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World’s largest database on sheep genetics

Australia launched the world’s largest database on sheep genetics, with the aim of improving breeding and boosting returns for producers. More than two million sheep, drawn from Australia’s 100 million-strong flock, will be incorporated into the database, which brings together the fragmented genetic records used in the past to produce a new comprehensive national system. “We have some tremendously exciting opportunities,” Australia’s Agriculture Minister Peter McGauran said. The new, consolidated service would allow stud breeders, sheep classers and commercial sheep producers to compare animals from different flocks on genetic merit for the first time, McGauran said, helping them to improve their revenue.

The new system will work with sheep producers, using scientific evaluation of their sheep to produce the best breeding outcomes. For example, the characteristics of sheep can be fed into the database, desired traits selected and a match produced for the most appropriate breeding rams. The new system, called Sheep Genetics Australia, is a joint initiative of the wool industry’s main marketing and research body Australian Wool Innovation and the meat industry’s marketing body Meat & Livestock Australia. Variations between genetic systems in the past had held back the industry’s development, McGauran said.

Reuters
November 8, 2005

Original web page at Reuters

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Lawyers fire opening shots in Intelligent Design case

The opening shots were fired on Monday in the first court trial to scrutinise the Intelligent Design movement. ID proposes that life is so complex it cannot have emerged without the guidance of an intelligent designer – it is seen as a religion-friendly alternative to Darwin’s theory of evolution.

“It is going to be the role of the plaintiffs to argue that ID is a form of religious advocacy,” says Eugenie Scott of the US National Center for Science Education in Oakland, California, which is advising the plaintiffs. “The defence will argue that ID is actually science and is valid. We will argue the opposite.” Backed by the American Civil Liberties Union, the plaintiffs in the civil case are 11 parents who believe their high school’s board is encouraging children to consider ID as an alternative to evolution because of their evangelical Christian motivations. It is unconstitutional to teach anything in US schools that does not primarily have a secular motive and effect on pupils.

The plaintiffs’ attorneys are deploying a double-barrelled strategy, aiming to show that ID is not science and highlighting its similarities to creationism. Following a Supreme Court ruling in 1987, it is now illegal to teach creationism in schools. In his opening statement, Eric Rothschild, attorney for the plaintiff, said: “ID is not new science, it’s old theology. There is no controversy in the scientific community.” The plaintiffs then called their first expert witness to the stand, biologist Kenneth Miller of Brown University, Rhode Island. He criticised the content of a book “Of Pandas and People”, which promotes ID and was recommended by the Dover School Board for students.

Miller used several examples to argue that it inaccurately interprets Darwin’s theories, e.g. that apes and humans share a common ancestry, and omits scientific research in order to denigrate the theory of evolution. He also said that ID could not be considered as science because it is incapable of providing testable hypotheses. He explained the process of peer review – through which scientists critique each other’s work – and the process by which hypotheses are generated and then tested by experiment. These approaches have been employed for evolution, elevating it from hypothesis to theory, but not for ID, he said.

A defence attorney cross-examined Miller, asking him to admit that evolution is “just a theory” and that there are “gaps” in Darwin’s theory. Miller only partially agreed to modified versions of these statements, but defence lawyer Richard Thompson claimed at the end of the day that Miller had agreed to these statements. The case continues.

Trial time line
• Monday 26th September 2005: opening statements
• First week: testimony from plaintiffs’ expert witnesses, including scientists Kenneth Miller of Brown University, Robert Pennock of Michigan State University and Barbara Forrest of Southeastern Louisiana University, followed by John Haught a theologian at Georgetown University
• Next two to three weeks: continuation of plaintiffs’ case – more expert witnesses including Brian Alters at Harvard University and Kevin Padian at the University of California, Berkeley.
• Last two to three weeks: defence’s case, including expert witnesses such as scientists Michael Behe, Scott Minnich of the University of Idaho and Warren Nord of the University of North Carolina at Chapel Hill. Also, Dick Carpenter of US Evangelical Christian group Focus on the Family and sociologist Steve Fuller of the University of Warwick, UK.
• Early November: closing arguments
• Early December: Judge’s verdict

New Scientist
October 25, 2005

Original web page at New Scientist

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How a zebra lost its stripes: rapid evolution of the quagga

DNA from museum samples of extinct animals is providing unexpected information on the extent and effect of the Ice Age as well as the path of species evolution, according to a report by scientists from Yale University, the Smithsonian Institute and the Max Planck Institute for Evolutionary Anthropology.
The quagga, Equus quagga, a South African relative of horses and zebras, having a front half with zebra-like stripes and a back section like a horse with no marking, became extinct about 100 years ago. The pelt from a quagga museum specimen was the subject of tissue sampling that launched the field of ancient DNA analysis.

“Twenty years ago this exact species opened the field of ancient DNA studies on extinct animals,” said one of the authors, Gisella Caccone, senior research scientist in the Department of Ecology and Evolutionary Biology at Yale. “Now, thanks to technological advances in the field, we revisited the story and used a population level approach to this question by analyzing a larger fragment of DNA and multiple specimens.” In the past, the quagga has alternatively been described as a species and a subspecies of the Plains zebra. These researchers asked how and when the quagga diverged from all the remaining related horses, zebras, and asses. They compared the genetics, coat color and habitats of existing zebras with related extinct species.

The mitochondrial DNA markers from 13 museum specimens, including the only skeleton in museum collections, which is at Yale’s Peabody Museum of Natural History, showed that quagga likely diverged from Plains zebra about 120,000 to 290,000 years ago during the Ice Age. These results suggest that the quagga descended from a population of plains zebras that became isolated and the distinct quagga body type and coloring evolved rapidly. This study reveals that the Ice Age was important not just in Europe and North America, but also in Africa. “The rapid evolution of coat color in the quagga could be explained by disrupted gene flow because of geographical isolation, an adaptive response to a drier habitat, or a combination of both of the two forces,” said Caccone.

Science Daily
October 25, 2005

Original web page at Science Daily

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Human Y chromosome stays intact while chimp Y loses genes

The human and the chimpanzee Y chromosomes went their separate ways approximately 6 million years ago. But ever since this evolutionary parting, these two chromosomes have experienced different fates, new research indicates. Since the time of the divergence of the X and Y chromosome roughly 300 million years ago, the Y chromosome has lost nearly all of its unpartnered genes. This has led some to predict that, given a constant rate of decay, the Y chromosome will be completely devoid of functional genes in 10 million years. The chimpanzee ancestors diverged from ours about 6 million years ago. By comparing the gene catalog of the chimpanzee Y chromosome to ours, it is clear that the human Y chromosome has not lost any of its unpartnered genes in the past 6 million years. While the human Y has maintained its count of roughly 27 genes and gene families over the last 6 million years, some of these same genes on the chimp Y have mutated and gradually become inactive. The authors speculate that one likely reason for such disparity is due to chimpanzee mating habits.

