Giant Fossil Bats Out Of Africa, 35 Million Years Old

When most of us think of Ancient Egypt, visions of pyramids and mummies fill our imaginations. For a team of palaeontologists interested in fossil mammals, the Fayum district of Egypt summons an even older and equally impressive history that extends much further back in time than the Sphinx.

In a recent issue of the Journal of Vertebrate Paleontology, scientists report on the discovery of six new bat species dating to around 35 million years ago, which sheds new light on the early evolution of bats.

It took over 25 years of fieldwork to collect the 33 specimens that form the basis of the new study. “That translates to a little over one specimen per year – a lot of effort for a single fossil,” said Erik Seiffert, a palaeontologist at Stony Brook University. “But it shows just how important patience and long term field programs are to science. Our long-term commitment to field work certainly paid off in this case.” Among the new species is “a giant among bats; though weighing in at less than a half-pound, it is one of the largest fossil bats ever discovered,” said Greg Gunnell, a palaeontologist at the University of Michigan.

Fossil bats of Eocene age are rare in Africa. Only a few fragmentary remains from Egypt, Morocco, Tanzania and Tunisia were previously known. The discovery of six new kinds of bats illustrates the remarkably rich, and previously unsuspected, diversity of bats in Africa 37-34 million years ago. These discoveries provide important new information for understanding the evolution of modern bat families.

It was thought that most Old World families of bats evolved and diversified in the northern hemisphere, but the new study indicates that many modern bat families only diversified and radiated after their initial dispersal into Africa. Seiffert noted that the Fayum bats include members of the most common and widespread group of living bats, “Clearly the modern bat families have very ancient origins, and at least some of them probably originated in Africa.”

Elwyn Simons of Duke University said, “Interestingly, it seems that primitive modern bats may have entered Africa together with primitive anthropoid primates. Only then did they diversify and disperse into the rest of the Old and New Worlds.”

Gunnell hopes that “if we can come to understand the history of how bats came to be so intertwined within our ecosystem, then we can begin to appreciate them instead of fear them as many people seem to do.”

Source: Society of Vertebrate Paleontology (2008, March 5). Giant Fossil Bats Out Of Africa, 35 Million Years Old. ScienceDaily. Retrieved March 9, 2008, from http://www.sciencedaily.com­ /releases/2008/03/080304191213.htm

Darwin Was Wrong About Wild Origin Of The Chicken

Charles Darwin maintained that the domesticated chicken descended from the red jungle fowl, but new research from Uppsala University now shows that the wild origins of the chicken are more complicated than that.

Yellow-skinned chickens have a different version of a gene than their white-skinned cousins. Darwin believed that all chickens came from a wild species known as the red junglefowl. When the researchers looked for the yellow-skin gene in the red junglefowl, they only found the genetic variant that codes for white skin. More surprisingly, when they finally did find the yellow-skin version of the gene, it was present in a completely different wild species: the grey junglefowl.

“Our studies show that even though most of the genes in domesticated fowls come from the red jungle fowl, at least one other species must have contributed, specifically the grey jungle fowl,” says Jonas Eriksson, a doctoral student at Uppsala University.

It is most likely the case that the grey jungle fowl was crossed with an early form of the domesticated chicken. The genes for yellow skin are spread among billions of domesticated chickens around the world. Darwin’s studies of domesticated animals were of key importance to his theory of evolution, and he also explained the wild origins of domesticated animals.

“What’s ironic is that Darwin thought that more than one wild species had contributed to the development of the dog, but that the chicken came from only one wild species, the red jungle fowl. Now it turns out that it’s just the opposite way around,” says Greger Larson, a researcher at Uppsala University and Durham University in England.

The yellow leg color is a result of fodder: the more yellow carotenoids there are in the feed, the yellower the legs. The gene that these researchers have now identified codes for an enzyme that breaks down carotenoids and releases vitamin A. This gene is shut down in skin but fully active in other tissues in chickens with yellow legs. The consequence is that yellow carotenoids are stored in the skin in these chickens. This is called a regulatory mutation since the coding sequence of the gene is intact, but its regulation is modified.

“Our study is a clear example of the importance of regulatory mutations in the course of evolution. What we don’t know is why humans bred this characteristic. Maybe chickens with bright yellow legs were seen as being healthier or more fertile than other chickens, or were we simply charmed by their distinct appearance?” wonders Professor Leif Andersson, who directed the project.

