Sequencing of frog genome may offer new insights into human diseases

Washington, May 7 (ANI): An international team of researchers has cracked the genetic code of an amphibian, the African clawed frog Xenopus tropicali – the latest research aimed at understanding how genes work for potential applications in human health.

The genome of Xenopus tropicalis has been analysed by an international consortium of scientists from 24 institutions, and joins a list of sequenced model organisms including the mouse, zebrafish, nematode and fruit fly.

What’s most surprising, researchers say, is how closely the amphibian’s genome resembles that of the mouse, the chicken and the human, with large swathes of frog DNA on several chromosomes having genes arranged in the same order as in these mammals.

“A lot of furry animals have been sequenced, but far fewer other vertebrates,” said co-author Richard Harland, University of California, Berkeley, professor of molecular and cell biology.

“Having a complete catalog of the genes in Xenopus, along with those of humans, rats, mice and chickens, will help us reassemble the full complement of ancestral vertebrate genes.”

The researchers found that nearly 80 per cent of all human genes associated with genetic diseases have counterparts in the western-clawed frog, Xenopus tropicalis.

This discovery could lead to a better understanding of the genetic and chemical basis for many of the human diseases.

The research, published this week in the journal Science, was led by the Department of Energy’s Joint Genome Institute (JGI) and the University of California, Berkeley. (ANI)

Human and frogs share the ‘kissing cousin’ bond

Washington, April 30 (ANI): An international team of researchers has cracked the genetic code of an amphibian, the African clawed frog Xenopus tropicali – the latest research aimed at understanding how genes work for potential applications in human health.

The genome of Xenopus tropicalis has been analysed by an international consortium of scientists from 24 institutions, and joins a list of sequenced model organisms including the mouse, zebrafish, nematode and fruit fly.

What”s most surprising, researchers say, is how closely the amphibian”s genome resembles that of the mouse, the chicken and the human, with large swathes of frog DNA on several chromosomes having genes arranged in the same order as in these mammals.

“A lot of furry animals have been sequenced, but far fewer other vertebrates,” said co-author Richard Harland, University of California, Berkeley, professor of molecular and cell biology.

“Having a complete catalog of the genes in Xenopus, along with those of humans, rats, mice and chickens, will help us reassemble the full complement of ancestral vertebrate genes.”

The researchers found that nearly 80 per cent of all human genes associated with genetic diseases have counterparts in the western-clawed frog, Xenopus tropicalis.

This discovery could lead to a better understanding of the genetic and chemical basis for many of the human diseases.

The research, published this week in the journal Science, was led by the Department of Energy”s Joint Genome Institute (JGI) and the University of California, Berkeley. (ANI)

Procedure to knock out genes in nematode discovered

London, Apr 26 (ANI): After developing knockout mice and fruit flies, scientists have now devised a procedure for knocking out genes in nematode worms.

By knocking genes out of action, researchers led by biologist Erik Jorgensen University of Utah at, could learn what genes do by seeing what goes wrong without them.

“We developed a method that allows us to walk through the worm genome and determine the function of each gene, and thereby infer the function of these genes in humans,” Nature quoted Jorgensen as saying.

The study shows how a transposon or “jumping gene” can be used to delete specific genes from the 1-millimeter-long nematode worm, Caenorhabditis elegans.

“We are trying to understand how genes work and are regulated, and the easiest way to do that is to use a simple organism. The amazing thing is that cellular processes in a lowly worm are similar to the biology in humans. We”ve made it much easier and faster to change the genetic blueprint of a simple worm so we can study and understand how genes are regulated,” said Christian Frokjaer-Jensen, the study”s first author.

Jorgensen added: “We want to know what human genes do because they allow us to do all the wonderful things we do – run, speak, live – and understand what goes wrong in genetic diseases and how we can possibly treat them.”

“Mario figured out a way to delete genes in mice. Golic figured out how to do it in fruit flies. And we figured out how to delete genes in worms. There is an institutional excellence in genetics at the University of Utah,” said Jorgensen.

In nematode worms, “we”re knocking out the entire gene, but we cannot knock out every individual gene in the worm yet,” although the method should be able to delete 20,043 of 20,160 nematode genes, or 99.4 percent, he added.

The new knockout method is named MosDel – for Mos-mediated deletion – because it involves a transposon or jumping gene named Mos1.

Jumping genes are pieces of DNA that can jump from one chromosome to another, cutting the DNA where they leave one chromosome and cutting DNA to insert themselves in another.

The Mos1 gene carries the code to make an enzyme named Mos1 transposase.

That enzyme does the actual cutting of DNA, said Frokjaer-Jensen.

