“Dozens of human embryos with three parents have been created by British scientists,” reported the Daily Mail. Many papers covered this experimental technique aimed at preventing genetic disorders.
The technique, which has previously been tested in monkeys, results in embryos that have nuclear DNA from both parents and donor mitochondria from another woman. The embryos were destroyed after eight days of growth. Mitochondria are often referred to as the "batteries" of cells as they produce energy. Mutations in mitochondrial DNA cause at least 150 hereditary conditions.
This technique could potentially be used to help women with severe mitochondrial mutations to have children without these mutations. As mitochondrial DNA only makes up a very small part of the total DNA in cells, the offspring's characteristics would still mostly be derived from the nuclear DNA of the mother and father.
Several newspapers claim that this technique has similarities with cloning. This is not the case however and the technique is similar to types of IVF already in use. It does involve making genetic changes to unborn children who will have some DNA from two mothers, and the ethical issues of future research into this technique will need to be considered by the Human Embryology and Fertilisation Authority.
Where did the story come from?
The research was carried out by Dr Lyndsey Craven and colleagues from the Mitochondrial Research Group at the Institute for Ageing and Health in Newcastle University. The study received funding from several sources including the Muscular Dystrophy Campaign, the Wellcome Trust and the Medical Research Council. It was published in the peer-reviewed journal Nature.
The media covered the story in some depth, accurately reporting the technique, with diagrams in some cases, and the related ethical issues. However, some reports may have given readers the impression that the research is at a later stage of development than it is. The researchers estimate that the technique is three years away from being tested in trials for these conditions.
What kind of research was this?
This laboratory study investigated whether pronuclear transfer (transfer of DNA from the nucleus of one egg to another) in human embryos is possible and, if so, what proportion of embryos survive for six to eight days and how much donor mitochondrial DNA is carried over to the new embryo.
The study was appropriately designed to answer these questions. Researchers are currently prohibited from allowing embryos, such as the ones in this study, to develop beyond six to eight days and from implanting them back into the womb. For this technique to progress further, appropriate ethics approval and a change in the law would be necessary.
What did the research involve?
The researchers explain that mutations in mitochondrial DNA are a common cause of genetic disease, responsible for at least 150 hereditary conditions. Mitochondria are present in all cells and are often referred to as the cells’ “batteries” as they produce energy. They are found in the membrane-bound structures that lie outside the nucleus. The nucleus is where most DNA is found, but mitochondria have some DNA of their own.
Mitochondrial DNA mutations can result in neurological, muscular and heart problems and deafness. Some of these conditions are serious and can be fatal at birth. Around 1 child in 6,500 is born with a mitochondrial disease, and at least 1 adult in every 10,000 is affected by disease caused by mutations in their mitochondrial DNA. As each cell has multiple mitochondria, whether or not a person is affected by a mitochondrial disease depends on the proportion of their mitochondria that carry the mutation. Disease occurs in people carrying the mutation in at least 60% of their mitochondria.
The study used abnormally fertilised one-cell embryos (called zygotes), which had been donated by patients having IVF treatment at the Newcastle Fertility Centre. These eggs are usually not used in fertility treatment as they are not normal and typically do not survive. These abnormally fertilised eggs were identified at day one of their development at the Fertility Centre.
The researchers took the nucleus together with some plasma membrane and a small amount of the surrounding cytoplasm out of the cell and transferred it to an empty recipient cell. The recipient cell was also an abnormally fertilised zygote, at the same stage as the donor’s cell. This cell had had its nuclear DNA removed, using a similar process to that used on the donor cell. After the nucleus from the first embryo had been inserted into the recipient cell, it was either cultured for six to eight days to monitor development or cultured for a short period before being analysed for its mitochondrial DNA content.
Accepted genotyping techniques were used to determine the carry-over of mitochondrial DNA from the donor zygote into the recipient cell. This is important because, if the technique were to be used to prevent mitochondrial mutation disease in humans, it would need to be known how much, if any, mutated mitochondrial DNA is transferred along with the nucleus.