The scientists believe that the same gene may well be of significance in explaining the pink color of the flamingo, the yellow leg color of many birds of prey, and the reddish meat of the salmon. These characteristics are all caused by carotenoids. The gene may also influence the skin color of humans to some extent.

Journal reference: Eriksson J, Larson G, Gunnarsson U, Bed’hom B, Tixier-Boichard M, et al. (2008) Identification of the Yellow Skin Gene Reveals a Hybrid Origin of the Domestic Chicken. PLoS Genet 4(2): e1000010. doi:10.1371/journal.pgen.1000010

Source: Uppsala University (2008, March 3). Darwin Was Wrong About Wild Origin Of The Chicken, New Research Shows. ScienceDaily. Retrieved March 4, 2008, from http://www.sciencedaily.com­ /releases/2008/02/080229102059.htm

The Potato

What is the Potato?

• The potato that is known as an important world crop is a single species, Solanum tuberosum, belonging to the family Solanaceae.
• Other well-known crops in that family are the tomato (Lycopersicon esculentum), the aubergine (S. melongena), various species of chilli peppers (Capiscum) and tobacco (Nicotiana tabacum).

What is its Distribution?

• Seven cultivated species are recognised, of which Solanum tuberosum has a world-wide distribution in the form of its sub-species tuberosum. Another subspecies, andigena, is cultivated in the Andes of South America. The other cultivated potatoes are restricted to the high Andes in an area stretching roughly from central Peru to central Bolivia.
• The potato possesses more related wild species than any other crop plant, a recognised total of 228. These are widely distributed through the Americas.

The Potato in Prehistory:

• Ceramics showing human/potato hybrids from the Moche culture of Peru date to c. AD 1-600.
• Earlier evidence is found freeze-dried (chuno) or partly cooked in rubbish pits. Dating shows the crop has been cultivated from at least 7000 BP.

The Potato and Europe:

• The first recorded account of potatoes by Europeans dates to 1537 when a group of Spaniards led an expedition to the Opón Valley in Colombia.
• Sir Francis Drake saw potatoes in Chile in 1578.
• The potato arrived in Europe towards the end of the 16th century.
• It reached Spain c. 1570.
• It then spread to Italy and Portugal.
• Charles d’Ecluse, or Clusius, a herbalist, was a central figure in the spread of the potato through Germany, Low Countries, France and Switzerland.
• 1590 is a likely date for the potato’s arrival in England in the ships of John Gerard. Contrary to popular belief, it is unlikely that Sir Walter Raleigh was responsible for this, although he may have been instrumental in taking them to Ireland in the mid-17th century.
• The first botanical description was that of Caspar Bauhin in 1596.
• Bauhin sent potatoes to France c. 1600.
• Taken to Norway, and thence Sweden and Denmark from Scotland by mid 18th century.
• General adoption in Eastern Europe from Germany in late 18th – early 19th century.

The Potato and the Rest of the World:

• Directly introduced to Canary Islands from Peru c. 1622.
• Taken to India and China by British missionaries in late 17th century and known in Japan and parts of Africa by same period.
• New Zealand c. 1769 and adopted by Maoris c. 1840.

The Irish Potato Famine:

• In 1845 Ireland was struck by an epidemic of the fungal disease Phytophthora infestans, commonly known as potato blight or potato murrain.
• There had been shortages prior to then due to bad weather or less destructive diseases.
• A likely source for the blight was the eastern United States, where blight had largely destroyed the potato crops of 1843 and 1844.
• Once introduced diffusion was rapid. By late summer and early autumn of 1845 it had spread throughout the greater part of northern and central Europe; an area stretching from Switzerland to Scandinavia and Scotland, and from Poland to the west coast of Ireland.
• For the tenant farmers, or cottiers, the blight destroyed their winter stores, imperilled their seed for the coming year, and reduced them to killing and eating the pig by which they paid the rent because they had no potatoes on which to feed it.
• The crop of 1846 was also almost completely destroyed.
• By 1847 the traditional relationship between farmer and labourer was thoroughly disrupted. There was also an enormous deficiency of potato seed and prices of Indian meal were such that people were reduced to eating those potatoes they would have used for seed.
• Mass death and emigration reduced the population from almost 8.2 million in 1841 to fewer than 6.6 million in 1851.

