Leprosy is a chronic, disabling disease caused by a bacterium (Mycobacterium leprae) that infects only humans and armadillos. The disease affects the skin and peripheral nerves, leading to sores, numbness in the limbs, muscle weakness, and, in severe cases, disfiguring nodules on the skin. Known since biblical times, leprosy was highly stigmatized until the latter part of the 19^th century, when the Norwegian doctor Gerhard Hansen discovered that it was caused by a microorganism.

Although multi-drug therapy has cured millions of people of leprosy in recent decades, hundreds of thousands of new cases still occur per year, mostly in developing countries. Finding a way to eradicate the disease is therefore considered important for reducing the number of preventable disabilities worldwide.

Because Mycobacterium leprae is specific to humans and cannot be grown in lab dishes, research into factors influencing disease susceptibility and clinical outcomes has been limited. But the host environment as well as the bacterium itself can affect the course of the disease; in other words, human genetic factors may play an important role in determining who is more susceptible to infection. Since leprosy has been shown to cluster in families, scientists suspect that much of the variability in disease susceptibility and symptoms stems from diversity in individual human immune systems rather than differences between and within strains of the bacteria.

In a new study published today in New England Journal of Medicine, a team of researchers reports new human genetic factors associated with susceptibility to leprosy in Asians. Led by Fu-Ren Zhang of the Shangdong Academy of Medical Sciences in China and Jian-Jun Liu of the Genome Institute of Singapore, the scientists tested 93 variants across an estimated 50 genes in 3254 Chinese individuals with leprosy and 5955 Chinese individuals without the condition. Their analysis identified variants in seven of these genes to be significantly associated with leprosy.

“The discovery of these genes is a major breakthrough for research in leprosy and infectious diseases in general, and will be significant in the early diagnosis and development of new treatments,” said Dr. Liu in a press release.

The strongest of the associations were rs602875 in HLA-DR-DQ, rs3764147 in C13orf31, and rs9302752 in NOD2. In addition, some of the genetic variants were more strongly associated with a form of leprosy that results in more severe symptoms, known as the multibacillary form. These included rs9302752 in NOD2 and the variant rs1491938 in LRRK2.

(23andMe Complete Edition customers can check their data for SNPs reported in this study using the Browse Raw Data feature. See table at the end of this post.)

Altogether, five of the seven genes identified in the study could be shown to interact biologically in the context of immune response to infection. Two of these five genes, NOD2 and TNFSF15, harbor genetic variants that are also associated with Crohn’s disease (see 23andMe’s report on this condition). Crohn’s manifests some common features with leprosy at the cellular level and other researchers have suggested that mycobacterial infection may be a risk factor for Crohn’s. The findings reported by Zhang and Liu and their colleagues provide additional evidence for shared disease mechanisms between Crohn’s disease and leprosy and may increase the range of treatment options for both conditions.

Variants significantly associated with leprosy in individuals of Asian ancestry

* As reported on the 23andMe website through the Browse Raw Data feature.

** Effect only applicable to the multibacillary form of leprosy. LRRK2 is better known as a susceptibility gene for Parkinson’s disease (see 23andMe’s report on this condition). Interestingly, PARK2, another gene linked to Parkinson’s, was associated with leprosy in earlier studies. The reason for the connection between Parkinson’s and leprosy is unclear, though researchers have speculated that some of the same treatments may be effective for both conditions.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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Each of us is made up of about 50 trillion cells, which is pretty mind-blowing until you consider the number of microbial cells living on or in each of us.  It’s estimated that a healthy adult is lugging around 10 times more bugs, most of them bacteria, than human cells.

Just as the tiny differences we each harbor in our DNA can reveal information about our health and our ancestry, so too might the subtle differences in the types of bacteria we all carry.  The NIH has initiated a large project to explore the so-called “human microbiome” and its implications for our health.  Other projects are using bacteria to trace ancient migrations and human interactions.

Today scientists published the first in-depth study of global diversity in a specific human microbiome – the mouth. Surprisingly, although there is wide variety around the world in dietary and other cultural factors that could influence the types of bacteria found in a person’s mouth, the researchers discovered that the an individual’s “salivary microbiome” is likely to be just as different from a neighbor’s as it is from someone on the other side of the world.

“While there is significantly more diversity in bacterial genera [types of bacteria] compared from different individuals than from the same individual, the diversity among individuals from the same location is nearly the same as the diversity among individuals from different locations,” the authors write.  Their results appear online in Genome Research.

The researchers studied the oral bacteria of 120 people – 10 individuals from each of 12 worldwide locations: Oakland, CA; Baton Rouge, LA; La Paz, Bolivia; Buenos Aires, Argentina; Pointe Noire, Congo; Johannesburg, Sought Africa; Surigao, Philippines; Shanghai, China; Batumi, Georgia; Ankara, Turkey; Warsaw, Poland; and Dessau/Leipzig, Germany.

Overall, DNA analysis identified a total of 101 known types of bacteria, 39 of which had not previously been found in the human mouth.  The scientists also found evidence for another 64 unknown bacterial types lurking in people’s mouths.

