<img loading="lazy" decoding="async" class="alignright size-full wp-image-2958" title="cocainelabel" src="https://blog-api.23andme.com/wp-content/uploads/2009/03/cocainelabel.jpg" alt="" width="350" height="215" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/03/cocainelabel.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/03/cocainelabel-300x184.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Cocaine use, and its attendant dangers, cut across all regional, age, ethnic and socioeconomic lines. A 2002 survey revealed that almost six million Americans 12 and older used cocaine during the preceding year, with more than one million compulsively taking the drug and meeting the criteria for being deemed “dependent”.
Several studies have suggested that genes play a part in determining how a person will react to cocaine.   Identifying these genetic factors could help scientists understand why some people become dependent on the drug and might provide clues as how to best treat addiction. In a study published online this week in the <a href="http://archpsyc.ama-assn.org/cgi/content/short/66/3/267" target="_blank" rel="noopener">Archives of General Psychiatry</a>, researchers show that one piece of the genetic puzzle might be an unlikely candidate — a gene involved in quality control of proteins within cells.
“This finding…suggests that drug dependence and associated behaviors may involve biological pathways not typically associated with brain metabolism and opens a new pathway to understanding these highly prevalent disorders and their psychopathologic manifestations,” the author write.
Based on evidence from a <a href="https://www.ncbi.nlm.nih.gov/pubmed/18438686?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" target="_blank" rel="noopener">previous study</a> of substance abuse disorders that suggested that the MANEA gene plays a part in cocaine dependence, the researchers studied 11 genetic variations scattered throughout the gene in approximately 4,000 Americans of either European or African ancestry. The protein encoded by MANEA is involved in regulating how sugar molecules are attached to certain proteins, a process important for the proper function of many proteins.
Although the results varied somewhat between the study groups examined, and the evidence was stronger for a link between MANEA and cocaine-induced paranoia than it was for cocaine dependence in general, the researchers conclude that the gene is a good candidate for further research.   The strongest association across all groups studied was between cocaine-induced paranoia and the SNP .   Having the A version of this SNP increased odds of paranoia.
The authors say that additional studies, in both cocaine dependent people and perhaps in people with other disorders involving paranoia, will be necessary to determine whether the variations in the MANEA gene are specifically associated with cocaine-induced paranoia.
Even if variations in MANEA are confirmed to be associated with cocaine dependence and/or cocaine-induced paranoia, the question of why will still remain. The authors suggest that one possibility is that changes in the protein encoded by the MANEA gene could interfere with the sugar modifications on another protein, dopamine Î²-hydroxylase, which is involved in the conversion of dopamine to norepinephrine in the brain.   The dopamine pathway is a key target of cocaine, and abnormally low levels of dopamine Î²-hydroxylase have been associated with psychotic symptoms in several psychiatric disorders, including cocaine dependence.   Changes in the MANEA protein could also affect how cocaine is processed in the liver.

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Unlikely Gene May Contribute To Cocaine Dependence and Paranoia

<img loading="lazy" decoding="async" class="alignright size-full wp-image-2950" title="cutemouse" src="https://blog-api.23andme.com/wp-content/uploads/2009/03/cutemouse.jpg" alt="" width="350" height="184" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/03/cutemouse.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/03/cutemouse-300x158.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Our bodies need iron: to form the oxygen-carrying hemoglobin for our red blood cells, maintain our immune systems and keep our muscles and brains functioning properly.
But not too much.
<h6>Iron Build Up</h6>
Excess iron can build up in tissues like the liver, heart and pancreas, causing damage and possibly organ failure.
Other than blood loss, there’s no way for the human body to rid itself of excess iron.   The only way to regulate iron levels is by adjusting how much is taken in from food. Low iron levels in the body lead to more absorption in the gut, high iron leads to less.
There are several known genetic mutations that interrupt this iron absorption control mechanism, leading to a condition called hereditary hemochromatosis.   But there are some forms of this disease for which the causative mutation isn’t known, and not everyone with one of the known mutations actually ends up having hemochromatosis.   These observations suggest there are genetic factors affecting iron level control that have yet to be identified.
<h6>Iron Overload</h6>
Two reports published online yesterday by the journal <a href="https://dx.doi.org/10.1038/ng.335" target="_blank" rel="noopener noreferrer">Nature</a> <a href="https://dx.doi.org/10.1038/ng.320" target="_blank" rel="noopener noreferrer">Genetics</a> may have identified one of these additional genetic factors.   Researchers working with mice have found that disrupting the function of the BMP6 gene can lead to iron overload much like that seen in the severe childhood-onset forms of human hemochromatosis.
“Although no human patients with BMP6 mutations have yet been described, our data …suggests that BMP6 mutations or BMP6 gene variants may function as another cause of hereditary hemochromatosis or a modifier of disease penetrance,” write the authors of <a href="https://dx.doi.org/10.1038/ng.335" target="_blank" rel="noopener noreferrer">one of the studies</a>.
23andMe customers can learn whether they are carriers of the mutations that cause adult-onset hemochromatosis using the Health and Traits feature.

