Researchers have identified another region of the genome associated with childhood asthma, a condition that affects more than seven million American kids.

Analysis of DNA from about 1,700 children with asthma and 3,500 controls, all of European ancestry, identified several genetic variations on chromosome 1 associated with the risk of developing asthma.  Many of these same SNPs were then also found to be associated with risk for asthma in a sample of more than 1,600 African American children with asthma and 2,045 controls.  All of the newly identified SNPs are located near the gene that encodes DENND1B, a protein known to be involved in the body’s response to foreign particles.

“Many of these particles are well-known triggers of asthma.  In asthma, patients have an inappropriate immune response in which they develop airway inflammation and overreaction of the airway muscle cells,” explained Hakon Hakonarson, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia and the senior author of the study, in a press release.

The chromosome 1 variations identified by the researchers affected the odds of childhood asthma in different ways depending on ethnicity.  Versions of the SNPs associated with increased risk in African Americans were associated with decreased risk in the European sample.  This is not unusual in genetic studies, and often reflects differences in population history.

One of the most promising SNPs is rs1775456.  In African American children, each copy of the less common G version of this variation was associated with 1.86 times increased odds of asthma.  In children with European ancestry, each G was associated with 0.75 times odds of the condition.  The results were published recently in the New England Journal of Medicine.

(23andMe Complete Edition customers can view their data for rs1775456 using the Browse Raw Data feature.)

Hakonarson suggests that his team’s finding that DENND1B has a genetic link to asthma could lead eventually to the development of new types of treatments.

“Other asthma-related genes remain to be discovered, but finding a way to target this common gene variant [found in the study] could benefit large numbers of children,” he said.

Previous research linked genetic variants on chromosome 17 with the risk for childhood asthma in Europeans.  Some of these studies suggested that these variants have an effect only in children who are exposed to tobacco smoke.  More research will be needed to work out the details, but the importance of chromosome 17 in asthma was further supported by the current study, which replicated the previous findings in addition to identifying the new variants on chromosome 1.

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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A recent study led by Carlos Bustamante of Cornell and Sarah Tishkoff of the University of Pennsylvania has shown that genetically speaking, African American can mean a lot of different things.

The researchers and their co-workers analyzed DNA data from 365 African Americans, 203 West Africans from 12 different countries, and 400 Europeans from 42 countries.  Their results, published in the Proceedings of the National Academy of Sciences, show that the average amount of DNA in an African American’s genome that could be traced back to West Africa was about 77%, but ranged from as little as one percent to as much as 99%.

These findings have important implications not only for understanding the ancestry of African Americans and the history of human migrations, but also for medical treatment.

“That some individuals who self-identify as African American show almost no West African ancestry and others show almost complete West African ancestry has implications for pharmacogenomics studies and assessment of disease risk… caution should be used in prescribing treatment based on differential guidelines for African Americans, ” the authors write.

The researchers also undertook an analysis to determine if any particular stretches of DNA found in African Americans were more often descended from their West African ancestors.  The strongest finding was that there are elevated levels of African ancestry on the X chromosome, most likely reflecting a history in which interracial mating primarily happened between mothers with African ancestry and fathers with European ancestry.

The African groups studied by the research team represent just a few of the ten ethnicities mentioned most often in slave trade records. Future studies might examine other relevant populations from Sierra Leone, Senegal, Guinea Bissau, and Angola, providing further insights into the genetic ancestry of African Americans.

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Colorectal cancer is the third most commonly diagnosed cancer in the U.S., and the third leading cause of cancer death.  In 2008 close to 50,000 people succumbed to the disease.

But not all groups are affected equally.  An American Cancer Society study found that colorectal cancer incidence rates are more than 20% higher for African Americans than Caucasians. Death rates from the disease are 45% higher.

Lifestyle factors, access to healthcare and cultural differences have all been proposed as reasons to explain the racial disparities in colorectal cancer survival. But new research from the University of Alabama, published today in the journal Clinical Cancer Research, shows that for some African Americans, genetics may play a part too.

