Tag: genetics

Categories : PaediatricsTags :

Siblings of Autistic Children have Higher Risk of Autism

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Siblings of autistic children have a 20% chance of being autistic themselves – about seven times higher than the rate in infants with no autistic siblings, according to new research published in Pediatrics.

The study, by UC Davis MIND Institute distinguished professor Sally Ozonoff and the Baby Siblings Research Consortium, is based on a large, diverse group of families at research sites across the United States, Canada, and the United Kingdom. It confirms the same research group’s 2011 findings about the likelihood of autism in siblings, and adds news information suggesting it is more common, not less, in historically underrepresented groups.

Increasing autism rates prompt new study

“The rate of autism diagnosis in the general community has been steadily increasing since our previous paper was published,” Ozonoff explained. Ozonoff has studied the recurrence of autism in families for decades.

The latest estimates from the Centers for Disease Control and Prevention show that about 1 in 36 children has autism.  In 2011, the estimate was 1 in 68.

Ozonoff noted that there have also been changes in autism diagnostic criteria over the past decade. In addition, there is a growing awareness of autism in girls.

“So, it was important to understand if these had any impact on the likelihood of autism recurrence within a family,” she said.

The 2011 paper found a recurrence rate of 18.7%, while the new paper found a rate of 20.2% – a small but not significant increase.

“This should reassure providers who are counseling families and monitoring development. It should also help families plan for and support future children,” Ozonoff said.

A larger, more diverse study

The new study included data from 1605 infants at 18 research sites. All infants had an older autistic sibling.

“This study was much larger than the first and included more racially diverse participants,” Ozonoff said. The original study included 664 children.

Researchers followed the children from as early as six months of age for up to seven visits. Trained clinicians assessed the children for autism at age three using the Autism Diagnostic Observation Schedule (ADOS-2), a well-validated tool. The data were gathered from 2010 to 2019.

Sex of first autistic child, multiple autistic siblings key factors

Researchers found that the sex of the first autistic child influenced the likelihood that autism would recur within a family.

“If a family’s first autistic child was a girl, they were 50% more likely to have another child with autism than if their first autistic child was a boy,” Ozonoff said. “This points to genetic differences that increase recurrence likelihood in families who have an autistic daughter.”  

The researchers also found that a child with multiple autistic siblings has a higher chance of autism (37%) than a child with only one sibling on the spectrum (21%).

The sex of the infant was also associated with the likelihood of familial recurrence. If the later-born infant was a boy, they were almost twice as likely as a girl to be diagnosed themselves.

“The familial recurrence rate if the new baby was a boy was 25%, whereas it was 13% if the new baby was a girl,” Ozonoff explained. “This is in line with the fact that boys are diagnosed with autism about four times as often as girls in general.”

Race, maternal education level influence recurrence

The researchers found that race and the mother’s education level were likely factors as well. In non-white families, the recurrence rate was 25%. In white families, the recurrence rate was about 18%. In families where the mother had a high school education or less, recurrence was 32%. With some college, the rate was 25.5%, and with a college degree the rate was 19.7%. When the mother had a graduate degree, it dropped to 16.9%.

“These findings are new – and critical to replicate,” Ozonoff explained. “They do mirror the recent CDC findings that autism is more prevalent in children of historically underrepresented groups.” She noted that this reversed a longtime trend of lower prevalence in those groups. 

Most importantly, said Ozonoff, if these findings are replicated, they may indicate that there are social determinants of health that may lead to higher rates of autism in families. She emphasized that this study was not designed to answer those critical questions, and more research is needed.

Tracking outcomes

Unlike the first study, the researchers also tracked families who dropped out of the three-year study to see if their outcomes differed from those who did. “We wondered whether families who stayed in the study may have had children who were more affected — making them more worried about their development,” she explained.

That could have biased the estimates of recurrence to be higher than they really were. The current study showed that was not the case.

“So, now we have two large, independent studies that report familial recurrence in the same range,” Ozonoff said. “This reinforces how important it is that providers closely monitor the siblings of autistic children for delays in social development or communication. This is especially true in families who have reduced access to care, because early diagnosis and intervention are critical.”

Categories : Cardiovascular Disease GeneticsTags :

A Genetic Clue to Pulmonary Hypertension Risk

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Photo by Sangharsh Lohakare on Unsplash

University of Pittsburgh Schools of Medicine researchers uncovered a fundamental mechanism that controls the body’s response to limited oxygen and regulates blood vessel disease of the lung.

