Module Directory

This module aims to provide an introduction to the field of human genetics from understanding the molecular basis of genetic disease, to the application of techniques for genome analysis in the clinical genetics laboratory.

The inheritance of single gene diseases and more complex multifactorial disorders will be addressed. The types of abnormalities found in the human karyotype will be studied. The origins and types of defects observed, their effect at a molecular level and on the individuals and families affected will be considered. The impact of the human genome project, molecular diagnostic techniques and potential therapeutic options such as gene therapy will be considered.

The aims of the module are to:

• Explain the significance of an individual`s genetic make-up in their risk of inherited and common disease, how the development of gene and genome sequencing has led to greater understanding of the role of genes and genetic variation, and how `high-throughput` rapid and cheap methods to sequence DNA are becoming embedded in the National Health Service in the UK.


• Explain the inheritance patterns of recessive, dominant and X-linked Mendelian genetic diseases using appropriate terminology, understanding the statistical likelihood that relatives are affected or carriers.


• For named examples of Mendelian genetic disorders, describe the incidence and clinical features, explain the causative mutations and how they result in disease by impacting on the structure and function of the normal gene product.


• Describe the UK neonatal (new-born) blood spot screening programme for genetic disorders, the key diseases screened, and interventions or treatments applied.


• Describe examples of neurodegenerative disorders caused by coding sequence CAG expansion and explain the molecular pathology of triplet repeat disorders, including inheritance and anticipation.


• Explain the structure, function and inheritance of the human mitochondrial genome.


• Explain examples of mitochondrial genetic disease and the complexity of diagnosis and transmission of mitochondrial disorders.


• Explain how `three-parent` IVF may allow parents with mitochondrial mutations to have unaffected children.


• Explain the applications of genetic testing in the context of families and populations.


• Describe the methods used to identify genetic disease alleles, including DNA sequencing, Southern blotting and PCR-based approaches.


• Discuss the relevance of animal models for human disease.


• Describe the generation of transgenic and `knock-out` mice.


• Describe the use of genetically manipulated mice in studies of disease.


• Discuss the general approaches used for gene therapy.


• Describe the viral and non-viral methods of gene delivery.


• Describe the characteristics of oncogenes and tumour suppressor genes.


• Describe the ways in which proto-oncogenes can be activated into oncogenes.


• Describe the role of important oncogenes and TS genes in cancer development (with reference to specific examples).


• Discuss the involvement of genetic predisposition in the development of cancers.


• Describe an example in which genetic screening for cancers can impact on the treatment given.


• Discuss the general approaches used for cancer gene therapy.


• Understand the role of cytogenetics in the development of cancers.


• Discuss an example of a chromosomal translocation that causes cancer.


• Describe the normal human karyotype and explain how errors in chromosome number arise.


• Describe examples of the common types of trisomy found in humans.


• Explain the techniques used to study the chromosome content of cells and to investigate abnormalities of chromosome number and structure, including FISH, MLPA and array CGH.


• Explain the process of prenatal screening for Down syndrome: maternal blood tests, ultrasound and karyotype analysis.


• Discuss the advantages and disadvantages of CVS, amniocentesis and the new non-invasive (NIPT) approaches being developed.


• Describe how chromosome structural abnormalities can lead to syndromes such as cri-du-chat and Charcot-Marie-Tooth disease, or to developmental delay.


• Explain the interaction of genetics and environment in determining the risk of complex diseases.


• Explain the approaches used to study complex diseases, including twin, family and population (genome wide association) studies.


• Explain the basis of genetic predisposition and environmental factors in the development of disease in asthma, coronary heart disease and atherosclerosis.


• Explain how recent developments in DNA analysis are setting a new agenda in approaches to predicting and treating human disease, including pharmacogenetics, precision medicine and gene editing.


• Access the key online sources for information about human genetic disease, such as OMIM (Online Mendelian Inheritance in Man), conduct BLAST searches of the databases storing human gene and protein sequences, and know how to use some of the tools available to investigate them (translating, aligning).


• Apply the molecular methods of DNA extraction, PCR, restriction enzyme digestion and gel electrophoresis to investigate a human mitochondrial DNA polymorphism (RFLP), then to present and interpret critically the data to identify the alleles present.

By the end of this module, students will be expected to be able to:

1. Define the structure and organisation of the human genome and genes and explain modern methods used to study genome variation and expression.


2. Explain the nature of single gene and complex genetic disease, including the mechanisms of disease and the inheritance patterns observed.


3. Explain the mechanisms leading to abnormalities in the human karyotype, the resulting disorders and the molecular techniques used to study chromosomes.


4. Evaluate the different genetic screening tests, when they are applied and their application in genetic counselling.


5. Demonstrate competence in information retrieval and data analysis and interpretation.

This module will be delivered via:

• One 2-hour lecture per week.
• Two 3-hour practicals.
• Two hours revision.