Watch out HIV virus, we know your secrets.

If you’ve ever taken a class on sexually transmitted diseases, you were probably taught this fact: once you contract HIV, you will eventually get AIDS. Yet for about 1 in every 300 people this simply isn’t true. These ‘HIV controllers‘ have bodies which are somehow able to fight off the development of AIDS for years, sometimes for decades. Scientists may have finally pinpointed the reason why. Researchers lead by a team at Massachusetts General Hospital, have found the region of the genome that seems to be responsible for determining who will be a controller and who will not. Just five amino acids associated with the HLA-B gene/protein seem to be the key. This discovery, recently published in Science, is unlikely to lead to immediately available therapies or treatments in the short term. Eventually, however, knowing how controllers ‘naturally’ fight off AIDS could help us provide that same resistance to everyone who has contracted HIV.

The presence of HIV controllers has been acknowledged for a long time, but scientists have lacked the genetic tools needed to probe their resistance until recently. In 2006 Florencia Pereyra started the Controllers Consortium, gathering information and genetic samples from HIV controllers from all over the world. Since then, 300 collaborators at over 200 facilities on 6 continents have been gathering data on controllers. For the publication in Science, Pereyra along with lead co-authors Bruce Walker and Paul de Bakker, performed a genetic study using 974 HIV controllers and 2648 normal HIV patients. This genome wide association study (GWAS) looked at single nucleotide polymorphisms (SNPs) that differed between groups. After exhaustive examination, the global team of experts settled on the HLA-B gene as the crucial difference that allowed HIV controllers to outlive their peers.

This HLA-B protein has a section that identifies it with the immune system (red), and a stabilizing structure (pink).

HLA, or human leukocyte antigen, is part of the area of your genome that dictates immune system function. It’s a natural place to look for resistance to HIV. HLA-B gene helps your cells create proteins that rest on the cell’s surface. Those proteins use peptides to communicate with your immune system. If the peptide gives the wrong signal (say, because it’s been infected with a virus) your body will destroy the cell. Hundreds of different variations for the HLA-B gene are known, and it’s among one of these variations that five key peptides are developed that help an HIV controller’s body fight off HIV more efficiently.

This is some amazing information, but it’s going to take years before it really does us any good. First, these findings have to be confirmed and re-examined before we can even trust them. Luckily, the Controllers Consortium is continuing to gather genetic samples (1500+ and counting). Also, I don’t want to detract from SNP based GWAS because these studies can reveal some interesting insights into diseases. However, time and again we’ve been faced with reactions in the body that are the result of complex genetic interactions that SNPs simply cannot adequately track. HLA-B may be a crucial part of HIV controlling, it could even be the whole basis of HIV controlling, but there could also be a larger system of gene variations that work with it. Eventually, I suspect that whole genome sequencing may be needed to completely understand these interactions (and not just for this experiment, but many other genetic studies as well).

Even once we completely understand the genetic basis for HIV controlling, it will take time to develop therapies using that knowledge. Do we create a vaccine-like treatment that somehow spurs the body to produce more of the right kind of HLA-B amino acids? Do we pump patients with HIV full of these amino acids, or try to give them gene therapy? Whatever solution we adopt will need several years to test before we can apply it to large populations with HIV/AIDS.

Knowing how long it will take to apply this new understanding of the body’s response to HIV doesn’t keep me from being very hopeful about its eventual use. This is a good time in HIV/AIDS research. Mimicking the genes of an HIV controller is going to be a great tool in fighting the AIDS epidemic. Not only do controllers live longer without developing AIDS, they also have a reduced risk of transmitting HIV. Even if we can’t develop a vaccine, we could still get vaccine-like benefits and slow the spread of the disease. I have this growing hope that one day HIV/AIDS will follow the same path to destruction that we’ve managed for Small Pox, and are looking to find for Polio. As devastating as AIDS has been there’s always a chance that we’ll one day be able to eradicate it from the Earth completely. That day seems closer now than it has in a long time. I’m very, very happy about that.

*I’d like to mention some of the various organizations whose funding directly made this research possible:
Phillip T and Susan M Ragon Institute
Mark and Lisa Schwartz Foundation
Harvard Center for AIDS Research
Bill and Melinda Gates Foundation
Broad Institute

…If you know any more, please mention them in the comments section and I’ll add them up here.

[image credits: Ragon Institute, Broad Institute ]
[sources: The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation. Science, November 02, 2010, Ragon Institute, MGH/Ragon Press Release, ]

23andMe is hunting for connections between genetics and athletics, especially as we age.

Back in October, 23andMe generated a little PR buzz by examining the genetic codes of 100 current and former NFL players and comparing them to non professional athletes. That genome wide association study (GWAS) didn’t actually turn up any remarkable results. Yet the GWAS wasn’t the first or last of 23andMe’s attempts at determining how genetics shapes athletics. Their SNP tests include examinations for key gene variants which may code for muscle growth and sprinting prowess. They have an associated study to find genes linked to sports injuries. Teaming up with the National Senior Games Association, 23andMe is offering discounts to older athletes who get tested and submit athletic surveys. They even offered free testing at the Palo Alto Senior Games (see page 15 of this pdf). No doubt about it, 23andMe is taking strides to understand the genetic variations that help some become athletic stars and force others to sit on the bench.