Mouse Research May Shed Light On Human Iron Disorder

<img loading="lazy" decoding="async" class="alignright size-full wp-image-2941" title="istock_000005831286xsmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/02/istock_000005831286xsmall.jpg" alt="" width="301" height="309" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/02/istock_000005831286xsmall.jpg 342w, https://blogcms.23andme.com/wp-content/uploads/2009/02/istock_000005831286xsmall-292x300.jpg 292w" sizes="auto, (max-width: 301px) 100vw, 301px" />
Each of us is made up of about 50 trillion cells, which is pretty mind-blowing until you consider the number of microbial cells living on or in each of us.   It’s estimated that a healthy adult is lugging around 10 times more bugs. Most of them are bacteria rather than human cells.
Just as the tiny differences we each harbor in our DNA can reveal information about our health and our ancestry. It might also reveal the subtle differences in the types of bacteria we all carry.
<h6>Human Microbiome</h6>
The NIH has initiated a large project to explore the so-called “human microbiome” and its implications for our health.   Other projects are using bacteria to trace ancient migrations and human interactions.
Today scientists published the first in-depth study of global diversity in a specific human microbiome — the mouth. There is wide variety around the world in dietary and other cultural factors that could influence the types of bacteria found in a person’s mouth. However, the researchers discovered that the an individual’s “salivary microbiome” is likely to be just as different from a neighbor’s as it is from someone on the other side of the world.
“[T]here is significantly more diversity in bacterial genera [types of bacteria] compared from different individuals than from the same individual,&#8221; the authors write. &#8220;[But] the diversity among individuals from the same location is nearly the same as the diversity among individuals from different locations.”
Their results appear online in <a href="https://genome.cshlp.org/content/early/2009/02/23/gr.084616.108" target="_blank" rel="noopener">Genome Research</a>.
<h6>Oral Bacteria</h6>
The researchers studied the oral bacteria of 120 people — 10 individuals from each of 12 worldwide locations: Oakland, CA; Baton Rouge, LA; La Paz, Bolivia; Buenos Aires, Argentina; Pointe Noire, Congo; Johannesburg, Sought Africa; Surigao, Philippines; Shanghai, China; Batumi, Georgia; Ankara, Turkey; Warsaw, Poland; and Dessau/Leipzig, Germany.
Overall, DNA analysis identified a total of 101 known types of bacteria. Thirty-nine of those had not previously been found in the human mouth.   The scientists also found evidence for another 64 unknown bacterial types lurking in people’s mouths.
Their results lay the groundwork for future studies that will explore the influence of environmental, dietary and genetic factors on the types of bacteria found in a person’s saliva.   This may lead to a better understanding of the role of saliva bacteria in mouth diseases. It can also shed light on the interaction of the salivary microbiome with other microbial environments in the body, such as the intestines.
Their work could also help expand the use of bacteria in the study of human history. The stomach bacteria H. pylori has already been used in several studies to investigate human history. Just last month a study using this bacteria revealed new information about <a href="https://blog.23andme.com/2009/01/22/thinking-outside-the-box-bacterial-genetics-and-the-peopling-of-the-pacific/" target="_blank" rel="noopener">how Polynesia was colonized</a>.   But while these H. pylori studies have been impressive, they do have a downside: a stomach biopsy is needed to get the samples.
“There would be obvious advantages if similarly-informative bacterial species could be identified in saliva,” the authors write, suggesting that their work might help identify just such a species.

