Brent Cornell

    
A gene mutation is a change in the nucleotide sequence of a section of DNA coding for a specific trait

• New alleles are formed by mutation

Gene mutations can be beneficial, detrimental or neutral

• Beneficial mutations change the gene sequence (missense mutations) to create new variations of a trait
• Detrimental mutations truncate the gene sequence (nonsense mutations) to abrogate the normal function of a trait
• Neutral mutations have no effect on the functioning of the specific feature (silent mutations)

Types of Gene Mutations

    
Sickle cell anaemia is an example of a disorder caused by a gene mutation

• The disease allele arose from a base substitution mutation – where a single base was changed in the gene sequence

Cause of Sickle Cell Anaemia

Sickle cell anaemia results from a change to the 6th codon for the beta chain of haemoglobin

• DNA:  The DNA sequence changes from GAG to GTG on the non-transcribed strand (CTC to CAC on the template strand)
• mRNA:  The mRNA sequence changes from GAG to GUG at the 6th codon position
• Polypeptide:  The sixth amino acid for the beta chain of haemoglobin is changed from glutamic acid to valine (Glu to Val)

Consequence of Sickle Cell Anaemia

The amino acid change (Glu → Val) alters the structure of haemoglobin, causing it to form insoluble fibrous strands

• The insoluble haemoglobin cannot carry oxygen as effectively, causing the individual to feel constantly tired

The formation of fibrous haemoglobin strands changes the shape of the red blood cell to a sickle shape

• The sickle cells may form clots within the capillaries, blocking blood supply to vital organs and causing myriad health issues
• The sickle cells are also destroyed more rapidly than normal cells, leading to a low red blood cell count (anaemia)