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Five years ago, Alice Collins Plebuch made a decision that would alter her future or really, her past.

She sent away for a "just-for-fun DNA test." When the tube arrived, she spit and spit until she filled it up to the line, and then sent it off in the mail. She wanted to know what she was made of.

Plebuch, now 69, already had a rough idea of what she would find. Her parents, both deceased, were Irish-American Catholics who raised her and her six siblings with church Sundays and ethnic pride. But Plebuch, who had a long-standing interest in science and DNA, wanted to know more about her dad's side of the family. The son of Irish immigrants, Jim Collins had been raised in an orphanage from a young age, and his extended family tree was murky.

After a few weeks during which her saliva was analyzed, she got an email in the summer of 2012 with a link to her results. The report was confounding.

About half of Plebuch's DNA results presented the mixed British Isles bloodline she expected. The other half picked up an unexpected combination of European Jewish, Middle Eastern and Eastern European. Surely someone in the lab had messed up. It was the early days of direct-to-consumer DNA testing, and Ancestry.com's test was new. She wrote the company a nasty letter informing them they'd made a mistake.

But she talked to her sister, and they agreed she should test again. If the information Plebuch was seeing on her computer screen was correct, it posed a fundamental mystery about her very identity. It meant one of her parents wasn't who he or she was supposed to be and, by extension, neither was she.

Eventually, Plebuch would write to Ancestry again. You guys were right, she'd say. I was wrong.

We are only just beginning to grapple with what it means to cheaply and easily uncover our genetic heritage.

Over the past five years, as the price of DNA testing kits has dropped and their quality has improved, the phenomenon of "recreational genomics" has taken off. According to the International Society of Genetic Genealogy, nearly 8 million people worldwide, but mostly in the United States, have tested their DNA through kits, typically costing $99 or less, from such companies as 23andMe, Ancestry.com and Family Tree DNA.

The most popular DNA-deciphering approach, autosomal DNA testing, looks at genetic material inherited from both parents and can be used to connect customers to others in a database who share that material. The results can let you see exactly what stuff you're made from as well as offer the opportunity to find previously unknown relatives.

For adoptees, many of whom can't access information about their birthparents because of closed adoption laws, DNA testing can let them bypass years, even decades, of conventional research to find "DNA cousins" who may very well lead them to their families.

But DNA testing can also yield uncomfortable surprises. Some testers, looking for a little more information about a grandparent's origins, or to confirm a family legend about Native American heritage, may not be prepared for results that disrupt their sense of identity. Often, that means finding out their dad is not actually their dad, or discovering a relative that they never knew existed perhaps a baby conceived out of wedlock or given up for adoption.

In 2014, 23andMe estimated that 7,000 users of its service had discovered unexpected paternity or previously unknown siblings a relatively small fraction of overall users. The company no longer provides data on surprise results. However, its customer base has more than doubled since 2014, and now contains more than 2 million people and as more people get involved with recreational genomics, bloodline surprises are certain to become a more common experience. The 2020s may turn out to be the decade that killed family secrets, for better and for worse.

"We see it every day," says CeCe Moore, a genetic genealogist and consultant for the PBS series "Finding Your Roots." She runs a 54,000-person Facebook group, DNA Detectives, that helps people unravel their genetic ancestries. "You find out that a lot of things are not as they seem, and a lot of families are much more complex than you assume."

Alice Plebuch found herself in this place in the summer of 2012. To solve the mystery of her identity, she needed more help than any DNA testing company could offer. After all, genetic testing gives you the what, but not the why.

Plebuch would turn out to be uniquely suited to the role of private eye in her own detective story. Now living in the suburbs of Vancouver, Washington, she worked as an IT manager for the University of California before her retirement. "I did data processing most of my life, and at a fairly sophisticated level," she says. Computers do not intimidate her, and neither do big questions that require the organization and analysis of complex information. She likes to find patterns hidden in the chaos.

Just the skills necessary to solve a very old puzzle.

