Scientists Discover Pain Genes

Jessica Berman | Washington 11 November 2010

Scientists have discovered hundreds of genes that appear to play a role in determining pain sensitivity. Researchers say slight variations in one pain gene in particular seem to affect how intensely pain is felt.

Under normal circumstances, scientists say pain serves an important biological function; a sharp poke with a needle or knifepoint, or slight burn, causes most people to recoil, protecting them from further harm.

Then there is another type of pain, according to Clifford Woolf a neurobiologist at Children's Hospital in Boston, Massachusetts.

"The other kind of pain is when the fire alarm system is on all the time, and these would be patients who have chronic persistent pain," Woolf explained. "And that is a situation where pain has become a disease in its own right. It's no longer warning of damage; the fire alarm is on all the time and there's no fire."

Scientists say studies of twins show that the degree to which an individual feels pain is largely inherited.

In an effort to identify genes involved in pain, an international team of researchers led by Woolf identified some 600 potential genes in fruit flies which are similar in humans.

Scientists focused on one gene in particular called "Alpha 2 Delta 3."

In a study of 189 healthy volunteers, researchers found reduced sensitivity to heat among participants who had slight alphabet variations to the DNA code within or close to the location of the Alpha 2 Delta 3 gene.

Researchers also found in another study that back pain patients who had the rarer genetic variants were less likely to experience persisting pain after surgery.

By learning the genetic underpinnings of pain, Woolf says it will someday be possible to develop medications to treat a variety of pain syndromes.

"There's pain associated with damage to the nervous system. Pain associated with the inflammatory diseases," neurobiologist Woolf noted. "There's post-operative pain. And each of them operates in slightly different ways, and so there will be different targets and different analgesics required for these different kinds of pain."

Researchers say it may one day be possible to develop genetic risk profiles to determine who is at greatest risk of chronic pain following surgery. Such information could be useful in helping patients decide whether to go forward with an operation.

An article describing the pain genes is published in the journal Cell.

Stem Cell Therapy Gaining Ground in Asia

Heda Bayron | Hong Kong 25 November 2010

Asians are beginning to warm up to the idea of using their own stem cells to treat a host of illnesses such as heart disease, cystic fibrosis or leukemia. Some parents are preserving their babies' umbilical cords, hoping that as technology advances their children can use the umbilical blood to cure future illnesses.

It is a nightmare for parents to hear their child has developed a disease that requires a bone marrow transplant. For instance, patients with leukemia, a type of blood cancer, sometimes have a hard time finding a bone marrow match.

Scientists say the umbilical cord that attaches a baby to its mother is a rich source of stem cells, which can treat diseases like leukemia. They can be collected immediately after birth and stored in freezers by companies such as Cordlife, which operates cord blood banks in Hong Kong, Singapore, Indonesia, India and the Philippines. If a child needs it, doctors can retrieve cord blood for treatment.

"We're seeing an explosion umbilical cord blood banking as a source of biological insurance for parents in Asia and their children," said Andrew Wu, Cordlife's technical and laboratory director.

Scientists around the world are finding new ways to use cord blood stem cells to treat problems such as spinal cord damage, diabetes, cerebral palsy and heart disease.

At Cordlife, parents pay about $4,000 to keep their children's cord blood for 18 years.

"I'm most excited to see the use of stem cell in therapy becoming a standard of care, where clinicians when they look at a disease would ask, 'What's my stem cell option in terms of therapy? How I can look to stem cells to treat this disease or regenerate this organ or to combat this tumor?'" Wu said.

Asia appears striding toward the use of stem cells for treatment.

Dr. Supachai Chaithiraphan, a professor emeritus of Thailand's Mahidol University and director of the cardiac center at Chao Phya hospital in Bangkok, conducted a clinical trial in 2004 that injected stem cells derived from human blood to treat people with end-stage heart disease.

"Eighty percent showed improvement in terms of New York Heart Association classification and also the Canadian [Cardiac Society] angina classification. So we feel that this group of patients can derive benefit from their own stem cell therapy," Supachai said.

In Asia, there are fewer regulations regarding the use of stem cells than in the United States, which encourages research and clinical uses.

In the U.S., the use of stem cells has been controversial because of ethical concerns over the use of embryonic stem cells - derived from early-stage embryos that develop from human eggs fertilized in a laboratory. Under President Bush, the government limited funding to a few batches of stem cell lines. But the Obama administration has since relaxed those rules.