By combing through genomes of more than 20 000 individuals in the US, France, England and Japan and combining the results with molecular studies in the lab, the team discovered a shared genetic trait that could predict a higher risk of pulmonary hypertension and its more severe form, pulmonary arterial hypertension, and influence the development of drug therapies that target the body’s response to limited oxygen. The findings were published in Science Translational Medicine.

“This new level of knowledge will help identify people who may be at a higher genetic risk of pulmonary hypertension and jump-start precision medicine practices to offer customised treatments,” said senior author Stephen Chan, MD, PhD.

Pulmonary hypertension encompasses a range of conditions of various causes that manifest in high blood pressure in the arteries of the lung and the right side of the heart.

The disease is accompanied by a decreased supply of oxygen to the lung tissue and the blood, is chronic and deadly, and its molecular origins and genetic background remain unsolved.

Using a combined approach of genomics and biochemistry, the Chan lab found a gene pair that had an important function in regulating blood vessel metabolism and disease.

This gene pair included a long non-coding RNA molecule – a messenger that facilitates the transformation of the body’s genetic code into protein products – and a protein binding partner, and their interaction was frequently active in cells exposed to low oxygen compared to normal cells.

Taking the findings a step further, the team discovered that a single DNA letter change directing expression of this RNA-protein pair under low oxygen conditions was associated with a higher genetic risk of pulmonary hypertension across diverse patient populations.

According to Chan, pulmonary hypertension is a borderline orphan disease, and the limited number of patients with pulmonary hypertension makes it challenging to find genetic variations that are rare but still impactful enough to eclipse individual differences.

With that in mind, Pitt scientists turned to collaborators around the globe and to public research datasets to ensure that the findings are relevant across a diverse global population.

Chan hopes that his findings will spur the development of targeted therapies relevant to oxygen sensitivity in blood vessel lining and that their pending patent application will contribute to the growth on an entirely new field of epigenetic and RNA drug therapeutics that work not by manipulating the genome but by changing how it is being read.

Source: University of Pittsburgh

Categories : Ageing Obstetrics & GynaecologyTags :

Rethink Needed for the Genetic Cause of Very Early Menopause

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A new study showed that it may be necessary to rethink the genetic cause previously held to be behind very early menopause. Until now, variants in any one of more than 100 genes were thought to cause premature ovarian insufficiency (POI), which results in menopause before age 40. This affects around 1% of women, making it a leading cause of infertility. Under current guidance, a variation in one of these genes is cause for clinicians to consider a genetic diagnosis of POI.

Now, in the largest study to date, published in Nature Medicine, researchers analysed genetic data from more than 104 733 women in UK Biobank, of whom 2231 reported experiencing menopause before the age of 40.

The study found evidence that 98% of women carrying variations in the genes that were previously considered to be causes of premature menopause in fact had menopause over 40, therefore ruling out a diagnosis of POI in these women.

Anna Murray, Professor of Human Genetics at the University of Exeter Medical School is a senior author on the study. She said: “Our research means rethinking what causes very early menopause. The presence of specific genetic variants in multiple women who experience premature menopause has led to the assumption that they are causing the condition – but we have shown that these gene variations are also found in women with a normal age of menopause and therefore in many cases the link could just be coincidence. It now seems likely that premature menopause is caused by a combination of variants in many genes, as well as non-genetic factors. As genomic medicine evolves, we need to apply this standard of evidence to other conditions, so we can tailor diagnosis, treatment and support.”

Dr Julia Prague, Consultant Endocrinologist and Clinical Academic at the University of Exeter, and an author on the paper, said: “Having a very early menopause is often extremely distressing because it means losing fertility and treatment with hormone replacement is required to prevent negative health consequences. Clinicians need to understand the reasons why premature menopause occurs so that they do not miss the true underlying cause and can counsel patients appropriately. Misinterpreting genetic tests could have negative implications for women, such as suggesting that their relatives may also be at risk of very early menopause due to their genes, when in fact they may not be.”

Stasa Stankovic, of the University of Cambridge’s MRC Epidemiology Unit, and co-lead analyst of the study, said: “Each woman’s unique genetic combination shifts menopause timing, either earlier or later. Although genetic variation in the studied genes were not sufficient to cause very early menopause, we did identify genetic drivers that had a much more subtle impact on reproductive longevity. For example, women carrying genetic variation in TWNK and SOHLH2 genes experienced menopause up to three years earlier than the general population. Our future studies will continue using the power of human genomics to better understand the underlying biology of reproductive ageing in women and key genetic drivers of its extreme forms, including very early menopause. With this knowledge, we are also paving the path towards development of next-generation treatments for reproductive disorders.”