After the initial shock of her test results, Plebuch wondered if her mother might have had an affair. Or her grandmother, perhaps? So, she and her sister, Gerry Collins Wiggins, both ordered kits from DNA testing company 23andMe.

The affair scenario seemed unlikely certainly out of character for her mom, and besides, all seven Collins children had their father's hooded eyes. But she couldn't dismiss it. "My father, he was in the Army and he was all over the world, and it was just one of those fears that you have when you don't know," she says.

As they waited for their results, they wondered. If the Ancestry.com findings were right, it meant one of Plebuch's parents was at least partly Jewish. But which one?

They had a gut sense that it was unlikely to be their mother, who came from a large family, filled with cousins Plebuch and her siblings all knew well. Dad, who died in 1999, seemed the likelier candidate. Born in the Bronx, Jim Collins was a baby when his mother died. His longshoreman father, John Collins, was unable to care for his three children and sent them to live in orphanages. He died while Jim was still a child, and Jim had only limited contact with his extended family as an adult.

But still, the notion Jim could somehow be Jewish seemed far-fetched. His parents had come to the United States from Ireland, and that history was central to Jim's sense of himself. "He was raised in an orphanage; he didn't have anything else," Plebuch says. "He had his Irish identity."

She plunged into online genealogy forums, researching how other people had traced their DNA and educating herself about the science. She and her sister came up with a plan: They would persuade two of their first cousins to get tested their mother's nephew and their father's nephew. If one of those cousins was partly Jewish, they'd know for sure which side of the family was contributing the mysterious heritage.

The men agreed. The sisters sent their kits and waited.

Then Plebuch's own 23andMe results came back. They seemed consistent with her earlier Ancestry.com test, indicating lots of Ashkenazi Jewish ancestry from areas such as Belarus, Russia, Ukraine and Lithuania. She also discovered that her brother Bill had recently taken a 23andMe test. His results were a relief sort of.

"No hanky-panky," as Plebuch puts it. They were full siblings, sharing about 50 percent of the relevant DNA, including the same mysterious Jewish ancestry. This knocked out another theory they had considered that Plebuch might have been adopted.

Plebuch found a feature on 23andMe's website showing what segments along her chromosomes were associated with Ashkenazi Jews. Flipping back and forth, comparing her DNA to her brother's, she had a sudden insight.

There was a key difference between the images, lurking in the sex chromosomes. Along the X chromosome were blue segments indicating where she had Jewish ancestry, which could theoretically have come from either parent because females inherit one X from each. But males inherit only one X, from their mothers, along with a Y chromosome from their fathers, and when Plebuch looked at her brother's results, "darned if Bill's X chromosome wasn't lily white." Clearly, their mother had contributed no Jewish ancestry to her son.

"That was when I knew that my father was the one," Plebuch says.

The next day, her sister Gerry Wiggins's results came back: She, too, was a full sibling who also displayed significant Jewish ancestry. Then, Plebuch got an email from a retired professor known for his skill at interpreting ancestry tests, to whom she'd sent hers. "What you are is 50 percent Jewish," he wrote. "This is in fact as solid as DNA gets, which in this case is very solid indeed."

But how could their father have been Jewish? Could Jim Collins's parents have been secret Irish Jews? Or maybe Jews from Eastern Europe who passed themselves off as Irish when they came to the country as immigrants?

Now they really needed the data from the cousin on their father's side. If he also had Jewish ancestry, Plebuch figured, that could point to a family secret buried in Europe.

They waited for months, through a series of setbacks problems in the lab, problems with the mail. Meanwhile, the sisters emailed back and forth.

Plebuch asked her younger sister: Did this revelation about their father's ethnicity unnerve her? They'd been so certain of their family roots, and "now we know nothing," she wrote.

"It is the first thing I think about when I wake up in the morning," Wiggins replied, "and the last thing I think about as I drift off to sleep."

At last, Plebuch was alerted that her cousins' results were ready. The data from their mom's nephew revealed that he was a full first cousin, as expected sharing about 12.5 percent of his DNA with Plebuch.