“Contrary to the dire predictions that have become popular over the last decade, the sky is *not* falling on the Y,” says Whitehead Member and Howard Hughes Medical Institute investigator David Page, senior author on the study that appeared in the September 1 issue of the journal Nature. “This research clearly demonstrates that natural selection has effectively preserved regions of the Y chromosome that have no mechanisms with which to repair damaged genes.” For many years, it’s been assumed that the Y chromosome is headed for extinction because, unlike other chromosomes, it has no genetic “mate” with which to swap genes. In 2003, Page published a landmark paper in Nature challenging that claim by demonstrating how a certain region of the Y chromosome possessed a unique mechanism for repairing mutated genes.

Through sequencing the Y, the Page lab and collaborators at Washington University School of Medicine in St. Louis discovered that many of its genes were located in palindromes–long stretches of DNA letters that read the same forwards and backwards. By folding into a hairpin, the authors suggested, a gene might then swap the appropriate genetic material with itself. This demonstrated a process for the Y chromosome to maintain its integrity despite lacking a mate. However, there is another region of the Y, called the “X-degenerate” region, where the genes are not situated in palindromes.

“The genes in the palindrome region are primarily sperm-producing genes, and most other genes unique to the Y aren’t located there,” says Jennifer Hughes, a postdoctoral scientist in Page’s lab and first author on the paper. These other genes have no obvious means for self-repair. Because of this, many proponents of the “Y’s demise” theory remained undaunted. Once again collaborating with Richard Wilson from the Washington University School of Medicine in St. Louis Missouri, Page and his research team sequenced this X-degenerate region of the chimpanzee Y chromosome and compared it to the human Y. “We were looking for any evidence that the human Y has lost genes since parting ways with the chimp,” says Hughes. “Had we found active genes on the chimp Y that had become inactive on the human, that would be the smoking gun. But we didn’t find any such evidence. In fact, we found the opposite.”

On the chimp Y, five genes have suffered mutations that rendered them inactive. On the human Y, those same genes continue to function perfectly. “So then,” says Hughes, “even though the Y has lost many genes since its origin about 300 million years ago, it’s been holding steady in humans for the last 6 million years.” In other words, if the one region of the Y can depend on itself for survival, the other region has found a friend in evolution. “We now see that natural selection *is* working to conserve this unpartnered region of the Y,” says Page, who is also a professor of biology at MIT. “If mutations do occur in any of these genes, they don’t seem to pass on in the lineage. This is a clear example of how evolution is not just about moving ahead, it’s also about not falling behind.”

Fortunately for the primate world, male chimps, just like male humans, are probably not bound for early extinction. Those genes in the X-degenerate region are what scientists call “housekeeping” genes, meaning that they are active in most cells in the body and don’t carry out any male-specific functions. Page and his team speculate that the loss of genes on the chimpanzee Y may be due to the chimp’s mating habits. Both male and female chimps engage with multiple partners when they mate. This gives a strong selective pressure on those genes that produce sperm. Conversely, it puts less pressure on evolution to preserve those genes on the Y whose functions have nothing to do with reproduction. Because humans historically have been largely monogamous, our Y chromosomes have been spared such selective-pressure imbalance. “Of course,” acknowledges Page, “this is a hypothesis that we have no way to scientifically prove or disprove. However, we believe it’s currently the best explanation.”

Science Daily
October 11, 2005

Original web page at Science Daily

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Researchers find human brain still evolving

Human evolution, University of Chicago researchers report, is still under way in what has become our most important organ: the brain. In two related papers, published in the September 9, 2005, issue of Science, they show that two genes linked to brain size are rapidly evolving in humans. “Our studies indicate that the trend that is the defining characteristic of human evolution–the growth of brain size and complexity–is likely still going on,” said lead researcher for both papers Bruce Lahn, PhD, assistant professor of human genetics at the University of Chicago and an investigator at the Howard Hughes Medical Institute. “Meanwhile, our environment and the skills we need to survive in it are changing faster then we ever imagined. I would expect the human brain, which has done well by us so far, will continue to adapt to those changes.”

Evolution, Lahn said, doesn’t occur at the species level. Rather, some individuals first acquire a specific genetic mutation; and because that variant confers on those who bear it a greater likelihood of survival, it then spreads in the population. “We’re seeing two examples of such a spread in progress,” he said. “In each case, it’s a spread of a new genetic variant in a gene that controls brain size. This variant is clearly favored by natural selection.” Lahn previously showed that there was accelerated evolution in humans among numerous genes, including microcephalin and abnormal spindle-like microcephaly-associated (ASPM). Both of these genes regulate brain size, and therefore “were good candidates to look for signatures of selection. We indeed found such signatures when we compared humans to other species,” he said. “As a natural extension of that, we asked, could it be that selection on these genes is still ongoing in humans?”

In the two Science papers, the researchers looked at variations of microcephalin and ASPM within modern humans. They found evidence that the two genes have continued to evolve. For each gene, one class of variants has arisen recently and has been spreading rapidly because it is favored by selection. For microcephalin, the new variant class emerged about 37,000 years ago and now shows up in about 70 percent of present-day humans. For ASPM, the new variant class arose about 5,800 years ago and now shows up in approximately 30 percent of today’s humans. These time windows are extraordinarily short in evolutionary terms, indicating that the new variants were subject to very intense selection pressure that drove up their frequencies in a very brief period of time–both well after the emergence of modern humans about 200,000 years ago.

Each variant emerged around the same time as the advent of “cultural” behaviors. The microcephalin variant appears along with the emergence of such traits as art and music, religious practices, and sophisticated tool-making techniques–which date back to about 50,000 years ago. The ASPM variant coincides with the oldest-known civilization, Mesopotamia, which dates back to 7000 BC. “Microcephalin,” the authors wrote in one of the papers, “has continued its trend of adaptive evolution beyond the emergence of anatomically modern humans. If selection indeed acted on a brain-related phenotype, there could be several possibilities, including brain size, cognition, personality, motor control or susceptibility to neurological/psychiatric diseases.” “The next step is to find out what biological difference imparted by this genetic difference causes selection to favor that variation over the others,” Lahn said. Both microcephalin and ASPM have numerous genetic variations. The authors show that certain variants are subject to very strong positive selection over others.