Source: University of Exeter

Categories : Genetics Immune SystemTags :

Neanderthal Genetic Influences on Human Immune System and Metabolism

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Diagram comparing the nose shape of a Neanderthal with that of a modern human by Dr Macarena Fuentes-Guajardo.

Neanderthal genes comprise some 1 to 4% of the genome of present-day humans whose ancestors migrated out of Africa, and new research has shown that their lingering presence shapes the immune systems and metabolism of people of non-African ancestry. Some of these genetics changes are detrimental, but are slowly being replaced by human versions.

A multi-institution research team including Cornell University has developed a new suite of computational genetic tools to address the genetic effects of interbreeding between humans of non-African ancestry and Neanderthals that took place some 50 000 years ago. (The study applies only to descendants of those who migrated from Africa before Neanderthals died out, and in particular, those of European ancestry.)

In a study published in eLife, the researchers reported that some Neanderthal genes are responsible for certain traits in modern humans, including several with a significant influence on the immune system. Overall, however, the study shows that modern human genes are winning out over successive generations.

“Interestingly, we found that several of the identified genes involved in modern human immune, metabolic and developmental systems might have influenced human evolution after the ancestors’ migration out of Africa,” said study co-lead author April (Xinzhu) Wei, an assistant professor of computational biology in the College of Arts and Sciences. “We have made our custom software available for free download and use by anyone interested in further research.”

Using a vast dataset from the UK Biobank consisting of genetic and trait information of nearly 300 000 British people of non-African ancestry, the researchers analysed more than 235 000 genetic variants likely to have originated from Neanderthals. They found that 4303 of those differences in DNA are playing a substantial role in modern humans and influencing 47 distinct genetic traits, such as how fast someone can burn calories or a person’s natural immune resistance to certain diseases.

Unlike previous studies that could not fully exclude genes from modern human variants, the new study leveraged more precise statistical methods to focus on the variants attributable to Neanderthal genes.

While the study used a dataset of almost exclusively white individuals living in the United Kingdom, the new computational methods developed by the team could offer a path forward in gleaning evolutionary insights from other large databases to delve deeper into archaic humans’ genetic influences on modern humans.

“For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many present-day humans, this study can fill in some of those blanks,” said senior investigator Sriram Sankararaman, an associate professor at the University of California, Los Angeles. “More broadly, our findings can also provide new insights for evolutionary biologists looking at how the echoes of these types of events may have both beneficial and detrimental consequences.”

Source: Cornell University

Categories : Antibiotics GeneticsTags :

Scientists Discover New Antibiotic Resistance Genes in Common Bacteria

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Genes that make bacteria resistant to antibiotics are much more widespread in our environment than was previously realised. A new study published in Microbiome shows that bacteria in almost all environments carry resistance genes, with a risk of them spreading and aggravating the problem of bacterial infections that are untreatable with antibiotics.

“We have identified new resistance genes in places where they have remained undetected until now. These genes can constitute an overlooked threat to human health,” says Erik Kristiansson, a professor in the Department of Mathematical Sciences.

According to the World Health Organisation (WHO), antibiotic resistance is one of the greatest threats to global health. When bacteria become resistant to antibiotics, it becomes difficult or impossible to treat illnesses such as pneumonia, wound infections, tuberculosis and urinary tract infections. According to the UN Interagency Coordination Group on Antimicrobial Resistance (IACG) 700,000 people die each year from infections caused by antibiotic-resistant bacteria.

Looking for resistance genes in new environments

The genes that make bacteria resistant have long been studied, but the focus has traditionally been on identifying those resistance genes that are already prevalent in pathogenic bacteria. Instead, in the new study from Sweden, researchers have looked at large quantities of DNA sequences from bacteria to analyse new forms of resistance genes in order to understand how common they are. They have traced the genes in thousands of different bacterial samples from different environments, in and on people, in the soil and from sewage treatment plants. The study analysed 630 billion DNA sequences in total.

“The data requires a great deal of processing before information can be obtained. We have used metagenomics, a methodology, that allows vast quantities of data to be analysed,” says Juan Inda Díaz, a doctoral student in the Department of Mathematical Sciences, and the article’s lead author.

