1. TOPIC 4: GENETICS

2. 4.1: Chromosomes, genes, alleles and mutations • ★State that eukaryote chromosomes are made of DNA and proteins. • ★Define gene, allele and genome. • ★Define gene mutation • ★Explain the consequence of a base substitution mutation in relation to the processes of transcription and translation, using the example of sickle-cell anemia.

3. 4.1: Chromosomes, genes, alleles and mutations • Review: • During the phase of the cell cycle known as interphase, chromosomes are in long thin threads called chromatin. • We can only see DNA under large microscopes when chromatin condenses to form chromosomes. • Eukaryotic cells (plants and animals) contain chromosomes, surrounded by a nuclear envelope.

4. 4.1: Chromosomes, genes, alleles and mutations • New: • The chromosomes of eukaryotic cells are associated with proteins. • Each chromosomes contains a single molecule of DNA along with these associated proteins. • Some proteins are structural (ex: histones) and others regulate DNA activities.

5. 4.1: Chromosomes, genes, alleles and mutations • Review: • DNA is a sequence of nucleotides, held together by weak hydrogen bonds between the bases. • This sequence of bases contains the genetic code in the form of triplets of bases. • A triplet of bases in the DNA is transcribed into a triplet of bases in the mRNA, which is then translated into a specific amino acid.

6. 4.1: Chromosomes, genes, alleles and mutations • New: • Gene: a heritable factor that controls a specific characteristic, or a section of DNA that codes for the formation of a polypeptide. • Allele: a specific form of a gene occupying the same position on the DNA as other alleles of that gene, but differing by small differences in its base sequence. • Genome: the entire genetic information of an organism. (human genome has 20,000-25,000 that serve as directions to build all our proteins) • Gene mutation: a change in the sequence of bases in a gene.

7. 4.1: Chromosomes, genes, alleles and mutations • Mutations: • DNA replication can be tricky: a nucleotide can be left out, an extra one may be added, or the wrong one inserted. • These mistakes are called gene mutations. • The insertion of an incorrect nucleotide is called a base substitution mutation. • When the DNA containing the incorrect nucleotide is transcribed and translated, errors can occur in the polypeptide.

8. 4.1: Chromosomes, genes, alleles and mutations • Mutations: • If you look at a codon chart, many codons code for the same amino acid so many substitution mutations have no effect on the polypeptide that is produced. • EX: UCU, UCC, UCA, UCG all code for Serine, so if there was an incorrect nucleotide substitution in the last slot of the codon, Serine would still be placed in a polypeptide.

10. 4.1: Chromosomes, genes, alleles and mutations • Cystic Fibrosis: • A deletion of 3 nucleotides that results in a loss of the amino acid phenylalanine at the 508th position of 1,480 amino acids on that specific protein. • The protein that is incorrectly made should regulate and control components of sweat and mucus. • Heavy mucus in lungs builds up, and is 80% cause of death in CF patients.

11. 4.1: Chromosomes, genes, alleles and mutations • Cystic Fibrosis: • Mucus in the sinuses builds up, blocking passage, leading to infection, inflammation and breathing difficulties. • Also, bile secreted by the liver and pancreas to aid in digestion may block the bile ducts, causing a build up and failure to rid the blood of toxins. • This all results from these people having 3 nucleotides deleted among 4,440 in a single protein!

12. 4.1: Chromosomes, genes, alleles and mutations

13. 4.1: Chromosomes, genes, alleles and mutations • Sickle Cell Anemia: • Point mutation in the DNA

15. 4.1: Chromosomes, genes, alleles and mutations • Sickle Cell Anemia: • Blood disorder where red blood cells (RBC) become sickle shaped (look like a half moon) and cannot carry oxygen properly. • These RBC lose their elasticity and flexibility because Glutamic Acid is hydrophilic and Valine is hydrophobic. • This change of polarity causes the RBC membrane to change shape and become rigid, so they don't pass through capillaries easily.

16. 4.1: Chromosomes, genes, alleles and mutations • Sickle Cell Anemia: • The mutation doesn't make the correct protein: hemoglobin. This protein is how the RBC carry oxygen to other tissues. • The RBC odd shape results in clots and allows them to deliver less oxygen because the surface area to volume ratio is affected. • Symptoms: fatigue, rapid heart rate, shortness of breath, kidney problems and possible infections.

17. 4.1: Chromosomes, genes, alleles and mutations • 1. What is meant by the term 'base substitution mutation' and 'silent mutation'. • 2. Find 3 'silent mutations' using your codon chart. Give the normal amino acid and the amino acid after the mutation. • EX: normal codon = CAU = Histidine • silent mutation = CAC = Histidine

18. 4.1: Chromosomes, genes, alleles and mutations • 3. In the normal allele for hemoglobin, there is a triplet on the coding strand of the DNA that is C-T-C. In people suffering from sickle cell anemia, what has this triplet mutated to? • 4. Because of this mutation, one amino acid in the polypeptide chain in hemoglobin is abnormal. Name the normal amino acid and the amino acid that is from the sickle cell mutation. • 5. Explain why this mutation leads to sickle-cell anemia