Why is the Potato so important?

• Important source of carbohydrates
• Useful amounts of vitamins and minerals e.g. 1lb cooked new potatoes = 75 mg vitamin C.
• Deficient in vitamins A and D, although this was made good by drinking milk in 18th century Ireland or pre-war Poland.

References:

Donnelly, Jr. J.S. 2001. The Great Irish Potato Famine. Sutton Publishing: Stroud.

Hawkes, J.G. 1990. The Potato: Evolution, Biodiversity and Genetic Resources. Belhaven Press: London.

Salaman, R.N. 1949. The History and Social Influence of the Potato. Cambridge University Press: Cambridge.

Globetrotting Black Rat Genes Reveal Spread Of Humans And Diseases

DNA of the common Black Rat has shed light on the ancient spread of rats, people and diseases around the globe. Studying the mitochondrial DNA of 165 Black Rat specimens from 32 countries around the world, an international team of scientists has identified six distinct lineages in the Black Rat’s family tree, each originating from a different part of Asia.

“Black Rats are carriers of many different human diseases, including plague, typhus and leptospirosis,” says CSIRO mammal expert Dr Ken Aplin, lead author of the study. “It has been unclear why certain rodent-borne diseases are more common in some places than others, but our work raises the possibility that the different lineages of Black Rats each carry a different set of diseases, which is something medical science now needs to consider. We need to know more about what types of Black Rats are moving around the world and what disease risks each of them might pose.”

The six different lineages originated in India, East Asia, the Himalayas, Thailand, the Mekong Delta, and Indonesia. The Indian lineage spread to the Middle-East around 20,000 years ago, then later to Europe. It reached Africa, the Americas and Australia during the Age of Exploration. The East Asian lineage moved from Taiwan to Japan, the Philippines, and Indonesia, arriving in Micronesia only 3,500 years ago. The other four lineages have not become so widespread but they could be set to expand their ranges in the future.

“Our findings also show a good match between the historic spread of each lineage and ancient routes of human migration and trade, but there are a few surprises that raise new questions about human prehistory,” Dr Aplin says. “The genetic evidence points strongly to there being more than one species of black rat, but more work is needed before we can say exactly how many species there are.”

The Black Rat (Rattus rattus) is one of the most common of the world’s 56 Rattus species, and is also known as the house, roof or ship rat. It is found throughout Africa, Asia, Australia, Europe and the Americas.

Reference: CSIRO Australia (2008, February 6). Globetrotting Black Rat Genes Reveal Spread Of Humans And Diseases. ScienceDaily.

Cats’ Family Tree Rooted In Fertile Crescent

The Fertile Crescent of the Middle East has long been identified as a “cradle of civilization” for humans. In a new genetic study, researchers at the University of California, Davis, have concluded that all ancestral roads for the modern day domestic cat also lead back to the same locale.

“This study confirms earlier research suggesting that the domestication of the cat started in the Fertile Crescent region,” said Monika Lipinski, lead researcher on the study and a doctoral candidate in the School of Veterinary Medicine. “It also provides a warning for modern cat fanciers to make sure they maintain a broad genetic base as they further develop their breeds.”

Leslie Lyons, an authority on cat genetics and principal investigator on this study, said: “More than 200 genetic disorders have been identified in modern cats, and many are found in pure breeds. We hope that cat breeders will use the genetic information uncovered by this study to develop efficient breed-management plans and avoid introducing genetically linked health problems into their breeds.”

Earlier archaeological evidence and research on the evolutionary history of cats has suggested that domestication of the cat originated about 5,000 to 8,000 years ago in the Fertile Crescent, a region located today in the Middle East. This is the area around the eastern end of the Mediterranean, stretching from Turkey to northern Africa and eastward to modern day Iraq and Iran. This domestication of the cat occurred as humans transitioned from nomadic herding to raising crops and livestock.

Cats, with their penchant for hunting mice, rats and other rodents, became useful companions as people domesticated, grew and stored wild grains and grasses. Eventually, cats also became pets but were never fully domesticated. Even today, most domestic cats remain self-sufficient, if necessary, and continue to be efficient hunters, even when provided with food.

