An examination of the immune genes of the southern African Khoe-San people has revealed a completely new kind of mutation, according to researchers at the Stanford University School of Medicine. The gene variant likely contributes to healthier babies, although the variant can also lower resistance to disease.

The findings grew out of a long-term effort by Peter Parham, PhD, professor of structural biology and of microbiology and immunology, to understand how immune system genes make us reject organ transplants.

A paper detailing the findings were published online Aug. 20 in PLOS Genetics. The gene variant was one of two they found that would be expected to alter the formation of the placenta during early pregnancy, leading to larger, healthier babies and a reduced risk of pre-eclampsia, a major cause of maternal death.

“Only a handful of studies have investigated the function of immune genes in African populations. As a result, we have probably greatly underestimated the breadth of human immune variation,” said Parham, the study’s senior author. “So we were excited to investigate the Khoe-San, a divergent, modern human population known to harbor enormous genetic diversity.”

A genetic ‘railway’ switch

Mutations can alter genes in all kinds of ways. A mutation can have no effect on how a gene operates, it can change functionality in minor or important ways, or it can completely destroy normal function. Geneticists have never seen this type of mutation before, the researchers said. Originating among the Khoe-San, the mutation does two things at once: It simultaneously turns off one function and turns on another, much like a railway switch, pushing gene function off one track and onto another.