Genes for Gaucher disease may have protected Jewish people against TB

Gaucher disease, a genetic condition more common in Ashkenazi Jews, may confer protection against tuberculosis, according to zebrafish study

To Claire Wilson

A genetic condition called Gaucher disease, more common in some Jewish groups, may help protect people from tuberculosis, possibly explaining why it persists.

Giving zebrafish the same mutation that causes Gaucher disease makes them less susceptible to infection by the bacteria that cause tuberculosis.

Ashkenazi Jews, who make up about eight in ten Jews, have a higher-than-average rate of Gaucher’s disease, which can cause symptoms ranging from pain and fatigue to an enlarged liver and spleen.

It is caused by a malfunction of a type of immune cell called macrophages.The job of macrophages is to engulf bacteria within internal compartments called lysosomes where microbes are killed. Unlike most bacteria, the bacterium that causes tuberculosis is Mycobacterium tuberculosiscan survive within the lysosomes, allowing the infection to spread within the macrophages of the lung.

There are hundreds of mutations that cause Gaucher disease, but they all cause a type of fat to accumulate inside the lysosomes. We investigated the effects of these mutations in zebrafish, which are sometimes used to study tuberculosis because they develop . Mycobacterium marinusa close relative of Mycobacterium tuberculosis.

The team fed fish with the most common mutation that causes Gaucher disease in Ashkenazi Jews. As expected, fat accumulated within the lysosomes of macrophages.

Two methods made the fish less susceptible to infection. For example, in a test in which fish were injected with one bacterium, 42% of mutated animals were uninfected compared to 13% of fish without mutations. “The host is more likely to kill the bacteria,” says Ramakrishnan.

Further experiments have shown that the type of fat that accumulates within the lysosomes is toxic to both human tuberculosis bacteria and fish equivalents when cultured in dishes. There is it [disrupts] It’s a tuberculosis membrane,” says Ramakrishnan.

Tuberculosis has been a leading cause of death in Europe for centuries, especially in densely populated environments. Today, about 1 in 800 Ashkenazi Jews has Gaucher’s disease, but hundreds of years ago, when tuberculosis was more common in Europe, the rate may have been higher. He said Ramakrishnan.

The variants that cause Gaucher disease in Ashkenazi Jews tend to cause a milder condition than some other variants, and they may have been selected to make people less vulnerable to tuberculosis. She supports the idea that there is.

Mark Thomas, of University College London, says another explanation is that the Jewish population was previously small, so an accidental mutation in one person was passed on to many of its descendants. . “There is good evidence that population bottlenecks were few in the Middle Ages, but that does not rule out the possibility that [Gaucher mutations causing] It has some advantages in some situations. “