From genes to genomes and back again: the future of affordable healthcare

Aims

This course aims to: 

• introduce you to fundamental principles in Mendelian genetics
   
• familiarise you with high throughput “’omic” analyses and some basic analysis tools
   
• introduce you to current clinical practice in genomic medicine

Content

The rediscovery of the work of Gregor Mendel at the turn of the 20th Century was quickly followed by Archibald Garrod’s description of a disease that followed a Mendelian inheritance pattern (alkaptonuria). Only a small number of single-gene disorders were known for some time afterwards although it was apparent that a great many diseases had at least some genetic basis. 

While the discovery in 1953 of the structure of DNA by Watson and Crick and the information encoded therein (using Rosalind Franklin’s x-ray crystallography data) promised a new dawn in the understanding of human health and disease, it wasn’t until the completion of the Human Genome Project that the promise of genetic medicine began to be realised. 

By the late 1980s, DNA sequencing technology (pioneered by double Nobel prize winner Fred Sanger) had developed to the point where scientists were confident in undertaking the “moon-shot” of determining the sequence of all 3 billion nucleotides in a reference human genome. While a reasonably complete sequence was published in Nature in 2003, it was the technological advances in DNA sequencing driven by this project, as much as the information revealed, that facilitated advances in individualising care. This technology allowed such initiatives as the 1000 Genomes Project in 2008 (unthinkable in 1990), which sought to investigate human variation and the 100000 Genomes Project in 2015. The latter sought to investigate the genetics of rare disorders and cancer, as well as creating a reference database for future studies. This means that whole genome sequencing can now effectively identify risk alleles, inform management and improve outcomes for an increasing number of disorders.

Presentation of the course 

Key concepts will be explored in traditional lectures using PowerPoints, but these will be interactive through the use of, for example, quizzes. There will also be opportunities for you to perform analysis of your own using freely available on-line resources in group tasks.

Course sessions

1. Mendelian inheritance and information flow (genes to proteins to phenotypes)
   Traits encoded by a single gene can be inherited in a number of ways (autosomal, sex-linked, dominant, recessive). The flow of information (DNA-RNA-protein) underlying genotype/ phenotype relationships will also be explored.
    
2. The genetics of populations (guest lecturer)
   The frequency of an allele in a population tells us much about the selective advantage/ disadvantage that it confers. While deleterious (harmful alleles) are strongly selected against, these can be maintained in a population if there is an advantage in the heterozygous state (for example in sickle cell trait). We will discuss the Hardy-Weinburg equilibrium, founder effects, and the genetic remnants of migratory patterns seen in the DNA.
    
3. Large scale analysis of genes and genomes
   In the late 1980s, scientists could determine the sequence a few hundred bases a day, or study the expression of a single gene across a demanding series of experiment. Technological innovation driven by the Human Genome Project means that an entire genome can now be sequenced in a few days (for a few hundred pounds) and the activation status of every gene in a cell or tissue can be profiled in an afternoon.
    
4. Making sense of complex data
   High-throughput analysis generates lots of data requiring sophisticated statistical analysis to extract biology relevant information (signal) from normal background and technical variation (noise). Genomics looks at the relationship between genetic variation and disease at either the individual or population levels, while transcriptomics relates the expression status of every gene in a cell or tissue to defined outcomes. Both require crunching a lot of data, and analysis pipelines must be robust if findings are to inform clinical decision making.
    
5. Genomics and clinical practice
   You will learn how genomics is increasingly informing the treatment of disease, from breakthroughs in cancer through the diagnosis and management of rare disorders to implementation in a broader spectrum of medical specialties. 

Learning outcomes

You are expected to gain from this series of classroom sessions a greater understanding of the subject and of the core issues and arguments central to the course. 

By the end of the course you will be able to:

• explain the principles of inheritance at individual and population levels
   
• interpret simple output from transcriptomic and genome sequencing studies
   
• list example of advances in diagnosis and management for individuals with genetic disease (including cancer)

Required reading

There is no required reading for this course.

Typical week: Monday to Friday 

Courses run from Monday to Friday. For each week of study, you select a morning (Am) course and an afternoon (Pm) course. The maximum class size is 25 students.   

Courses are complemented by a series of daily plenary lectures, exploring new ideas in a wide range of disciplines. To add to your learning experience, we are also planning additional evening talks and events. 

Evaluation and Academic Credit  

If you are seeking to enhance your own study experience, or earn academic credit from your Cambridge Summer Programme studies at your home institution, you can submit written work for assessment for one or more of your courses.  

Essay questions are set and assessed against the University of Cambridge standard by your Course Director, a list of essay questions can be found in the Course Materials. Essays are submitted two weeks after the end of each course, so those studying for multiple weeks need to plan their time accordingly. There is an evaluation fee of £75 per essay. 

For more information about writing essays see Evaluation and Academic Credit. 

Certificate of attendance 

A certificate of attendance will be sent to you electronically after the programme.