Genetics

Dr Claire Palles studies whole genome sequencing data and targeted analyses with the aim of discovering genetic variants that affect susceptibility to colorectal cancer and Barrett’s oesophagus. The gastrointestinal track is responsible for more cancers than any other system. A condition called Barrett's oesophagus, characterised by a change in the cells lining the oesophagus, can lead to oesophageal adenocarcinoma. Only few people with Barrett's oesophagus will go on to develop cancer, and genome sequencing studies aim to identify genetic risk factors and therefore better target high-risk patients.

Chorea-Acanthocytosis: ChAc is a rare progressive neurological disorder caused by mutations in a very complex gene. Dr Antonio Velayos-Baeza is interested in two main projects: Chorea-acanthocytosis (ChAc), a rare autosomal-recessive disorder that is characterised by progressive neurodegeneration and red cell acanthocytosis (spiky red blood cells), and Developmental dyslexia, the most common of the childhood learning disorders.

Resistance to drugs in bacteria can be aquired by swapping genes between individual bacteria. Computer programs developed by Dr Iqbal enable doctors to predict which antibiotics will be met with drug resistance, enabling the selection of the right drug. BIOINFORMATICS & PATHOGEN GENOMICS Dr Zamin Iqbal studies the DNA of bacteria and parasites, and compares the genomes of individual pathogens to track the spread of antibiotic resistance. Pathogens accumulate small genetic changes over time, and by tracking these changes, it is possible to map the spread of an infection. This enables better surveillance of pathogen evolution, within a host, within a hospital and across the world.

Computational and stastistical methods help us understand evolution as well as genetic disease. Professor Gerton Lunter is interested in investigating the processes of evolution and biology using computational methods. His focus is on sequencing data; Professor Lunter develops methods to investigate evolutionary questions in population genetics.

DNA replication and Cancer The process of DNA replication is complex, and mistakes can lead to genome instability. Surveillance systems are not always successful which results in mutations that have the potential to inactivate genes or change their activity. This can lead to cancer, and many chemotherapeutic drugs are designed to disrupt DNA replication. A better understanding of these mechanisms can help us develop new drugs with reduced side effects.

Over the past decade, data-driven science has produced enormous sets of data. The convergence of statistics and computer science, in the field known as machine learning, provide the means to understand these large datasets. Ultimately, machine learning algorithms will be develop into clinical decision making support systems.

Professor Peter Donnelly tells us how genetics helps us to understand common diseases and develop new drugs. Understanding which variations in our DNA affect susceptibility to diseases can provide new insights into the disease process and lead to new treatments. Professor Peter Donnelly leads large collaborative human genetic studies, and his group develops and applies statistical methods to extract maximal information from the large datasets generated by genomic studies.

Every psychiatric disorder has a genetic contribution. Although anxiety and depression are very common diseases, current treatments are not very good. A better understanding of the contribution of genetic variants might help us better diagnose as well as develop new therapies.

Professor Gil McVean tells us how statistical genetics helps us understand and treat disease. Genomic technology and statistical analysis of the genome is a powerful tool in understanding disease. Prof Gil McVean is the Head of Bioinformatics and Statistical Genetics at the Wellcome Trust Centre for Human Genetics. Professor McVean's research covers several areas in the analysis of genetic variation. Combining the development of methods for analysing high throughput sequencing data, theoretical work, and empirical analysis, this research may lead to genetic diagnosis and targeted treatments for disease.

Dr Dianne Newbury talks about the contribution of genetics to specific language impairment. Specific Language Impairment (SLI) is a complex genetic disorder in the development of language. Dr Dianne Newbury is looking for the genes that predispose to SLI. Two regions, located on chromosomes 16 and 19, are linked with this disorder. Interactions between several normal genetic variants and environmental factors make certain individuals more vulnerable to language problems. A better understanding of these underlying biological pathways will lead to the development of more accurate identification systems and better therapies.

Dr Silvia Paracchini talks about the influence of genetics in dyslexia. Dyslexia is a reading impairment that effects up to 10% of children. Dr Silvia Paracchini aims to identify the genetic components of dyslexia to better understand its underlying biology. Working to uncover the biological mechanisms involved in human cognition, Dr Paracchini is looking for connections between dyslexia and other cognitive disorders such as Specific Language Impairment or Attention Deficit Hyperactivity Disorder. Dr Paracchini is looking for possible common genes for these clinically distinct disorders.

Dr Cecilia Lindgren explores the links between obesity and genetics. Obesity and its consequences are major and growing challenges for health care providers worldwide. While lifestyle is a contributor, over 30 genes associated with body mass index have also been identified. Dr Cecilia Lindgren uses genetic and genomic approaches to better understand the underlying mechanisms and pathways involved in the regulation of overall energy balance, to establish improved therapies and preventive measures.

Dr Julian Knight explains how genetic variants modulate gene expression and influence the susceptibility to commom diseases. Genetic variation plays an important role in individual susceptibility to common diseases. Dr Julian Knight's research focuses on how genetic variation between individuals affects the way immune and inflammatory genes are expressed. This helps understand genetic susceptibility to common conditions such as infectious, inflammatory or autoimmune diseases, leading to more targeted and effective treatments for patients. Dr Knight recently published a book titled 'Human Genetic Diversity, functional consequences for health and disease'.

Dr Erika Mancini explains the role of chromatin in the regulation of gene transcription. Chromatin, the physical packaging of DNA within the nucleus, plays an important role in the regulation of gene expression. All our cells contain the same set of genes, but only some of them are transcribed at any point in a particular tissue. The movement of nucleosomes, packing and unpacking DNA, is governed by chromatin remodelling ATPases. Malfunctions in chromatin structure regulation often leads to complex multi-system diseases and cancer, notably leukemia. Dr Erika Mancini is interested in the role of chromatin in the regulation of gene transcription.

Dr Krina Zondervan talks about endometriosis, an incapacitating women's health condition. Endometriosis is a gynaecological condition, which often causes severe pelvic pain and may lead to infertility. In women suffering from endometriosis, cells similar to those lining the uterus appear and flourish in areas outside the uterine cavity. Causes of endometriosis remain unknown and treatments are limited to either surgery or the use of hormonal drugs. Dr Krina Zondervan studies genetic, molecular and environmental factors influencing this complex disorder.