To determine the variation frequency of the two genes, the researchers surveyed more than 1,000 individuals representing 59 ethnic populations worldwide. For each gene, the scientists identified a large number of haplotypes, or variant copies. They found that one class of haplotypes, called haplogroup D, shows two distinct characteristics. First, they are very young. Because not enough evolutionary time has passed since the first copy of these variants appeared for them to diversify, all the haplogroup D variants are nearly identical. Second, despite recent emergence they have spread rapidly. “In a very short period of time, this class of variants arose from a single copy to many copies. That implies that this must have happened because of positive selection,” Lahn said, pointing out that it’s statistically unlikely for a haplogroup this young to have such high frequency due merely to random genetic drift.

The team also observed geographic differences. For haplogroup D of ASPM, they found that it occurs more frequently in Europeans and surrounding populations including, North Africans, Middle Easterners, and South Asians, and at a lower incidence in East Asians, New World Indians and sub-Saharan Africans. For microcephalin, the researchers found that haplogroup D is more abundant in populations outside of sub-Saharan Africa. The biochemical functions of these two genes are not fully understood. There is, however, some information as to what they do. Mutations that render either gene completely nonfunctional in humans cause microcephaly, a medical condition in which the brain is much smaller than normal. In many cases there are often no other abnormalities, which indicates that these two genes play an important role in brain size.

A series of studies suggest that there is some correlation between brain size and intelligence, but with some exceptions. Although, on average, a man’s brain is 3 to 4 percent larger than a woman’s, both sexes score similarly on IQ tests. Lahn also points out that “brain size is very heritable. Bad nutrition is typically not a factor; the brain is very privileged within the body.” The researchers emphasize that very little is known about the impact of these variants. They may not have anything to do with cognition or intelligence. “Just because these genes are still evolving, doesn’t necessarily mean they make you any smarter,” Lahn said. “We’ve evolved genes for selfishness, violence, cruelty–all of which are in place because they may make survival easier. But in today’s society, they’re certainly not condoned.”

Lahn and colleagues stress these studies only examine two genes, and that the genetic variations within a population are often almost as great as the differences between groups. “If we look at multiple genes, the ethnic variations–such as the ones we found–are likely to be counterbalanced by other differences,” Lahn said. “It just happens that we looked at two genes for which the variants favored by selection have a higher frequency in some populations, such as Europeans. It might be that for the next two brain size genes we find, the variants favored by selection will have a higher frequency in Asians or Africans.” Scientists know of about a half dozen other genes that are primarily linked to brain size and several others that may also play a role in regulating brain size.
According to Lahn, these are all primary candidates for learning more about human evolution.

Science Daily
October 11, 2005

Original web page at Science Daily

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The chimpanzee genome is unveiled

The chimp genome sequence, which consists of 2.8 billion pairs of DNA letters, will not only tell us much about chimps but a comparison with the human genome will also teach us a great deal about ourselves. The major accomplishment is that we now have a catalogue of the genetic differences between humans and chimps,” says lead author, Tarjei Mikkelsen of the Broad Institute in Cambridge, Massachusetts, US. In keeping with previous studies comparing much smaller portions of the chimp and human genomes, the new comparison shows incredible similarity between the genomes. The average number of protein-changing mutations per gene is just two, and 29% of human genes are absolutely identical. What is more, only a handful of genes present in humans are absent or partially deleted in chimps. But the degree of genome similarity alone is far from the whole story. For example, the mouse species Mus musculus and Mus spretus have genomes that differ from each other to a similar degree and yet they appear far more similar than chimps and humans.

Domestic dogs, however, vary wildly in appearance as a result of selective breeding and yet their genome sequences are 99.85% similar. So most of the differences between chimp and human genomes will turn out to be neither beneficial nor detrimental, in evolutionary terms. The real challenge then will be finding the changes that played a major role in the evolution of chimps and humans since the two lineages split, 5 to 8 million years ago. Nothing obvious has leapt out of the initial analysis. “From this study, there’s no silver bullet of what makes chimps chimps and humans humans,” says Evan Eichler of the University of Washington at Seattle, US.

Comparing the two genomes has thrown up numerous candidates for what makes humans different though. One such set came by comparing 13,454 specific genes in the chimp and human genomes, looking for signs of rapid evolution. For each gene, the researchers compared the number of single letter mutations that alter the encoded protein versus silent mutations that have no effect. Silent mutations are possible because most amino acids are coded by more than one 3 letter DNA ‘word’ – for example, proline is coded by CCU, CCC, CCA, and CCG, so a change at the third position makes no difference to the protein. Comparing the two types of mutations allowed the team to spot genes that have had changes favoured by natural selection while taking into account the background mutation rate. And 585 of the genes studied in this set – many involved in immunity to infections and reproduction – had more protein-altering mutations than silent ones. Mikkelsen believes these will be a good place to look for genes that make humans different from chimps.

But comparing genome sequences can only tell scientists so much. Now begins the methodical job of homing in on the promising parts of the sequence and identifying the differences that count. “This is best viewed as an exciting starting point,” says Simon Fisher at the Wellcome Trust Centre for Human Genetics at Oxford University, US. “In the same way that knowledge of our own genome sequence has not automatically led to a full understanding of human biology, so the decoding of other primate genomes will not, by itself, reveal exactly what sets us apart.” But he admits: “Coming face to face with the details of evolution is really spectacular.”

Source: Nature (vol 437, p69)

New Scientist
September 27, 2005

Original web page at New Scientist

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95% of thoroughbreds linked to one superstud

Virtually all 500,000 of the world’s thoroughbred racehorses are descended from 28 ancestors, born in the 18th and 19th centuries, according to a new genetic study. And up to 95% of male thoroughbreds can be traced back to just one stallion. Thoroughbred horses were developed in 18th century in the UK. English mares were bred with Arabian and other stallions to create horses with great stamina for distance racing. Today, thoroughbreds are the most valuable of breeds, representing a multi-billion dollar annual industry, worldwide.

To assess the genetic diversity of modern racing horses, geneticist Patrick Cunningham of Trinity College in Dublin, Ireland, compared 13 microsatellite DNA loci – repeating sequences of DNA which vary in length – in 211 thoroughbreds and 117 other Shetland, Egyptian and Turkish horses. He also examined studbooks dating back to 1791. He found the majority of the half million progeny alive today are descended from just 28 “founder” horses.