However, cord blood storage appears to be increasing in the U.S. A new national cord blood bank has been established at Duke University in the state of North Carolina.

Some practitioners, such as Wu worry that Asia's lax regulations may lead to inflated expectations and false promises.

"A lot still needs to go into building this understanding and building appropriate regulations around the use of these stem cells so that the industry as a whole can develop within a legal framework that not only benefits the companies but most importantly benefits the clinicians and the patients at the end of the day," Wu said.

Poor medical facilities in some developing Asian nations also hold back use of stem cells.

But Supachai says in time, stem cell therapy will be more accessible.

"I would foresee that in the near future more doctors would come to realize that this cell therapy is really of help to certain number of patients with certain diseases, in particular heart disease," Supachai said.

The World Health Organization estimates that about 20 million people worldwide will die from cardiovascular disease annually by 2015. The number of people in developing nations suffering from heart disease is expected to rise as incomes increase.

Scientists say DNA provides 'historical archive'

Edinburgh scientists say they have developed a genetic test that can tell if people's ancestors were from a large populated area or a rural village.

The team found that a person's DNA records provide a "historical archive" of where they are from.

The test can also detect if a person's ancestors were related, such as if they are from a community where marriage between cousins was commonplace.

It could help identify people who are more prone to genetic illnesses.

Gene pool

A team at Edinburgh University analysed the DNA of more than 1,000 people across 51 different ethnic groups, ranging from Europeans to Amazonian tribes, during the study.

They identified those who had inherited the same genetic material from both parents The study found that native South Americans had the highest amount of shared DNA, suggesting that those communities were small and isolated over many generations.

By contrast, African communities had the lowest degree of genetic similarity, indicating a more diverse population over time.

The team believe this could be explained by the fact that humans originated in Africa and so have had the most time to develop a diverse gene pool.

Dr Jim Wilson, Royal Society research fellow at Edinburgh University, said: "The exciting thing about these results is that it shows our genes are recording the history of movements in our population.

"It's like an archive being written in genetic code, so that we can understand the way our populations have developed from the distant past.

"The findings are also important because it highlights those areas of the world where genetic similarity is common and this can be a risk factor for some diseases like cystic fibrosis, which can be caused when you inherit a faulty gene from both parents."

The scientists said DNA records provided a "historical archive" of where people are from

(source: BBC)

Genes Predict Who Will Live Longer

Technique may also help predict disease

Art Chimes | St. Louis, Missouri

Researchers at Boston University have identified a kind of genetic signature in people who are likely to live to age 100 or older. The technique may also help doctors predict whether you're likely to get a disease, decades before the symptoms show up.

Living a long, healthy life tends to run in families. If your grandparents and parents lived into their 90s and remained relatively healthy until the end, there's a pretty good chance you will, too.

So it's pretty clear genetics plays some role in longevity.

In this study, the research team developed a new statistical way of analyzing the genetic code of people who had reached age 100 as compared with people who had a more typical lifespan. Tom Perls, who heads the New England Centenarian Study, explains what they found.

"We discovered 150 or so genetic markers that can highly predict whether or not a person has the genetic propensity to live to extreme old age."

Using just that large number of genetic markers, the team was able to predict in almost four out of five cases whether a person would live to be 100.

Perls says the key to successfully predicting long life was the sophisticated statistical analysis of many different gene variations that each played some role.

"And that's what this method does - it captures the complexity of the puzzle and the interaction of all these genes together to produce exceptional longevity."
Perls and his colleagues publish their study in the online edition of the journal Science.

The Boston University researcher says this kind of analysis could play a role, not just in predicting who will live longest, but in actually helping people live longer and healthier lives.

In an interview via Skype, Tom Perls said the same technique used to predict long life may also be used to predict whether a person might eventually develop certain diseases. He gave the example of Alzheimer's Disease as one in which genetics plays a role.

"And we think that this methodology can very much be used to capture the bunch of genes that are playing an important role in one's susceptibility to that disease," he said. "And the same can be true, perhaps, for looking at adult-onset diabetes, or cardiovascular disease, or stroke. Again, where I think there is at least a moderate impact from genetic variation."

As the cost of the needed genetic tests continues to decline, he predicts doctors will be able to screen patients for diseases they may not develop until later in life, and recommend ways to avoid them.