The Mix of DNA in a Saliva Sample

<img loading="lazy" decoding="async" class="alignright size-full wp-image-2926" title="istock_000002352237xsmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/02/istock_000002352237xsmall.jpg" alt="" width="377" height="249" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/02/istock_000002352237xsmall.jpg 425w, https://blogcms.23andme.com/wp-content/uploads/2009/02/istock_000002352237xsmall-300x199.jpg 300w" sizes="auto, (max-width: 377px) 100vw, 377px" />
Genome wide association (GWA) studies of SNPs are helping scientists learn about the underlying biology of many complex diseases.
But even the most enthusiastic proponents of this relatively new type of research admit that many studies simply can’t find genetic variations that have real, but very small, effects.
<h6>Using Genetics to Study Crohn&#8217;s</h6>
This means information that might be useful for diagnosis, prevention or treatment of a disease is being left on the table. The 23andMe research initiative, <a href="https://www.23andme.com/research/" target="_blank" rel="noopener">23andWe</a>, is one way of addressing this problem.
Researchers from Children’s Hospital of Philadelphia have devised a different method.   Instead of focusing on individual SNPs, they are grouping SNPs together by gene pathway &#8212; collections of genes known to work together — and using sophisticated mathematics to identify those groups that appear to be related to disease status.
Using this approach, the researchers have identified the IL12/IL23 pathway &#8212; a collection of genes involved in regulating the immune system — as important in Crohn’s disease.
<h6>Study Published</h6>
Their results, published online today by the <a href="http://www.cell.com/AJHG/abstract/S0002-9297(09)00065-2" target="_blank" rel="noopener">American Journal of Human Genetics</a>, not only show the utility of their new method, but may point the way toward the development of new treatments for Crohn’s disease.
“Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies,” the authors write.
The researchers used data from four previous GWA studies for their analysis.   Three of the studies were done in people with European ancestry, and the fourth was a small study of African Americans.
“Despite the drastically different association results on the level of individual SNPs across studies, the [IL12/IL23] pathway was consistently picked up as being associated with CD [Crohn’s disease] in all four GWA studies, demonstrating the power and effectiveness of pathway association approach in identifying disease-susceptibility mechanisms,” the author’s write.
It is not completely surprising that the IL12/IL23 pathway was identified as being involved in Crohn’s disease in this study.   Several genes from the pathway have previously been linked to Crohn’s disease through GWA studies.
Treatments that inhibit the protein encoded by the IL12 gene can reduce symptoms in people with Crohn’s disease, in some cases putting them into complete remission.   The authors say that their analysis suggests that more members of this gene pathway — including genes that might never be picked up in a standard GWA study — could also be promising therapeutic targets for the disease.
23andMe customers can learn more in the Crohn’s Disease Clinical Report.

