Effects of Genetic Knockouts on human Health

The Challenge

Genetics and Genomics is playing an ever increasing role in healthcare. We wished to understand the genetic make up of people in Born In Bradford. South Asian communities in particular are less well studied (http://www.genesandhealth.org/genes-your-health/genetics-south-asian-populations).

We are studying healthy adults who have “knockout” genes, (naturally occurring variations), as this has not been done before (http://www.genesandhealth.org/genes-your-health/its-knockout) . During fertilisation, humans inherit two copies of every gene, one from each parent, so that if one copy is inactivated, the other may make up for it. When two inactive copies are inherited, this is called a ‘knockout’.

We can learn a huge amount from these naturally occurring variations. Sometimes, having a gene knocked out has no effect, as a separate protein may have a similar function to the inactivated one. In other cases, a knockout has the potential to offer an advantage or a disadvantage. Such knockouts are more common in people whose parents are related, but can also be found in isolated populations such as Iceland or Finland.

 What we are doing about it

We have studied the human genomes of 2,162 Born in Bradford participants. The genetic code is the set of rules by which information encoded within genetic material (DNA or mRNA sequences) is translated into proteins by living cells. We have already made some information(without individual identifiers) available to other scientists, because  knowing what is normal in the population can be very helpful when trying to understand what is going on in children born with rare diseases.

We have also sequenced individuals from Born in Bradford born with congenital anomalies, to try to understand more about these conditions.

 Our future plans

Although we have completed a lot of sequencing, it is still early days for the analysis which only began in early 2015.

We have commenced a new and broader project, East London Genes & Health aiming to improve health in East London and wider (http://www.genesandhealth.org). It is possible that we may expand this study into Bradford as an additional site.

We are also working to increase public knowledge of genetics and genomics, through www.genesandhealth.org and through our Centre of The Cell (www.centreofthecell.org) science education programme. We developed the “Mummy for Melissa” genetics show for younger children for the Born in Bradford festival 2014.*

Changes that have been implemented as a result 

It is too early for changes to be implemented. We have already provided data which will be helpful to those studying rare diseases. We also have some findings suggesting that some types of sequence changes thought to cause rare diseases may not in fact do so – it is very important to get such facts right now that more and more adults are getting their genomes sequenced, and for pre-natal testing.

David Van Heel

I was born and brought up in Bradford, where my family still live. I trained as a Doctor (doing my paediatrics in St Luke’s Hospital) and then as a researcher. I am now Professor of Genetics at Queen Mary University of London, and Consultant Gastroenterologist at Barts Health NHS Trust (http://www.blizard.qmul.ac.uk/staff/90-centre-for-genomics-and-child-health/516-van-heel-david.html). I am very excited by genetics and genomics, and how we can use this to improve healthcare in both Bradford and East London.