Tag: mutation

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CRISPR used in viable human embryos and germline genetic modification. An ethical apprach

From an ethical point of view, the use and destruction of human embryos, members of our species and worthy of full dignity is completely unacceptable and, it should be noted,  these experiments involve genetic modification of the germline, the safety of which is still far from being guaranteed

On 9th March this year, New Scientist reported the first results obtained by a team of scientists in China who had applied the CRISPR gene editing technique in normal human embryos.

This technique has already been applied in China on two occasions in non-viable human embryos, which have a limited capacity for development and so would be unable to result in the birth of a child, even if implanted in a woman. The efficacy of the technique was very low in both studies, giving rise to numerous off-target mutations (in parts of the genome where nothing should have happened).

In England, gene editing in embryos has already been approved, which in theory will use embryos left over from in-vitro fertilisation treatments. However, the results of this research have yet to be published.

Details of technique applied

In the aforementioned study published in New Scientist, the technique was applied to six embryos with some mutation in their DNA (they had been created purposely to have these mutations, fertilising eggs with sperm from men who had a hereditary disease). The genome was correctly repaired in only one of these embryos, but in another two, the repair occurred only in some cells. In a fourth embryo, CRISPR introduced an undesired mutation, while in another two, the technique did not work.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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Ethical questions about mitochondrial replacement in humans. Three parents babies

We thus consider it necessary to establish a moratorium on their use in humans, at least until more is known about these aspects. If this knowledge is obtained, ethical questions would still remain to be resolved, among which we consider the most relevant to be those related to the dignity and identity of the human embryo.

Children with two mothers and a father

In January 2017, the prestigious scientific journal Bioethics published a special edition dedicated to the ethical aspects of nuclear transfer techniques aimed at preventing the transmission of mitochondrial diseases, a topic that we have extensively addressed in our Observatory (see HERE).

Its editorial, Ethics of mitochondrial replacement, starts by referring to the recent birth of the first baby resulting from these techniques (see HERE). It then provides a brief description of the main characteristics of mitochondrial diseases, which are inherited exclusively from the mother. It explains that mothers who carry mutations in their mitochondrial DNA (mtDNA) face the uncertainty of not knowing if their genetic children will or will not inherit a serious mitochondrial disease. However the emergence of mitochondrial replacement techniques (MRT) offers these mothers hope, as healthy mitochondria from a donor are used to replace those of the mother. These techniques are maternal spindle transfer (MST) and pronuclear transfer (PNT), which consist, respectively, in removing the nucleus from a healthy egg or zygote, which will keep its mitochondria. The nucleus of the mother’s oocyte (patient or carrier of the mutation) or of another zygote obtained by fertilising the mothers egg is then transferred into the enucleated oocyte or zygote.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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Dueling BRCA Databases: What About the Patient?

The news release Monday morning grabbed my attention:

“Study finds wide gap in quality of BRCA1/2 variant
classification between Myriad Genetics and a common public database.”

Myriad Genetics had been exclusively providing tests, for
$3000+ a pop for full BRCA gene sequencing, for 17 years before the Supreme
Court invalidated key gene patents back in 2013. Since the ruling a dozen or so
competitors have been offering tests for much lower prices. Meanwhile, Myriad
has amassed a far deeper database than anyone else, having been in the business
so much longer. And it’s proprietary.

CLASSIFYING GENE VARIANTS

(NHGRI)

Public databases of variants of health-related genes have
been around for years too. The best known, ClinVar, collects and curates data
from the biomedical literature, expert panels, reports at meetings, testing
laboratories, and individual researchers, without access to Myriad’s database.
ClinVar uses several standard technical criteria to classify variants as
“pathogenic,” “benign,” or “of uncertain significance.” (“Likely pathogenic”
and “likely benign” were used more in the past.)

ClinVar lists 5400 variants just for BRCA1. The criteria
come from population statistics, how a particular mutation alters the encoded
protein, effects on the phenotype (symptoms), and other information.
Bioinformatics meets biochemistry to predict susceptibility. The BRCA1 protein
acts as a hub of sorts where many other proteins that control DNA repair
gather. DNA Science discussed the genes behind breast and ovarian cancers here.

As gene sequences accumulate in the databases and troops of
geneticists and genetic counselors annotate them, the proportion of pathogenic
and benign entries will increase as that of the unsettling “variants of
uncertain significance” — VUS — will decrease.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Uncategorized

Dueling BRCA Databases: What About the Patient?

The news release Monday morning grabbed my attention:

“Study finds wide gap in quality of BRCA1/2 variant
classification between Myriad Genetics and a common public database.”

Myriad Genetics had been exclusively providing tests, for
$3000+ a pop for full BRCA gene sequencing, for 17 years before the Supreme
Court invalidated key gene patents back in 2013. Since the ruling a dozen or so
competitors have been offering tests for much lower prices. Meanwhile, Myriad
has amassed a far deeper database than anyone else, having been in the business
so much longer. And it’s proprietary.

CLASSIFYING GENE VARIANTS

(NHGRI)

Public databases of variants of health-related genes have
been around for years too. The best known, ClinVar, collects and curates data
from the biomedical literature, expert panels, reports at meetings, testing
laboratories, and individual researchers, without access to Myriad’s database.
ClinVar uses several standard technical criteria to classify variants as
“pathogenic,” “benign,” or “of uncertain significance.” (“Likely pathogenic”
and “likely benign” were used more in the past.)

ClinVar lists 5400 variants just for BRCA1. The criteria
come from population statistics, how a particular mutation alters the encoded
protein, effects on the phenotype (symptoms), and other information.
Bioinformatics meets biochemistry to predict susceptibility. The BRCA1 protein
acts as a hub of sorts where many other proteins that control DNA repair
gather. DNA Science discussed the genes behind breast and ovarian cancers here.