Understanding Crohn’s Disease

<img loading="lazy" decoding="async" width="350" height="260" class="alignright size-full wp-image-2914" title="lung_xray" src="https://blog-api.23andme.com/wp-content/uploads/2009/02/lung_xray.jpg" alt="" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/02/lung_xray.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/02/lung_xray-300x223.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
In the 1950s, a child born with <a href="http://www.23andme.com/topics/carrier/cystic-fibrosis/">cystic fibrosis</a> didn’t have much chance of making it to elementary school.   But now, thanks to a better understanding of the disease and improved treatments, people with cystic fibrosis live well into adulthood.
A person must inherit a mutated copy of the CFTR gene from each parent in order to develop cystic fibrosis.   Hundreds of disease-causing mutations have been documented, and the different mutations and combinations of mutations are known to lead to varying constellations of symptoms and degrees of disease severity.   But even in patients with the same combination of mutations there can be differences in how the disease manifests, suggesting that factors beyond CFTR — either environmental or genetic — are involved.
The results of a new study, published online today by the journal <a href="https://dx.doi.org/10.1038/nature07811" target="_blank" rel="noopener noreferrer">Nature</a>, identify a gene that appears to modulate the severity of obstructive lung disease, the major cause of morbidity and mortality in cystic fibrosis patients.   And paradoxically, although cystic fibrosis lung disease is largely the result of inflammation brought on by repeated bouts of infection, a variation that leads to reduced levels of lung disease seems to make certain immune cells known as neutrophils less effective at fighting infections.
“Neutrophils appear to be particularly bad actors in cystic fibrosis.   They are important to the immune system’s response to bacterial infection.   In cystic fibrosis, however, neutrophilic airway inflammation is dysregulated, eventually destroying the lung,” said the study’s senior author, Dr. Christopher Karp, director of Molecular Immunology at Cincinnati Children’s Hospital Medical Center, in a statement.
The researchers tested the DNA of more than 3,000 people with cystic fibrosis and found that the IFRD1 gene was associated with lung disease severity. Specifically, people having the CT genotype at rs7817 showed worse lung function than people with either two Cs or two Ts at this SNP.
That would suggest a lung function advantage for CF patients with one copy of each version of rs7817. But in laboratory experiments with cells taken from healthy volunteers, a different and more plausible pattern emerged: Each C at rs7817 led to reduced neutrophil activity. This reduced activity may be the link between IFRD1 and lung disease severity in cystic fibrosis patients.
Research in mice supports that view. Mice genetically engineered to lack the IFRD1 gene show less neutrophil activity, further supporting the importance of this gene in controlling the activity of these cells.   When infected with P. aeruginosa, a type of bacteria that often infects the lungs of people with cystic fibrosis, IFRD1-deficient mice were less able to rid their lungs of the bacteria than normal mice.   But, as would be predicted from the results in humans, these mutant mice showed fewer signs of inflammation and were actually healthier than the normal mice.
The researchers reason that variations in IFRD1 that reduce neutrophil activity prevent excess inflammation, and therefore reduce the severity of lung disease. The scientists did not address why patients with two Ts had better, not worse, lung function compared to those with one.
Although they caution that more research will be needed, the authors of the study conclude that, “the current data suggest probable benefit for therapeutic targeting of neutrophils in this devastating disease.   These data also suggest that [IFRD1] may provide a tractable therapeutic target in CF, and other diseases in which neutrophils have an important pathogenetic role.”
(23andMe customers can find out about their data for one of the most common CFTR mutations, Delta F508, in the Carrier Status Clinical Report for cystic fibrosis.   It is important to note that not carrying this mutation does not mean that another mutation is not present.)

Genetic Variation That Reduces Immune Cell Activity May Lessen Severity of Lung Damage in Cystic Fibrosis Patients

