Tag: twins

Categories : Genetics Metabolic DisordersTags :

Twin Study Reveals Epigenetic Signature for Obesity

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A susceptibility to gain weight may be written into the epigenetic information of human cells, a Washington State University study indicates.

The proof-of-concept study with a set of 22 twins found an epigenetic signature in buccal cells appearing only for the twins who were obese compared to their thinner siblings. The findings could lead to the development of a simple cheek swab test for an obesity biomarker and enable earlier prevention, the researchers said.

“Obesity appears to be more complex than simple consumption of food. Our work indicates there’s a susceptibility for this disease and molecular markers that are changing for it,” said Michael Skinner, a WSU professor of biology and corresponding author of the study published in the journal Epigenetics.

The study focused on twins to help eliminate the role of genetics and instead focus on epigenetics, molecular processes which are separate from DNA but influence how genes are expressed. The fact that the epigenetic signature was found in cheek cells rather than fat cells also suggests that the obesity signature is likely found throughout the human system.

The signature’s systemic nature also suggests that something may have occurred early in one twin’s life that triggered obesity susceptibility, Skinner added. It’s also possible that it was inherited by one twin and not the other.

For this study, Skinner worked with lead author Glen Duncan, director of the Washington State Twin Registry based at WSU, to identify 22 twin pairs, both identical and fraternal, who were discordant for obesity: one sibling had a body mass index (BMI) of 30 or higher, the standard for obesity defined by the Centers of Disease Control and Prevention, while the other sibling was in the normal range of 25 and below.

The research team analysed cells from cheek swabs provided by the twins. In the cells from the twin siblings who were obese, they found similar epigenetic changes to DNA methylation regions, areas where molecular groups made of methane attach to DNA, regulating gene expression or turning genes on or off.

The study would need to be replicated with larger groups of people to develop a biomarker test for obesity, the authors said.

The goal would be able to identify people earlier in life before they become obese so health care providers might help create interventions such as lifestyle changes, medication or both, said Duncan.

“Ultimately we would like to have some kind of preventative measure instead of our usual approach which is treatment,” he said. “It’s a simple fact that it’s better to prevent a disease, then try to treat it after you have it.”

Source: Washington State University

Categories : Diseases, Syndromes and ConditionsTags :

In MS, Twin Study Reveals Disease-causing T Cells

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By studying the immune system of pairs of monozygotic twins to rule out genetics in cases of multiple sclerosis, researchers may have discovered a smoking gun: precursor cells of the disease-causing T cells.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system CNS and the most common cause of neurological impairment in young adults. In MS, the patient’s own immune system attacks the CNS, resulting in cumulative neurological damage. The cause of MS still unclear but a variety of genetic risk factors and environmental influences have already been linked to the disease.

Genetics have already been found to be a necessary condition for developing multiple sclerosis. “Based on our study, we were able to show that about half of the composition of our immune system is determined by genetics,” said Florian Ingelfinger, a PhD candidate at the UZH Institute of Experimental Immunology. The study shows that these genetic influences, while always present in MS patients, are not on their own sufficient to trigger multiple sclerosis. In the study, 61 pairs of monozygotic twins where one twin is affected by MS whereas the co-twin is healthy were examined. From a genetic point of view, the twins were thus identical. “Although the healthy twins also had the maximum genetic risk for MS, they showed no clinical signs of the disease,” said Lisa Ann Gerdes.

With this cohort of twins, the researchers were  tease out environmental differences. “We are exploring the central question of how the immune system of two genetically identical individuals leads to significant inflammation and massive nerve damage in one case, and no damage at all in the other,” explained Professor Burkhard Becher, leader of the research team. Using identical twins let the researchers block out the genetic influence and focus on the immune system changes that were ultimately responsible for triggering MS in one twin.

The researchers harnessed state-of-the-art technologies to describe the immune profiles of the twin pairs in great detail. “We use a combination of mass cytometry and the latest methods in genetics paired with machine learning to not only identify characteristic proteins in the immune cells of the sick twin in each case, but also to decode the totality of all the genes that are switched on in these cells,” Florian Ingelfinger explained. 

“Surprisingly, we found the biggest differences in the immune profiles of MS affected twins to be in the cytokine receptors, ie the way immune cells communicate with one another. The cytokine network is like the language of the immune system,” said Ingelfinger. Increased sensitivity to certain cytokines leads to greater T cell activation in the bloodsteams of patients with multiple sclerosis. These T cells are more likely to migrate into the CNS and cause damage there. The identified cells were found to have the characteristics of recently activated cells, which were in the process of developing into fully functional T cells. “We may have discovered the cellular big bang of MS here – precursor cells that give rise to disease-causing T cells,” said Prof Becher.

“The findings of this study are particularly valuable in comparison to previous studies of MS which do not control for genetic predisposition,” said Prof Becher. “We are thus able to find out which part of the immune dysfunction in MS is influenced by genetic components and which by environmental factors. This is of fundamental importance in understanding the development of the disease.”

The study findings were reported in Nature.

Source: University of Zurich

Categories : Obstetrics & GynaecologyTags :

Rate of Twin Births At A Global High

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The first comprehensive global survey of twinning has reported an enormous increase in the number of twin births around the world, but appears to be plateauing.

One main reason for the increase is that, due to IVF and other fertility services being more readily available, the number of non-identical twin births is increasing. This is due to practices such as hormone stimulation releasing multiple ova, as well as the now discouraged practice of releasing multiple embryos into the womb in IVF. A systematic review also found that with IVF, letting embryos mature before implantation is also linked to increased odds of monozygotic twins. as well as women becoming pregnant later in life – age increases the likelihood of having natural, non-identical twins, peaking at age 35 to 39.

However, instead of continuing to climb, there are signs that twin births have reached a maximum.

“The trends are really quite striking,” said Christiaan Monden, a professor of sociology and demography at Oxford University. “Over the past 40 to 50 years we’ve seen a strong increase in twinning rates in rich, developed countries, and that has led to more twins in both a relative and an absolute sense than we’ve seen ever before.”

The researchers analysed twinning rates from 2010 to 2015 in 165 countries, which covered 99% of the world’s population. In 112 of those countries, they examined further birth records for 1980 to 1985. 

Although Africa is still the leading continent for twin births, other regions are catching up. The researchers found that, since the 1980s, twinning rates have risen from 9 to 12 per 1000 births, with the greatest rise in more developed regions such as  America (71%), Europe (60%) and Asia (32%).

In the UK, twinning rates rose about 62% but are thought to have fallen since the launch of a campaign to reduce multiple births in 2007. 

Raj Mathur, the chair of the British Fertility Society and a consultant gynaecologist at St Mary’s Hospital, said: “It doesn’t surprise us that twinning rates have increased because the availability of assisted reproduction has increased and also because women are slightly older when they have their first children, and both those things will increase the twin rate.[…]

“I think we’ve reached a peak in terms of twinning rates from medical interventions, certainly in the developed world, but the spread of IVF in Africa and South America is still rather limited on a per capita basis, and there are vast numbers of sub-fertile people in Africa particularly who don’t have access to IVF.

Dr Mathur added a note of caution about IVF, as twins have more risks such as lower birth weights and higher still birth and infant mortality rates

“The challenge will be how to spread IVF to them without also giving them higher twin rates. The majority of twin babies are absolutely fine, but there is no doubt that a twin pregnancy carries greater risks for the mother and the baby, so when we can avoid it we should avoid it. The principle we follow is neatly summed up by the phrase ‘one at a time’,” Mathur said.

Source: The Guardian