The transposons in the new study came from fruit flies and were placed into the worm genetic blueprint by French scientists who provided them to the Utah team.

Frokjaer-Jensen said that the Utah researchers crippled the jumping genes put into worms “so we can control when and where they hop.”

The Utah biologists used a plasmid – a circular piece of DNA – as a carrier by injecting it with the gene for Mos1 transposase, the “scissors” that cut DNA. Then, a glass needle was used to inject the combination into a worm”s gonad.

The transposase-carrying plasmid then cuts out a Mos1 jumping gene adjacent to a gene that researchers want to knock out, leaving a break in the chromosome”s DNA.

Cell machinery kicks in to repair the DNA break.

Since chromosomes come in pairs, the repair process normally uses the undamaged twin chromosome as a template for repairing the break.

But “in this case, we flood the cell with DNA that”s similar to where the DNA was broken. We essentially trick the DNA machinery into repairing off a template we supply,” said Frokjaer-Jensen.

But the template provided by the biologists lacks the DNA for the gene they want to delete. Thus, the gene is knocked out in the worm”s offspring.

The study has been published in the journal Nature Methods. (ANI)

Roxon ‘uncomfortable’ over parents picking children’s sex

The Federal Health Minister Nicola Roxon says she would be very uncomfortable about allowing parents to choose their children’s sex.

The Health and Medical Research Council is reviewing whether to allow any parents who use IVF to select their baby’s gender.

The practice is currently only allowed when there is a risk that parents will pass on genetic diseases.

The Federal Health Minister Nicola Roxon says the Government has no plans to overturn the ban.

“I must say on a personal level I am very apprehensive about such a change,” she said.

“I’m happy to see any review of the science and the arguments that people might want to make for and against the case.

“But I need to flag that the governments had not set down the path because we want to make any changes, and at a personal level I’m very uncomfortable about the suggestions that a change might be made.”

Leading IVF specialist Professor Gab Kovacs says that is ridiculous and not allowing parents to choose the sex of their child could have negative results.

“If a couple are determined enough to go through IVF rather than natural pregnancy to have a child of one particular sex, then it’s possible that if they have a child of the opposite sex, that child may not be as appreciated and well looked after,” he said.

Professor Kovacs says parents can already travel to countries like the US and Thailand to choose their child’s gender.

He says if parents are willing to pay up to $15,000 for the technique, then they should be allowed.

“There are a small number of couples who are so determined they want a child of a particular sex, they’re prepared to go for the cost and the difficulty of IVF to get pregnant, rather than just do it naturally,” he said.

“I can’t see any reason why it should be forbidden. I’ve seen a number of couples who have maybe three or four children of one particular sex and they’re very keen on family balancing. That’s the type of couple that most often ask about sex selection.”

Dr Sandra Hacker, chair of the council’s Australian Health Ethics Committee, says the review will consider all sides of the controversial and emotive issue.

She says previous consultations have found the majority of Australians are opposed to the practice being widely available.

“There is considerable interest from the general public about this,” she said.

“But on the other hand, the idea that gender selection should be available for reasons other than genetic abnormalities seems to be one that has a general disaffection within the general population.”

Boy or girl? Push for parents to choose

Couples in Australia having fertility treatment could soon be able to choose their babies’ sex.

Sex selection is only allowed in Australia when there is a risk that parents will pass on genetic diseases.

The five-year moratorium on the practice expires this year and the National Health and Medical Research Council is reviewing whether to continue the general ban.

But the Government is yet to be convinced it is the right move.

Dr Sandra Hacker, chair of the council’s Australian Health Ethics Committee, says the review will consider all sides of the controversial and emotive issue.

She says previous consultations have found the majority of Australians are opposed to the practice being widely available.

“There is considerable interest from the general public about this,” she said.

“But on the other hand, the idea that gender selection should be available for reasons other than genetic abnormalities seems to be one that has a general disaffection within the general population.”

Professor Gab Kovacs, the international medical director of Monash IVF, says if parents are willing to pay up to $15,000 for the technique, then they should be allowed.

“There are a small number of couples who are so determined they want a child of a particular sex, they’re prepared to go for the cost and the difficulty of IVF to get pregnant, rather than just do it naturally,” he said.

“I can’t see any reason why it should be forbidden. I’ve seen a number of couples who have maybe three or four children of one particular sex and they’re very keen on family balancing. That’s the type of couple that most often ask about sex selection.”

Professor Kovacs says some parents already travel to countries like the United States and Thailand to choose the sex of their children.

He says it is ridiculous the practice is not available here in Australia.

“If a couple are determined enough to want to go through IVF rather than natural pregnancy to have a child of one particular sex, then it’s possible that if they have a child of the opposite sex, that child may not be as appreciated and well looked after, as if they were able to choose the sex they wanted,” he said.