But the results from her dad's nephew, Pete Nolan, whose mother was Jim Collins' sister, revealed him to be a total stranger, genetically speaking. No overlap whatsoever with Plebuch or, by extension, with her father.

In other words, Plebuch's cousin wasn't actually her cousin.

And her dad's sister wasn't actually his sister.

Plebuch was devastated. This finding knocked out the secret-Jews theory but if it put Plebuch closer to the truth, she still felt unmoored. She was deeply fond of Nolan, with whom she shared a birthday. "I was afraid he was going to reject me because we were no longer biological cousins."

She called Nolan to share the results of his DNA test. "He was sad," Plebuch says, "but he also told me I was the best cousin he ever had."

Plebuch and Wiggins came to the stunned conclusion that their dad was somehow not related to his own parents. John and Katie Collins were Irish Catholics, and their son was Jewish.

"I really lost all my identity," Plebuch says. "I felt adrift. I didn't know who I was you know, who I really was."

For Wiggins, the revelation confirmed a long, lingering sense that something was amiss with her father's story. Studying the family photographs on her wall, she'd thought for years that their paternal grandfather looked like no one in her immediate family. Visiting Ireland in 1990, she had searched the faces for any resemblance to her 5-foot-4, dark-haired father. "There was nobody that looked like my dad," Wiggins says.

The sisters set about methodically pursuing several theories. With Jim Collins and his parents long dead, Plebuch knew she needed to unravel his story through the living. She signed up to take a class in Seattle on how to use DNA to find her father's relatives.

If the woman Jim called his sister was not his sister, was there evidence of an actual sibling out there somewhere? Might that sibling have children? Might Plebuch and her siblings have first cousins they'd never known about?

---

The dystopian novelistMargaret Atwood is fond of saying that all new technologies have a good side, a bad side, and a "stupid side you hadn't considered." Doing DNA testing for fun can carry consequences few of us might anticipate. It requires little investment at the outset, but it has the potential to utterly change our lives.

After researching her family history, Laurie Pratt decided five years ago to enhance her genealogical knowledge by testing herself and her parents. This was how she discovered that her dad was not related to her.

Pratt, 52, an airline ground operations supervisor in Orange County, California, went to her mother, who at first said the results were "impossible." But over time, her mother divulged hazy memories of a short-lived relationship during a period when she and her husband were briefly separated.

Her mother couldn't recall a name before she died. The man who raised Pratt also died; she never told him he was not, biologically speaking, her father.

She searched over several years, eventually identifying a potential candidate within the family tree of previously unknown cousins she found through DNA matching. She sent this man a letter and days later, in February of this year, he suddenly popped up in the Ancestry.com database, identified by a saliva test as her biological father.

The man called her, and they spoke briefly on the phone. Though he was unmarried when Pratt was conceived, he fretted over the idea that he had abandoned a baby without knowing it. Pratt asked if they could meet, and the man agreed, but asked if he could take some time first to process the news and tell his wife and daughter.

Two days later, Pratt logged onto Ancestry.com and discovered that the man's test had been deleted.

Reactions to DNA testing surprises vary dramatically. Moore, the genetic genealogist, says that, in her experience, even those who are initially dismayed end up glad that "they learned about the truth of themselves."

But seekers may be a self-selecting bunch, and those who find the truth thrust upon them by someone else's quest are not always happy about it. Gaye Sherman Tannenbaum, an adoptee who spent decades searching for her birthparents and now helps others on their quests, says in some instances, people are "outright hostile" when they learn of a newly discovered relative.

The reaction is understandable: DNA surprises often imply extramarital affairs, out-of-wedlock births and decades-old secrets.

Researchers from theUniversity of Leuven in Belgium recently examined the English-language websites of 43 direct-to-consumer DNA testing companies and found that few companies warn consumers about the possibility of discovering "misattributed paternity."

23andMe is unusual in offering multiple warnings. ("Unexpected relationships may be identified that could affect you and your family.") "We are as transparent as possible," says Kate Black, the privacy officer for 23andMe, brought on in 2015after the company was criticized for failing to prepare consumers for such surprises. "We try to educate and inform people in every tool."

