1. Name the 4 gene mutations that can occur State the effect of gene mutations on amino acid sequences

2. Definition; Genetic disorders are caused by changes to genes or chromosomes that result in the proteins not being expressed or the proteins expressed not functioning correctly. Examples; Sickle cell anaemia Duchenne muscular dystrophy Tay-Sachs syndrome Cystic fibrosis Huntingdons Fragile X syndrome Beta thalassemia PKU Cri-du-chat syndrome Chronic myeloid leukaemia Down’s syndrome Genetic Disorders

3. Mutation Types Mutation – change in structure/composition of organisms genome If the change in the genotype is in phenotype – individual is called mutant Mutations are random occurrences (spontaneously) and low frequency (rarely) ROLF! Mutagens/ mutagenic agents can artificially increase the rate of mutations. Thus these mutations are called induced Chemicals include – mustard gas Radiation – gamma rays/ X-rays + UV light

4. Mutation Types Single gene mutations involve the alteration of a DNA nucleotide sequence; Point Mutations –Substitution (missense, non-sense and splice-site) –(Inversion) Frameshift Mutations –Insertion –Deletion Gene Mutations Video

5. Gene Mutations SINGLE GENE MUTATIONS – involve changes in one nucleotide (deletion, insertion and substitution) bring about only a minor changes as only 1 nucleotide (ie one different amino acid); sometimes the organism is affected only slightly or not at all FRAMESHIFT MUTATIONS – (insertion & deletion) leads to a large portion of the gene’s DNA to be misread; the protein produced differs from the normal protein by many amino acids and is usually dysfunctional

6. Substitution – replace a base; Missense Single-nucleotide substitutions include: missense (replacing one amino acid codon with another). Diseases caused by missense;  Sickle-cell disease  PKU

7. Sickle cell anaemia Blood disorder where rbc change shape into an abnormal, rigid, sickle shape. This causes problems such as blocking blood vessels Delayed growth Fatigue Shorter life Infections Jaundice BUT Protects against malaria

8. Substitution – replace a base; Non-sense Single-nucleotide substitutions include: non-sense (replacing one amino acid codon with a premature stop codon). Diseases caused by nonsense;  Duchenne muscular dystrophy DMD

9. Splice-site mutation Do you remember what splicing is?

10. Splicing..... Hint..... Exon Protein Translation Processing Mature mRNA Primary mRNA Transcription ExonIntronExonIntronDNA

11. Splice-site mutation Do you remember what splicing is? Splicing is the post transcription and pre- translational of mRNA ; removing introns and exons joined together (primary to mature mRNA), then using certain exons (alternative splicing) Splicing is controlled by a specific nucleotide sequence at the splice site on introns which flank (beside) exons. Mutation occurs here.

12. Splice-site mutations (creating or destroying the codons for exon-intron splicing). Diseases caused by splice-site Substitution – replace a base; Splice-site  Beta (β) thalassemia Exon 1 Altered mRNA DNA Altered mRNA Exon 3 IntronExon 2IntronExon 1 Exon 2 Exon 3 IntronExon 2Intron Exon 1 Creating codon Destroying codon

13. Single Gene (point) mutations - DIGS; Deletion Insertion (Gene mutations) Substitution (inversion not in arrangements)

14. Frameshift; Insertion & repeat expansion Nucleotide insertions or an expansion of a nucleotide sequence repeat (essentially insertion of a large number of copies of the nucleotide sequence). Results in extra copies of amino acid/ or fails to express (silenced) Examples of repeat expansion diseases;  Huntingdon's disease  Fragile X syndrome Disease of insertion;  Tay-Sachs syndrome

15. Tay-Sachs syndome Recessive chromosome 15 disease that affects the nervous system. Body lacks hexosaminidase A (protein which breaks down chemicals in ganglioside, fatty substance GM2, thus builds up and prevents nerve functioning) Slow development at 6 month Loss of movement/ vision/hearing Most die at 5yrs old

16. Frameshift; Deletion Nucleotide deletion of a nucleotide sequence is the removal of bases, causing a frame shift Examples of diseases;  Cystic Fibrosis 

17. Consequences ?? So if you tweaked the DNA – what is the consequence?

18. The effect of missense, nonsense, splice-site, frameshift and nucleotide sequence repeat expansion mutations....... On the structure of the protein synthesised, its function and the effect of this on individuals.

19. Demonstrate your understanding 1.What are the types of gene mutations? 2.Which types do you think will have the greatest affect on the organism – explain/justify why. 3.Which mutations are frameshift mutations and can you explain why? 4.Which type of mutations are these;

20. Summary Single Gene (Point) mutations Point mutations occur at a single point – substitution. They are generally not harmful, most of the protein remaining unaffected. Since only one amino acid is affected, the protein will probably be functional. (single nucleotide polymorphism) Frameshift mutations After a deletion or insertion the open reading frame is moved one base pair forwards or backwards. This is generally harmful since all the amino acids in the primary structure of the protein will have changed from the mutation onwards. The protein will probably be non-functioning.

21. Mutations are always a negative thing A gene mutation is a change in the genetic code Gene mutations can result in cancer Every characteristic of your body is coded for by one gene Substitutions can be as harmful as additions Cystic fibrosis is caused by the deletion of 3 bases T F T T F F

22. Learning Outcomes Explain chromosome structure mutations Give some examples of chromosome mutations Compare gene to chromosome mutations

23. Structure of a chromosome altered! These mutations can take the form of a; Deletion (loss of a segment of a chromosome) Duplication (repeat of a segment of a chromosome) Translocation (the rearrangement of chromosomal material involving two or more chromosomes). The substantial changes in chromosome mutations often make them lethal.

24. Examples.... Cri-du-chat syndrome (deletion of part of the short arm of chromosome 5) Chronic myeloid leukemia (CML) (reciprocal translocation of a gene from chromosome 22 fused with a gene on chromosome 9)

25. Examples.... Familial Down’s syndrome (in 5% of cases one parent has the majority of chromosome 21 translocated to chromosome 14)

26. Conclusion How frequent are mutations? (1) What is a mutant? (1) Name 4 mutagenic agents.(4) Name and describe 2 chromosome mutations.(4)