It was already known that just a handful of stallions (but many mares) were used to found the thoroughbred breed. But startlingly, the new research finds that, in 95% of modern racehorses, the Y-chromosome can be traced back to a single stallion – the Darley Arabian, born in 1700. Related work on sequencing the horse genome is also uncovering genes in thoroughbreds linked to speed and stamina. Screening for these traits could one day guide owners’ and breeders’ decisions when buying horses, which may sell for many millions of dollars. “We hope to produce sounder, faster and better-performing horses,” says Cunningham. He and colleague Emmeline Hill at University College Dublin is also using the horse genome to uncover genes that explain why one animal runs faster than another.

“Horses are flight animals naturally selected for speed and stamina in the wild,” explains Hill. “With domestic selection, speed was further augmented in the thoroughbred.” Thirty-five per cent of the difference in racing performance between horses can be explained by genetics alone, says Hill. She is cross-referencing up to 140 recently discovered human genes for fitness and performance in a bid to track down equine equivalents. These genes are involved in traits related to the cardio-respiratory system, muscle strength and metabolism, she says.

However, the analysis of thoroughbred genetics is also revealing the other side of the coin, notes Matthew Binns of the Royal Veterinary College in London, UK. Many negative traits are associated with inbreeding in the diminutive gene pool, he says. “The selections we’ve made for fantastic beasts have had some detrimental consequences.” One tenth of thoroughbreds suffer orthopaedic problems and fractures, 10% have low fertility, 5% have abnormally small hearts and the majority suffer bleeding in the lungs, says Binns. But as well as allowing breeders to select for performance-related genes, elucidating the horse genome may allow researchers to breed out negative traits, he says. “Now we have a good amount of the horse genome, there are interesting times ahead,” says Binns. “Over the next 10 years there will be some changes in this very traditional industry.”

New Scientist
September 27, 2005

Original web page at New Sientist

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Chimp papers by the barrel

A detailed comparison of the human and chimpanzee genomes reveals that some genes coding for transcriptional regulators may be evolving faster in humans, an international research consortium comprising 67 authors reports today in Nature. The paper, arriving a year and a half after the chimp draft, is accompanied by a cluster of studies in Science, Genome Research, and Nature that use this powerful comparative tool to assess gene-expression patterns across different organs, test a prevailing theory about Y-chromosome evolution, and find elements and mediators of genomic variation. The sequence should expand the scope of chimpanzee research say those involved, and may aid in investigations into what makes humans human. “The chimp genome is exciting because it gives us the raw material to ask that question,” said Michael Eisen at the University of California, Berkeley, who did not participate in these studies.

Chimps and humans split from a common ancestor 6 million years ago; the comparison shows that human and chimpanzee genomes are 96% identical, but it is the differences between the species–as many as 3 million of which fall in functional areas of the genomes–on which research now focuses. According to the main study, the catalog of genetic differences includes about 35 million single-nucleotide changes, 5 million insertion/deletion events, and a number of other chromosomal rearrangements. Members of the consortium assessed deviations from expected mutation patterns. In the human genome, they found evidence of selective sweeps in the past quarter million years in regions containing genes like FOXP2—which has been associated with speech acquisition in humans.

Some genes are evolving more rapidly in humans than in chimps, particularly transcriptional regulators, according to the paper. They also found that both humans and chimps have acquired more potentially deleterious mutations than mice, rats, and other rodents—perhaps making them better able to adapt to a changing environment.

In another study, Wolfgang Enard and colleagues at the Max-Planck Institute for Evolutionary Anthropology in Germany looked at protein sequences and expression patterns for genes in various chimp and human tissues and found a gradation of selective constraints on the organs they studied. While the brain showed the fewest differences between the species, genes active in the brain have accumulated more changes in humans than in chimpanzees. The researchers also found evidence of positive selection in human evolution for X-chromosomal genes expressed in testis. According to Enard, this is probably because “it’s so directly relevant for reproduction. If I am a sperm and I have a mutation that lets me divide faster…it will have a huge effect on my distribution,” he told The Scientist.

A group at the Whitehead Institute, which had previously sequenced the human Y chromosome, compared it to the chimp’s Y-chromosome sequence to assess the widely held “impending demise” hypothesis: that the 16 unique genes on the human Y chromosome which don’t have gene-conversion partners, will completely disappear in the next 10,000 years. Contrary to the hypothesis, they found that all of the genes were actually maintained in humans since they diverged from chimps, but that five of them had been inactivated in the chimp’s Y chromosome.

For our more “promiscuous” cousins, “sperm competition is intense,” said Jennifer Hughes, a postdoctoral scientist at the Whitehead Institute and first author on the study. So her group speculated that the strong selective pressure on the Y-linked genes coding for such male fertility traits–which are found in palindromes that give the genes pairing partners–outweighs the drive to maintain those 16 “partnerless” genes in chimpanzees. Hughes said these unique genes are “civilian casualties in the sperm wars.” She told The Scientist, “We’re hoping this will put the [impending] demise theory to rest once and for all.”

Two other studies looked more at elements of genomewide variation. A team led by Evan Eichler at the University of Washington School of Medicine in Seattle showed that segmental duplications have a much greater impact on genome differences between species than previously realized. They found that these “large-scale genetic events” altered about 2.7% of the genome, while the more commonly studied single base-pair changes account for changing 1.2% of the genome. The researchers found that several duplicated genes associated with developmental disorders in humans were single-copy in the chimp genome, suggesting that the chimpanzees may not be disposed to the same diseases. They also connected much of the species-specific duplications to differences in gene expression.

A study by researchers in Canada and Sweden compared human and chimp genomes with that of the more primitive Rhesus monkey and found that retroelements, or “jumping genes,” have been deleted in the course of evolution; they also found a possible mediator of these retroelement deletions and of thousands of insertion-deletion sequence differences between human and chimp genomes: short identical sequences flanking deleted regions.

The Scientist
September 27, 2005

Original web page at The Scientist

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Gene therapy to treat haemophilia; cure achieved in dogs

Progress in gene therapy to treat haemophilia has been impressive in the past few years. Gene therapy has been used to successfully treat haemophilia in dogs. A leading researcher from Philadelphia USA, Professor Katherine High, is examining the obstacles to successful gene therapy in human patients with haemophilia. She hopes that the problems may be overcome in the next five years to develop a successful gene transfer approach for sufferers of haemophilia.

“It has taken approximately 5 to 8 years to move from a cure for haemophilia in mice to a cure in dogs. This has been achieved by multiple gene transfer strategies. Clinical studies have identified which aspects of gene transfer therapy in dogs are directly applicable in humans and have identified potential problems, such as mode of delivery, which must be overcome before applying this approach in humans,” said High. Professor High will review these exciting findings and the steps to achieving a successful outcome in humans at the XXth Congress of the International Society on Thrombosis & Haemostasis in Sydney.