Still, consumers may skim those warnings, or refuse to believe such surprises might lurk within their own families. Jennifer Utley, the director of research at Ancestry.com, says that even though she had seen many cases of surprise relatives in her work, she still found herself in "complete shock" when she tested her own DNA and discovered a first cousin she hadn't known existed.

"I had no idea who this person was," says Utley, who has since learned that her cousin was the product of a teenage relationship, raised by an adoptive family. Of her family, she now concludes: "We're the best secret-keepers on the planet."

Pratt says she doesn't regret testing her DNA. She found herself both "devastated and curious" after the initial discovery about her genetic heritage. But, of course, that discovery was not hers alone, because her genes are not hers alone. Cases of unexpected paternity and secret adoptions implicate other people.

"I think this jars him," she says of her biological father. "He goes to bed the good guy he's always been very religious, very Catholic. And he wakes up, he's Mick Jagger. He has a baby. It blew his mind a little bit."

In late April, Pratt sent the man another letter. She had "no desire to push myself into your family," she wrote, nor make a financial claim. What she sought were stories about him and his family, to help her build a sense of where she came from. Just one meeting, a few hours, was all she asked.

She still hasn't heard back.

By early 2013, the Collins children were hot on the trail of a hundred-year-old mystery.

They had their father's birth certificate, indicating that he'd been born on Sept. 23, 1913. They wrote to his orphanage and learned that their dad had been sent there by the New York Society for the Prevention of Cruelty to Children.

Plebuch wondered if Jim Collins, just a baby at the time, had somehow been confused with another child when he was taken from his father's home.

She found a forensic artist said to be skilled in understanding how faces change over time. She sent her a picture of her dad sitting on his father's lap when he was about 11 months, along with photos of him as an adult. Were these of the same person?

Probably, the forensic artist ruled. The ears hadn't changed, and the mouth, chin and facial proportions seemed the same.

If the mystery of their father didn't begin with his parents' life in Ireland, nor with his own time in the orphanage, Plebuch and her sister concluded it must have happened shortly after Jim was born. Unusually for the era, his mother gave birth not at home but at Fordham Hospital in the Bronx.

Could something have happened there?

Wurts Bros./Museum of the City of New York

By this time, the sisters were using techniques developed by Moore and others to help adoptees try to find relatives in a vast universe of strangers' spit. Every time a site like 23andMe informed them of what Plebuch calls a "DNA cousin" on their Jewish side someone whose results suggested a likely cousin relationship they would ask to see that person's genome. If the person agreed, the site would reveal any places where their chromosomes overlapped.

The idea, Plebuch explains, was to find patterns in the data. A group of people who share segments on the same chromosome probably share a common ancestor. If Plebuch could find a group of relatives who all shared the same segment, she might be able to use that along with their family trees, family surnames, and ancestors' home towns in the old country to trace a path into her father's biological family.

The work was slow and painstaking, complicated by the fact that Ashkenazi Jews frequently marry within the group and often are related in multiple ways. This can make distant relatives look like a closer match than they actually are. But the sisters forged on, sending at least 1,000 requests for genome-sharing to DNA cousins through 23andMe. It became Plebuch's full-time job.

Some ignored their overtures, while others were drawn in by the saga and devoted their own efforts to helping the sisters untangle it. It was as if the Collins sisters had plugged into a larger family, a web of strangers who wanted to help because generations before, their ancestors had shared soup, shared heartache, slept in the same bed.

One DNA cousin made a clever suggestion: Why not search for evidence of a baby born around the same time under a common Jewish surname, Cohen? He reasoned that the nurses, perhaps relying on an alphabetical system, might have confused a Collins baby with a Cohen baby. CeCe Moore was by now volunteering to advise Plebuch, and with additional help from Tannenbaum and the New York City Birth Index of 1913, Plebuch found a Seymour Cohen born in the Bronx on Sept. 23. DNA cousins fanned out on the Internet, tracking down a descendant of Seymour's sister.