<img loading="lazy" decoding="async" class="alignright size-full wp-image-2896" title="442px-reproduction-of-the-1805-rembrandt-peale-painting-of-thomas-jefferson-new-york-historical-society_1" src="https://blog-api.23andme.com/wp-content/uploads/2009/02/442px-reproduction-of-the-1805-rembrandt-peale-painting-of-thomas-jefferson-new-york-historical-society_1.jpg" alt="" width="300" height="406" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/02/442px-reproduction-of-the-1805-rembrandt-peale-painting-of-thomas-jefferson-new-york-historical-society_1.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2009/02/442px-reproduction-of-the-1805-rembrandt-peale-painting-of-thomas-jefferson-new-york-historical-society_1-222x300.jpg 222w" sizes="auto, (max-width: 300px) 100vw, 300px" />
As we have shown time and again here at the Blog, our DNA can greatly illuminate the lives of our most ancient ancestors.   We&#8217;ve learned how the ancient <a id="em14" title="Phoenicians" href="../2008/10/30/ripples-in-the-mediterranean-tracing-the-genetic-origins-of-the-phoenicians/" target="_blank" rel="noopener noreferrer">Phoenicians</a> left their genetic footprints scattered across the Mediterranean Sea, and seen the DNA signatures of the first <a id="ou4o" title="farmers" href="../2008/12/24/hidden-in-plain-sight-new-genetic-discoveries-shed-light-on-the-spread-of-farming-in-eastern-europe/" target="_blank" rel="noopener noreferrer">farmers</a> sprinkled everywhere from Iraq to Germany to England.   But DNA can also tell us many things about our species&#8217; more recent history as well. Just yesterday we discussed the most recent discoveries regarding the fate of Russia&#8217;s last royal family, the <a id="is69" title="Romanovs" href="https://blog.23andme.com/articles/leaving-no-stone-unturned-dna-analysis-confirms-identities-of-missing-romanovs" target="_blank" rel="noopener noreferrer">Romanovs</a>.   Below we delve deeper into that mystery, as well as two others that reveal how scientists have harnessed the power of DNA to solve some of history&#8217;s seemingly unsolvable mysteries.
<h6> 
Which was Jefferson&#8217;s Son?</h6>
Tales of an affair between our third president, Thomas Jefferson, and his household slave, Sally Hemings, began circulating as soon as the two returned from Paris in 1790.   For her entire life, Hemings served Jefferson and his family at his residence in Virginia.   She bore at least four children throughout her life.   And though the father of Sally&#8217;s children was never divulged, anecdotal evidence, combined with the efforts of a persistent political reporter named James T. Callender, helped spread rumors that the third President of the United States fathered at least one of Hemings&#8217; children.
Two of Hemings&#8217; sons were of particular interest.   The first, Thomas Woodson, was believed to have been conceived while Hemings and Jefferson were living in Paris.   Convincing the public that Woodson was indeed the illegitimate son of Hemings and Jefferson was one of Callender&#8217;s primary goals.
The other child of interest, Eston Hemings, was Sally&#8217;s youngest.   He was born in 1808 and was said to have resembled Thomas Jefferson, and clearly the potential connection was not lost on him: later in his life Eston Hemings moved to Madison, Wisc., and changed his name to Eston Hemings Jefferson.
Yet even with this name change, many of Eston&#8217;s descendants seemed to have no knowledge of their potential ancestry.   And most historians placed more credence on the idea that Woodson was Jefferson&#8217;s son.   In order to discover the true ancestry of both Thomas Woodson and Eston Hemings, researchers turned to DNA.
Geneticists found living males who could document their descent from either Thomas Woodson, Eston Hemings, or Thomas Jefferson along a purely male line. Because the Y chromosome is passed down directly from father to son, the paternal descendant of any of Thomas Jefferson&#8217;s sons would have the same Y chromosome as a descendant of Jefferson himself.
The first thing the geneticists found when they examined the Y chromosomes of all these descendants was that Jefferson himself had a very rare Y chromosome type hardly ever found among people of western European ancestry. Then, when they examined the DNA of Woodson&#8217;s and Hemings&#8217; descendants, they found a perfect match: but only with Eston Hemings&#8217; descendants.   Woodson&#8217;s descendants all had a Y chromosome that is common among West Africans.
So even though DNA evidence disproved historians&#8217; suspicion that Sally Hemings&#8217; first son, Thomas Woodson, was fathered by our nation&#8217;s third president, it strongly suggested that her youngest, Eston Hemings, was indeed Jefferson&#8217;s offspring.
<h6>The Case of the Missing Mozart</h6>
On December 6, 1791, famed composer Wolfgang Amadeus Mozart was laid to rest at St. Mark&#8217;s Cemetery in Vienna.   Despite his fame, he was buried in a pauper&#8217;s grave, along with several dozen others. But 10 years later, gravedigger Joseph Rothmayer unearthed Mozart and removed his skull, speculating that there was money to be made from selling the relic.   For the next 200 years, the skull would disappear and and then reappear into the hands of various collectors and Mozart enthusiasts.   Its authenticity could never be verified, so scientists finally turned to DNA to fill in the gaps that other research could not.
In 2005, two independent teams of geneticists analyzed DNA extracted from a tooth in the skull.   They compared this DNA to various members of Mozart&#8217;s family, including his father, grandmother, and niece, who were all buried in the Mozart family tomb.
Both teams arrived at the exact same conclusion: the skull could not have been Mozart&#8217;s.   The DNA extracted from the skull differed too much from that of every family member buried in the Mozart tomb.
<h6>Lost and Found:   The Grand Duchess Anastasia</h6>
On July 16th, 1918, a family of seven, along with their three servants and physician, were murdered outside the small town of Ekaterinburg, Russia.   But this was no ordinary family.   This father was Tsar Nicolas &#8211; the last Romanov Emperor of Russia.   As the Russian Revolution was coming to a head, the imperial family was arrested and held by the Bolshevik rebels.   Then, over a year later, they were held at gunpoint and shot execution style; their bodies were hastily burned and thrown in a shallow grave in the woods outside the town.
Just a few short years after their murder, rumors began circulating that at least one member of the Romanov family had escaped execution.   At exactly the right moment, a young woman emerged in Germany and claimed to be Grand Duchess Anastasia, one of the Tsar&#8217;s daughters.   For the next 60 years, this woman, known as Anna Anderson, stood by her claim that she was Anastasia, and that she had managed to escape the execution in Ekaterinburg.   Her assertions were given extra credence when two amateur historians unearthed a grave site that they claimed contained the remains of the Romanov family, minus the body of Anastasia.   The rumors grew.   Yet the royal houses of Europe, to whom the Romanovs were related, never believed Anderson&#8217;s story. The two sides were in a constant struggle for the truth up to Anderson&#8217;s death in 1984.
<h6>More on the Tsarina</h6>
As with Jefferson and Mozart, researchers finally turned to DNA evidence to test Anderson&#8217;s claim. Scientists retrieved DNA from a tissue sample that had been stored in a hospital after Anderson had a biopsy, and extracted her mitochondrial DNA.   Because mitochondrial DNA is passed down from mother to children, scientists could compare Anderson&#8217;s mtDNA to a living maternal relative of Anastasia.   The relative they chose happened to be Prince Phillip of Great Britain: husband to Queen Elizabeth II and grand-nephew of Nicolas&#8217; wife, Tsarina Alexandra.
Anderson&#8217;s mtDNA did not match that of Prince Phillip, however.   And when new techniques allowed for the extraction of DNA from the burial site in Ekaterinburg, scientists found that Anderson&#8217;s DNA did not match that of the Tsarina or the other children.   To finally close this case, in 2007 archaeologists discovered another grave in Ekaterinburg, near the original, that held more bodies.   Forensic analysis strongly suggested that one of these bodies was the missing Anastasia.
Even though some die-hard fans of Anderson maintain she was always telling the truth, the vast majority of scientists and historians consider her simply a master of deception.   Once again, DNA analysis has been able to prove &#8211; or in this case, disprove &#8211; a seemingly unsolvable mystery.