Science Daily
August 30, 2005

Original web page at Science Daily

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Why cats prefer meats to sweets

As cat owners know, their feline friend would much rather chase and eat a live mouse than snack on the chocolate equivalent, and now researchers have discovered the reason – cats are simply unable to taste sweet things.

An examination of feline genetics has shown a significant defect in one of the genes that codes for part of the sweet taste receptor. This “huge deletion” of 247 base pairs in the gene that codes for the T1R2 protein – one of two proteins that make up the sweet taste receptor in mammals – has left cats unable to detect sweet-tasting compounds like sugars and carbohydrates. It explains the indifference that domestic cats, lions, tigers, leopards and jaguars have been reported to show towards sweet foods. And it may also explain why they have evolved into such accomplished hunters, says Joseph Brand, professor of biophysics at Monell Chemical Senses Center in Philadelphia, US, and one of the study’s authors. “But it could be the other way around,” he suggests. “What came first: carnivorous behaviour or the loss of the T1R2 protein? With regard to the gene, is this a case of use it or lose it?” he asks.

Looking down the family tree may provide clues. Brand has also found the mutant gene in cheetahs and tigers, and in their more distant relation, the hyena. So, although it seems clear that an ancestor of the big cats and the hyena must have possessed the faulty gene, Brand does not know on which branch of the evolutionary tree it first occurred. “Almost certainly the ancestral mammal would have been a successful hunter, or it would not have survived losing its sweet taste bud. “And losing it may well have given wild cats a certain food niche that other animals can’t get into – most other animals need to hunt in packs, but big cats have developed the strength to hunt alone,” Brand told New Scientist. “But it’s a hard way of getting nutrition: they must hunt it, eat it, remove the nitrogen and only then can they use it.”

Carnivores’ diets are much less efficient than the omnivorous diets of many other large mammals, although parts of a hunted animal do contain carbohydrate – especially the liver – so it is possible that cats may be able to metabolise these energy stores. Coupled with the loss of sweet taste receptors in cats is a deficiency of sucrase in cats – the enzyme that digests sucrose. A consequence of this can be seen in cats that accidentally drink water containing sucrose. This makes them violently ill, but, since they cannot taste the sugar, they are unable to develop an aversion and so often drink more of the liquid, with the same results.

The mouth is not the only place where taste buds occur, Brand says. They also exist in the digestive tract and pancreas, where the sweet tasting receptors are also defective. Since the role of taste buds in places other than the mouth is unknown, the consequence of defective ones is also unclear, he says. But, cats may be compensating for their lack of a sweet tooth. “Felines have very complex amino acid taste receptors. We have no idea what meats taste like to a cat: they may have sophisticated receptors to other taste stimuli that we just don’t know about,” Brand says. “Our results account for the common observation that the cat lives in a different sensory world to the cat owner,” comments team member Véronique Legrand-Defretin, director of the global feeding behaviour research programme at the Waltham Centre for Pet Nutrition in Leicestershire, UK.

Journal reference: Public Library of Science Genetics

New Science
August 16, 2005

Original web page at New Science

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Mystery of Gibraltar monkeys explained

Scientists have used DNA to figure out the origin of Gibraltar’s Barbary macaques, which may have played a small part in winning World War II. The macaques have long been figures of Gibraltar lore. As the story goes, when they are gone, the disputed British colony will return to Spanish rule.

In 1942, a handful of the monkeys remained. Gibraltar was militarily important, and any jolt to morale had to be avoided. Britain’s Prime Minister Winston Churchill sent out a secret edict: Get more monkeys and bring them to the rock. “Nobody knows where they got the macaques — they just suddenly appeared in Gibraltar,” said Robert D. Martin, provost for academic affairs at the Field Museum in Chicago. Martin and colleagues Lara Modolo and Walter Salzburger provided a partial answer in a paper published online this week in the Proceedings of the National Academy of Sciences.

The scientists used DNA comparisons to conclude that the creatures came from two places — Morocco and Algeria, the only regions where Barbary macaques still reside in the wild. Macaques from these two places are genetically distinct. Martin said the mixed origins of the imported macaques helped explain why the roughly 200 macaques now in Gibraltar were relatively healthy despite the inevitable inbreeding. “My expectation was that the macaques in Gibraltar would be a genetic disaster area,” he said. “But when we looked, their genetics was a lot more varied than I expected.” If the legend is true, Spain may have to wait a while before it gets Gibraltar back.

Yahoo
May 24, 2005

Original web page at Yahoo

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Microbial metagenome analysis

The volume of sequence required to assemble representative whole genomes from complex microbial communities in environmental samples is enormous: upto 100 megabases of sequence is needed to draft a single genome at eightfold coverage, which is feasible for a predominant species, but near impossible for rare species. The scientists took the alternative strategy of analyzing the gene content of samples from disparate environmental microbial communities. Distinctive metabolic hallmarks indicated selection pressures within the respective habitats. For example, cellobiose phosphorylase was only found in the soil sample but not in the marine samples, and bacteriorhodopsins were found in the surface water samples but none in the deep sea or in soil. The most discriminating operons were for transport of ions and inorganic components. This approach offers a pragmatic and informative route to sifting the enormous volumes of data obtained from metagenome studies.

E-mail address Science Mailer
May 10, 2005

Original web page at Science Magazine

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Rare condor chick hatches at Oregon zoo

A rare California condor chick pecked its way out of its egg at the Oregon Zoo’s captive breeding compound Monday, bringing the known number of the endangered species to 245. The chick’s foster mother wrapped the downy newborn in her soft breast feathers and delivered the first feeding of regurgitated raw meat.

It is the first chick this season for the zoo, which opened the nation’s fourth California condor captive breeding program in 2003. Two more eggs from different females are due to hatch in early May. Monday’s chick is about 4 inches long and an estimated 8 ounces to 9 ounces. Its sex is unknown.
The egg was laid Feb. 21 and moved to an incubator two weeks later. During a routine check Friday, keeper Shawn St. Michael saw evidence that the chick was ready to bust out because of the pattern of cracks in the shell. He moved it to a nest where another pair had been incubating a phony egg. Monday afternoon, Joe Burnett, assistant curator for condors, tossed fresh food into the enclosure, luring the female from the nest. He watched the chick pop the top off its shell “like a little lid,” Burnett said.

