That Is Far
|| January 21: 2019: University of Exeter News || ά. A new way of
screening babies and adults for future risk of Type One Diabetes
will be much more effective at identifying the condition than the
current methods, new research has concluded. Researchers at the
University of Exeter and the Pacific Northwest Research Institute in
Seattle have developed a new risk score, which takes into account
detailed genetic information known to increase the chances of Type
This could be used to help identity babies at highest risk of
developing the condition in the future. The score, may, also, be
used at the time of Diabetes diagnosis to help decide, if, someone
has Type One or Type Two Diabetes, which need very different
treatments. In a study published on Thursday, January 17 in Diabetes
Care, the research team found that their new risk score, the
T1DGRS2, which uses detailed analysis of key regions of the genome,
was nearly twice as efficient at identifying babies at high risk of
Type One Diabetes as existing methods, which use more simplistic
The research, funded by Diabetes UK, found the new test was, also,
better at predicting Type One Diabetes in adults in the general
population. The Senior Author of the research Dr Richard Oram, said,
"Prediction of what diseases we, might, get in the future is an
important area and Type One Diabetes has a strong genetic element,
that we are now able to measure very well.
Measurement of the Type One Diabetes genetic risk score could help
predict who will develop the condition from early life could help
with research into potential early life interventions and with
classifying diabetes correctly at diagnosis."
To develop the test, the researchers analysed genetic variation and
gene interactions across the entire genome in 6,581 people with Type
One Diabetes in the Type One Diabetes Genetics Consortium. They
compared that to 9,247 control participants. This helped them
incorporate all known and recently-discovered genetic elements, that
can indicate Type One Diabetes. They, then, conducted simulations to
see how their test compared to current genetic methods of diagnosis
Type One Diabetes develops when the body’s own immune system attacks
insulin-producing beta cells in the pancreas. The immune attack,
usually, begins several years before the symptoms of Type One
Diabetes appear. Being able to identify who’s will develop the
condition before its onset could help parents and doctors identify
the condition before it becomes severe and help the development of
effective treatments to prevent the disease occurring.
Current methods of early diagnosis involve measuring of islet
auto-antibodies, proteins in the blood, indicating beta cell
destruction. However, monitoring auto-antibodies is expensive and
difﬁcult in young children. The Exeter team recently discovered that
half of all cases of Type One Diabetes develop in adulthood and can,
often, be misdiagnosed. But the new risk score can help distinguish
between Type One and Type Two Diabetes, helping healthcare
professionals to make the right diagnosis.
Co-author Dr William Hagopian, from the Pacific Northwest Research
Institute in Seattle, said, ‘’Gathering all this genetic information
together allows the test to perform better. This makes prediction of
Type One Diabetes among all children much more affordable in public
health settings. Parents can be warned to watch for early symptoms
to avoid hospitalisation for life-threatening complications. Kids
with the greatest future risk can get access to research trials to
develop ways to delay or prevent progression to clinical diabetes."
Ms Anna Morris, the Assistant Director of Research Strategy and
Partnership at Diabetes UK, said, "It's exciting to see the power of
genetics being harnessed to help predict who might develop Type One
Diabetes in the future, particularly, from a young age. If,
successful, this approach could help to reduce someone's risk of
being misdiagnosed or developing complications during diagnosis.
In the future, this research could, also, open up new insights into
what could be done to stop Type One Diabetes from progressing."
The Paper: Development and Standardisation of an Improved Type One
Diabetes Genetic Risk Score for Use in Newborn Screening and
Incident Diagnosis: Published in Diabetes Care: Seth A. Sharp,
Stephen S. Rich, Andrew R. Wood, Samuel E. Jones, Robin N. Beaumont,
James W. Harrison, Darius A. Schneider, Jonathan M. Locke, Jess
Tyrrell, Michael N. Weedon, William A. Hagopian,and Richard A. Oram
Readmore || 220119 || Up ||
New Research Gains New Insights Into How Genes are Activated
|| January 14: 2019: Karolinska Institutet News || ά. In a study,
published in Nature, researchers at Karolinska Institutet present a
new method for analysing how instructions in the genome control how
our genes are activated in individual cells. The results give new
insights into how the genome encodes for its own use, which
increases our basic understanding of how genes are activated in
different types of cell in the body in both good and ill health.
Almost, all cells in the body have the same set of DNA and can, in
principle, become any kind of cell. What distinguishes the cells is
the way, in which, the genes in our DNA are used. All the DNA in a
cell is called the genome, our genetic material but, only, a very
small part of a human’s genome consists of genes. Instead, extensive
areas of the genome are used to regulate when and in which cells
nearby genes are active. These regions contain ‘enhancers’ and the
gene sequences located right next to the genes, ‘promoters’.
In a diseased body, these regions are, often, mutated and a deeper
understanding of the function of these regions would bring light to
the course of the disease in question. In order for a gene to be
used, it, must be, translated from DNA to copies of RNA. RNA is
similar to DNA but its structure is slightly different and it can be
used as a template for producing protein. The translation of DNA to
RNA is called transcription.
There are still many things, that are not clearly understood about
how transcription takes place and how it is regulated. For example,
if, a gene is used by a cell, the gene’s DNA is not translated to
RNA all the time. That would require too much energy. Instead, the
transcription takes places in bursts, when the transcription
machinery is recruited and several RNA molecules are produced in a
short time. The transcription of each gene can be characterised on
the basis of the kinetics of this process, that is, the frequency of
the bursts and the number of molecules produced during the bursts.
”It used to be difficult to measure the kinetics and how many RNA
molecules had been produced by a gene in an individual cell. The
methods, that have existed up to now were only able to follow a few
genes at a time. Moreover, mammals have two sets of, almost, all
their genes so it has been difficult to distinguish between the RNA,
that comes from the mother’s version of the gene and that from the
father’s version.” says Professor Rickard Sandberg, at the
Department of Cell and Molecular Biology at Karolinska Institutet,
who has led the study in question.
In the study, the researchers used a method, which they had
developed themselves to sequence RNA in individual cells. The method
makes it possible to measure the number of RNA molecules for,
almost, all the genes used in a cell.
The researchers sequenced cells of connective tissue and embryonal
stem cells from a crossbreed of two distantly related mice. With the
help of the natural variation found in the genes of the two
different types of mouse, the researchers were able to distinguish
between the sequenced RNA from the mother’s and the father’s
versions of the gene and in that way measure the transcription
exactly. They, then, used a mathematical model to make estimations,
for each of the version, of how often the gene is transcribed and
how much RNA is, then, produced.
”We discovered that enhancers did affect how often a gene was
transcribed in the two different cell types but not how many RNA
molecules were produced. We, also, found that certain DNA sequences
located at the beginning of a gene can influence how much RNA is
produced in a burst. In that way, we have begun to chart how the
genome encodes for its own use.” says Mr Anton Larsson, the First
Author of the study and a doctoral student in Professor Rickard
Sandberg’s research group.
”It will be possible to make wide use of our method to chart at a
much deeper level how different proteins affect the transcription
process.” says Professor Rickard Sandberg.
The research was funded with support from the European Research
Council, the Swedish Research Council, the Knut and Alice Wallenberg
Foundation and the Vallee Foundation.
encoding of transcriptional burst kinetics: Anton Larsson, Per
Johnsson, Michael Hagemann-Jensen, Leonard Hartmanis, Omid R.
Faridani, Björn Reinius, Åsa Segerstolpe, Chloe M. Rivera, Bing Ren
and Rickard Sandberg: Published in Nature Online January 02: 2018:::ω.
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