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Human Genetics

Overview

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.

Our Work

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 underpinning 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.

Related groups

Associated research