History’s Mysteries:  Finding Answers in our DNA

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There are many mysteries surrounding the final days of the last Emperor of Russia, Tsar Nicholas, and his family.
The most perplexing of them all is the fate of one of the Tsar&#8217;s daughters, the Grand Duchess Anastasia.
Even after Bolsheviks  murdered the family in the summer of 1918, rumors circulated throughout Europe that Anastasia (and sometimes her brother Alexsei as well) may have escaped the slaughter.   When the remains of the Romanovs were discovered several years later, minus two of the Tsar&#8217;s children, the idea that at least one child escaped seemed much more credible.
<h6>Second Burial Site</h6>
But in 2007, these rumors were quelled when a second burial site was discovered a few miles from the first.   This grave contained the remains of two children; preliminary forensic analysis identified them as the Tsar&#8217;s son Alexsei and one of his sisters.   With the discovery of this second burial all family members, servants, and physicians who were killed that summer evening over 90 years ago were finally accounted for, or so it seemed.
Yet in spite of this new discovery, many remained unconvinced.
<h6>Looking at the DNA</h6>
They called for the new remains to be scrutinized &#8211; that both the physical remains and their DNA be tested &#8211; to make certain that these were in fact the Tsar&#8217;s children.
So, an international team of scientists undertook this daunting task by examining the DNA of the children in the new burial as well as the DNA in the original burial, to finally put to rest the rumors that have persisted for so long.   The team of scientists reports their findings online this week in the <a href="https://www.pnas.org/" target="_blank" rel="noopener noreferrer">Proceedings of the National Academy of Sciences</a>.
<h6>Tracing mtDNA</h6>
The researchers began by extracting and sequencing the mitochondrial DNA of the skeletons in the second burial.   Because mitochondrial DNA (mtDNA) is present in great quantities in each cell of our bodies, they reasoned it would be easier to find and therefore easier to analyze.
In addition, because mtDNA is passed down from mother to children, the scientists knew that they could compare the mtDNA of these skeletons to that of their mother, the Tsarina Alexandra, who was among the skeletons in the first burial.
Upon comparing the two children in the second grave, the scientists found their mtDNA to be identical &#8211; meaning that they must be related, and probably shared the same mother.   And when they analyzed the mtDNA of the Tsarina, they found that she matched the two children from the second burial. Additional tests revealed one of the children to be a boy, and the other a girl, also lending support to the notion that one of the children was the Alexsei, and the other one of his sisters.
But the scientists did not stop there.
<h6>Tsar Nicholas</h6>
They decided to perform one final test.   This test centered around the remains of Tsar Nicholas, found among his family at the first burial site.   While most scholars agreed that the Tsar was among the skeletons in this grave, it had not been conclusively proven.   To tie up any loose ends, the scientists needed some method of confirming the Tsar&#8217;s idenitity.
That method came by way of a piece of clothing formerly belonging to the Tsar.   One of the Tsar&#8217;s shirts, preserved at the Hermitage Museum in St. Petersburg, was stained with some of his blood; blood that contained the Tsar&#8217;s DNA.   After examining the DNA from the blood on the shirt, the scientists found it to be an exact match to the DNA of the remains at the first burial.
Almost 91 years after their murder, Russia&#8217;s last royal family is finally all present and accounted for.
Be sure to check the <a href="https://blog.23andme.com" target="_blank" rel="noopener noreferrer">Blog</a> again tomorrow, when we delve deeper into the Romanov mystery and explore other puzzles in recent history that have been solved using DNA.