“So in fact it may have been in the best interests of the child to allow this to happen.”

Federal Health Minister Nicola Roxon says the Government has no plans to overturn the ban.

“I’m happy to see any review of the science and the arguments that people might want to make for and against the case,” she said,

“But I need to flag that the governments had not set down the path because we want to make any changes, and at a personal level I’m very uncomfortable about the suggestions that a change might be made.”

Mechanism related to onset of genetic diseases identified

Washington, Sept 18 (ANI): Scientists from Universitat Autonoma de Barcelona (UAB) have identified a mechanism that could trigger onset of various genetic diseases.

They have found a process by which proteins with a tendency to cause conformational diseases such as amyotrophic lateral sclerosis, familial amyloidotic polyneuropathy, familial amyloidotic cardiomyopathy, etc. finally end up causing them.

The answer can be found in the separation of the proteins.

According to the researchers Salvador Ventura and Virgmnia Castillo, every day cells produce thousands of new proteins, which renew themselves every second and which, by obeying the orders prescribed in our genetic code, work towards the proper functioning of our body.

However, these proteins occasionally suffer genetic mutations, which can cause changes in their composition, thus preventing them from carrying out their functions and the activities they are assigned.

In many cases this gives way to the formation of toxic macromolecular aggregates – amyloid fibrils – which block our body’s protein quality control system and finally provoke cell death.

Protein aggregation and the misfolding of proteins can be linked to the origin of many conformational diseases, which can be either genetic or spontaneous.

As possible strategies to prevent the dissociation of proteins, the authors propose introducing genetic mutations into the proteins to strengthen their association and developing specific molecules to block the risk regions of already dissociated proteins.

The study appears in journal PLoS Computational Biology. (ANI)

‘DNA Sudoku’ to revolutionise genome sequencing, medical genetics

Washington, June 25 (ANI): Sudoku, the popular mathematics puzzle that has taken people by storm, is now set to revolutionize the world of genome sequencing and the field of medical genetics, according to a new study.

Researchers at Cold Spring Harbor Laboratory (CSHL) have combined 2,000-year-old Chinese math theorem with concepts from cryptologyto develop what they dubbed as the “DNA Sudoku”, because of its similarity to the logic and combinatorial number-placement rules used in the popular game.

The strategy allows tens of thousands of DNA samples to be combined, and their sequences – the order in which the letters of the DNA alphabet (A, T, G, and C) line up in the genome – to be determined all at once.

The accomplishment is quiet contrary to past approaches that allowed only a single DNA sample to be sequenced at a time.

It also has an upper hand on current approaches that, at best, can combine hundreds of samples for sequencing.

“In theory, it is possible to use the Sudoku method to sequence more than a hundred thousand DNA samples,” said CSHL Professor Gregory Hannon, leader of the team that invented the “Sudoku” approach.

With such efficiency, the approach promises to reduce costs dramatically.

The new method has tremendous potential for clinical applications. It can be used, for example to analyse specific regions of the genomes of a large population and identify individuals who carry mutations that cause genetic diseases – a process known as genotyping.

The key to the team’s innovation is the pooling strategy, which is based on the 2,000-year-old Chinese remainder theorem.

The method is currently best suited for genotype analyses that require only short segments of an individual’s genome to be sequenced to find out if the individual is carrying a certain variant of a gene or a rare mutation.

However, with the improvement in sequencing technologies and researchers gaining the ability to generate sequences for longer segments of the genome, Hannon envisions wider clinical applications for their method such as HLA typing, already an important diagnostic tool for autoimmune diseases, cancer, and for predicting the risk of organ transplantation.

The report will be published as the cover story in the July 1 issue of the journal Genome Research.(ANI)

Breakthrough in ‘floppy baby’ syndrome

Washington, May 26 (ANI): Australian researchers have successfully treated mice with a devastating muscle disease that causes a Floppy Baby Syndrome.

The breakthrough could ultimately help thousands of families across the globe.

The research, published online today in the Journal of Cell Biology, reveals how a team at the Western Australian Institute for Medical Research (WAIMR) has restored muscle function in mice with one type of Floppy Baby Syndrome – a congenital myopathy disorder that causes babies to be born without the ability to properly use their muscles.

The currently incurable genetic diseases render most of the affected children severely paralysed and take the lives of the majority of these children before the age of one.

Dr Kristen Nowak, lead author on the publication, said the team was extremely encouraged that it had been able to cure a group of mice born with the condition.

“The mice with Floppy Baby Syndrome were only expected to live for about nine days, but we managed to cure them so they were born with normal muscle function, allowing them to live naturally and very actively into old age,” she said.

