LSBR 1133

Next Generation Sequencing in extremes to identify functional genetic variants affecting red blood cell volume. (LSBR 1133)
Project leader: Prof. dr. Pim van der Harst, Dept. of Genetics, University Medical Center Groningen, Groningen
Postdoc: Suzanne J.A. Korporaal PhD (Jan. 2011 – Nov. 2015)
Post-doc investigator: Dr. I. Mateo-Leach (Jan. 2012 – Dec. 2016)


We have three types of blood cells: red cells to carry oxygen to our tissues, white cells to fight infections and platelets to prevent bleeding. Red cells are the most abundant cells in the blood and retrieve in the lungs oxygen from the inhaled air for delivery to tissues. Oxygen is bound to the red cells’ main protein named haemoglobin. Haemoglobin is a special molecule that binds oxygen at places where there is plenty of it, i.e. when the red cells pass through the lung circulation, and release it at locations of low oxygen tension, in the tissues. Red cells have a limited lifespan of about 120 days, and each day a new supply of red cells (in size equal to that of a middle finger) is required to replace the ones that have come to the end of their lifespan.
The new red cells are produced by a limited number of blood stem cells, which reside in the bone marrow.

Researchers have for decades studied the processes by which stem cells form red blood cells. Through this research many insights have been gained, many of which have led to improvements in the care of patients, in particular for those with anaemia. It is hoped that one day it will become possible to produce red cells for transfusion in the laboratory. We do not envisage that this will become possible soon, because we first need to better understand all the minute details of the formation of red blood cells by stem cells.

One way to uncover new molecules and pathways that regulate the formation of red blood cells is by studying the DNA code from thousands of healthy individuals and by correlating the DNA code to simple metrics like the number of red blood cells and their volume. Initially we have done such studies by using ‘genetic fingerprint techniques’ because this DNA test was relatively affordable. However, to fully appreciate how our genes control the formation of red blood cells we need to read the entire DNA code.

With funding from the LSBR we have performed the first study of this kind and analysed the 3.2 billion letters of DNA from >750 healthy individuals. Researchers will analyse this large amount of big data in the first half of 2017. It is hoped that new genes and DNA variants that regulate red blood cell formation will be uncovered.

Our belief is that the knowledge gained from the LSBR project will facilitate the discovery of new genes and proteins that are important for the formation of red blood cells. The research may bring immediate benefits to the care of patients with inherited blood cell disorders because we can then readily introduce a DNA test for more rapid diagnosis. We also hope that in the long term the discoveries made by our research will make it possible to produce red cells for therapeutic use in the laboratory.