Gene Abnormality Found To Predict Childhood Leukemia Relapse

Scientists have identified mutations in a gene that predict a high likelihood of relapse in children with acute lymphoblastic leukemia (ALL). Although the researchers caution that further research is needed to determine how changes in the gene, called IKZF1 or IKAROS, lead to leukemia relapse, the findings are likely to provide the basis for future diagnostic tests to assess the risk of treatment failure. By using a molecular test to identify this genetic marker in ALL patients, physicians should be better able to assign patients to appropriate therapies.

The findings of the Children Oncology Group (COG) study, led by scientists from St. Jude Children Research Hospital, Memphis, Tenn., the University of New Mexico Cancer Research and Treatment Center, Albuquerque, N.M., and the National Cancer Institute (NCI), part of the National Institutes of Health, appear online Jan. 7, 2009, in the New England Journal of Medicine, and in print on Jan. 29, 2009.

ALL, a cancer of white blood cells, is the most common childhood cancer, in that it is diagnosed in about one in 29,000 children annually. Using currently available therapies, cure rates for ALL are now upwards of 80 percent. However, those therapies carry with them substantial side effects, and even with treatment, only 30 percent of children who experience a relapse of ALL will survive five years. Determining the risk of relapse faced by an individual patient would help physicians tailor treatment intensity appropriately, but until now there has been no good marker for predicting outcome.

"Great progress has been made in recent years in improving the cure rate of childhood ALL," said Stephen Hunger, M.D., chairman of the COG ALL committee and the lead COG investigator on this study. "The findings of this study help us further subdivide those patients who are unlikely to be cured, and identify patients in whom different therapies should be tested."

In the study, researchers analyzed genetic data on leukemia cells obtained at diagnosis from 221 children with high-risk leukemia (i.e., a high chance of relapse) who had been treated in an existing COG study. They conducted their analysis using microarrays and DNA sequencing � technologies which allow researchers to quickly and efficiently identify and analyze multiple genes simultaneously in the same cell. Using these technologies to identify genetic abnormalities in leukemia cells, the investigators examined the DNA of the leukemia cells at the time of diagnosis and then determined if any of the identified genetic changes predicted relapse. To confirm that specific genetic changes were associated with relapse, the scientists also examined a second group of 258 children with ALL who were treated at St. Jude.

"We looked across the genome in an unbiased fashion in an attempt to pull out any genes that were significantly associated with outcome," said Charles Mullighan, M.D., Ph.D., assistant member in the St. Jude Department of Pathology and the paper抯 first author. "From these findings, we identified a group of genetic abnormalities that together predicted poor outcome."

The most significant association was with the deletions or changes in the IKAROS gene. Mutations of IKAROS were shown to identify a subgroup of patients who were treated in the COG study that had a very poor prognosis. The prognostic significance of these genetic alterations was validated in the independent St. Jude patient group, a finding of particular importance since different types of therapies were used in these two groups of patients.

Previous research has shown that the IKAROS gene serves as the blueprint for production of the IKAROS protein, which regulates the activity of many other genes. The IKAROS protein plays an essential role in the development of lymphocytes, the white blood cells that, when changed, give rise to pediatric ALL. The way in which IKAROS abnormalities contribute to the development of relapse remains to be determined.

The study also examined gene expression in the leukemia cells using microarray chips, and found that leukemia cells from patients with IKAROS alterations expressed primitive, stem cell-like genes, suggesting that the cells are less mature and possibly more resistant to the effects of drugs used to treat ALL. "These findings show how detailed analysis of leukemic cells using complementary techniques can enhance our understanding of the genetic basis of leukemia," said co-author Cheryl Willman, M.D., director and CEO, University of New Mexico Cancer Research and Treatment Center.

The researchers also tested whether the presence of IKAROS alterations was associated with levels of minimal residual disease, another measure of treatment response in ALL.

"Measurement of levels of minimal residual disease is widely used to monitor treatment responsiveness and also to alter patients� therapy if they have a very poor response to treatment," said James Downing, M.D., St. Jude scientific director and the paper抯 senior author. "An important analysis we conducted was to see whether identifying the association of IKAROS alterations with poor outcome added anything to just measuring levels of minimal residual disease. And, indeed, it did."

The researchers� analysis indicated that identifying IKAROS alterations may be clinically useful and will complement existing diagnostic tests and measurement of minimal residual disease levels.

While a clinical test for alterations of IKAROS could prove valuable for predicting poor outcomes in children with ALL, complexities remain. There are different types of deletions in the gene, some that involve the entire IKAROS gene and others that involve only parts of the gene. Because the genetic alterations in IKAROS in ALL are not uniform or limited to a single mutation or deletion, it may be necessary to develop a panel of different tests to detect IKAROS lesions and identify which patients are at highest risk for relapse.

