In our last post we highlighted a few of the coolest (in our opinion!) health-related developments of 2009.  But human genetics isn’t all about disease.  Here are a few more favorites:

The Romanovs

2009 saw the identification of the remains of the missing members of this Russian royal family, as well as identification of the mutation that caused the hemophilia that plagued their youngest son.

Leaving No Stone Unturned: DNA Analysis Confirms Identities of Missing Romanovs

Researchers Discover the True Identity of the “Royal Disease”

The Celtic Fringe

The genetics of adorable little critters helped scientists understand the prehistory of the British Isles.

Life on the Fringe: Shrews and Voles Reveal Clues to British Prehistory

Link Between Australian Aborigines and India

Scientists discovered mitochondrial DNA markers shared by isolated tribes in India and native Australians…and nobody else.

Direct Genetic Link between Australia and India Provides New Insight into the Origins of Australian Aborigines

Largest Ever Study of Modern African Genetics

2,432 DNA samples from 113 diverse and distinct groups of people from across the African continent as well as 60 non-African groups. Everyone from the Mozabite Berbers of Morocco to the hunter-gatherer San of the Kalahari Desert, and many in between.

Scientists Publish Largest-Ever Study on the Genetics of Modern Africans

Dogs

We can’t forget all those dog genetics studies.  Man’s best friend is certainly a friend of the Spittoon’s!

Single Gene Responsible For Stubby Legs In Dogs

Whence Rover? Genetic Study Suggests Africa May Have Whelped Man’s Best Friend

Study Sniffs Out Genes Behind Doggy ‘Dos

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Some people want to know everything their genetics can tell them, while others are interested in only part of the story.  That’s why starting next week, on Thursday November 19^th , we will begin offering our service as two distinct products to better meet the needs of our customers:  The 23andMe Ancestry Edition and The 23andMe Health Edition.  If you are interested in both the ancestry and the health aspects of your genetics, you’ll have the option of purchasing the combined 23andMe Complete Edition.

Prices for all versions of the 23andMe Editions will be changing November 19^th, but if you act quickly you can get our Personal Genome Service, which will automatically be converted to the Complete Edition, for the lower price of $399.

23andMe Ancestry Edition – $399

23andMe has always offered the most comprehensive look at your DNA ancestry.  With the 23andMe Ancestry Edition we will continue to provide maternal, paternal and autosomal ancestry information, but we’ll also be adding an exciting new feature: Relative Finder.  This innovative tool will allow you to grow your family tree like never before, and discover relatives you never knew you had.

The Relative Finder algorithm compares your SNPs to those of other 23andMe customers.  Using the frequency and length of shared DNA segments, we calculate whether there is a possible relationship between two people. What you’ll see is a list of these potential relatives (with their identity and yours kept anonymous) who you can then directly and anonymously contact.  Some of our early testers have already found new relatives and identified the great-great-great-great-great grandparent that they have in common!

To complement Relative Finder we’ll also be launching a new ancestry lab feature, Family Inheritance: Advanced.  This tool will allow you to look at your Relative Finder matches in more detail and trace segments of DNA across multiple generations.

Raw data browsing and download will be available only for Y and mitochondrial SNPs for customers who purchase the 23andMe Ancestry Edition.

23andMe Health Edition – $429

With 23andMe, you can use your DNA to help you plan for the important things in life.  We give you access to information on genetic variations and mutations that may influence your risk for various conditions, report carrier status for inherited diseases, or affect how you react to certain medications.

With the launch of the 23andMe Health Edition we are releasing 13 new carrier status reports.   These reports will help you know more about what may be in store for the next generation.  We are expanding our cystic fibrosis panel report to cover the full panel of mutations recommended by the American College of Medical Genetics, as well as several additional mutations.  We will also be providing data for most of the mutations routinely screened for in the Ashkenazi Jewish population, including those associated with Tay-Sachs disease, Canavan disease and Bloom’s syndrome.

We are also continuing to expand our drug response offerings.  The next report to come out, Pseudocholinesterase Deficiency, contains information for anyone who will be undergoing surgery.

23andMe’s scientists are constantly sifting through the scientific literature, adding to existing articles and creating new reports as genetic research advances.  Customers who purchase the Health Edition will have access to these regular updates.