In the early 1980s the known California condor population had dropped to 22. The Oregon Zoo’s program is part of an effort to revive the species. In a recent contest, the zoo decided on a name for the chick: Tatoosh. In Yurok tribal legend, Tatoosh was the thunderbird that shook the mountains with its flapping wings. The two chicks produced in Oregon last year are in California. The male is to be set free this year at Pinnacles National Monument, south of San Jose. The female, who was to be released in Baja, Mexico, is recovering from tail injuries at the Los Angeles Zoo.

Yahoo
May 10, 2005

Original web page at Yahoo

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Mining the canine genome

Man’s best friend, the dog, is proving that it has one more way to lend a helping paw. The identification of canine genes is not only improving the health of dogs, but is also helping researchers identify genes controlling human diseases and develop treatments. Dr. Dennis O’Brien, a professor of neurology at the University of Missouri’s College of Veterinary Medicine and an expert on neurodegenerative diseases, says he is thrilled about the recent identification of genes that cause two types of rare epilepsy in dogs and humans. “It’s very exciting. I think it shows the power of canine genomics to (be able) to start answering some of these questions,” Dr. O’Brien said.

Berge Minassian, MD, and other scientists at the Hospital for Sick Children in Toronto, turned to the dog in their hunt for genes that cause Lafora disease in humans. With Lafora, seizures begin in the teenage years and increase in frequency until they cause death, usually within five years after the onset of the first symptoms. The researchers had identified one gene in humans but knew there was at least a second gene, because some families couldn’t be linked to the first gene. “I knew that Lafora is, relatively, frequently reported in dogs,” Dr. Minassian said. “I thought perhaps if we found families of dogs (that) have this disease, it may help us find the gene and, from there, the human gene.”

Dogs with Lafora have myoclonic seizures, which are characterized by brief short jerks of a muscle or a group of muscles. Animals develop signs between the ages of six and nine, and death follows within three years. After learning that five percent of purebred miniature wirehaired Dachshunds in the United Kingdom suffered from Lafora, the Canadian researchers began collaborating with veterinary neurologists Dr. Clare Rusbridge at The Stone Lion Veterinary Centre in London and Dr. Sue Fitzmaurice at Wey Referrals in Surrey, England. Veterinarians from the United States and France also contributed.

In the Jan. 7, 2005, issue of Science, the investigators report that affected dogs carry two copies of a gene with an expansion mutation. These “stutters” or repetitions of base pairs have also been implicated in other neurodegenerative diseases, such as Huntington’s disease.
Scientists have developed a test so that breeders can identify dogs that carry the gene. Canadian researchers had continued their efforts to map the gene responsible for Lafora in humans and actually finished mapping the gene in dogs and humans at the same time. Nevertheless, the identification of the gene in dogs will greatly benefit human medicine. Mice don’t make good models for Lafora, in part, because their lives are too short. “The dog models the disease almost perfectly,” Dr. Minassian said. “In terms of when we start developing treatments, it is going to be great to have the dogs to treat first, before we try (a treatment) in humans. This applies not only to any kind of medication-type treatment, but if and when we are ready to do gene therapy.”

The canine genome also recently proved valuable in identifying a gene that causes neuronal ceroid-lipofuscinosis in humans, otherwise known as Batten’s disease. Over time, children with this disease suffer mental impairment, worsening seizures, and progressive loss of sight and motor skills. The disease is usually fatal in the late teens or 20s. In the 1950s, a Norwegian veterinarian identified an NCL-like disease in a group of related English Setters. Affected English Setters develop signs similar to Batten’s and die at approximately two years of age from intractable seizures. The canine disorder most closely resembles the juvenile form of Batten’s disease.

This past February, researchers at the University of Missouri-Columbia and Indiana University-Indianapolis announced in the journal Biochemical and Biophysical Research Communications that they had identified the gene involved in this type of epilepsy. The canine model will help scientists study the disease in humans; the genetic test will help breeders. “When the American Kennel Club surveys dog breeders about what diseases they consider the most pressing problems, epilepsy is always in the top five,” Dr. O’Brien said. “We hope these kind of genetic mapping studies will ultimately lead us to find the genes that are responsible for the more common forms of epilepsy.”

The two epilepsy genes are only the most recent success stories involving the canine genome. Scientists have identified genes for conditions including vision disorders, heritable kidney cancer, narcolepsy, severe combined immunodeficiency (often called bubble boy disease), cystinuria, and bleeding disorders. The narcolepsy gene is one example of how identifying a gene for a rare condition can uncover the molecular biology of common cellular processes. In 1999, researchers showed that a mutation in the HCRT2 gene caused narcolepsy in Doberman Pinschers.
This gene was found to affect hypocretin, a protein neuropeptide. Since then, further studies have proved that hypocretin deficiency is associated with most cases of narcolepsy in humans, and that hypocretin might have a key role in circadian clock-dependent alertness and in regulating metabolic rate, appetite, mood, and sleep.
Targeting hypocretin could lead to therapies for narcolepsy and more common sleep disorders.

According to Dr. Gustavo Aguirre, a professor of medical genetics and ophthalmology at the University of Pennsylvania School of Veterinary Medicine, almost half of the roughly 30 genes identified for diseases in dogs are for vision disorders. Scientists have even successfully used gene therapy to cure two of them, one being Leber congenital amaurosis. In humans, this condition causes vision loss starting in infancy. “We treated dogs, restored vision, and that (treatment) will be used to treat human patients, if that continues to be successful,” says Dr. Aguirre, who was involved in the study. He anticipates that phase I clinical trials for humans could begin at the end of 2005 or early 2006.

So why are researchers having such success? It is often easier to find a gene in a dog than in another mammal, because of breeding. Dog breeds are similar to geographically isolated human populations, which offers an advantage when tracking down genes. Nearly half of genetic diseases reported in dogs occur predominantly, or exclusively, in one or a few breeds. When genes are identified, the development of genetic tests allows dog breeders to reduce the incidence of disease. The first such test was developed in 1995 for progressive renal atrophy in Irish Setters. For some time, canine geneticists have understood the promise of the pooch to help human health.
The top 10 diseases of greatest concern in purebred dogs include several that are of concern to human health, among them, cancer, epilepsy, autoimmune diseases, heart disease, and diseases causing cataracts.

Elaine Ostrander, PhD, chief of the cancer genetics branch of the National Human Genome Research Institute, believes canine genome research could be particularly useful in studying cancer. “By using dogs as an animal model and comparing what we learn in them to what we know about human cancer, we are slowly but surely putting together the basic vocabulary of cancer susceptibility,” Dr. Ostrander says. She and others believe that we are seeing only a small hint of what is to come. Drafts of the canine genome, the first of which was published in 2003, will help researchers identify genes more quickly. “With the canine genome, we know what the normal sequence is in a normal dog, so it makes it much easier to then see (whether a) dog with a disease has the normal kind of gene or if there is something different,” Dr. O’Brien said. Subsequent drafts of the genome will provide more information.