Cats and their gene pools spread rapidly around the world as ancient civilizations developed trade routes. Unlike other domesticated species, there has been little effort to improve on the cat for functional purposes. Instead, development of cat breeds has been driven more by preferences for certain aesthetic qualities like coat colour and colour patterns.

Today, there are 50 recognized cat breeds. Of that total, 16 breeds are thought to be “natural breeds” that occurred in specific regions, while the remaining breeds were developed during the past 50 years.

In this study, the UC Davis research team focused on:

* tracing the movement of the modern cat through the ancient world and to the Americas;
* measuring changes in genetic diversity as cats dispersed throughout the world; and
* measuring any loss of genetic diversity that might have occurred in the development of the older or more contemporary breeds.

The researchers collected samples of cheek cells from more than 11,000 cats. These cats represented 17 populations of randomly bred cats from Europe, the Mediterranean, Asia, Africa and the Americas, as well as 22 recognized breeds.

DNA samples of most breeds were obtained at cat shows or were sent in upon the lab’s request by cat owners in the United States. The study was assisted by a host of collaborators from throughout the world. DNA, or deoxyribonucleic acid, is the hereditary material in humans, other animals and plants. It carries the instructions or blueprint for making all the structures and materials that the organism needs to function.

Genetic markers called “microsatellite markers,” commonly used for DNA profiling, were used to determine the genetic relationships of cat breeds, their geographic origins and the levels of genetic loss that have resulted from inbreeding.

From the DNA analysis, the researchers found that the cats were genetically clustered in four groups that corresponded with the regions of Europe, the Mediterranean basin, east Africa and Asia.

They discovered that randomly bred cats in the Americas were genetically similar to randomly bred cats from Western Europe. They also found that the Maine coone and American shorthair — two breeds that originated in the United States — were genetically similar to the seven Western European breeds. This suggests that cats brought to the New World by European settlers have not had sufficient time to develop significant genetic differentiation from their Western European ancestors.

The study yielded many interesting breed-specific findings. For example, the researchers found that the Persian breed, perhaps the oldest recognized pure breed, was not genetically associated with randomly bred cat populations from the Near East, but rather was more closely associated with randomly bred cats of Western Europe.

In addition, the researchers found that, of the Asian cat breeds, only the Japanese bobtail was genetically clustered with Western cats, although it did retain some Asian influence.

Cats from the Mediterranean region were found to be genetically uniform, perhaps a result of the constant movement of ships and caravans during the early era of the cat’s domestication, the researchers suggested.

The study found that genetic diversity remained surprisingly broad among cats from various parts of the world. However the data indicated that there was some loss of diversity associated even with the long-term development of foundation cat breeds — those breeds that provided the genetic basis from which modern pure breeds were developed.

The researchers note that, given the relatively short time span during which modern breeds are emerging, cat breeders should proceed cautiously as they develop their breeds, making sure to maintain a broad genetic base that will minimize introduction of genetically based health problems.

Reference: University of California – Davis (2008, January 29). Cats’ Family Tree Rooted In Fertile Crescent, Study Confirms. ScienceDaily.

Yersinia pestis, ancient DNA and the Black Death

Introduction:

The Black Death is the name given to a pandemic which killed up to a third of the European population between 1347 and 1352. Over the next three hundred years this pandemic was followed by further plagues of lesser mortality. These are historically ascribed to bubonic plague whose aetiological agent is the bacterium Yersinia pestis.

Recently, DNA specific for Y. pestis was amplified from 16th and 18th century human teeth believed to be French plague victims (Drancourt et al., 1998) and 14th century French Black Death victims (Raoul et al, 2000). The lead authors of these reports now believe that the consideration of any cause for the Black Death other than Y. pestis is now speculative.

Ancient DNA analysis:

The study of aDNA involves the extraction and analysis of DNA from the remains of organisms preserved as fossils, skeletons or mummified tissues. Studies are hampered by extremely low levels of preservation, often coupled by the presence of much greater levels of modern contaminants. Characteristically only short aDNA fragments can be amplified and easy amplification of longer fragments is an indication that contamination has occurred.