Raw data access will not be available to customers who purchase the 23andMe Health Edition.

23andMe Complete Edition – $499

If you’re interested in seeing all your DNA has to offer, you can purchase the 23andMe Complete Edition.  You’ll get all the features of both the Health and Ancestry Editions, along with the ability to browse and download all of your genetic information.  This means you’ll be able to see what your data means in the context of the latest in genetic research through our regular SNPwatch posts here in The Spittoon.

Start with Health or Ancestry, Upgrade Later

You can always buy one version, either the Health or Ancestry Edition, and upgrade to the Complete Edition at a later date.  You won’t even need to spit again!

Upgrading from the Health Edition will cost $100.  Upgrading from the Ancestry Edition will cost $150.

Buy Now Before the Price Goes Up!

If you are a current customer, your account will be converted to the Complete Edition automatically.  Customers who purchase 23andMe’s Personal Genome Service before November 19^th for the current price of $399 will also automatically have their accounts converted to the 23andMe Complete Edition after that date — a savings of $100.  If you purchase now, you can also save $25 on each kit you buy when you buy two or more at full price.

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We may be another step closer to discovering what makes us human.

A new study published online this week in Genome Research has pinpointed three genes in humans that may genetically differentiate us from chimps and other primates. Genetically we are very similar to chimps, so most of the differences researchers have observed to date regard physical appearance and behaviors.

The new study found several genes that were once silent and nonfunctional in our primate ancestors, and seem to have awakened around the time that humans formed a new evolutionary branch.

Researchers at the University of Dublin compared sections of the human genome with those of chimps and other primates to find active genes that are absent from the chimp genome. They found three human genes, CLLU1, C22orf45 and DNAHI0OS, that were present but inactive in non-human primates.

At the location of each of the three human genes, a disabling sequence of DNA was found in the genomes of the chimp, macaque, gorilla, gibbon and partially in the orangutan. The study suggests that the awakened human genes not only shed their disabling components, but gained “enabling” sequences that helped them do the work of forming proteins in the body.

Previous research found that genes arising from inactive DNA were present in flies and yeast. The study suggests there may be a total of 18 awakened genes in humans, but researchers were limited to analyzing only a part of the 24,000-gene human genome.

The functions of these novel genes are not yet known, but it is tempting to infer that these genes, specific to humans, are responsible for the attributes that differentiate us from other primates.

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When scientific research is published, the authors often confess that they wish they’d collected more data. Critical reviews of research studies often say the same thing. Indeed, if there’s anything scientists love, it’s more data.

Which is why the members of an international team of genetic anthropologists led by Sarah Tishkoff of the University of Pennsylvania are probably quite pleased with themselves. In a new study published this week in Science, the team took the concept of “more is more” to heart by collecting and analyzing the DNA of thousands of people, mostly from Africa, so that they might uncover more clues to not only the genetic make-up of modern Africans, but also the genetic history of Africans and non-Africans alike.

The scientists’ first step was to collect DNA from a diverse set of Africans. Africa is the most culturally and linguistically diverse place on Earth, so it was important to take a wide sample of individuals from all corners of the continent. In total, they collected 2,432 DNA samples from 113 diverse and distinct groups of people from across the African continent as well as 60 non-African groups. They sampled everyone from the Mozabite Berbers of Morocco to the hunter-gatherer San of the Kalahari Desert, and many in between.

But the hard work didn’t stop there. The scientists then examined 1,327 genetic markers across the human genome for each individual studied. While many studies focus on a particular part of the genome such the mitochondrial DNA or the Y chromosome, this study took a comprehensive approach. Finally, the researchers used sophisticated statistical techniques, piecing together how these populations from Africa and around the world were the same, and how they were different.

The results confirmed that Africa has the highest genetic diversity of any continent, as many scientists have proposed. In fact, the authors found genetic diversity to decrease the further one traveled away from Africa. Genetic diversity is often used as a measure of how long ago humans inhabited a region — conventional wisdom places the earliest humans in East Africa, which had exceptionally high genetic diversity according to this study, though an analysis by the researchers put the origin of the human expansion farther south near the border of Namibia and Angola.