This research was done as part of the NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative, which seeks to utilize the study of genomics to identify therapeutic targets in order to develop more effective treatments for childhood cancers. The first two cancers being studied in the program are ALL and neuroblastoma, a cancer that arises in immature nerve cells and affects mostly infants and children. Combined, these two cancers account for 3,000 new cases each year, and in both cancers, there are some children who have a very favorable prognosis and others who are at high risk for treatment failure. By determining the genetic factors that distinguish these groups, the hope is that researchers can use this information to improve patient outcomes and develop better treatments, particularly for those in the high-risk group.

"In the long term, our goal is to develop effective therapeutic interventions, directed toward vulnerabilities that leukemia cells acquire as a result of the genomic abnormalities identified through the TARGET initiative," said Malcolm Smith, M.D., Ph.D., of NCI抯 Cancer Therapy Evaluation Program. These are the first results to come out of this initiative. For more information about TARGET, please visithttp://target.cancer.gov

St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. For more information, please visit www.stjude.org.

The Children抯 Oncology Group/CureSearch
Children抯 Oncology Group (COG), the world抯 largest cooperative pediatric cancer research organization, which includes every recognized pediatric cancer program in North America, comprises a network of more than 5,000 physician, nurse, and other clinical and laboratory investigators whose collaboration in clinical and translational research has turned childhood cancer from a virtually incurable disease to one with an overall cure rate approaching 80 percent. COG is committed to conquering childhood cancer through scientific discovery and compassionate care. For more information, please visit www.childrensoncologygroup.org

The University of New Mexico Cancer Research and Treatment Center
The UNM Cancer Center is New Mexico抯 only National Cancer Institute-designated cancer center, and is home to the state抯 largest and most experienced team of cancer experts with 81 board-certified oncology physicians and more than 120 research scientists, supported by more than $50 million in grants annually. As the Official Cancer Center of the State of New Mexico, the Center served 7,600 new patients last year in 84,000 patient visits, treating nearly half of all adults with cancer in the state and virtually all the children.

The National Cancer Institute

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The National Institutes of Health

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Reference: Mullighan CG, Su X, Zhang J, Radtke I, Phillips LAA, Miller CB, Ma J, Liu W, Cheng C, Schulman BA, Harvey RC, Chen I, Clifford RJ, Carroll WL, Reaman G, Bowman WP, Devidas M, Gerhard DS, Yang W, Relling MV, Shurtleff SA, Campana D, Borowitz MJ, Pui C, Smith M, Hunger SP, Willman CL, Downing JR, and the Children's Oncology Group. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia. NEJM. Vol. 360, No.

DNA&RNA Databases and Tools

Databases

BioSystems

Database that groups biomedical literature, small molecules, and sequence data in terms of biological relationships.

Database of Expressed Sequence Tags (dbEST)

A divison of GenBank that contains short single-pass reads of cDNA (transcript) sequences. dbEST can be searched directly through the Nucleotide EST Database.

Database of Genome Survey Sequences (dbGSS)

A division of GenBank that contains short single-pass reads of genomic DNA. dbGSS can be searched directly through the Nucleotide GSS Database.

GenBank

The NIH genetic sequence database, an annotated collection of all publicly available DNA sequences. GenBank is part of the International Nucleotide Sequence Database Collaboration, which comprises the DNA DataBank of Japan (DDBJ), the European Molecular Biology Laboratory (EMBL), and GenBank at NCBI. These three organizations exchange data on a daily basis. GenBank consists of several divisions, most of which can be accessed through the Nucleotide database. The exceptions are the EST and GSS divisions, which are accessed through the Nucleotide EST and Nucleotide GSS databases, respectively.

NCBI Website Search

A database of static NCBI web pages, documentation, and online tools. These pages include such content as specialized online sequence analysis tools, back issues of newsletters, legacy resource description pages, sample code, and other miscellaneous resources. Searching this database is equivalent to a site search tool for the whole NCBI web site. FTP site is not covered.

Nucleotide Database

A collection of nucleotide sequences from several sources, including GenBank, RefSeq, the Third Party Annotation (TPA) database, and PDB. Searching the Nucleotide Database will yield available results from each of its component databases.