DNA Analysis Confirms Identities of Missing Romanovs

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Almost since the 1871 publication of &#8220;The Descent of Man,&#8221; in which Charles Darwin applied his theory of natural selection to the human species, biologists have argued over whether the dramatic series of evolutionary events that led to the emergence of Homo sapiens continues to this day.
<h6>Modern Humans</h6>
Some have argued that culture and technology have eclipsed the powerful biological forces that shaped our species in its formative years. In their view the species, no longer faced with a daily struggle for survival, is  adrift in an evolutionary Sargasso Sea.
&#8220;There&#8217;s been no biological change in humans in 40,000 or 50,000 years. Everything we call culture and civilization we&#8217;ve built with the same body and brain,&#8221; the famed evolutionary biologist Stephen J. Gould once said in an interview.
<h6>An Evolution Acceleration</h6>
In their new book &#8220;The 10,000 Year Explosion,&#8221; anthropologists Henry Harpending and Gregory Cochran argue the contrary position. They claim that in fact, far from grinding to a halt, human evolution has accelerated dramatically since the origins of agriculture about 10,000 years ago.
&#8220;We intend to make the case that human evolution has accelerated in the past 10,000 years, rather than slowing or stopping, and is now happening about 100 times faster than its long-term average over the 6 million years of our existence,&#8221; they write.
In evolutionary terms, 10,000 years is no time at all – about 400 human generations. Rabbits can go through 400 generations in not much more than a century – can you imagine rabbits being substantially different than they were 100 years ago?
<h6>Cognition</h6>
Far from ending the chain of dramatic evolutionary changes that led to upright walking, advanced cognitive abilities and spoken language, Cochran and Harpending argue, the adoption of agriculture so dramatically changed the human environment that a new wave of genetic innovations flourished.
These new genetic variants thrived because they helped people cope with the challenges an agricultural way of life presented, such as the shift to a low protein, high carbohydrate diet; the creation of an organized, stratified society and the rise of infectious diseases in response to increased population density.
In fact, many of the genetic variations that 23andMe provides information about are relics of those evolutionary changes. The SNP that confers lactose tolerance, for example, appears to have arisen in Europe about 8,000 years ago among the first people to herd cows and other milk-producing animals. The lactose-digesting variant quickly spread throughout the parts of Eurasia that were ecologically suited to pastoralism.
There are also a number of genetic variations covered by 23andMe that cause physiological problems when two mutated copies are present, but provide protection against infectious disease when a person has one of each version of the gene.
For example, the genetic variations that cause sickle cell anemia and G6PD deficiency confer resistance to malaria. Geneticists call this situation balancing selection; over the entire population, the reproductive cost to those who end up with the genetic disease is outweighed by the benefit to others who are resistant to the infectious one.
<h6>Natural Selection</h6>
At the end of the book, Cochran and Harpending make the controversial argument that balancing selection is responsible for the increased incidence of a number of genetic diseases among people of Ashkenazi Jewish descent – and for their higher intelligence relative to other groups.
The authors do raise some interesting points about the anomalously high frequency among Ashkenazi of genetic disorders that stimulate the growth of neurons in the brain. And they cite studies that have shown increased intelligence among people with some of these diseases.
But genetic explanations for between-group differences in intelligence are best taken with a whopping dose of skepticism. Even the definition of intelligence is a matter of intense debate, not to mention the degree to which it can be inherited through genetics. in the end, their case is little more than a <a href="https://en.wikipedia.org/wiki/Just-so_story" target="_blank" rel="noopener">just-so story</a>.
In telling it Cochran and Harpending blunt the rest of their book&#8217;s powerful message: human evolution is not over by a long sight.