The study also shed light on the incredible genetic diversity among African populations, said Roy King, a professor of psychiatry and anthropological geneticist from Stanford University:

Not only did farming and pastoral communities differ from hunter-gatherers, but within the broad range of agricultural populations of West and West-Central Africa — from which many African Americans derive their ancestry — the authors also found some genetic diversity. For example, the Dogon of Mali, although geographically near the Mandinka of Senegal, cluster with North African Berber populations. Thus, this study supports the notion that not only is Africa varied in culture — art, music, religion and language — but also harbors a rich genetic diversity across its multitude of ethnic groups.

The authors also found a loose connection between the genetics of a population and its language. However, there were a few exceptions, most often the result of a population adopting a new language within the last few thousand years.

The sheer size and diversity of the DNA samples collected allowed the researchers to construct a human family tree based on their analyses. Not unexpectedly, the tree they constructed fits well with current theories on the genetic relationship between Africans and non-Africans; namely that all non-Africans are descended from a particular group or groups of people who were the first humans to migrate out of Africa tens of thousands of years ago.

This study is important for a multitude of reasons. It has been able to confirm theories from the archaeological, cultural, and linguistic records on the origins and movements of Africans and non-Africans.

“It fits nicely with earlier genetic studies, while subverting the early 20th century colonialist idea of sub-Saharan Africa as constituting a homogeneous genetic an cultural unit,” King said.

It also creates a new resource that historians, linguists, archaeologists and scientists from a range of other disciplines can use in their own work. If we are lucky, this study will bring forth a flurry of activity surrounding the origins and history of the African continent, and the people who live there.

Credit: istockphoto/Erie

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Every family has its legends. Maybe it’s a story about how they’re descended from a passenger on the Mayflower, a Confederate soldier or Charlemagne.

Of all the classic American family legends, stories of a Native American ancestor are among of the most common. Many times there’s a well-documented link to a Native forbear: Two First Ladies (Edith Wilson and Nancy Reagan) and one Duchess of Windsor (Wallis Simpson) are proven descendants of Pocahontas.

Other times, the evidence amounts to little more than vague tales about a rugged pioneer and a Cherokee princess. (Learn what’s wrong with that scenario here.)

Now 23andMe customers who are curious about whether they may have Native American ancestors can look for evidence of it in their genes. The Native American Ancestry Finder uses some existing 23andMe features — Ancestry Painting, Maternal Line and Paternal Line — to look for genetic signatures that are likely to have come from a Native American ancestor.

The Maternal Line and Paternal Line elements of the Finder are pretty straightforward; certain mitochondrial DNA (maternal) and Y chromosome (paternal) haplogroups are often found among Native Americans. These include mitochondrial haplogroups A2, B2, C1, D1 and X2a — which are found exclusively among Native Americans. People in some other branches of the A, B, C and D haplogroups may also have Native American ancestry, but their maternal lines could also trace to Asia. On the paternal side, only Q3 is exclusive to Native Americans, though anyone with a Y chromosome in the C, C3 or Q haplogroup could conceivably have Native American forbears.

A Native American’s Ancestry Painting.

The part of the Finder that uses Ancestry Painting to find evidence for Native American forbears is a little more complicated. It relies on the fact that people of full Native American descent have Ancestry Paintings that are consistently about 75% orange (Asian) and 25% blue (European). This is due to the fact that Native Americans are ultimately descended from populations that lived in northern and central Asia about 15,000 to 20,000 years ago, and the fact that those regions are intermediate between the reference populations that Ancestry Painting classifies as fully Asian (Japanese and Chinese) and fully European (European-Americans living in Utah).

Then the Finder compares your Ancestry Painting proportions to a table that contains the results of an extensive series of simulations that we performed to determine what would happen to that three-to-one Asian/European proportion over the generations if a Native American and a partner of all-European descent had a child who then reproduced with another all-European partner, and so on. We did the same analysis for a Native American marrying into an all-Asian pedigree. Unfortunately, partly due to inadequate sampling of Africa’s genetic diversity, this method cannot yet establish Native American ancestry for African Americans.