“This is an important step towards one day hopefully being able to better the lives of human patients – mice who were cured of the disease lived more than two years, which is very old age for a mouse,” the expert added.

Dr Nowak said the team was able to cure the mice with the recessive form of the genetic condition by replacing missing skeletal muscle actin – a protein integral in allowing muscles to contract – with similar actin found in the heart. (ANI)

Nine new X chromosome genes linked to learning disabilities identified

London, Apr 20 (ANI): An international team of researchers has identified nine new genes linked to learning disabilities.

The team of 70 researchers has found nine new genes on the X chromosome, which when knocked-out, led to learning impairment.

Learning disability is significantly more common in males than in females and genetic causes have long been sought on the X chromosome because males have only one X chromosome and so a gene mutation on the X is more likely to have an effect in males than in females.

“We sequenced 720 out of the approximately 800 known genes on the X chromosome in more than 200 families affected by X-linked learning disabilities,” Nature Genetics quoted Professor Mike Stratton, from the Wellcome Trust Sanger Institute as saying.

“This is the largest sequencing study of complex disease ever reported,” he added.

The new genes play roles in a wide range of biological processes suggesting that disruption to many cellular machines can damage the nervous system.

“As well as these important new gene discoveries relating to learning disability, we have also uncovered a small proportion – 1% or more – of X chromosome protein-coding genes that, when knocked out, appear to have no effect on the characteristics of the individual,” said Stratton.

“It is remarkable that so many protein-coding genes can be lost without any apparent effect on an individual’s normal existence – this is a surprising result and further research will be necessary in this area.”

Same genetic variants have been linked to some characteristics in common cold.

Researchers suggest that a similar strategy can be used to find disease causing sequence variants implicated in other complex genetic diseases.

“This new research uncovers yet more genes that can be incorporated to improve the provision of diagnostics to families with learning disabilities and allow us to develop more omprehensive genetic counselling in the future, allowing parents and the extended family to make the most informed family planning decisions,” said Dr Lucy Raymond, Reader in Neurogenetics, Cambridge Institute for Medical Research at the University of Cambridge. (ANI)

Genetically mixed populations can help understand human diversity, origins: Expert

Washington, February 15 (ANI): A Penn State physical anthropologist says that genetic diseases and genetically mixed populations can prove useful in understanding human diversity and human origins.

“We wanted to get to a strategy to predict what a face will look like. We want to understand the path of evolution that leads to that part of the selection process,” said Mark D. Shriver, associate professor of biological anthropology.

He revealed that with an eye on pinpointing genes that influence the shape of the human face and head, he began with an online database of genes linked to disease-Online Mendelian Inheritance of Man.

If the symptoms of the disease involved the face or skull the gene implicated in the disease became a candidate for those facial traits, said the researcher.

Shriver says that the his approach works because, though he looked at genes implicated in disease, those same genes in a healthy person may also influence the same physical trait-length, width, shape, size-but within the range normal for healthy individuals.

The researcher highlights that fact that facial traits vary among humans, but do tend to group by population.

In general, according to him, West Africans have wider faces than Europeans and Europeans have longer faces than West Africans.

“There is a strong relationship between genetic ancestry and facial traits. Using individuals of combined ancestry, European and African, we can see how the target genes alter facial traits,” he told attendees at the 2009 Annual Meeting of the American Association for the Advancement of Science.

The study was concentrated on a combined sample of African Americans with West African and European ancestry, whose genetic makeup was known through DNA testing.

The researchers made it simpler by eliminating anyone with Native American ancestry, so that only two genetic pools were represented-West African and European.

They reported on a sample of 254 individuals using three-dimensional imaging, and measured the distances between specific portions of the face.

Each individual had provided a DNA sample.

“We started with 22 landmarks on the faces that could be accurately located in all the images,” said Shriver, adding that these landmarks might be the tip of the nose, the tip of the chin, the outer corner of the eye or other repeatable locations.

The research team then recorded the distances between all the points in all directions, in order to have a distance map of each of the faces.

From their DNA profiles, Shriver could determine the admixture percentages of each individual, how much of their genetic make up came from each group.

He could then compare the genetically determined admixture to the facial feature differences and determine the relative differences from the parental populations.

“This type of study, done on admixed populations shows that each person is a composite of their ancestors and that the range of facial features is a continuum,” says Shriver.

He and his colleagues observed that there was a very strong statistical correlation between the amounts of admixture and the facial traits.

“We chose to look at African Americans because they were a large enough and available admixed population. We are trying to solidify our understanding of the origins of humans and the evolutionary processes. Looking at admixed populations shows us the influence genes have and how they relate to physical features,” said Shriver. (ANI)