Researchers analyzed 373 colorectal tumors – 137 taken from African Americans and 236 taken from non-Hispanic Caucasians.  They found that African American patients with two Gs at rs1042522 in the p53 gene were 2.15 times more likely to die of colorectal cancer than those with one or no copies of a G at this SNP.  In Caucasians there was no association between survival and rs1042522.

Seventeen percent of African American patients had two Gs, while only 7% of Caucasian patients did.

(23andMe customers can check their data for rs1042522 using the Browse Raw Data feature.)

The p53 gene encodes a tumor suppressor protein that protects against cancer, in part, by telling damaged cells to self-destruct instead of turning into tumors.  Mutations in the p53 gene that disrupt its function are a common feature of many cancers. (These mutations are distinct from the rs1042522 variation.)

Although the findings will need to be replicated in larger studies, the study’s authors suggest that rs1042522 might be a race-specific prognostic marker for African American patients with colorectal cancers and that someday analysis of this SNP might aid in designing optimal treatment regimens.

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Because their ancestors often were slaves during the 18th and 19th centuries, and therefore usually lacked birth or death certificates, it is very difficult for African American genealogists to trace their ancestors further than a few generations. Even when they can trace their ancestry to the slavery era, it is virtually impossible to find exactly where their ancestors originated because slave ships did not keep passenger lists of the people they captured from Africa.

As a consequence, many have been turning to genetics as a tool to help trace their African ancestry. But how reliably can genetics trace a person’s ancestry back to a specific African location or ethnic group? Using genetics this way is quite complex; even the most advanced analysis can’t provide all the answers.

Relying on genetic data for genealogical purposes can be problematic, especially if your expectations are too great. For example, Henry Louis Gates, Jr., the Director of the W.E.B. Du Bois Institute for African and African American Research at Harvard, had his Y-chromosome genotyped by two different companies. The first told him that his ancestors likely traced back to Nubia or Egypt, while the second test more accurately placed his paternal ancestry in Europe. As an African American, Gates believes that the first company may have simply ‘told him what he wanted to hear’: that all of his ancestry traced back to Africa. But, as is often the case, one’s genetic ancestry can be more complex than meets the eye.

One problem is that genetic analyses predominantly trace deep ancestry. Because genetic information does not change significantly within one or two generations, genetics generally shows where a person’s ancestors lived thousands of years ago. This is hardly useful to genealogists who are looking for information about ancestors who lived only a few hundred years ago.

That isn’t to say we can’t learn anything useful about the deep ancestry of many African Americans – in fact, studies of genetic ancestry have yielded much information about prehistoric population movements across the continent. For example, there are clear genetic ‘footprints’ in modern Africans — and African Americans — indicating massive expansions of Bantu-speaking peoples from West Africa into the eastern and southern part of the continent over 4,000 years ago. This has helped archaeologists understand the extent to which not only the Bantu culture and language, but the people themselves, spread throughout the continent.

Most African Americans have the signature of this Bantu migration in their genes because they are descended from populations that were affected by it. But many, including Gates, have the genetic signature of another widespread group: Europeans. Indeed, European ancestry is not uncommon among African Americans, whose ancestors can include white slave owners who fathered children with their slaves. The use of genetic data can be useful in confirming anecdotal evidence of a non-African ancestor in an African American’s family tree.

Many African American genealogists want greater detail and resolution from their genetic information, even a link to a specific nation or tribe. But in many cases this is simply not possible. The population history of Africa – especially sub-Saharan Africa – is older and more genetically complex than that of any other region of the world. Homo sapiens evolved in East Africa more than 150,000 years ago, and has been living throughout Africa continuously since that time. There have been countless migrations, dispersals, and expansions of African peoples to all parts of the continent – in addition to the Bantu expansions. As a result, the genetic diversity of present-day Africans is incredibly complex.

In many cases, scientists are unable to associate a specific genetic classification with a specific tribe or ethnic group. There are of course a few exceptions – isolated hunter-gather groups like the !Kung of the Kalahari Desert and the Pygmies of the Central African Rainforest have lower levels of genetic diversity as a result of their relative isolation. But in West Africa, where the majority of slaves were captured, there is significant genetic diversity both within countries and within tribal or ethnic affiliations. The high level of diversity means that scientists have a difficult time pinpointing where a particular person’s genetic roots trace beyond a more general geographical region (i.e. West Africa). For example, the paternal haplogroup E3a, found in more than half of African American men, is just as common in Africa itself – and spread throughout the continent. So, for an African American male who’s paternal ancestry falls within the E3a haplogroup, it could be virtually impossible to narrow down the place of origin of his African ancestors.