Dr. Ostrander believes that, in the future, canine geneticists will turn their attention even to genes involved in behavior, such as obsessive-compulsive tail chasing seen in Bull Terriers, which could provide clues to human behavior. Other possibilities are separation anxiety, impulse control disorders, and even aggression. She cautions, however, that with this latter behavior, legal and social implications come into play.

Source: Kate O’Rourke

JAVMA
March 29, 2005

Original web page at JAVMA

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X-chromosome sequenced

The complete sequence of the human X chromosome was published in Nature this week. The work, led by Mark Ross at the Sanger Institute in Cambridgeshire, UK, shows that large segments of it match parts of normal chromosomes in birds, confirming the X chromosome’s “non-sex” origins.

Despite the fact that X is much larger than the tiny Y, it seems that both evolved from a pair of conventional chromosomes in early mammals sometime in the past 300 million years – an idea first proposed in 1967. Previously, our main clue that X and Y had a common ancestry was that they swap a few small sections during one kind of cell division, just as pairs of ordinary chromosomes swap much larger chunks.

After X and Y had taken up their role in sex determination, their paths diverged. We already know that the Y shrank and lost almost all of its genes (New Scientist, 24 August 2002). Non-sex chromosomes have also changed greatly, acquiring or losing huge chunks. Now sequence comparisons with rats, mice and dogs show that the X chromosome seems to have changed little since the evolution of placental mammals, supporting the idea that once genes are transferred to X, they stay there. This is thought to be a result of X inactivation, the process whereby most of the genes on one X chromosome are switched off to prevent an “overdose” of X genes.

New Scientist
March 28, 2005

Original web page at New Scientist

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Looking at variation in numbers

The massive efforts to systematically find and catalog single nucleotide polymorphisms (SNPs) bear witness to the conviction that small genomic changes may provide clues to the origins of such things as heart problems, obesity, and pharmacologic responses.

But another type of variation, largely overlooked by the genetics community, might ultimately make equally important contributions to health. Large, submicroscopic rearrangements comprise about 5%-10% of the human genome. Many of these contain duplications that vary in the number of times and ways they are repeated: tandemly, at distal parts of the same chromosome, or even on other chromosomes. At least three papers last summer dealt with the advantage of new technologies used to discover the extent to which these polymorphic rearrangements are duplications of genes found elsewhere in the genome. And research published in January documented the first instance of the resulting gene-dosage effect on disease susceptibility: the effect of copy number of the CCL3L1 chemokine gene on susceptibility to HIV infection and progression to AIDS.

“In a sense, we’re just seeing the tip of the iceberg here in terms of the potential importance of copy-number variation to human disease, to human health, and to evolutionary change,” says James Sikela, professor in human medical genetics at the University of Colorado Health Sciences Center in Aurora. “I think there’s a newly-found appreciation for how important these copy numbers can be.”

HIV-1 uses the CCR5 chemokine receptor like a keyhole to unlock and enter a cell. “There’s a battle going on for this keyhole,” says Sunil Ahuja, director of the Veterans Administration Center for AIDS and HIV-1 Infection in San Antonio, and one of the recent study’s corresponding authors. The most potent endogenous key is CCL3L1, a chemokine whose gene is found anywhere from zero to at least 14 times in a normal diploid genome. CCL3L1 is also known to be a potent anti-HIV-1 chemokine. “You can imagine that if there are individuals who produce high amounts of the chemokines, there might be a possibility that they would gum up this keyhole and prevent the entry of the virus,” says Ahuja.

Robert Nibbs and his group at Beatson Institute for Cancer Research in Glasgow, Scotland, discovered the CCL3L1 copy-number polymorphism (CNP) and the copy-number correlation with production of the chemokine. “The prediction would be,” says Nibbs, “that those individuals with high copy number would be protected from HIV infection, and also be protected from progression once they have become infected.” He adds, “What Professor Ahuja has done is to prove that that hypothesis is correct.”

Ahuja teamed up with Matthew Dolan, who oversees the US military’s Tri-Service AIDS Clinical Consortium (TACC) cohort. A unique feature of that cohort, comprising 1,300 HIV-positive individuals who were in the US Air Force, is that the participants “all had uniform access to health care and were a racially balanced population,” says Dolan. “You can look at questions that are constrained by ethnicity, and you can also eliminate the factor of adequate access to health care,” he explains, pointing out that patients with HIV often do not join a prevalent cohort until years after they become infected. As predicted, Ahuja and Dolan found that individuals who had a higher number of CCL3L1 copies were less likely to become infected with HIV, or to progress to AIDS once they were infected. But there was a twist. Individuals of African origin had an average of about six copies per genome, whereas those of European ancestry had an average of two per genome. They found that a person’s copy number relative to the population average matters more than absolute gene dosage. The contribution of CCL3L1 gene dosage could be teased apart from that of the noncopy-dependent variant of CCR5, already known to confer some resistance to HIV infection and HIV progression.
Such an analysis could not have been done in the United Kingdom, says Nibbs, “We don’t have the access to the kind of cohorts that Professor Ahuja and his collaborators do.”

Indeed, in a paper last year that examined a different cohort, the researchers found no correlation between the absence of CCL3L1 and susceptibility to HIV infection or the rate of its progression. Graeme Stewart, corresponding author from Westmead Millennium Institute at West-mead Hospital in Sydney, writes in an E-mail: “Our study doesn’t contradict their results, as we only examined the proportion of people with HIV who fail to express any CCL3L1.” He adds, “Since such people are few we did not have the power to detect a partial effect.”

The TACC study may be the first to correlate CNPs with disease susceptibility, says Evan Eichler, associate professor of genome science at the University of Washington, Seattle. He calls it “a beautiful piece of work … a Christmas present,” a sentiment shared by many. But it was not the first time that researchers have seen a gene-dosage effect. Genes for the Rhesus factor blood group, cytochrome P450, glutathione S-transferase, and drug susceptibility, for example, “are all known to be copy-number variants in the population,” Eichler says.

Baylor College of Medicine pediatrician and genetics professor James Lupski argued in 1991 that a common inherited neuropathy, Charcot-Marie-Tooth disease, was due to the duplication of a large segment of chromosome 17. The 1.5-megabase segment comprises 21 different genes, and only the one for peripheral myelin protein 22 is gene-dosage sensitive. “At the time, there was a lot of resistance to the idea that you could get clinical phenotype related to just gene dosage, not having an aberrant protein or abnormal gene,” Lupski says. Yet it was already well known that Down syndrome, caused by duplication of an entire chromosome 21, is the most common genetic disease, affecting one in 600 live births. “We were so fixated on mutations,” Lupski says. “Dosage can obviously have phenotypic consequences.”

