Genetics of Brazilian Populations

Investigator: Mark Seielstad, PhD
Sponsor: Wellcome Trust

Location(s): Brazil


Visceral leishmaniasis affects the internal organs, and is caused by parasites of the Leishmania genus, which are transmitted through the bite of sandflies and take up residence inside cells in the bloodstream. It is particularly prevalent in Brazil, India and South Sudan, and affects up to 400,000 people per year. Many people carry the parasite without becoming ill; however, of the one in five who do fall ill with visceral leishmaniasis, a high proportion will die.

Although it is an infectious disease, some families are more susceptible than others. The team carried out a genome-wide association study in one Brazilian and one Indian populations – a total of almost 2000 individuals. Scientists at the WTCHG led by Dr Chris Spencer looked at over half a million single-letter differences in the genetic code to see if any were associated with increased disease susceptibility. They found a group of common variants associated with visceral leishmaniasis clustered in the part of the genome known as the major histocompatibility complex (MHC), a finding later confirmed in a second Indian population. Genes in this region enable the body to distinguish between its own tissues and those of invading organisms, and to call in immune cells to destroy invaders.

Interestingly, people with the MHC variant known as DRB*15 were least likely to fall ill with the infection. This variant has been associated in other studies with increased susceptibility to multiple sclerosis, a disease in which the immune system attacks the body’s own tissues. ‘The immune system evolved to fight infection’, says Peter Donnelly. ‘But in environments where infection is less of a problem, there appear to be downsides to having such a revved-up immune system, such as an increased susceptibility to autoimmune disease.’