Plebuch wrote to the woman, a professor in North Carolina, and offered to pay for her test kit if she'd contribute something completely free and absolutely priceless: her saliva. The woman agreed.

Weeks later, the results came back. No relation.

After that red herring, Plebuch decided to dive deeper into the 1913 birth index, to find babies who were in the hospital at the same time as her father. It was no easy task: The list of children born in the Bronx in 1913 ran 159 pages, was not ordered by date, and didn't distinguish hospital births from home births. But she manage to isolate all the male children born on Sept. 23, as well as the day after and the day before. She further narrowed the list to names that sounded either Jewish or ethnically neutral 30 babies in all.

Her hope was that one of those babies would share a surname with one of the people that the DNA matching sites identified as a likely relative. So she searched methodically.

"Appel" nothing. "Bain" nothing. "Bamson" nothing.

It was another dead end.

The sisters went back to the chromosome segment matching, both at 23andMe and Family Tree DNA, where they had also uploaded their genetic data. They bought at least 21 DNA test kits for themselves, relatives and strangers suspected of being relations. Plebuch found she and her siblings matched to 6,912 likely DNA relatives, with 311,467 "segment matches" among them segments along the chromosomes that overlapped with those of the Collins children. Which is to say, 311,467 potential clues.

The data they had kept on spreadsheets quickly became overwhelming, so their brother Jim, a retired software and systems engineer who had worked on NASA supercomputers, designed an iPad app called DNAMatch to help them and other seekers keep their data straight.

Plebuch was determined, and unusually well suited to the task of solving a puzzle hidden in big data. She and Wiggins searched this way for two and a half years. But she was having no luck finding someone closely related to her father's biological family they simply weren't in the system.

Perhaps they didn't know about DNA testing, or couldn't afford it, or weren't interested.

All the sisters could do was keep working and waiting, hoping the DNA testing revolution would make its way to strangers who shared their blood.

---

Ultimately, the crack in the case came not through Plebuch's squad of helpful DNA cousins, but through a stranger with no genetic connection.

It was Jan. 18, 2015, a Sunday, and Plebuch was feeling down. She was writing an email to her cousin Pete Nolan the beloved relative it turned out she wasn't really related to to update him on her stalled search.

As administrator of his 23andMe account, she had permission to check the list of his DNA relatives yet rarely did so, since new relatives rarely showed up. But she decided to check it this day and this time, there was a new person. A stranger had just had her saliva processed, and she showed up as a close relative of Nolan.

Plebuch emailed the woman and asked if she would compare genomes with Nolan. The woman agreed, and Plebuch could see the segments where her cousin and the stranger overlapped. Plebuch thanked her, and asked if her results were what she expected.

"I was actually expecting to be much more Ashkenazi than I am," the woman wrote. Her name was Jessica Benson, a North Carolina resident who had taken the test on a whim, hoping to learn more about her Jewish ethnicity. Instead, she wrote, she had discovered "that I am actually Irish, which I had not expected at all."

Plebuch felt chills. She wrote back that her father had been born at Fordham Hospital on Sept. 23, 1913. Had anyone in the Benson family been born on that date?

Jessica replied. Her grandfather, Phillip Benson, might have been born around that date, she wrote.

Plebuch began to cry.

She started combing through her list of baby names from the 1913 Index. No "Benson" born that day in the Bronx. But then, well after midnight, she found it:

The New York City Birth Index had a "Philip Bamson," born Sept. 23 one of the names she had searched among her DNA cousins. This had to be Phillip Benson, his name misrecorded on his birth certificate.

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She thought she was Irish until a DNA test opened a 100-year-old mystery - Chicago Tribune

The Canaanites lived at the crossroads of the ancient world. They experienced wars, conquests and occupations for millennia, and as a result evolutionary geneticists expected that their DNA would become substantially mixed with incoming populations.

