Professor Alex Blakemore
Professor in Human Genomics

Research Interests

Alex Blakemore’s main scientific interests centre on understanding the role of genetic variation in obesity and diabetes, as well as on autism-related traits and emotion processing. Mutation and variation our genes is a normal part of being human. However, we are still discovering how changes in the exact sequence of a gene, and the how variations in the structure of the human genome, affect our health and these are both areas which Alex continues to explore. From some of her previous research it has become clear that there are differences in the number of copies of genes we have and that, as part of our make-up, we all have extra or missing pieces of genome as well as differences in the DNA sequence itself. It remains a challenge to determine which changes within the genome are harmless, ‘normal’, human variations and which might cause disease. A further puzzle is how genetic variations interact with our lifestyle, diet and environmental exposures to affect health.

Alex’s PhD research was on MCAD deficiency, a genetic disorder that can cause sudden unexpected death. Alex was the first in the UK to provide DNA-based diagnosis for this condition and to estimate how common it is in the general population. It turns out to be the most common “inborn error of metabolism” in northern European populations. Since 2009 all babies in the UK have been screened for this disorder soon after birth, preventing many needless deaths.

More recently, she has investigated the genetics of obesity. By looking at unusual cases of obesity, such as Prader-Willi syndrome (a genetic condition in which appetite regulation is dysfunctional leading to severe early-onset obesity and other problems) she was able to narrow down the gene region which, when the copy inherited from the father is lost or damaged, is responsible for the clinical features of the disorder.

In carrying out this type of research, Alex and her co-workers have also discovered that deletions and duplications of part of chromosome 16p11.2 cause ‘mirror effects’; that is the loss of one copy of the region that causes obesity, large head circumference, language problems and high risk of autism. Having an extra copy (that is three copies instead of the normal two) of the very same region causes underweight, small head size and increased risk of schizophrenia.

Alex is now investigating how many cases of Mendelian (genetic) obesity are hidden among severely obese people being referred to hospital for weight-loss operations – and what other factors influence how well they respond to the surgery. She currently leads a clinical study calledPersonalised Medicine in Morbid Obesity, which includes around 2,000 participants. Her research team investigates this population group in a range of ways, including psychology (emotion-handling and autism, as well as engagement with treatment), physical activity (including theQuantified Self in Obesity sub-study, which includes using smartphone apps to track walking habits), gene expression (using RNA sequencing to investigate the molecular mechanisms of improvement in diabetes after gastric bypass surgery) and genetics (including looking for both severe genetic forms of obesity caused by recessive or dominant mutations in genes important for appetite regulation, and more subtle genetic effects from common variants of DNA sequence).

In 2015, she discovered the first case of a new form of monogenic obesity and diabetes in humans: CPE deficiency. The initial patient and her brother suffered from obesity, diabetes, learning disability, and lack of proper reproductive development. The mutation found in this family results the complete loss of a specific peptide processing enzyme (carboxypeptidase E), which is needed for the proper production of a number of neuropeptides and hormones, including several involved in appetite control and glucose metabolism.