Inherited disorders and copy number changes in human alpha-globin genes

A researcher from the University of Leicester has shed new light on the way genetic material is exchanged between chromosomes, the effect this 'aberrant exchange' has had on inherited disorders like thalassaemia (a form of anaemia), and its link with malaria.

Natural selection has made alpha-thalassaemia the most common inherited disease on the planet, affecting in a mild form many millions of people. Despite its importance, almost nothing is known about the process that generates these gene copy number changes when DNA is transmitted from parent to child.

Dr Gabriel Lam, from the University's Department of Genetics, has used single-DNA-molecule techniques to study these processes during his three-year PhD research and will be presenting his findings at a doctoral inaugural lecture on Wednesday 8th October.

He will introduce the background and importance of alpha-globin genes, and then explain strategies for tackling the dynamics and mechanisms of the disease-initiating process, ectopic recombination.

The exchange of genetic material between chromosomes is essential for increasing genetic diversity, greatly enhancing the genetic uniqueness of individuals. However, mistakes in this recombination process can sometimes alter the number of genes, generating inherited disorders like thalassaemia.

Dr Lam commented: "Alpha-globin genes are extremely important because of their role in the formation of haemoglobin. Normal individuals usually have four alpha-globin genes.

"However, ectopic recombination can change this gene copy number from zero to, theoretically, infinity. Without sufficient normal alpha-globin proteins, individuals can develop alpha-thalassaemia, a potentially life-threatening form of anaemia."

"Malaria in regions like Africa and Southeast Asia, however, favours people with fewer-than-normal numbers of alpha-globin genes.

"My research on detecting spontaneous changes in gene copy number has shed completely new light on processes of ectopic recombination in humans.

"One big surprise was just how commonly these alpha-globin gene changes occur in sperm. This implies the action of natural selection, not only in malarial regions, but also in regions free of malaria to maintain gene copy number in the face of what is clearly a powerful mutational force that is trying to alter the number of alpha-globin genes in human populations."

Dr Gabriel Lam will explain his research at a public lecture on Wednesday 8th October, 5.30pm in the Frank and Katherine May Lecture theatre in the Henry Wellcome Building, Lancaster Road, Leicester.