According to the authors, their results lay the groundwork for future studies that will explore the influence of environmental, dietary and genetic factors on the types of bacteria found in a person’s saliva.  This, in turn, may lead to a better understanding of the role of saliva bacteria in mouth diseases or the interaction of the salivary microbiome with other microbial environments in the body, such as the intestines.

Their work could also help expand the use of bacteria in the study of human history. The stomach bacteria H. pylori has already been used in several studies to investigate human history. Just last month a study using this bacteria revealed new information about how Polynesia was colonized.  But while these H. pylori studies have been impressive, they do have a downside: a stomach biopsy is needed to get the samples.

“There would be obvious advantages if similarly-informative bacterial species could be identified in saliva,” the authors write, suggesting that their work might help identify just such a species.

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Not all bacteria are bad.  Sure, there are plenty of nasty bugs that can make life pretty unpleasant; the ones that cause leprosy, anthrax, and cholera immediately come to mind.

But there are also plenty of beneficial bacteria living inside of us that we may not even know about. Some of them help us synthesize vitamins, digest milk protein, and even stop other, more harmful microbes from infiltrating our immune system.

Many of those bacteria are so tightly connected to their human hosts that they can even be used to answer questions about our ancient ancestors. It might sound far fetched, but in a new study published in this week’s Science, an international team of scientists has managed to do this by analyzing a specific kind of bacteria hidden in the digestive system of nearly half the world’s population.  It is their hope that, by doing so, they can finally shed new light on how and when the first humans set foot on the Pacific islands.

Unearthing the origins and prehistory of the inhabitants of such islands as New Guinea, Samoa, and Polynesia has been no easy task.  Archaeological evidence has been spotty, due to the poor preservation in the tropical climate, while genetics has often been unable to distinguish between ancient migrations and more recent, historical movements.  As a result, researchers have begun turning to other disciplines to help fill in the gaps left by the more traditional fields.  In this most recent case, scientists thought outside the box, using the bacteria Helicobacter pylori – or, more accurately, differences in the genetic code of Helicobacter pylori strains – to discover when various parts of the Pacific were colonized.

Helicobacter pylori (H. pylori) is a kind of bacteria in that it is present in about 50% of the world’s population.  This makes it the most widespread bacterial infection on Earth.  It lives in our stomachs, and is sometimes associated with ulcers or an increased risk for stomach cancer.  However, more than 80% of those infected with it never know it, which may be why it is so widespread.  In fact, scientists believe that an ancient strain of H. pylori was present in the stomachs of the first humans to leave Africa more than 50,000 years ago.  Over the many thousands of years, H. pylori evolved into distinct strains found in distinct geographic regions.  For example, one strain is only found in Europe, another only in Africa, and a third only in East Asia.  So, just as genetic anthropologists use differences in our DNA to trace ancient human migrations, so too have scientists used H. pylori to reveal how humans first colonized some of the most remote parts of the world.

The current thinking about how and when the Austronesian peoples – that is, people who speak one of the many languages of island Southeast Asia and Oceania - came to colonize the Pacific Islands is, to put it mildly, unclear. While the majority of archaeologists, geneticists, and linguists all agree that the Austronesian peoples probably began their journey in present-day Taiwan, the timing and speed of their movements towards the outer rim of the Pacific Islands is a topic of great contention.  So, the authors of this most recent study hoped that an analysis of H. pylori among modern-day Austronesians might give researchers new information to go on.

The authors collected samples of the bacteria from the stomachs of more than 200 individuals living in Taiwan, New Guinea, Polynesia, and dozens of other Pacific islands.  Using techniques similar to those used in human DNA studies, the authors were able to track the different strains of H. pylori back to their common origin: Taiwan, about 5,000 years ago.

But how do these results stack up to findings by other researchers?  Interestingly, a companion piece in the same issue of Science also examined the peopling of the Pacific, this time focusing on the linguistic history of the Austronesian peoples.  That study analyzed more than 400 languages in the Austronesian linguistic family, using the similarities and differences to figure out when and where the group originated. The results of this study also support an origin of Austronesian peoples in Taiwan about 5,000 years ago.  In addition, both studies argue that people expanded in a similar direction: from Taiwan eastward towards Melanesia, Oceania, and finally Polynesia and the Hawaiian Islands.

It is not hard to believe that both the study of H. pylori and of the Austronesian languages would have yielded a similar date of origin of the Austronesian peoples, especially as both studies used the same archaeological record as a point of reference.  What is intriguing, however is that both studies – independent of each other – also point to similar paths of expansion of the Austronesian people once they left Taiwan.

The conclusions of these studies are far reaching, most especially because they illustrate how seemingly unrelated disciplines can be used to tackle a single question about the past.  Noted Cambridge archaeologist, Professor Colin Renfrew, believes these methods – combined with the more traditional archaeological or genetic methods – allow us to see how our past is still ‘within us’ today, whether it be in our genes, in our languages, or “the bacterial flora in our guts.”

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