We found that it takes at least five generations after the appearance of a single Native American in an otherwise all- European pedigree for the percentage of Asian (orange) DNA to reach zero. In an otherwise all-Asian pedigree that process is much faster — in two generations, the grandchild of that single Native American can have no trace of European in his or her Ancestry Painting.

There are, of course, plenty of Eurasian populations that also have blue-and-orange Ancestry Paintings. So the Native American Ancestry Finder performs a second analysis that can distinguish people of South Asian, Central Asian, Middle Eastern and Ashkenazi descent from those with Native American ancestry. Unfortunately, there is still some uncertainty when it comes to distinguishing people with Native American ancestry.

It’s still a work in progress — that’s what Labs are all about. But we hope customers will help us by trying out the Native American Ancestry Finder and letting us know if anything doesn’t mesh with what they know about their genealogy. You can also contribute by taking the “Where Are You From?” survey in 23andWe.

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The 23andMe Personal Genome Service™ offers information about customers’ maternal and paternal ancestry by examining their mitochondrial DNA (which we all inherit from our mothers) and the Y chromosome (which is passed by fathers to their sons).

Over our species’ history new genetic variations have arisen spontaneously in those pieces of DNA, and been passed down through the generations. So researchers know that every person alive today who has a particular variation — say a T instead of a G at a certain spot on the mtDNA — is descended from a single common ancestor. By sampling people from around the world, scientists have been able to assemble “family trees” that trace all the way back to the dawn of the human species in eastern Africa more than 100,000 years ago. Those trees are the basis of the haplogroup assignments we give our customers. Each haplogroup represents a particular branch — and therefore a unique sequence of SNPs.

Now you can see exactly which SNPs we use to generate the 23andMe mitochondrial and Y chromosome haplogroup trees, using a feature we’ve developed called the Haplogroup Tree Mutation Mapper. This isn’t the kind of information everyone would necessarily want, but a number of customers who are especially interested in genetic genealogy have requested it. It can be used to compare our haplogroup assignments to those obtained elsewhere, for example.

The Haplogroup Tree Mutation Mapper is the first arrival in 23andMe Labs, our new technology sandbox where we will showcase experimental features not currently available in our Personal Genome Service™.  These features may still be in development, require specialized knowledge or be of interest only to a subset of our customers. Each lab will have its own community so customers can compare notes, ask questions and share ideas.

Some labs will be requested by customers. In fact, we welcome your suggestions. Others will be dreamed up by our scientists.

Finally, you can expect labs to be a little less refined than what’s available within the Personal Genome Service, and somewhat fluid as well. A feature could be discontinued at any time, or it might be elevated to full integration with our Personal Genome Service.

We’re really excited about having this new outlet for our ingenuity, and we hope it will engage some of yours as well!

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Since 23andWe debuted in May, we’ve asked our customers about all sorts of things: their hair color, earwax consistency, whether they tend to look on life’s bright side. Sometimes people have been surprised to learn that something like your susceptibility to motion sickness — or even which way the hair swirls on top of your head — may be influenced by genetics.

Now we’re introducing three new surveys that ask our customers a few more thought-provoking questions that could help science understand more about genetics:

1. Our new ancestry survey, “Where are You From?” inquires about the birthplaces of our customers, their parents and grandparents. We’re hoping the survey can help us do an even better job of correlating peoples’ genetics to their ancestral homelands. It could also help us address questions geneticists have had little opportunity to ask in the past, such as how regional genetic differences within the United States may reflect the different ethnic backgrounds of the people who settled in the country. And finally, recent papers such as this one suggest that ancestry information can be vital to any study that tries to associate genes and traits.
2. Our second survey, “Health Habits,” asks about things like exercise, diet, smoking and drug use. It’s not that we want to determine whether there are genetic influences on whether a person smokes (though there probably are) so much as we’d like to know these things so we can see if they are more likely than genetics to account for the way people respond to certain surveys.
3. Researchers often struggle to distinguish between the contributions of nature and nurture when they study things like personality, IQ and athletic ability. Our final new survey — “What Do You Do?” — tries to account for some elements on the nurture side of the gene-environment equation.

