The number of rare monogenic disorders is estimated to be greater than 7000, but only in approximately half of these are the underlying genes known. Common diseases such as intellectual disability, diabetes, schizophrenia and autism are thought to arise from a complex interplay of genetic and environmental factors but deeper understanding of the genetic and mechanistic basis of these diseases is necessary for clinical translation.

The module offers a comprehensive overview of the traditional and current strategies and techniques used to identify genes responsible for both common multifactorial and rare inherited diseases, focusing mainly on the latter. This module will initially explore the clinical presentation and course of a range of common and rare inherited diseases. The principles and practise of medical genetics, and the management and treatment of probands and their families will be discussed. In addition, the role of genomics in a care pathway will be examined including the patient and family perspective. Building on knowledge gained in GM2, students will further explore the analytical challenges in genomics as applied to rare inherited diseases.

In GM3 you will learn about:

• Clinical presentation and course of a range of rare inherited and common diseases

• Principles and practise of medical genetics; risk stratification and management of patients and their families

• Approaches and techniques used to identify genes responsible for common and rare inherited diseases (e.g. candidate gene, positional mapping, genome wide association studies, exome/whole genome sequencing, use of population data sets)

• An overview of the techniques used for functional validation of putative disease- associated mutations

• Basic statistics to aid interpretation of Genome Wide Associated Studies (GWAS) and analysis of populations

• The Genomics England 100,000 Genomes Project and data infrastructure

• Selection of tractable cases with unmet diagnostic need suitable for whole genome analysis

• Analytical challenges in genomics as applied to rare inherited diseases including; the potential of electronic health records to enrich patient data, the importance of phenotyping and use of databases such as ClinVar, the use of large population datasets and sharing information e.g. Human Variome Project

• Impact of patient on-line access to their health records, test results etc. on medical genomics.

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

• Examine the landscape of common and rare inherited diseases

• Explain the genetic architecture of common and rare inherited diseases

• Critically evaluate traditional and current approaches used to identify genes for common and rare inherited diseases

• Synthesise information gained from exome/whole genome analysis with patient information / medical records to determine diagnosis, penetrance or prognosis for a number of examples of common and rare inherited conditions

• Discuss and evaluate the Genomics England Programme and the Data Infrastructure

• Identify phenotype, select cases and relevant family information for whole exome or whole genome based approaches for hypothesis free whole exome or whole genome sequencing

• Discuss and critically evaluate the implications of patient access to their medical records and clinical information for medical genomics, inter- professional practice and multidisciplinary care

• Have an understanding of the range of methodologies that can be used to functionally validate putative disease mutations.