23andMe has made throwing DNA studies at a topic of interest into something of a hallmark for the company. They’ve worked hard collecting samples for an extensive test on Parkinson’s Disease. Likewise, they’ve begun a “research revolution” aimed at letting users determine which diseases will receive the benefit of their ever growing DNA sample collections. The NSGA study shows that 23andMe is at it again, focusing on what helps us age gracefully and athletically. The work also suggest that 23andMe is actively throwing its weight behind learning about the key genetic ingredients for athleticism at all ages.

I’d like to thank Daniel MacArthur of Genetic Futures for providing great insight into the NFL GWAS and Palo Alto Senior Games study. He points out that the NFL study was simply too small to really generate any meaningful correlations between gene variants and athleticism. 100 samples, even of outlier athletes, isn’t enough. However, MacArthur also points out that the thousands of samples taken for the NGAS study, and other 23andMe endeavors (i.e. the Parkinson’s study) could yield major insight.

What that insight will be is unclear. While a few genetic variants, such as a mutation in the ACTN3 gene, may provide an edge for athletes it’s unclear how big of a factor genes are in determining your physical prowess. As I was recently informed by Malcolm Gladwell’s book, Outliers, the greatest determinant for your success in a sport may be the month in which you are born (due to asymmetry in training over a lifetime). A host of genetic variants that give you a 15% better chance at naturally stronger muscles or a more resilient cardiovascular system may be small compensation for breaking your leg at age nine and choosing to pursue writing over track and field. It’s hard to know if/when/how genetics will trump experience when it comes to something as broad as athleticism.

Still, all things being the same, your genes are likely to form an important part of your athletic potential. Understanding that potential could not only help us compensate for our bodies’ natural tendencies it could lead to treatments for those with debilitating illnesses. Already, we’ve seen scientists pursue gene therapy to harness some of the incredible strength benefits of myostatin blockers in order to help fight muscular dystrophy. With companies like 23andMe discovering new genetic variants linked to life-long athletic talent, we may one day see therapies that could ramp up anyone’s athletic potential to match that of the beefiest NFL line backer.

[image credit: 23andMe]

New studies in the US and Japan highlight important genetic links to Parkinson's disease. Good news for those suffering from the debilitating illness.

Affordable genetic testing continues to enable scientists to find exciting new discoveries that may help doctors predict, prevent, and treat disease. Two teams of researchers recently published in Nature Genetics (a Japanese team from Kobe University, and a US team from NIH) have collaborated to find that five important genetic variants are linked to Parkinson’s. This debilitating brain disease degrades muscle control through a reduction in brain chemicals and affects 1-2% of those over 65. This research was the largest case of genetic testing for Parkinson’s, ever. With the amount of genetic data that can now be processed quickly and cheaply, studies like these are just the beginning.

These two Genome Wide Association Studies (GWAS) rely on finding important comparisons of single nucleotide polymorphisms (SNPs). 23andMe declared war on Parkinson’s by analyzing SNPs one individual at a time and hope to gather 10,000+ samples total. These two GWAS, however,  have already examined the genetics of many thousands of volunteers. By sifting through this massive amount of data, scientists can glean which genetic markers may indicate increased risks of the disease. It’s only been in the last few years that genetic testing has been cheap enough to facilitate such studies. As whole genome sequencing becomes cheaper, researchers will be able to study more DNA than just SNPs. This may lead to an even better understanding of the links between genes and illness. We live in a very exciting time – there is an ocean of data in our DNA that is going to be explored in the next few years.

The Japanese team, led by Dr. Tasishi Toda of Kobe University, discovered four important loci for Parkinson’s named PARK16, BST, SNCA, and LRRK2. Information was taken from 2011 patients with the disease and 18,381 healthy individuals, all of Japanese descent. In the US, Dr. Andrew Singleton of the NIH led researchers to confirm the SNCA locus and add a new one: MAPT. Their sampling consisted of 1713 patients, and 3978 healthy volunteers followed by 3361 patients and 4573 volunteers, all of European ancestory.

Why am I giving you all these numbers? To prove a point. We are talking about tens of thousands (30k+) of people each having their genome analyzed on the cheap. That’s remarkable, and something that would have been unheard of just five years ago.

The two teams confirmed that PARK16, SNCA, and LRRK2 are important loci for all Parkinson’s patients. Interestingly, MAPT was only an indicator for European ancestry, and likewise with BST for Japanese ancestry.

As SNP genetic analysis gets even cheaper, and whole genome studies fall within the budget of research institutions, we are going to see more and more studies like these two. Already individuals can gain access to affordable SNP analysis, and soon the same will be true for whole genome sequencing. That means that you will be able to know for yourself which important markers you carry that may indicate a predilection to an illness. Armed with such knowledge we will all be able to take better control of our health. Hang in there everybody, we’re making progress. (Not so) slowly but surely.

[photo credit: Kristen Ryder]