The field of human genetics had focused on characterizing single Mendelian traits found in very small portions of the population, Eichler says. But now geneticists are shifting that focus to more complex diseases: those with multiple, smaller contributions from several factors. With the TACC study, he notes, it became apparent that the “ability to become infected with HIV, or develop AIDS, [is] a complex interplay between the environment, single base-pair mutations, as well as copy-number variation.”

Eichler has been working on mapping genetic duplications, though he won’t discuss details. “We can safely say that we’ve mapped all the sites of duplication in at least three or four individuals.” To determine which of these sites have variants across the population, or the extent of that variation, requires a far larger and broader sampling. Those are the more interesting duplications, medically speaking: “If everyone has the same copy number, even though it’s duplicated, it probably doesn’t mean that there’s going to be any association there with disease,” Eichler notes. Determining the extent of variable duplication is another matter. At least three studies have used microarray screening, each in a different way, to screen the human genome for large-scale variation.

A group led by Michael Wigler of Cold Spring Harbor Laboratories in New York used representational oligonucleotide microarray analysis (ROMA) to measure the relative concentration of DNA segments in the population. About 85,000 oligonucleotides were printed onto a glass microarray and then hybridized with differentially labeled genomic digests from 20 different individuals. The experiment found 76 unique CNPs of about 100 kilobases and greater, with 70 genes among them, “including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.”

In another study, Stephen Scherer at the Hospital for Sick Children in Toronto and Charles Lee at Harvard University led a group that used array-based comparative genomic hybridization (aCGH) to look for CNPs. Arrayed BAC-derived genomic clones were hybridized with the labeled genome digests of 55 individuals. They found 255 variable loci, half of which overlap with genes. Of those 255 variable regions, only 11 were detected by both the Wigler group and the Lee/Scherer group.

A number of great ape and human lineage-specific gene copy-number variations are apparent from genome-wide cDNA array comparative genomic hybridization. Each horizontal row represents aCGH data for one cDNA clone on the microarray, while each vertical column represents data from one experiment, (H=human, B=bonobo, C=chimpanzee, G=gorilla, and O=orangutan). Regions shown contain lineage-specific genes (vertical black lines) and adjacent flanking genes ordered by chromosome map position using the UCSC Golden Path genome assembly (November 2002 sequence freeze).
Arrows denote from which hominoid lineage the copy number change is unique.
Methodological differences, such as different density and scope of the arrays used, and perhaps the use of different builds of the reference genome, probably account for much of the discrepancy between the studies, notes Nigel Carter in a commentary to the Lee/Scherer study. Carter writes: “It is common practice in selecting clones or probes for [aCGH] to avoid regions that hybridize to more than one genomic location or show variation,” concluding that “many more [large-scale copy-number variations] probably remain to be discovered.”

Also, only about half of the variable regions found in either study were detected in more than a single individual. This leaves open the question of whether these duplications arose uniquely in the individual screened, or perhaps the sample size was too small to detect a more common polymorphism. At about the time the latter papers appeared last summer, another group, from Stanford University and the University of Colorado Health Science Center, published work that used cDNA arrays to undertake what they call the first genome-wide gene-based survey of gene duplication across hominoid species. cDNAs representing nearly 30,000 human genes were spotted onto glass slides and then hybridized with human and either gorilla, chimpanzee, bonobo, or orangutan genomic digests. In all, the researchers found more than 1,000 genes that showed copy-number changes unique to one or more of the human and great ape lineages. Of these, 134 showed increases in copy number specific to the human lineage, including a number of genes thought to be involved in the structure and function of the brain.

One advantage of using cDNA instead of genomic oligonucleotides or BAC clones is that “we’re actually getting gene-specific information when we use these chips,” says co-corresponding author Sikela. “We’re really excited by some of the genes we’ve found that are either in-creased or decreased specifically in human, where you could relate it to cognition, language, those kind of things,” says Sikela. “Many different traits distinguish these organisms, and it’s plausible that copy-number change could be a major reason for that.”

Genomes are dynamic, fluctuating entities, which “evolved by duplicating and by inducing variation when they duplicate,” says Wigler. Focusing only on SNPs and point mutations, he says, is not enough. “There’s a big picture here that people are missing.” In some cases though, the extent of variation has long been under scrutiny. Barbara Trask, director of the human biology division at the Fred Hutchinson Cancer Research Center in Seattle, invokes the collection of human olfactory receptor genes and pseudogenes. Exactly how many, and which, of the 800 or so related sequences (grouped in 17 clades) individuals have varies throughout the population and affects the ability to detect and differentiate smells.

When genes duplicate, the selective pressure to keep them from mutating may no longer be present. Over time, copies may be rendered nonfunctional, or they may take on a new function. “There are going to be cases where additional copies themselves might have a phenotypic effect, and therefore might confer a selective advantage or disadvantage,” says Trask. Now, the technology is available to interrogate the genome for CNPs of such duplications, says Wigler. “What you’re going to see is that … some of the more subtle differences between humans – disease susceptibility genes, and the rates at which people age – are going to be caused by [gene-]dosage effects.”

The Scientist Daily
March 29, 2005

Original web page at The Scientist

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Chicken genome analysis reveals novel genes encoding biotin-binding proteins related to avidin family

A chicken egg contains several biotin-binding proteins (BBPs), whose complete DNA and amino acid sequences are not known. In order to identify and characterize these genes and proteins the researchers studied chicken cDNAs and genes available in the NCBI database and chicken genome database using the reported N-terminal amino acid sequences of chicken egg-yolk BBPs as search strings.

Two separate hits showing significant homology for these N-terminal sequences were discovered. For one of these hits, the chromosomal location in the immediate proximity of the avidin gene family was found. Both of these hits encode proteins having high sequence similarity with avidin suggesting that chicken BBPs are paralogous to avidin family. In particular, almost all residues corresponding to biotin binding in avidin are conserved in these putative BBP proteins. One of the found DNA sequences, however, seems to encode a carboxy-terminal extension not present in avidin.

The researchers described the predicted properties of the putative BBP genes and proteins. Our present observations link BBP genes together with avidin gene family and shed more light on the genetic arrangement and variability of this family. In addition, comparative modelling revealed the potential structural elements important for the functional and structural properties of the putative BBP proteins.

BioMed Central
March 29, 2005

Original web page at BioMed Central