The 10,000 Year Explosion

<img loading="lazy" decoding="async" class="alignright size-full wp-image-2857" title="bloodclot" src="https://blog-api.23andme.com/wp-content/uploads/2008/09/bloodclot.jpg" alt="" width="318" height="236" />
Each time a doctor writes a prescription for warfarin, a blood thinner given to about two million people each year in the United States, it’s a guessing game.
There is no “right” dose of the drug.   Everyone is different and it can take weeks of adjustment to find a patient’s ideal amount of the medication.
Too much puts the patient at risk for bleeding.   Too little can lead to clots and in turn, heart attack, stroke or even death.
<h6>New Labeling</h6>
In addition to clinical factors such as age, body size, other medications and ethnicity, genetic factors can affect a patient’s ideal dose of warfarin.
In 2007 the FDA added to warfarin’s label information about the importance of these genetic factors, but stopped short of directing doctors to carry out testing before prescribing the drug.
This may change, however, based on the results of a large international study published yesterday in the <a href="http://content.nejm.org/cgi/content/short/360/8/753" target="_blank" rel="noopener">New England Journal of Medicine</a>. The study shows that dosing decisions based on genetic information in addition to clinical data come significantly closer to the ideal dose for almost half of all patients.
<h6>Pharmacogenetics</h6>
Scientists from the International Warfarin Pharmacogenetics Consortium, comprised of research centers in Taiwan, Japan, Korea, Singapore, Sweden, Israel, Brazil, Britain and the United States, used the medical records and genetic information of about 4,000 patients who had been prescribed warfarin to develop a “pharmacogenetic” method for predicting the ideal dose. They then tested their method by applying it to the information from an additional 1,000 patients who had taken warfarin.
Compared to initial warfarin dosing decisions made with clinical data alone or based on a fixed starting dose of 35 mg per week for every patient, the pharmacogenetic method provided significantly better predictions of the final, ideal dose for many people.
“The greatest differences among the dose-prediction approaches were noted among patients whose stable therapeutic warfarin doses were 21 mg or less per week and among those whose stable doses were 49 mg or more per week, representing 46% of the cohort. These are the patients for whom an underdose or an overdose could have adverse clinical consequences,” the authors write.
<h6>Help Finding the Right Dose</h6>
The dosing method developed by the researchers did not provide a significantly better approximation for the 54% of patients whose ideal dose fell between 21 and 49 mg per week.
While the current study does show that genetic information can better predict the ideal dose of warfarin for a patient, it does not address whether this translates into less risk for bleeding or clotting. This question will be addressed by a soon-to-be-launched NIH-sponsored clinical trial called “Clarification of Optimal Anticoagulation through Genetics” (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00839657" target="_blank" rel="noopener">COAG</a>).
This large study being conducted at 12 sites will evaluate how a gene-based dosing strategy affects a patient’s ability to maintain the correct level of blood thinning, the risk for bleeding problems, quality of life and cost of therapy.
“A better understanding of individual differences in the response, either positive or negative, to medicines should be an overarching goal for pharmacotherapy over the next decade. Pharmacogenetics has the potential to increase benefit and reduce harm in people whose drug responses are not ‘average’,” write Janet Woodcock and Lawrence Lesko, of the Center for Drug Evaluation and Research at the Food and Drug Administration, in an <a href="http://content.nejm.org/cgi/content/short/360/8/811" target="_blank" rel="noopener">editorial</a> that accompanies the study.
But, they warn, the move toward using genetic information to make prescription decisions must be made prudently.
“Given the expected volume of genetic information and the relative paucity of randomized, controlled trials involving marketed drugs, we need clear thinking about what is required for the adoption of pharmacogenetic testing.”
23andMe scientific advisor Russ Altman is a lead investigator for the International Warfarin Pharmacogenetics Consortium.

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