In the case of Y. pestis, fatal infection would not be expected to leave any specific bony changes, so no osteological confirmation is available and any retrospective diagnosis is completely DNA-based. Two studies from the same research group reported the successful extraction and sequencing of Y. pestis-specific DNA retrieved from the dental pulp cavities of plague victims. Findings that pathogen-specific DNA can be recovered from this source in systemically infected animals have led Drancourt et al (1998) to hypothesise that teeth provide a lasting, contamination-free refuge where pathogen aDNA may survive.

Results:

• Previous extraction techniques are unsuited to preventing bacterial contamination of the DNA extract. Dental enamel is extremely resistant to diagenesis, but may be permeable to contaminating DNA using both the ‘ground’ and the ‘scraped’ methodologies. Encasing teeth in silicone appears to act as a barrier to movement of DNA between the tooth and the gloved hand and this may explain the reduction in contamination with this method.
• No evidence of surviving Y. pestis DNA was found in this study, despite the examination of a large number of samples from five mass graves, including two well-documented plague pits and several other probable plague-victim burial sites.
• Previous studies reported successful direct sequencing from ancient teeth. This implies a low-level of contaminating non-Y. pestis bacterial DNA, despite using a dentine extraction method demonstrated to be contamination prone. This raises two questions:
  1. why such levels of contaminating DNA from other bacteria were found in this study, and
  2. why it was not possible to amplify Y. pestis-specific DNA from samples of plague victims that yield what appears to be authentic human DNA.
• It is possible that diagenetic conditions in the relatively drier and warmer Southern French locations were more conducive to ancient DNA survival than those of north-western Europe. However, aDNA studies have repeatedly demonstrated an inverse correlation between average temperature, humidity and aDNA retrieval. It is, therefore, surprising that warmer locations would be more successful.
• An alternative environmental variable is groundwater. An inverse correlation has been noted between sample survival and exposure to water. However the ability to amplify host DNA suggests survival is not an issue.
• A further explanation is that the individuals from whom the samples derive were either infected by a Y. pestis strain lacking the plasmid-located sites for amplification or not infected with Y. pestis (because they were not victims of the Black Death, or because the infection did not seed the pulp cavity, or because the Black Death and subsequent plagues were not caused by Y. pestis). The first hypothesis is unlikely as the plasmid containing the pla gene is a consistent feature of contemporary isolates. The second hypothesis is plausible. There is no guarantee that bacteria causing a systemic infection entered the teeth. It is, therefore, possible that Y. pestis may not have been present in the teeth specimens but that infection by this bacteria caused death. The third hypothesis is controversial, but cannot immediately be discounted.

Reference:

Gilbert, M.T.P, Cuccui, J. White, W, Lynnerup, N, Titball, R.W, Cooper, A and Prentice, M.B. 2004. Absence of Yersinia pestis-specific DNA in human teeth from five European excavations of putative plague victims. Microbiology 150: 341-354.

Blog Carnival – Tangled Bank #97

It’s freezing over at the Inoculated Mind, but there’s plenty of scientific news to keep you company as you huddle up in the warm with the 97th edition of the Tangled Bank. There is lots to enjoy, but I was particularly intrigued by news from Greg Laden’s blog about recent research on the subject of Cooking and Human Evolution.

Extinct Marsupial Lion Tops African Lion In Fight To Death

Pound for pound, Australia’s extinct marsupial lion (Thylacoleo carnifex) would have made mince meat of today’s African lion (Panthera leo) had the two big hyper-carnivores ever squared off in a fight to the death, according to an Australian scientist.

New research published in the Journal of Zoology suggests that Thylacoleo killed prey rapidly, using its “bolt-cutter” type teeth to scissor through hide and flesh to produce major trauma and blood loss.

By contrast, African lions and similar big cats of today use their bite force to suffocate prey, using a “clamp and hold” technique that can take up to 15 minutes with large prey such as Cape buffalo.

“My results suggest that the marsupial lion employed a unique killing technique,” says research author Stephen Wroe. “It used its massive carnassial cheekteeth to effect major trauma and a rapid kill. Unlike any living mammalian carnivores, the marsupial’s carnassials were not only butchery tools but also active components in the killing process.”

Using a sophisticated computer modelling method [finite element (FE) analysis], that renders dynamic 3D models based on CT scans of the marsupial’s cranial mechanics and musculoskeletal architecture, Wroe has revealed that the creature’s skull, jaw, and head and neck muscles were well adapted to using the unique technique for killing large prey, but not for delivering the prolonged suffocating bite of living big cats.