Astonishingly, new genetic analysis shows that scientists were wrong. According to a new study in the American Journal of Human Genetics, todays Lebanese share a whopping 93% of their DNA with the ancient Canaanites.

The study also found that the Bronze Age inhabitants of Sidon, a major Canaanite city-state in modern-day Lebanon, have the same genetic profile as people living 300 to 800 years earlier in present-day Jordan.

Later known as Phoenicians, the Canaanites have a murky past. Nearly all of their own records have been destroyed over the centuries, so their history has been mostly pieced together from archaeological records and the writings of other ancient peoples.

Archaeologists at the Sidon excavation site have been unearthing ancient Canaanite secrets for the last 19 years in the still-inhabited Lebanese port city. The team has uncovered 160 burials from the Canaanite period alone, said Claude Doumet-Serhal, director of the excavation. They have found people of all ages in these Canaanite burials, she said children were buried in jars and adults were placed in sand.

Claude Doumet-Serhal / The Sidon Excavation

An aerial view of the Sidon excavation site.

An aerial view of the Sidon excavation site. (Claude Doumet-Serhal / The Sidon Excavation)

Aided by new DNA sampling techniques, a team of evolutionary geneticists including Marc Haber and Chris Tyler-Smith from the Wellcome Trust Sanger Institute stepped in.

They sequenced the whole genomes of five individuals found in Sidon who lived about 3,700 years ago. The team then compared the genomes of these ancient Canaanites with those of 99 Lebanese people currently living in the country, along with the previously published genetic information from modern and ancient populations across Europe and Asia.

First, they investigated the genetic ancestry of the Canaanites themselves. They found that these Bronze Age inhabitants of Sidon shared about half their DNA with local Neolithic peoples and the other half with Chalcolithic Iranians. Interestingly, this genetic profile is nearly identical to the one evolutionary geneticist Iosif Lazaridis and his team found last year in Bronze Age villagers near Ain Ghazal in modern-day Jordan.

This suggests that Canaanite-related ancestry was spread across a wide region during the Bronze Age and was shared between urban societies on the coast and farming societies further inland. This evidence supports the idea that different Levantine cultural groups such as the Moabites, Israelites, and Phoenicians may have had a common genetic background, the authors said.

The researchers were also able to determine that the genetic mixing of the Levantine and Iranian peoples happened between 6,600 and 3,550 years ago, a range they would be able to narrow down with more ancient DNA samples from the region.

Claude Doumet-Serhal / The Sidon Excavation

The buried remains of a Canaanite adult whose DNA was sequenced in the study.

The buried remains of a Canaanite adult whose DNA was sequenced in the study. (Claude Doumet-Serhal / The Sidon Excavation)

Next, the team wanted to compare the Canaanite genome with the genetic makeup of the people who currently inhabit the ancient Canaanite cities. To do this, they collected DNA from 99 Lebanese people Druze, Muslim, and Christian alike.

As expected, they found some new additions to the modern Lebanese genome since the Bronze Age. About 7% of modern Lebanese DNA originates from eastern Steppe peoples found in what is now Russia, but wasnt represented in the Bronze Age Canaanites or their ancestors. What surprised the team was what was missing from their genetic data.

If you look at the history of Lebanon after the Bronze Age, especially it had a lot of conquests, Haber said. He and Tyler-Smith expected to see greater genetic contributions from multiple conquering peoples, and were surprised that as much as 93% of the Lebanese genome is shared with their Canaanite predecessors.

Though a 7% genetic influx from the Steppe seems very small, that number might be covering some hidden complexities, said Lazaridis, who worked on the Bronze Age Jordanian samples but was not involved in the new study.

Not much is known about the migrations of these eastern Steppe populations, he said. If the genomes of the incoming people were only half Steppe, for example, 14% of the Lebanese genome could have come from the new migrants.

Haber and Tyler-Smith said they want to explore this complexity further. Who were those eastern migrants? Where did they come from? And why did they migrate toward the Levant region? Haber asked. Analyzing more samples from different locations and periods could lead to an answer.