What were the basic results?
The researchers report that the transfer of the nucleus was successful. There was minimal carry-over of donor zygote mitochondrial DNA into the recipient cell (less than 2% after improving the procedure). Many of these early embryos contained no detectable donor mitochondrial DNA. The researchers say that this technique would allow onward development to embryo stage.
How did the researchers interpret the results?
The researchers concluded that pronuclear transfer between zygotes has the “potential to prevent the transmission of mitochondrial DNA disease in humans”.
Conclusion
Current treatments, including genetic counselling and pre-implantation genetic diagnosis, can help women who have only low levels of mutations in the mitochondria of their egg cells to have children of their own. This new technique could potentially help women who have more mutations and who may otherwise not be able to have children.
It is important to note that the third parent (the donor of the recipient egg) in the news reports only supplied a small, but essential, part of the genetic code for these embryos. This DNA affects energy production in cells and would probably not affect the offspring’s characteristics in a noticeable way.
There are further ethical and research obstacles to overcome before the technique could be available to affected families. First, an ethical debate about the procedure will need to occur. Second, how the procedure is regulated, if it is approved, will need to be agreed. Long-term safety of the procedure and refinements in the technique would also need be looked at in a research setting.
Tuesday, April 5, 2011
Defective DNA Repair and Neurodegenerative Disease
Defects in cellular DNA repair processes have been linked to genome instability, heritable cancers, and premature aging syndromes. Yet defects in some repair processes manifest themselves primarily in neuronal tissues. This review focuses on studies defining the molecular defects associated with several human neurological disorders, particularly ataxia with oculomotor apraxia 1 (AOA1) and spinocerebellar ataxia with axonal neuropathy 1 (SCAN1). A picture is emerging to suggest that brain cells, due to their nonproliferative nature, may be particularly prone to the progressive accumulation of unrepaired DNA lesions.
DNA chips detect disease
A DNA chip that can identify genetic mutations has been synthesised by Japanese scientists.
The most common form of genetic variation between individuals is caused by single-nucleotide differences in our DNA code. These are called single nucleotide polymorphisms (SNPs). SNPs can be used to identify disease genes and can highlight when a person is likely to develop a disease.
Kenzo Fujimoto and colleagues at the Japan Advanced Institute of Science and Technology have developed a simple and rapid method for identifying SNPs. The method could be the basis for automated, high-throughput diagnosis, they claim.
The method uses a short strand of DNA, known as an oligodeoxynucleotide probe, attached to a glass chip. The probe contains DNA bases complementary to those in the DNA strand containing the SNP of interest, except that one base is replaced by a vinyl-containing nucleoside known as cvP. When Fujimoto placed the target DNA onto the chip and shone ultraviolet light on it, the cvP reacted with an adenine base on the target DNA, in a reaction known as photocrosslinking. Fujimoto detected the photocrosslinked product using fluorescence imaging.
Because photocrosslinking only occurs when all the bases on the probe are complementary to those on the target DNA, if there is a mismatch in the strands the chip does not fluoresce.
'This method is an efficient reaction and proceeds with high sequence specificity,' said Fujimoto. 'Photochemical DNA manipulation is a highly original research theme.'
Hans-Achim Wagenknecht, an expert in molecular diagnostics at the University of Regensburg, Germany, believes the work represents a significant improvement for SNP detection. 'Such cheap, sensitive and reliable screening tools are clearly needed for the clinical diagnostics of genetic variations, infectious diseases and pharmacology,' he said.
The most common form of genetic variation between individuals is caused by single-nucleotide differences in our DNA code. These are called single nucleotide polymorphisms (SNPs). SNPs can be used to identify disease genes and can highlight when a person is likely to develop a disease.
Kenzo Fujimoto and colleagues at the Japan Advanced Institute of Science and Technology have developed a simple and rapid method for identifying SNPs. The method could be the basis for automated, high-throughput diagnosis, they claim.