PopSet

Database of related DNA sequences that originate from comparative studies: phylogenetic, population, environmental and, to a lesser degree, mutational. Each record in the database is a set of DNA sequences. For example, a population set provides information on genetic variation within an organism, while a phylogenetic set may contain sequences, and their alignment, of a single gene obtained from several related organisms.

Probe

A public registry of nucleic acid reagents designed for use in a wide variety of biomedical research applications, together with information on reagent distributors, probe effectiveness, and computed sequence similarities.

Reference Sequence (RefSeq)

A collection of curated, non-redundant genomic DNA, transcript (RNA), and protein sequences produced by NCBI. RefSeqs provide a stable reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. The RefSeq collection is accessed through the Nucleotide and Protein databases.

Sequence Read Archive (SRA)

The Sequence Read Archive (SRA) stores sequencing data from the next generation of sequencing platforms including Roche 454 GS System®, Illumina Genome Analyzer®, Life Technologies AB SOLiD System® , Helicos Biosciences Heliscope®, Complete Genomics®, and Pacific Biosciences SMRT®

Third Party Annotation (TPA) Database

A database that contains sequences built from the existing primary sequence data in GenBank. The sequences and corresponding annotations are experimentally supported and have been published in a peer-reviewed scientific journal. TPA records are retrieved through the Nucleotide Database.

Trace Archive

A repository of DNA sequence chromatograms (traces), base calls, and quality estimates for single-pass reads from various large-scale sequencing projects.

Tools

Batch Entrez

Allows you to retrieve records from many Entrez databases by uploading a file of GI or accession numbers from the Nucleotide or Protein databases, or a file of unique identifiers from other Entrez databases. Search results can be saved in various formats directly to a local file on your computer.

BLAST (Basic Local Alignment Search Tool)

Finds regions of local similarity between biological sequences. The program compares nucleotide or protein sequences to sequence databases and calculates the statistical significance of matches. BLAST can be used to infer functional and evolutionary relationships between sequences as well as to help identify members of gene families.

E-Utilities

Tools that provide access to data within NCBI's Entrez system outside of the regular web query interface. They provide a method of automating Entrez tasks within software applications. Each utility performs a specialized retrieval task, and can be used simply by writing a specially formatted URL.

Genome Workbench

An integrated application for viewing and analyzing sequence data. With Genome Workbench, you can view data in publically available sequence databases at NCBI, and mix these data with your own data.

Influenza Virus

Presents data from the NIAID Influenza Genome Sequencing Project and from GenBank, and provides tools for flu sequence analysis, annotation and submission to GenBank. It also provides links to other flu sequence resources, and publications and general information about flu viruses.

VecScreen

A system for quickly identifying segments of a nucleic acid sequence that may be of vector origin. VecScreen searches a query sequence for segments that match any sequence in a specialized non-redundant vector database (UniVec).

Downloads

BLAST (Stand-alone)

BLAST executables for local use are provided for Solaris, LINUX, Windows, and MacOSX systems. See the README file in the ftp directory for more information. Pre-formatted databases for BLAST nucleotide, protein, and translated searches also are available for downloading under the db subdirectory.

FTP: GenBank

This site contains files for all sequence records in GenBank in the default flat file format. The files are organized by GenBank division, and the full contents are described in the README.genbank file.

FTP: RefSeq

This site contains all nucleotide and protein sequence records in the Reference Sequence (RefSeq) collection. The "release" directory contains the most current release of the complete collection, while data for selected organisms (such as human, mouse and rat) are available in separate directories. Data are available in FASTA and flat file formats. See the README file for details.

FTP: UniVec

This site contains the UniVec and UniVec_Core databases in FASTA format. See the README.uv file for details.

Submissions

BankIt

A web-based sequence submission tool for one or a few submissions, designed to make the submission process quick and easy.

Barcode Submission

Tool to submit Barcodes, short nucleotide sequences from a standard genetic locus for use in species identification.

Sequin

A stand-alone software tool developed by the NCBI for submitting and updating entries to public sequence databases (GenBank, EMBL, or DDBJ). It is capable of handling simple submissions that contain a single short mRNA sequence, complex submissions containing long sequences, multiple annotations, segmented sets of DNA, as well as sequences from phylogenetic and population studies with alignments. For simple submission, use the online submission tool BankIt instead.

tbl2asn

A command-line program that automates the creation of sequence records for submission to GenBank using many of the same functions as Sequin. It is used primarily for submission of complete genomes and large batches of sequences.