“The marsupial lion also had an extremely efficient bite,” Wroe says. “In addition to very powerful jaw muscles for its size, its muscle and skull architecture were arranged in such a way as to take greater advantage of leverage than in living cats.”

Wroe, who has published findings about bite force in other hypercarnivores, such as great white sharks and sabre tooth tigers, believes there is now no doubt that Australia’s marsupial lion was a fearsome predator that punched well above its weight.

“Certainly, T carnifex was seriously over-engineered for dispatching small prey. These new findings support the conclusion that the creature regularly preyed on relatively large species and was able to effect quick kills and withstand large forces generated by large struggling prey.

“Hypothetically, had a large marsupial lion ever come face to face with an African lion of similar size, it could have use its deadly cheek teeth and incredibly powerful arms to inflict mortal wounds on the mammal,” Wroe says. “Had it not become extinct, it might now hold top spot over toady’s ‘king of the jungle.’”

University of New South Wales (2008, January 18). Extinct Marsupial Lion Tops African Lion In Fight To Death. ScienceDaily. Retrieved January 21, 2008, from http://www.sciencedaily.com­ /releases/2008/01/080117093440.htm

Secret Of Scottish Sheep Evolution Discovered

Researchers from the University of Sheffield, as part of an international team, have discovered the secret of why dark sheep on a remote Scottish Island are mysteriously declining, seemingly contradicting Darwin’s evolutionary theory.

Dr Jacob Gratten and Dr Jon Slate, from the University’s Department of Animal and Plant Sciences, led the team, which found that the gene responsible for dark coat colour is linked to other genes that reduce an animal’s fitness.

The researchers looked at coat colour in a feral population of Soay sheep on Hirta in the St Kilda Archipelago. On Hirta about three quarters of sheep have dark brown coats, while the remaining quarter have light sandy coats. However, despite the fact that the dark-coated Soay sheep are larger, which is usually linked to survival and reproductive success, the frequency of light-coated sheep has increased over the last 20 years.

Darwin’s theory would have predicted that because dark-coated sheep appear fitter that they would do better than light-coated sheep, until only dark-coated sheep remained in the population. However, this study shows that the process of evolution by natural selection in Soay sheep, although still evident, is actually more complex than this.

Dr Gratten and colleagues used a statistical genetics approach similar to that used by medical geneticists, when trying to map genes for human disease such as heart disease or diabetes. They found that the dark coat trait is usually co-inherited with a set of genes that increase size but decrease reproductive success. The light coat trait is usually co-inherited with a set of genes that decrease size but increase reproductive success.

This discovery means that sheep with one copy of the dark gene and one copy of the light gene are quite large and also have quite high reproductive success. Sheep with two copies of the dark gene are larger still, but have poor reproductive success. Sheep with two copies of the light gene are small, but still have quite high reproductive success. This means that the two types of dark sheep although indistinguishable visually, vary in Darwinian fitness.

The study was based on over 20 years of field data, and involved researchers from the University of Edinburgh and the Queensland Institute of Medical Research in Brisbane, as well as members of the University of Sheffield.

Dr Jacob Gratten said: “The aim of this study was to improve understanding of how evolution by natural selection operates. The study addresses an important problem in evolutionary biology. It shows that predicting the evolutionary response to selection is difficult without knowledge of which genes are in close proximity to each other. It also highlights that an understanding of the underlying genetic basis of a highly visible trait was necessary in order to understand its evolution.”

This research – ‘ A Localised Negative Genetic Correlation Constrains Microevolution of Coat Colour in Wild Sheep’ will be appear in the journal Science.

University of Sheffield (2008, January 20). Secret Of Scottish Sheep Evolution Discovered. ScienceDaily. Retrieved January 21, 2008, from http://www.sciencedaily.com­ /releases/2008/01/080117140834.htm

Genetic Diversity Of European Americans And Disease Gene Mapping

Labels such as “European American”, “white”, or “Caucasian” are often viewed as representing a homogeneous category in gene mapping studies and census reports, but each of these labels actually groups together multiple populations, which have diverse origins due to the complex history of European immigration to the United States. In a recent study an international team of researchers provide the first genetic dissection of the population structure of European Americans, focusing on identifying the contributions from different genetic ancestries that are important for disease gene mapping.

