Comparative genomics and population genetics

Research into comparative genomics and population genetics enables scientists to compare genetic differences and similarities between different species (in comparative genomics), and between sample members of the same species (in population genetics). In so doing they can study gene function and its relationship with health or disease.

Using comparative genomics, researchers can predict and test gene function using model organisms. At first glance, zebra fish, mice and C.elegans nematodes – among the most extensively used model organisms in genomics labs – bear little, if any, physical resemblance to humans. But their cells hold the key to a better understanding of how the human species has evolved. Their genomes have preserved the genetic trace of a distant common ancestry with humans and many of their genes have human equivalents – 90% of mouse genes, for example. Researchers can learn a great deal about the function of human genes by examining their counterparts in these, and other model organisms, used to study human development, disease and physiology, and to test therapies.

Unravelling the complexities

Comparing features of the genome such as sequence similarity, gene location and the regions that have remained highly conserved throughout evolution, can give an important insight into how complex biological processes operate and how they have evolved to create diversity between species.

Model organisms present many advantages for research into functional genomics. They have rapid development and short life spans allowing researchers to follow inheritance and gene function through many generations in a relatively short time, and they lend themselves to molecular manipulation, enabling researchers to induce random or directed genetic mutations.
Changing the pattern of gene expression by inducing random mutations (mutagenesis) is known as “forward genetics”. Researchers use this technique to see what happens in the cell when a mutation arises – absence or excess of a protein, for example. The ‘randomness’ of this approach can throw up unexpected results and lead to the identification of novel gene functions or new drug targets. Another technique, called “reverse genetics”, or “knockout”, involves targeting a known gene in the model animal and replacing it with a human gene, or other foreign DNA (transgenesis), to explore its function in following generations. Much current research is aimed at refining these techniques, providing researchers with powerful molecular tools to more accurately manipulate the genomes.

Many of the biochemical changes induced by mutagenesis or transgenesis can by tracked by in vivo molecular imaging. Multidisciplinary collaboration between researchers to improve the resolution of imaging systems and to create multimodal imaging platforms should result in spectacular new opportunities for analysing gene function.
The variety of life

Whilst the study and exploitation of the similarities that exist between model organism and human genomes are making important contributions to health-related research, work on the genetic variation that exists between humans is also essential in the study of the many common, yet complex diseases which involve both genetic and environmental or lifestyle risk factors – asthma, diabetes and heart disease, for example.

By compiling collections of DNA samples from large numbers of human volunteers representing cross-sections of the population, and associating these, in storage facilities called “biobanks”, with regularly updated information on the volunteers’ lifestyle and medical history, researchers can look for patterns in the data which may give clues to the underlying genetic basis for disease.
Whilst we all share the same 30 000 or so genes which make us humans, we also all have small variations in these genes – like words with alternative spellings – which make us unique individuals. Some of these variations – called polymorphisms – determine physical characteristics such as whether we have blue eyes or brown, but others can determine how likely we are to suffer from certain diseases, or how we will react to certain drug therapies.

When people sharing the same variation of a particular gene later develop the same disease, researchers can investigate this gene’s products and their function and see whether they have a role to play in disease development. Biobank collections make it easier for researchers – using high-throughput analytical tools for monitoring DNA variations combined with powerful bioinformatics – to systematically search for links between gene variation and disease, and to see whether certain lifestyle factors, like diet, make it more or less likely for an individual with this genetic variation to develop a given disease.

Because of the complexity of the relationship between disease and genetic, environmental and lifestyle factors, population geneticists need access to very large numbers of samples to ensure that any patterns they observe are statistically significant. For this reason, population studies increasingly necessitate international collaboration to ensure that large data sources can be shared. The ethical, legal and social aspects of this type of research are also extremely important factors to ensure that volunteers’ rights are respected.
Projects

Integrated Projects
ZF-models
Molecular Imaging

Streps
Nemagenetag
NFG