation of abnormal, rod like fibres which will distort the shape of red blood cells from biconcave to sickle shaped
• sickle shaped cells are more fragile and break easily, hence causing poor oxygen transport, it may also lodge into. small blood vessels, causing organ failure

Question 3

Chromosomal aberrations

Answer 3

• change in chromosome number of structure
  1. change in chromosomal number
• aneuploidy or polyploidy –> Trisomy 21, caused by non-disjunction, where there is improper separation of homologous chromosomes at anaphase 1 or improper segregation of sister chromatids at anaphase

2. change in chromosomal structure
   - duplication, deletion, translocation, inversion
   - result in phenotypic anomalies due to the reduced or additional genes
   - amount of genetic material remains the same but expression of gene can be influenced by location