This is a timely issue as the last year has seen a dramatic upswing in genetic association studies and the discovery of almost a hundred new risk factors for common genetic diseases such as cancer and diabetes. If the subtle population substructure that exists within European American populations is not understood and accounted for, genetic association studies can produce incorrect findings if disease cases are compared to healthy controls that on average have different ancestry.

By systematically examining data from four actual disease association studies in European Americans, this study describes and characterizes the majority of population substructure in European Americans that could lead to spurious associations. “Although our work is far from a complete description of European American population history, for the purpose of disease gene mapping studies it is adequate to measure how closely each person’s genetic ancestry resembles three populations that can be roughly described as northwest European, southeast European, or Ashkenazi Jewish,” says Dr. David Reich, one of the senior authors on the study, an Associate Professor of Genetics at Harvard Medical School and an Associate Member at the Broad Institute of Harvard and MIT. “With this approach, we can avoid most false-positive associations due to population substructure in European American disease gene mapping studies. Our previous work has addressed related challenges in studies of African Americans and Latino Americans.”

Based on their discovery that ancestry from only three populations accounts for most of the potentially problematic substructure in European American disease association studies, the researchers scoured through published data sets to identify places in the genome where common DNA sequence variants differ substantially in frequency among these three ancestral populations and are therefore potentially informative for estimating genetic ancestry.

The investigators then confirmed the utility of these genetic variants by testing them in DNA samples that their coauthors collected from the United Kingdom, Sweden, Poland, Spain, Italy, Greece and U.S. Ashkenazi Jews. “We identified 300 common genetic variants that have unusually different frequencies in the three ancestral populations: they are about 10 times more informative for predicting the ancestry of European Americans than random genetic variants”, says lead author Dr. Alkes Price, a post-doctoral researcher at the Harvard Medical School Department of Genetics and the Broad Institute of Harvard and MIT. “We can thus correct for population substructure in European American disease association studies using just these 300 markers.”

This panel of 300 markers should be valuable in targeted associated studies that follow up previously implicated candidate genes: by comparing the ancestry of disease cases to healthy controls using data from the panel of 300 markers, researchers can determine whether observed associations are genuine, and not false-positives due to population structure. The panel can also be used to match the ancestry of cases and controls prior to more comprehensive studies.

While the technology should provide a new tool in disease gene mapping studies, the researchers caution that the ability to roughly categorize individuals into populations with a small number of genetic markers is not useful in a clinical setting, nor does it completely eliminate the utility of self-described ethnicity. “Although these 300 markers give a reasonable estimate of the major components of genetic ancestry in European Americans, self-described ethnicity can still reflect environmental, social and cultural factors that may not be captured by estimating genetic ancestry,” says Dr. Joel Hirschhorn, one of the senior authors of the study, an Associate Professor of Genetics at Children’s Hospital Boston and Harvard Medical School, and a Senior Associate Member at the Broad Institute of Harvard and MIT, “Because the genetic differences between these populations are very small, the study is most important for helping in gene discovery efforts, which will lead to better understanding of human biology in health and disease, and hopefully improved care for all patients over the long term.”

Published simultaneously in PLoS Genetics is an independent study led by Michael Seldin, in which Chao Tian and colleagues also present panels of markers that can be used to correct for population structure in European American disease association studies. A commentary jointly authored by Michael Seldin and Alkes Price on the practical application of the panels developed by the two groups accompanies these articles.

Title and full author list: “Discerning the Ancestry of European Americans in Genetic Association Studies” PLoS Genetics.

Alkes L. Price*, Johannah Butler, Nick Patterson, Cristian Capelli, Vincenzo L. Pascali, Francesca Scarnicci, Andres Ruiz-Linares, Leif Groop, Angelica A. Saetta, Penelope Korkolopoulou, Uri Seligsohn, Alicja Waliszewska, Christine Schirmer, Kristin Ardlie, Alexis Ramos, James Nemesh, Lori Arbeitman, David B. Goldstein, David Reich*, Joel N. Hirschhorn*

* These three authors contributed equally

PLoS Genetics (2008, January 19). Genetic Diversity Of European Americans And Disease Gene Mapping. ScienceDaily. Retrieved January 21, 2008, from http://www.sciencedaily.com­ /releases/2008/01/080118093725.htm