The Human Genetics Programme is driving a step-change in our understanding of genetic causes and biological mechanisms of disease susceptibility and progression, focusing on developmental disorders and diseases of the blood and immune system. We integrate population-scale genetics, longitudinal clinical data, and large-scale genetic perturbation studies in cellular model systems. We aim to transform the clinical utility of human genetic variation.
The main areas of research of the Human Genetics Programme are:
Genetics and genomics of blood cell traits
We are determining the genetic architecture of the broad spectrum of phenotypic variation in blood cell traits seen in hundreds of thousands of healthy individuals. Many common diseases are mediated by blood cells, and we are using our understanding of this genetic architecture of healthy variation to determine the biological mechanisms underpining thousands of genetic associations for these diseases.
Integrated genomics of inflammation and immunity
We are using population-scale genetics and cellular genomics at scale to identify and characterise genetic associations with immune-mediated diseases. By integrating genetic data with rich health record data we identify genetic associations with disease progression and drug response, as well as with disease susceptibility. We are also using genetics and functional genomics to understand how and why there is substantial variation between individuals in how the immune system responds to challenges. Our research identifies potential new drug targets for treating immune-mediated diseases.
Causes, mechanisms and reversibility of developmental disorders
We are characterising the genetic architecture of rare, severe, developmental disorders through genome-wide sequencing and genotyping, and integrating studies in cells and mice to support inferences of causality, provide insights into disease mechanisms and highlight potential therapeutic opportunities. We are particularly interested in the influence of biological (e.g. germline mutation) and demographic (e.g. parental relatedness) factors on the risk of suffering from such disorders.
Genetic factors influencing fundamental cellular phenotypes
We undertake large-scale screens of fundamental cellular phenotypes in iPSCs (induced pluripotent stem cells) with diverse genetic backgrounds to measure and map the impact of genetic background on these phenotypes. We also use these methodologies to understand how cells respond differently to perturbation by genetic variants that cause disease (e.g. Mendelian disorders). These analyses will help us understand why some people are resilient to highly damaging genetic variants, while others are not.
Associated Research Programmes
The Human Genetics Core Research Programme collaborates with two of the Institute's Associated Research Programmes: Health Data Research UK (HDRUK) and Open Targets.
The BLUEPRINT Project is a five-year project to further the understanding of how genes are activated and repressed in healthy and diseased human blood cells and their precursors. The BLUEPRINT Consortium is made up of 42 leading European universities, research institutes and industry entrepreneurs, and ran from October 2011 to September 2016.
DECIPHER is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient. The patient’s variant is displayed in the context of both normal variation and pathogenic variation reported at that locus thereby facilitating interpretation.
The aim of the Deciphering Developmental Disorders (DDD) Study is to advance clinical genetic practice for children with developmental disorders by the systematic application of the latest microarray and sequencing methods while addressing the new ethical challenges raised.
Genes & Health is one of the world’s largest community-based genetics studies, aiming to improve health among people of Pakistani and Bangladeshi heritage by analysing the genes and health of 100,000 local people in select UK population centres.
Genomics England is a company wholly owned by the UK government, tasked with delivering genomic medicine in partnership with the NHS. GEL delivered the 100,000 genomes project, with a focus on whole genome sequencing of patients with rare diseases or cancer.
Health Data Research UK (HDR-UK) is the national institute for health data science. HDR-UK is uniting the UK’s health data to enable discoveries that improve people’s lives. By making health data available to researchers and innovators we can better understand diseases and find ways to prevent, treat and cure them.
The International Common Disease Alliance (ICDA) aims to improve prevention, diagnosis, and treatment of common diseases by accelerating discovery from genetic maps to biological mechanisms to physiology and medicine, to benefit people around the world.
The PAGE study is striving to gain a better understanding of genetic variants causing developmental problems during pregnancy. The ultimate aim is to improve prenatal diagnostics, allowing better genetics-derived prognoses and more informed parental counselling in the future.
The UKIBD Genetics Consortium (UKIBDGC) comprises clinicians and scientists with a track record of successful collaborative research in the genetics of inflammatory bowel disease. Our aims are to identify and understand the genes that determine disease susceptibility, course and response and side effects of treatment. The UKIBDGC is a major contributor to the International IBD Genetics Consortium.
The UK10K project enabled researchers in the UK and beyond to better understand the link between low-frequency and rare genetic changes, and human disease caused by harmful changes to the proteins the body makes.
The goal of our reseach is to use high-throughput screens to gain causal insights into the biological basis of human disease, identify new drug targets and determine the patients who will benefit most from these drugs. We focus on immune-mediated disease, and inflammatory bowel disease in particular, due to the significant burden of disease and the accessibility of disease relevant tissue.
DNA sequence remains at the heart of molecular biology and bioinformatics. The Birney Associate Faculty Research Group at the Sanger Institute focuses on developing sequence algorithms and using genetic variation to explore elements of basic biology within and between species
The Danesh group works as part of the Health Data Research (HDR) UK Cambridge site, using genomic, molecular and electronic health record data at population scale to understand disease at a deeper than ever biological level.
Our goal is to understand how genetic background influences outcome of mutations. To do so, we measure, model, and modulate cell state across healthy and disease-relevant human genetic diversity. In the lab, we develop tools for genetic perturbations, and use genome engineering and synthetic biology to create cell lines for screening cellular traits. In the office, we develop probabilistic models as well as software tools to accurately and efficiently analyse the readouts.
Human Genetics Informatics (HGI) supports the scientific aims of the Human Genetics programme by developing and operating computational analysis workflows, managing shared storage, and providing bioinformatics software tools for the use of researchers across all Human Genetics faculty groups.
We are interested in all aspects of gene regulation by non-coding RNA. Current research themes include: miRNA biology and pathology, miRNA mechanism, piRNA biology and the germline, endo-siRNAs in epigenetic inheritance and evironmental conditioning, small RNA evolution and the role of RNAi in host pathogen interaction.
Our research focuses on the application of large-scale genomic analysis to unravel the spectrum of human genetic variation associated with cardiometabolic diseases, and its interaction with non-genetic and environmental cues.
We study variation in the DNA of people from different parts of the world, and also in related species such as chimpanzees and gorillas. This tells us about the evolutionary history of human populations and also allows us to compare the different species.
We analyse large-scale genetic and electronic health record data to explore fine-scale population structure, its impact on disease risk, and the genetic architecture of both rare and complex diseases. We have a particular focus on populations in which parental relatedness (consanguinity) is common.
We developed algorithms and technologies that enable researchers to discover and share genetic variation using next-generation sequencing technologies. We were part of the Global Alliance for Genomics and Health consortium (GA4GH), an international, not-for-profit alliance formed to help accelerate the potential of genomic medicine to advance human health.
We are a multidisciplinary team that combines large-scale genetic and genomic approaches, and studies in model organisms, to understand the aetiology of various metabolic diseases. We are also actively engaged in developing partnerships with collaborators in Africa focused on applying genomic approaches to study diseases of relevance to Africa and its peoples. The knowledge of genetic predisposition is important to help those at high risk for these disorders to develop healthier lifestyles and to avoid risky behaviours (such as high fat diets). It can also lead to the development of better drugs that work in each affected individual.
This group consists of manual annotators and software developers. The HAVANA team provides the manual annotation of human, mouse, zebrafish and other vertebrate genomes that appear in the Vega browser. Our software is written and developed by the Annosoft team.
Global human genomes reveal rich genetic diversity shaped by complex evolutionary history