The team also wanted to know if the individuals from Sidon are more similar to modern-day Lebanese than to other modern Eurasian populations.

Despite small genetic variations between the three religious groups caused by preferential mating over time, the Lebanese genome is not widely varied. As a whole, the Lebanese people have more genetic overlap with the Canaanites from Sidon than do other modern Middle Eastern populations such as Jordanians, Syrians or Palestinians.

The difference is small, but its possible that the Lebanese population has remained more isolated over time from an influx of African DNA than other Levantine peoples, Lazaridis suggested.

Claude Doumet-Serhal - The Sidon Excavation

An archaeologist sorts pottery at the Sidon excavation site.

An archaeologist sorts pottery at the Sidon excavation site. (Claude Doumet-Serhal - The Sidon Excavation)

The findings have powerful cultural implications, Doumet-Serhal said. In a country struggling with the ramifications of war and a society fiercely divided along political and sectarian lines, religious groups have often looked to an uncertain history for their identities.

When Lebanon started in 1929, Doumet-Serhal said, the Christians said, We are Phoenician. The Muslims didnt accept that and they said, No, we are Arab.

But from this work comes a message of unity. We all belong to the same people, Doumet-Serhal said. We have always had a difficult past but we have a shared heritage we have to preserve.

mira.abed@latimes.com

Twitter: @mirakatherine

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The DNA of ancient Canaanites lives on in modern-day Lebanese, genetic analysis shows - Los Angeles Times

DNA is compressed in the nucleus in a disorderly way that allows flexibility in how genes are turned on and off, according to a study by scientists from the Salk Institute and University of California San Diego.

This discovery was made with a new imaging technology devised by Salk researchers led by Clodagh OShea and carried out by UCSD researchers led by Mark Ellisman.

Published in Science, the study is available at j.mp/salkdna. OShea is listed as senior author with Ellisman as collaborator. The first author was Horng Ou, a researcher in OSheas lab.

Understanding DNAs 3D structure is expected to yield a better understanding of how defects in that structure relate to senescence and diseases, according to a perspective piece published along with the study.

In the nucleus, DNA is bound to proteins called histones to make a complex called chromatin, which in turn forms chromosomes. The degree of compression is extreme. Stretched out to form a line, the DNA in a single cell would extend about two meters, or about 6 1/2 feet. It must all fit into a nucleus of about 10 millionths of a meter.

What that means is that not all your DNA is accessible, OShea said. So even though the same DNA sequence is in every cell in your body, its structure in any cell nucleus can be different, which determines whether those DNA sequences can be accessed and used.

The fundamental question then is, well what's the structure of DNA in the nucleus, she said.

Existing models envision DNA as being grouped in increasingly large fibers, one inside another. But determining whether these models are correct has been stymied by the lack of imaging technology that can visualize chromatin.

Electron microscopy, one of the common tools to visualize such minute structures, doesnt work well with chromatin, OShea said. Thats because the chemical elements in chromatin dont provide sufficient contrast.

The Salk team solved that problem by using a fluorescent dye to stain the chromatin. When the dye was illuminated, it caused a metal to coat the DNA and associated proteins so they can be more easily detected by electron microscopy. They call this method ChromEMT.

The dye was already known, but it was the Salk teams idea to use it for imaging chromatin. The actual imaging, called "multi-tilt electron tomography" was performed by colleagues at University of California San Diego.

They found that chromatin is packed in clusters of various densities. The denser clusters are not as accessible as the looser cluster, OShea said. This provides a mechanism for allowing selective access to genes.

Previous hierarchy-based models didnt fit the experimental evidence of gene activation and suppression, OShea said. These models suggested that access would be allowed or denied at predictable, periodic intervals. The trouble with that is that one error would cause the whole intricate structure to fail.

By allowing DNA to be compressed into many separate clusters, with no grand structure, gene regulation can be take place independently. Moreover, a defect in one cluster wouldnt affect other clusters.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Salk Institute, UCSD scientists decode DNA's 3D shape - The San ... - The San Diego Union-Tribune