The method uses a short strand of DNA, known as an oligodeoxynucleotide probe, attached to a glass chip. The probe contains DNA bases complementary to those in the DNA strand containing the SNP of interest, except that one base is replaced by a vinyl-containing nucleoside known as cvP. When Fujimoto placed the target DNA onto the chip and shone ultraviolet light on it, the cvP reacted with an adenine base on the target DNA, in a reaction known as photocrosslinking. Fujimoto detected the photocrosslinked product using fluorescence imaging.
Because photocrosslinking only occurs when all the bases on the probe are complementary to those on the target DNA, if there is a mismatch in the strands the chip does not fluoresce.
'This method is an efficient reaction and proceeds with high sequence specificity,' said Fujimoto. 'Photochemical DNA manipulation is a highly original research theme.'
Hans-Achim Wagenknecht, an expert in molecular diagnostics at the University of Regensburg, Germany, believes the work represents a significant improvement for SNP detection. 'Such cheap, sensitive and reliable screening tools are clearly needed for the clinical diagnostics of genetic variations, infectious diseases and pharmacology,' he said.
From DNA Data to Disease Diagnosis
What kind of information is used in association studies, and what answers can be obtained from them?
In a typical disease association study, a researcher collects DNA samples from a population of controls, or healthy individuals, and from a population of cases, who are individuals carrying the disease. The idea of such studies is that now we can search for differences in the DNA composition between the cases and the controls; such differences serve as an evidence for a relation between the disease and a genetic variant, which is a part of the DNA that varies across the population.
Due to the high cost of DNA sequencing, it is currently impossible to compare the entire DNA sequence across the set of individuals participating in the study; in a typical study there are thousands of cases and controls, and the cost of sequencing the entire genome of a single individual is still in the order of tens of thousands of dollars. For this reason, typically one will consider genetic variants that are common in the population. The most common variants are called Single Nucleotide Polymorphisms (SNPs), which are nucleotide base positions in the genome that differ across the population. Thus, if A,G,C, and T represent the four building blocks of the DNA, then for example in a SNP position you may find that 20% of the population carry the ‘A’ version and 80% carry the ‘C’ version. It is estimated that there are about 10 million SNPs in the genome, and in the other positions in the genome all individuals have the same DNA.
In a typical disease association study about 1 million SNPs are sampled per individual; we then search for differences between the frequencies of the SNPs in the cases and the controls. Once we discover such association we can further explore the reason for the association using ‘functional studies’ in which the specific genes are studied in the context of the disease. Furthermore, we can use the results of the genome-wide association studies to estimate the risk of an individual to develop a disease.
Where is this information obtained from? Are there specific, widely used processes for public and private researchers to obtain access to it?
The information is obtained in the lab, and is kept privately there, in order to protect the privacy of the study participants. In order to be able to share this information among scientists, there are databases maintained by the National Institute of Health in which the data is deposited and scientists can access the data if they need to use it for their research and if they prove that they can protect the privacy and rights of the study’s participants.
In a typical disease association study, a researcher collects DNA samples from a population of controls, or healthy individuals, and from a population of cases, who are individuals carrying the disease. The idea of such studies is that now we can search for differences in the DNA composition between the cases and the controls; such differences serve as an evidence for a relation between the disease and a genetic variant, which is a part of the DNA that varies across the population.
Due to the high cost of DNA sequencing, it is currently impossible to compare the entire DNA sequence across the set of individuals participating in the study; in a typical study there are thousands of cases and controls, and the cost of sequencing the entire genome of a single individual is still in the order of tens of thousands of dollars. For this reason, typically one will consider genetic variants that are common in the population. The most common variants are called Single Nucleotide Polymorphisms (SNPs), which are nucleotide base positions in the genome that differ across the population. Thus, if A,G,C, and T represent the four building blocks of the DNA, then for example in a SNP position you may find that 20% of the population carry the ‘A’ version and 80% carry the ‘C’ version. It is estimated that there are about 10 million SNPs in the genome, and in the other positions in the genome all individuals have the same DNA.
