TMJC DNA Mut & Conseq Notes

Page 1 of 39 Tampines Meridian Junior College JC1 H2/9744 Biology 2023 Core Idea 2D | 2E 6. Genetics & Inheritance (III) – DNA Mutations & Their Consequences SYLLABUS OVERVIEW No. Overarching Idea Topics 1 Core Idea 1 The Cell and Biomolecules of Life Cell – The Basic Unit of Life 2 Biomolecules of Life and Cellular Transport 3 Core Idea 3 Energy and Equilibrium Transformation of Energy – Photosynthesis and Cellular Respiration 4 Core Idea 2 Genetics and Inheritance Genetics and Inheritance (I) – The Cell Cycle 5 Genetics and Inheritance (II) – DNA Replication and Gene Expression 6 Genetics and Inheritance (III) – DNA Mutations and their Consequences 7 Genetics and Inheritance (IV) – Molecular Techniques in DNA Analysis 8 Genetics and Inheritance (V) – Organization of Genome & Control of Gene Expression in Eukaryotes [Includes Core Idea 1D: Stem Cells] 9 Genetics and Inheritance (VI) – Organization and Inheritance of Viral Genomes 10 Genetics and Inheritance (VII) – Organization of Genome & Control of Gene Expression in Prokaryotes 11 Genetics and Inheritance (VIII) - Inheritance 12 Core Idea 3 Energy and Equilibrium Communication and Equilibrium in Multicellular Organisms 13 Core Idea 4 Biological Evolution Biological Evolution 14 Extension Topic A Infectious Diseases Immunity and Infectious Diseases 15 Extension Topic B Impact of Climate Change on Animals & Plants Climate Change – Causes and Impacts on Animals and Plants

Page 2 of 39 TOPIC SYNOPSIS An understanding of Genetics and Inheritance that would help make sense of the transition from molecular to organismal level. Genetics and Inheritance provides the molecular basis to the understanding of how variations in populations arise and this is important in the study of biological evolution. At the cellular level, expression of genes involves cellular structures such as the nucleus, endoplasmic r eticulum and ribosome. Many essential products of gene expression are enzymes involved in biochemical pathways which control physiological functions. As such, mutation of genes may give rise to dysfunctional proteins which in turn could result in diseases. Sickle cell anemia and cancer are raised as examples of a monogenic and a multi -genic disease respectively. The following questions should help you frame your learning: • How does the genetic make-up of an organism influence its appearance, behavior and survival? • How can we ensure continuity of human as a species? Mutation arises from imperfect replication of genetic information. Together with other biological processes, such mutations increase genetic variation. Based on the central dogma, a change in the sequence of DNA nucleotide, i.e. gene mutation, may affect the amino acid sequence in the polypeptide and hence the phenotype of the organism. Many mutations are detrimental to the individual since they affect the normal functioning of the gene product, e.g. genetic diseases such as sickle cell anemia and cancer. Others are neutral, often because they have no effect on the phenotype, e.g. a change in a DNA triplet which still codes for the same amino acid. Occasionally, mutations may be beneficial. For example, individuals who are heterozygous for a mutated hemoglobin gene that causes sickle cell anemia have selective advantage in areas where malaria is common. Besides mutation of genes, chromosomal mutation and change in chromosome number may also occur. Down’s syndrome arises due to the presence of an additional copy of chromosome 21. The development of cancer is a multi -step process that comprises gene mutations caused by environmental factors, biological agents or hereditary predispositions. These mutations might cause cells to bypass cell cycle checkpoints. Normally, two groups of genes are involves in regulating cell division: tumor -suppressor genes and proto-oncogenes. Mutations in either or both of these groups of genes ma y lead to the development of cancer. Cancer has a much higher incidence in Singapore compared to other diseases and accounts for as much as 30% of the death in this country. The recorded incidence of cancer is on the rise and this could be due to the accumulation of mutations from one generation to the next, although other reasons have also been proposed: increased exposure to carcinogens and increased detection rates as a result of effective cancer screening programmes. As such, an understanding of how cancer develops is important as this would set the platform for discussion of developing anti-cancer drugs.

Page 3 of 39 LEARNING OUTCOMES Core Idea 2D: DNA Mutations Changes to the DNA sequence or amount of could have huge physiological impact on organisms. This concept illustrates how DNA mutations could result in sickle cell anemia and Down syndrome in humans. l) Explain what is meant by the terms gene mutation and chromosome aberration. For gene mutation, knowledge of how substitution, addition, deletion could change the amino acid sequence (e.g. frameshift) is required. For chromosomal aberration, knowledge of numerical (e.g. aneuploidy, as in the case of trisomy 21, i.e. Down syndrome) and structural (e.g. translocation, duplication, inversion, deletion) aberration is required. m) Explain how gene mutations can result in diseases (including sickle-cell anemia). Core Idea 2E: The Cell Cycle p) Identify the causative factors, including genetic, chemical carcinogens, ionizing radiation and loss of immunity, which may increase the chances of cancerous growth. q) Explain how the loss of function mutation of tumor suppressor genes, including p53, and gain in function mutation of proto-oncogenes, including ras, results in uncontrolled cell division. r) Describe the development of cancer as a multi -step process that includes accumulation of mutations, angiogenesis and metastasis. LECTURE OUTLINE 1. Overview of Mutation 2. Gene Mutations 2.1 Types of Gene Mutations 2.1.1 Base Pair Substitution 2.1.2 Base Pair Insertion and Deletions 2.2 Non-cancerous Genetic Disorders caused by Gene Mutations 2.2.1 Sickle Cell Anemia 2.2.2 Cystic Fibrosis (FYI only) 2.3 DNA Repair 3 Chromosomal Aberrations 3.1 Chromosomal Aberrations (Numerical) 3.1.1 Aneuploidy 3.1.2 Polyploidy 3.2 Chromosomal Aberrations (Structural) 3.2.1 Deletion 3.2.2 Duplication 3.2.3 Inversion 3.2.4 Translocation 3.2.5 Summary of Chromosomal Aberrations (Structural) 4. The Development of Cancer as a Result of Mutations 4.1 Introduction to Cancer 4.2 Control of the Eukaryotic Cell Cycle 4.3 The Role of Mutations in the Development of Cancer 4.4. Gain of Function Mutations in Proto-oncogenes 4.5 Loss of Function Mutations in Tumour-Suppressor Genes 4.6 The Development of Cancer as a Multi-step Process 4.7 Factors that Increase the Chances of Cancerous Growth

Page 4 of 39 1. Overview of Mutations Fig. 1.1: A summary of genetic mutations. a) Mutations • Mutation is the change in the amount, arrangement or structure of the DNA in an organism. • Mutations occur mostly during flawed DNA replication or nuclear division. • Mutations occurring in germ cells that produce gametes (sperms/eggs) can be inherited by the offspring during fertilization. This is known as germline mutation. • Mutations occurring in somatic cells (e.g. skin cells, breast cells) will not be passed down to the offspring. This is known as somatic mutation. • Mutations resulting from a change in nucleotide sequence of the DNA at a single locus are known as gene mutation. • Large scale mutations resulting from a change in the number or structure of chromosomes is known as chromosomal mutation or chromosomal aberration.

Page 5 of 39 2. Gene Mutations 2.1 Types of Gene Mutations • Gene mutations can be divided into two main categories: (a) base pair substitution and (b) ba