As gene sequences accumulate in the databases and troops of
geneticists and genetic counselors annotate them, the proportion of pathogenic
and benign entries will increase as that of the unsettling “variants of
uncertain significance” — VUS — will decrease.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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Open ethical debate: Are gene editing techniques ethical in reproductive medicine?

Author’s opinion: The use of these techniques is currently medically and ethically unjustifiable.

The United Kingdom has recently approved mitochondrial transfer (3 parents children) to prevent the development of mitochondrial diseases in the children of mothers affected by these types of conditions (See HERE). This has opened an ethical debate on the use of such techniques, especially if they can modify the germline.

Now, a recent article has addressed their use in the field of reproductive medicine and discussed their use in infertility treatment and disease prevention (see HERE).

It is well known that the efficacy of assisted reproduction techniques is limited, with pregnancy rates when in vitro fertilisation is used of 29.1% per aspiration cycle and 33.2% per embryo transferred; when intracytoplasmic sperm injection is used, these rates are 27.9% and 31.8%, respectively.

It is therefore thought that identifying possible genetic abnormalities and then applying personalised medicine could improve these figures. It is also believed that they could help to resolve human infertility, since half of the cases are thought to be due to a genetic cause, and could be remedied by correcting the corresponding mutation responsible for infertility using genome editing. This has already been applied in different cases of genetic mutations in sperm in the case of azoospermia.

Gene editing in reproductive medicine

However, in the author’s opinion, the use of these techniques is currently medically and ethically unjustifiable for three reasons. First of all, there is still very little experience in genetic modification in humans, as fewer than ten products have been approved for use in these diseases.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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Gene Editing Opens Doors to Seedless Fruit with No Need for Bees

Now Keishi Osakabe at Tokushima University in Japan and his colleagues have used the CRISPR gene-editing technique to deliberately introduce a mutation that makes tomatoes seedless.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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Creative Minds: A New Mechanism for Epigenetics?

Keith Maggert

To learn more about how DNA and inheritance works, Keith Maggert has spent much of his nearly 30 years as a researcher studying what takes place not just within the DNA genome but also the subtle modifications of it. That’s where a stable of enzymes add chemical marks to DNA, turning individual genes on or off without changing their underlying sequence. What’s really intrigued Maggert is these “epigenetic” modifications are maintained through cell division and can even get passed down from parent to child over many generations. Like many researchers, he wants to know how it happens.

Maggert thinks there’s more to the story than scientists have realized. Now an associate professor at the University of Arizona College of Medicine, Tucson, he suspects that a prominent subcellular structure in the nucleus called the nucleolus also exerts powerful epigenetic effects. What’s different about the nucleolus, Maggert proposes, is it doesn’t affect genes one by one, a focal point of current epigenetic research. He thinks under some circumstances its epigenetic effects can activate many previously silenced, or “off” genes at once, sending cells and individuals on a different path toward health or disease.

Maggert has received a 2016 NIH Director’s Transformative Research Award to pursue this potentially new paradigm. If correct, it would transform current thinking in the field and provide an exciting new perspective to track epigenetics and its contributions to a wide range of human diseases, including cancer, cardiovascular disease, and neurodegenerative disorders.

The cells of all eukaryotic organisms, whether a fruit fly or human, must continuously produce lots of small subcellular structures called ribosomes, which build the proteins that are essential to life.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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Betting on the First Disease to Be Treated by Gene Editing

March 15, 2017

(CNBC) – The recently discovered, hotly contested gene-editing enzyme CRISPR is poised to change the way we treat, even cure, many diseases. But treatment will come years before talk of any “cure” is reasonable, and researchers know where they’d put their money if they had to bet on which kind of disease will be the first to the clinic. Bet on CRISPR succeeding first against a rare, single mutation.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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The difficult way to eradicate a genetic mutation

The Journal of the American Medical Association (JAMA) has a section in each issue titled “A Piece of My Mind” in which one of the physician readers writes a personal essay. The February 28, 2017 issue includes an essay titled “Eradicating a Genetic Mutation” by Maryl Goldberg Sackheim, an OB/GYN physician, who gives a personal account of her choice to use IVF and PGD to… // Read More »

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

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It’s a Boy: Ethical Implications of the First Spindle Nuclear Transfer Birth

by Elisabeth Armstrong

On September 27, 2016 people across the world looked down at their buzzing phones to see the AP Alert: “Baby born with DNA from 3 people, first from new technique.” It was an announcement met with confusion by many, but one that polarized the scientific community almost instantly. Some celebrated the birth as an advancement that could help women with a family history of mitochondrial diseases prevent the transmission of the disease to future generations; others held it unethical, citing medical tourism and consequences for the future of the therapy.

The child in question was actually born a few months earlier on April 6, 2016, but the research was published a few months later in the October edition of Fertility and Sterility. The mother carries DNA that could have given the baby Leigh Syndrome, a severe neurological disorder characterized by psychomotor regression that typically results in death between ages two and three.[1] Also known as subacute necrotizing encephalomyelopathy, Leigh Syndrome is caused by genetic mutations in mitochondrial DNA, which causes defective oxidative phosphorylation. Because people with this condition cannot re-form ATP, “demyleniation, gliosis, necrosis, spongiosis, or capillary proliferation”[2] can occur, thereby producing bilateral lesions across the central nervous system.

The 36-year-old mother previously had four miscarriages and successfully birthed two children, both of whom survived less than six years due to the syndrome. For religious reasons, the mother opted for Spindle Nuclear Transfer instead of Pronuclear Transfer,[3] which many religious organizations oppose because it entails the destruction of fertilized eggs.[4]

In Pronuclear Transfer, both the parent and donor egg are fertilized.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.