Xinjiang discovery provides intriguing DNA link

CHANGCHUN, April 29 (Xinhua) -- The DNA of some 4,000 year-old bodies unearthed five years ago in Xinjiang, in northwest China, provides scientific evidence of early intermingling between people of European and Asian origin.

Zhou Hui, a professor of life science and her team discovered that some of the earliest inhabitants of the Tarim Basin in the Taklamakan Desert were of European and Siberian descent.

The basin, where hundreds of well-preserved mummies have been found since the 1980s, has attracted great attention from scientists worldwide.

Professor Victor Mair of Pennsylvania University claimed in 2006, "From around 1800 B.C. the earliest mummies in the Tarim Basin were exclusively Caucasoid, or Europoid," after he studied DNA samples derived from five bodies unearthed in the basin.

However, Professor Jin Li of Shanghai-based Fudan University, announced in 2007 that the mummies' DNA in the basin's Loulan area, including the 3,800-year-old Loulan Beauty, indicated East Asian, even South Asian origin.

Many archaeologists have accepted that people living in the basin as early as 3,800 years ago, or the Bronze Age, were of European descent, with Asians, mainly from east Asia, only arriving during the Iron Age, Zhou said. "But when the population from Europe and Asia began 'intermarrying' in the area still remains a mystery," she added.

Zhou and her team got DNA samples from the bones and teeth of 20 mummies, around 4,000-year-old. They were all excavated at the Xiaohe cemetery in the basin in 2004 and 2005.

The analyzed DNA profiles included the mitochondrial DNA, which is exclusively passed down through the mother, and the Y chromosome, passed down from father to son.

We found that DNA from five of the seven males derived from their mother, belonged to a lineage that came from Siberia, most likely from south or eastern Siberia, while their Y chromosome indicated European ancestry, Li Chunxiang, another researcher with the team, told Xinhua.

The seven males' Y chromosome had similarities to ancient Europeans who wandered the Eurasian Steppe, stretching roughly 3,000 miles from west to east, mainly in Central Asia.

People of the lineage can be found now in Eastern Europe, Central Asia and Siberia, but rarely in East Asia, Li said.

The mitochondrial DNA of five males and the nine other mummies (four females and five mummies whose gender is unknown) indicated they were related to an ancient lineage that can now be found mostly in modern Siberia, East Asia and Central Asia, Li said.

Their maternal lineage could be traced to Asian populations most likely lived in south Siberia, she said.

Two other females' DNA indicated their maternal ancestors had come from Western Europe.

"Our finding show the European and Siberian tribes began socializing with each other, even intermarrying, almost 4,000 years ago," Zhou said.

But scholars said the Europeans and Siberians might have met and intermarried outside the basin before their immigration into the basin.

"The civilization of the Tarim Basin, according to archaeological findings, arose very late. The 4,000-year-old mummies we found in Xiaohe are believed to be among the earliest inhabitants in the basin. But the Xiaohe people's DNA lineages are over 10,000 years old," Li said.

DNA with both European and Asian markings was also found in south Siberia. People of European origin had spread eastward into that region during the Bronze Age, she said.

The Xiaohe cemetery, 175 km west of the ancient city of Loulan, is located on the ancient Silk Road, once a booming trade route traversing the Asian continent.

The burial ground, with 167 graves, was first explored by Folke Bergman, a Swedish archaeologist in 1934. But it "vanished" until the Xinjiang Archaeological Institute rediscovered it in 2000, Zhou said.

The excavation of the cemetery began in 2002, but only experts with the institute and the Research Center for Chinese Frontier Archaeology of Jilin University were authorized to unearth the lowest layer where the oldest mummies were buried.

"We found 41 graves in this layer, and 37 of them had human remains. The corpses were lying in bottom-up-boat-like coffins. They all had distinctive European appearances and were well-preserved thanks to the dry air and good drainage." She said.

Some mummies unearthed in the Tarim Basin are displayed in a number of museums in Xinjiang, said Idelis Abdurisulu, former director with the Institute of Cultural and Historical Relics and Archaeology of Xinjiang Uygur Autonomous Region.

"The regional museum has six or seven mummies, while others are scattered around Xinjiang in some smaller museums," he said.

In late March, the Bowers Museum in Santa Ana in California began exhibiting two of the Tarim Basin mummies, including Xiaohe Beauty, a 3,800-year-old female, and Qiemo Baby, an infant aged eight to 10 months who died about 2,800 years ago.