Still, when traditional tools are unavailable or incomplete genetics can reveal useful genealogical information, whether a person’s roots trace back to Africa, Europe, or someplace else entirely.

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A gene variant found mainly in people with African ancestry increases the odds of HIV infection in African Americans exposed to the virus says a study published today. Once infection has set in, however, this same variant slows the progression of the disease, allowing people to live about two years longer.

The authors of the study, published today in Cell Host & Microbe, estimate that in Africa, this genetic variant may be responsible for 11% of the HIV burden.

In a cohort of close to 1,300 African Americans, He et al. found that those people who lacked a protein on their red blood cells called the Duffy antigen had 40% higher odds of being infected by HIV but were more likely to have a slower progression of their disease.

About 90% of sub-Saharan Africans, and close to 70% of African Americans, are “Duffy negative,” meaning they have two copies of a particular version of the Duffy antigen gene that prevents the protein from being made in red blood cells. Duffy negativity has previously been associated with resistance to one strain of malaria, Plasmodium vivax.

“After thousand of years of adaptation, this Duffy variant rose to high frequency because it helped protect against malaria,” said Matthew Dolan, one of the study’s authors. “Now, with another global pandemic on the scene, the same variant renders people more susceptible to HIV. It shows that complex interplay between historically important diseases and susceptibility in contemporary times.”

The slowing of disease progression seen in Duffy-negative HIV-positive individuals was comparable to that seen in Europeans who carry a genetic variant called “CCR5Delta32”. Two copies of CCR5Delta32 render people resistant to the most common strain of HIV, while having just one copy is associated slowed disease progression.

(23andMe customers can see their data for the Duffy antigen, CCR5Delta32, and other SNPs mentioned here at the end of this post.)

The authors of the current study speculate that the seemingly contradictory effect of the Duffy antigen on HIV – lacking the protein promotes infection but slows disease — are due to complex interactions between the Duffy antigen and chemicals called chemokines that bind to it and the HIV virus itself. They propose a model in which being Duffy-positive results in increased anti-HIV chemokines in the bloodstream, which helps fight off an HIV infection. But in the event the virus does get a foothold, the increased chemokines actually facilitate disease progression by increasing inflammation, and the Duffy antigen ends up being a liability by providing a binding site for the HIV virus.

“The parts of a car that get it into gear are separate from those that get it moving once in gear,” said Sunil Ahuja, senior author of the paper. “ A similar analogy applies to HIV; the factors that influence its transmission are not necessarily the same as those that influence disease progression.”

The results of the current study not only suggest that Duffy-negativity might be an important part of the picture when considering the global HIV pandemic; they also help explain previous studies, which showed genetic variants that increase the levels of two chemokines in particular – CCL2 and CCL5 – were associated with faster disease progression in European Americans.

The authors of the current study found that those other variants also accelerate disease progression among African Americans – but only among those who are Duffy positive. Among the majority of African Americans who are Duffy negative, the genes affecting CCL2 and CCL5 appear to make little difference. In their conclusion, the researchers point out that these results demonstrate the importance of understanding the interactions between genes that affect disease susceptibility.

If you are a 23andMe customer, you can use the links and tables below to check your data for each of the SNPs mentioned in this post.

Duffy Antigen

(this is the same SNP used in the 23andMe My Gene Journal (now called Health and Traits) article on Malaria Resistance)
rs2814778

CCR5Delta32
23andMe custom SNP i3003626

CCL2
rs1024611

CCL5
rs2107538

My Gene Journal (now called Health and Traits) also has articles about Duffy antigen and CCR5Delta 32 [Malaria Resistance (Duffy antigen) and HIV/AIDS Infection, respectively].

If you’re really interested, here are links to the original CCL2 and CCL5 studies that found that the SNPs detailed above increased the levels of these chemokines and the rate of disease progression in HIV infected European Americans.

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