Mutations & gene expression

• What are frameshift mutations?

  Huge effect on gene base sequence e.g, additon, duplication & deletion. Almost always change amino acid sequence. All change number of bases in DNA code. Causes shift in base triplets that follow, so triplet code read in different way.
• What is a mutation?

  Any change to base sequence of DNA. Can be caused by errors during DNA replication.
• Types of mutations

  Substitutions, addition, deletion, duplication, inversion and translocation.
• What are mutagenic agents?

  Increase rate of mutations, by acting as a base, altering bases or changing structure of DNA.
• Examples of mutagenic agents

  UV radiation, ionising radiation, some chemicals and some viruses.
• What are acquired mutations?

  Mutations occurring in individual cells after fertilisation (e.g, adulthood). If these occur in genes controlling rate of cell division, it can cause uncontrolled cell division. Results in tumour.
• What are tumour suppressor genes?

  Slow cell division by producing proteins that stop cells dividing or cause them to self-destruct.
• What are proto-oncogenes?

  Stimulate cell division by producing proteins that make cells divide. Oncogenes= mutated proto-oncogene.
• What are benign tumours?

  Not cancerous. Grow slower than malignant & often covered in fibrous tissue that stops cells invading other tissues. Often harmless, but can cause blockages & put pressure on organs. Some can become malignant.
• What are malignant tumours?

  Cancers- usually grow rapidly & invade & destroy surrounding tissues. Cells can break off tumours & spread to other parts of body in bloodstream or lymphatic system.
• How do tumour cells differ from normal cells?

  Larger & darker nucleus- sometimes have more than 1. Irregular shape. Don't produce all proteins needed to function correctly. Different antigens on their surface. Don't respond to growth regulating processes. Divide (mitosis) more frequently than normal cells.
• What are the 2 causes of tumour growth?

  Abnormal methylation of DNA & increased exposure to oestrogen overtime increases risk of breast cancer.
• Why is hyper & hypomethylation a problem?

  Growth of tumours caused by abnormal methylation of certain cancer-related genes.
• Why are some women exposed to more oestrogen?

  Starting menstruation earlier, menopause later or taking oestrogen-containing drugs, e.g, HRT.
• What does oestrogen stimulate?

  Certain breast cells to divide & replicate. More cell divisions, higher chance of mutations & higher chance of cells becoming cancerous.
• What is oestrogen able to introduce directly into DNA of certain breast cells?

  Mutations. This increases chance of cells becoming cancerous.
• Risk factors for cancer

  Genetics (cancer linked to specific inherited alleles) & environmental factors (alcohol, smoking, high-fat diet, exposure to radiation). Increase chance of cancer.
• Why does radiation shrink tumours?

  Radiation damages DNA of tumour cells, causing them to die & tumour to shrink.
• What are stem cells?

  Unspecialised cells-divide to become new cells which become specialised. Found in embryo & some adult tissues.
• What are totipotent stem cells?

  Can mature into any type of body cell, including those in placenta. Only present in first few cell divisions of embryo.
• What are pluripotent stem cells?

  Specialise into any cell in body, but lost ability to become cells that make up placenta. Found in advanced embryo & foetus.
• What are multipotent stem cells?

  Differentiate into a few different cell types. Present in adults.
• What are unipotent stem cells?

  Only differentiate into 1 cell type. Present in adults.
• What are cardiomyocytes?

  Heart muscle cells that make up heart tissue. Recent research suggests heart have some regenerative capability. Old/damaged cardiomyocytes replaced by new ones derived from small supply of unipotent stem cells in heart.
• Cell differentiation process

  Certain genes in stem cell expressed. These are transcribed into mRNA, then translated into proteins. Proteins modify cell- they determine cell structure & control cell processes. Causes cell specialisation.
• Bone marrow transplants

  Bone marrow stem cells can specialise into any type of blood cell. Transplants replace faulty bone marrow in patients with abnormal blood cells. Treats leukaemia & lymphoma, and some genetic disorders.
• Sources of stem cells

  Adult tissues, embryos and induced pluripotent stem cells created in lab from adult cells.
• How can transcription factors be introduced into adult body cells?

  Infect adult cell with specially-modified virus. Virus has genes coding for transcription factors within its DNA. Virus infects adult cell- genes passed into adult cell's DNA- cell now able to produce transcription factors.
• How are iPS cells created?

  Reprogramming specialised adult body cells so they become pluripotent. Cells made to express transcription factors associated with pluripotent stem cells. Transcription factors cause adult body cells to express genes associated with pluripotency.
• Benefits of stem cell therapy

  Save lives (e.g, transplants), improve QoL of people. Stem cells genetically identical to patient's own cells can grow tissues/organs that won't be rejected, e.g, iPS cells could be made from patient's own cells.
• What are transcription factors?

  Proteins that control transcription of genes. Move from cytoplasm to nucleus & bind to specific DNA sites (promoters) found near start of target gene. Can be activators or repressors.
• How does oestrogen affect expression of genes?

  Binds to transcription factor called oestrogen receptor- forms complex. Complex moves from cytoplasm into nucleus- binds to specific DNA sites near start of target gene. Acts as activator or repressor.
• What is RNAi?

  RNA interference- affects gene expression in eukaryotes. Small double-stranded RNA molecules-stop mRNA from target genes being translated. siRNA & miRNA. Small lengths of non-coding RNA.
• What does siRNA do?

  Single strand associated with proteins cuts mRNA into fragments, so it can't be translated. Fragments move into processing body where it's degraded. Could treat genetic disorders by stopping harmful genes being expressed.
• How does miRNA work?

  Single strand associated with proteins physically blocks translation of target mRNA. mRNA moved into processing body and either stored or degraded. Less specific than siRNA.
• How do cells control expression of genes?

  Transcriptional factors, RNA interference & epigenetics.
• Increased methylation of DNA

  Methyl group (epigenetic mark) attached to DNA coding for gene. Group attaches to CpG site. Methylation changes DNA structure so transcriptional machinery can't interact with gene- gene not expressed. Group attached to cytosine by enzymes called DNA methyltransferases.
• Decreased acetylation of histones

  Chromatin highly condensed & genes can't be transcribed as they can't be accessed. Histone deacetylase removes acetyl groups.
• What is epigenetics?

  Environment influences expression of genes. Can change gene function without changing DNA base sequence. Determines whether gene switched on or off.
• How does changes in environment affect epigenome?

  Epigenetic tags respond to environmental factors. Changes in tags can change shape of DNA-histone complex, exposing different genes & allowing them to be switched on & off. Epigenome more flexible than genome.