1. Gene Mutations Higher Human Biology Unit 1 – Human Cells

2. Reminder A gene mutation is the alteration of a nucleotide sequence in a gene`s DNA which leads to a change in the genetic code. This can occur in several different ways.

3. Point Mutations This involves a change in one nucleotide in the DNA sequence of a single gene. This results in one or more codons for one or more amino acids becoming altered. A single nucleotide is substituted, inserted or deleted.

4. Substitution Mutations A substitution can change the triplet code on a codon so that it still makes sense but produces a code for a different amino acid creating a different protein. This is called a missense mutation.

5. e.g. Phenylketonuria (PKU) e.g. Sickle Cell Anaemia

6. A substitution can sometimes cause a triplet code on a codon to change from coding for a particular amino acid to becoming a stop codon. This causes the premature halt to the production of a particular protein. This is called a nonsense mutation.

7. e.g. Duchenne Muscular Dystrophy (DMD)

8. The genetic code is read as a series of triplet bases during translation. The insertion or deletion of a nucleotide will affect the triplet grouping of the genetic code. It becomes shifted in a way that alters every subsequent triplet code (codon) from the point of mutation onwards.

9. This is highly likely to produce a non-functional protein. Such mutations are called frameshift mutations (see the example below).

10. e.g. Tay-Sachs Disease e.g. Cystic Fibrosis

11. Splice Site Mutations Before mRNA leaves the nucleus, introns (non- coding regions) are removed and exons (coding regions) are joined together. This is called RNA splicing. This process is controlled by the base sequences of the genetic code. Mutations can occur which cause mistakes in the splicing process: this can cause an intron to be retained in error resulting in modified mRNA. This may in turn result in the production of an altered protein.

12. e.g. Beta thalassemia

13. Nucleotide Sequence Repeat Expansion A gene mutation can sometimes be the result of certain triplet codes being repeated by the insertion of a large number of copies of a nucleotide sequence. This is called a nucleotide sequence repeat expansion. It can result in the production of a defective protein with a string of extra copies of one particular amino acid or it may result in the failure to express any protein at all.

14. e.g. Huntingdon’s disease e.g. Fragile X syndrome

15. There are many human genetic disorders caused by single gene mutations. Sickle cell disease, phenylketonuria, Duchenne muscular dystrophy, beta thalassemia, Tay- Sach`s disease, cystic fibrosis, fragile X syndrome and Huntington`s disease are all examples of such disorders. Carry out a case study on two of the genetic disorders listed above. For each chosen disorder describe the symptoms, the type of mutation that causes the disorder and any treatment that can be given to help sufferers. The internet or Torrance pages 55-59 will be useful.