These new surveys are a little different from some of the ones our customers have already taken. They’re not going to tell you if you’re less optimistic than average, or whether your tendency to sneeze in bright sunlight makes you a freak of nature (It doesn’t). But they’re just as critical to helping us reach our goal of advancing genetic research. So if you’re a 23andMe customer, we invite you to visit 23andWe and take our latest surveys. And if you haven’t joined the 23andMe community yet, we invite you to read more about 23andWe on our public site.

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People sometimes think of ancestry as the “fun” part of the 23andMe Personal Genome Service™, an intriguing glimpse at the past that is completely unrelated to our more serious Health and Traits features.

But a new paper shows how ancestry can actually reveal quite a bit about the genetics of disease. In the December issue of Cancer Research, Laura Fejerman of the University of California San Francisco and several colleagues show that among Latinas, a woman’s breast cancer risk increases with her proportion of European ancestry.

Most Latinos are descended from mix of Native American ancestors and European immigrants. In countries such as Brazil, where slavery was practiced until the late 19th century, many people have substantial African ancestry as well.

Fejerman and her colleagues used 106 ancestry informative markers (AIMs) to estimate the relative European and Native American ancestry of 440 Latina women from the San Francisco Bay area with breast cancer and 597 control subjects without the disease. With every 25 percent increase in European ancestry, the researchers found, a woman’s chances of having breast cancer rose 79 percent.

The finding is no surprise — Latinas have lower breast cancer rates compared to European women, as do Native Americans. But the study does demonstrate that ancestry and population history can be valuable tools for understanding the genetics of disease.

And researchers still have a lot more to learn about population differences in rates of breast cancer. Though environmental factors are known to play a role, the new study strongly suggests that genetics is worth investigating as well.

There’s also an intriguing puzzle in breast cancer mortality differences among different populations. Though Latinas, Native Americans and African Americans are less likely to develop the disease, when they do their chances of dying from it are greater. Researchers would like to know whether those differences are due to genetics, differences in access to health care, or other factors.

Image: Peruvian “casta” painting, late 18th c.

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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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The American Society for Human Genetics (ASHG) has released a statement outlining a set of recommendations for genetic ancestry testing.

At a press briefing on Thursday, members of the ASHG Ancestry Testing Task Force Committee discussed two main themes: the need for clear communication about the limitations of genetic ancestry testing, and the need for researchers and companies doing this type of testing to engage with the social sciences to put results in context.

Michael Bamshad of the University of Washington School of Medicine discussed at length the need for people to understand that ancestry assignments based on genetics are inherently uncertain and can be affected by several factors, including the reference populations used in the analysis, the type and number of genetic markers analyzed, and the statistical methods employed.

ASHG president Aravinda Chakravarti further emphasized that questions about the “accuracy” of genetic ancestry testing are aimed at the interpretation of the genetic data, not at the actual DNA analysis.

Task force co-chair Charmaine Royal of the Duke University Institute for Genome Sciences and Policy addressed the committee’s concerns about the psychological impacts of genetic ancestry testing, especially as related to issues of identity.

23andMe Senior Director of Research Dr. Joanna Mountain had a chance to talk with some of the members of the ASHG Ancestry Testing Task force about their statement.

“Members of the panel emphasized to me that their primary goal was to raise a set of concerns around identification of ancestry through genetics,” said Mountain.

“Because several of us at 23andMe were previously aware of these concerns, we developed our ancestry features with those concerns in mind. For instance, we consider a large number of markers for all the chromosomes of the human genome, including the mitochondrial genome. We also avoid being overly precise in reporting an individual’s ancestry. And we are currently creating educational tools to help our customers understand how genetic information can be informative about ancestry.”

The speakers stressed several times that their statement was not aimed just at consumer companies offering genetic ancestry testing, but also at academic researchers in the field.

Unfortunately, Mountain said, the ASHG guidelines leave out some of the potential benefits of ancestry genetic testing.

“For instance, ASHG President-Elect Ed McCabe encouraged the audience to ask their family elders about family history over Thanksgiving, as an alternative to learning about ancestry through genetics. But individuals who have signed up for 23andMe’s service may find themselves far more motivated to discuss family history than they would before seeing their genetic data.”

For a more thorough analysis from a genetic genealogist’s point of view, click here.

McCabe said the statement released this week is a preliminary document. The committee expects to issue a more detailed report in Spring 2009.

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