In a typical disease association study about 1 million SNPs are sampled per individual; we then search for differences between the frequencies of the SNPs in the cases and the controls. Once we discover such association we can further explore the reason for the association using ‘functional studies’ in which the specific genes are studied in the context of the disease. Furthermore, we can use the results of the genome-wide association studies to estimate the risk of an individual to develop a disease.
Where is this information obtained from? Are there specific, widely used processes for public and private researchers to obtain access to it?
The information is obtained in the lab, and is kept privately there, in order to protect the privacy of the study participants. In order to be able to share this information among scientists, there are databases maintained by the National Institute of Health in which the data is deposited and scientists can access the data if they need to use it for their research and if they prove that they can protect the privacy and rights of the study’s participants.
UNP and DNA to join hands to release Fonseka in Sri Lanka
The UNP and Democratic National Alliance (DNA) are likely to join hands and form an alliance once again to free former army commander Sarath Fonseka who is now imprisoned in Welikada.
The UNP has invited the DNA to join their protest campaign to free Fonseka who was sentenced last Friday to 30 months in jail. UNP General Secretary Tissa Attanayake told LAKBIMAnEWS that they have already sent out an invitation calling on the DNA to join them in their bid to release Fonseka.
The UNP and the JVP, for the first time in their political history joined hands during the last presidential election to work together to campaign for Fonseka s victory.
We believe that it s better to conduct the protests together because we can then create a bigger impact. This is the time that all political parties and civil society organizations should come together to free Fonseka who has been wrongfully imprisoned, he said.
UNP leader Ranil Wickremesinghe is scheduled to meet political parties and various organizations this week to come to a final agreement.
Attanayake added that they refuse to accept the court martial decision and they have already complained to the Human Rights Council in Geneva. Gampaha District parliamentarian, Dr. Jayalath Jayawardana is currently in Geneva to do the necessary spadework he added.
We have organized a series of religious ceremonies with the participation of all religious leaders which will commence at Pugoda from October, 3. We need to gather all those who are against this regime, he said.
Meanwhile the DNA has not yet taken a final decision about forming a formal alliance with the UNP, DNA General Secretary MP Vijitha Herath told LAKBIMAnEWS.
He added that their campaign is open to anyone and that the DNA launched its protest campaign demanding Fonseka s release in Kadawatha yesterday. Police have been meanwhile deployed to sabotage their poster campaign to protest Fonseka s arrest. Several JVPers who were putting up posters have been taken into custody at several places and in certain areas posters have even been torn by police personnel, Herath said.
The UNP has invited the DNA to join their protest campaign to free Fonseka who was sentenced last Friday to 30 months in jail. UNP General Secretary Tissa Attanayake told LAKBIMAnEWS that they have already sent out an invitation calling on the DNA to join them in their bid to release Fonseka.
The UNP and the JVP, for the first time in their political history joined hands during the last presidential election to work together to campaign for Fonseka s victory.
We believe that it s better to conduct the protests together because we can then create a bigger impact. This is the time that all political parties and civil society organizations should come together to free Fonseka who has been wrongfully imprisoned, he said.
UNP leader Ranil Wickremesinghe is scheduled to meet political parties and various organizations this week to come to a final agreement.
Attanayake added that they refuse to accept the court martial decision and they have already complained to the Human Rights Council in Geneva. Gampaha District parliamentarian, Dr. Jayalath Jayawardana is currently in Geneva to do the necessary spadework he added.
We have organized a series of religious ceremonies with the participation of all religious leaders which will commence at Pugoda from October, 3. We need to gather all those who are against this regime, he said.
Meanwhile the DNA has not yet taken a final decision about forming a formal alliance with the UNP, DNA General Secretary MP Vijitha Herath told LAKBIMAnEWS.
He added that their campaign is open to anyone and that the DNA launched its protest campaign demanding Fonseka s release in Kadawatha yesterday. Police have been meanwhile deployed to sabotage their poster campaign to protest Fonseka s arrest. Several JVPers who were putting up posters have been taken into custody at several places and in certain areas posters have even been torn by police personnel, Herath said.
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