The study showed that the new antibiotic resistance genes are present in bacteria in almost all environments. This also includes human microbiomes and, more alarmingly, pathogenic bacteria, which can lead to more infections that are difficult to treat. The researchers found that resistance genes in bacteria that live on and in humans and in the environment were ten times more abundant than those previously known. And of the resistance genes found in bacteria in the human microbiome, 75% were not previously known at all.

The researchers stress the need for more knowledge about the problem of antibiotic resistance.

“Prior to this study, there was no knowledge whatsoever about the incidence of these new resistance genes. Antibiotic resistance is a complex problem, and our study shows that we need to enhance our understanding of the development of resistance in bacteria and of the resistance genes that could constitute a threat in the future,” says Kristiansson.

Preventing bacterial outbreaks in healthcare

The research team is currently working on integrating the new data into the international EMBARK project (Establishing a Monitoring Baseline for Antibiotic Resistance in Key environments). The project is coordinated by Johan Bengtsson-Palme, an assistant professor in the Department of Life Sciences at Chalmers, and aims to take samples from sources such as wastewater, soil and animals to get an idea of the way in which antibiotic resistance is spreading between humans and the environment.

“It is essential for new forms of resistance genes to be taken into account in risk assessments relating to antibiotic resistance. Using the techniques we have developed enables us to monitor these new resistance genes in the environment, in the hope that we can detect them in pathogenic bacteria before they are able to cause outbreaks in a healthcare setting,” says Bengtsson-Palme.

The method used by the researchers is called metagenomics, and is not new, but so far has not been used to analyse new types of antibiotic resistance genes in such large quantities. Metagenomics is a method of studying the metagenome, which is the complete gene set of all different organisms in a given sample or within a given environment. Using the method, it is also possible to study microorganisms that cannot be grown in a lab.

Source: Chalmers Institute of Technology

Categories : GeneticsTags :

The Genes that Determine the Thickness of Eyebrows

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The first gene mapping study on eyebrow thickness in Europeans discovered three previously unreported genetic loci, as reported in the Journal of Investigative Dermatology. The study conducted by the International Visible Trait Genetics (VisiGen) Consortium demonstrates that eyebrow appearance has partly the same and partly different underlying genes in people from different parts of the world.

The appearance of human eyebrows is not just a matter of grooming but is in the genes. Eyebrow thickness, as any other appearance trait, is highly heritable. Thus far, genetic knowledge on eyebrow thickness has been very limited and solely restricted to non-Europeans. This study is the first genome-wide association study (GWAS) on eyebrow thickness in Europeans. By identifying new genes and rediscovering some of the genes previously identified in non-Europeans, the study expands genetic knowledge on human eyebrow variation, which is of broad interest and has implications for dermatology and other fields.

Previous studies were performed among Latin American and Chinese individuals, establishing four eyebrow thickness -associated genetic loci. Because no European eyebrow thickness GWAS had been reported, researchers did not know whether the genetic eyebrow thickness effects described in non-Europeans persist in Europeans, or whether there are European-specific genetic loci involved in eyebrow thickness, or both.

Lead investigator Prof Dr Manfred Kayser, Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, and co-chair of the VisiGen Consortium responsible for this study, commented, “Despite the immense efforts in mapping genes underlying human complex traits, we still know much more about the genes that make us sick than about those behind our healthy looks. For the first time, we performed a gene mapping study on eyebrow thickness variation in Europeans. Previous genetic knowledge on eyebrow thickness was limited and solely restricted to non-Europeans. We discovered new genes involved in eyebrow variation in Europeans and rediscovered some of the genes previously identified in non-Europeans.”

The study among 9948 individuals from four groups of European ancestry not only discovered three previously unreported genetic loci associated with eyebrow thickness, but also rediscovered two of the four genetic loci previously found in non-Europeans. Two other genetic loci previously reported in non-Europeans had minimal effects in Europeans, due to very low allele frequencies in Europeans.

Prof Dr Kayser concluded, “Our study significantly improves the genetic knowledge of human eyebrow appearance by increasing the number of known genes from four to seven and delivers new targets for future functional studies. By having demonstrated that eyebrow variation is determined by both shared and distinct genetic factors across continental populations, our findings underline the need for studying populations of different ancestries for unveiling the genetic basis of human traits, including, but not restricted to, physical appearance.”

Source: Elsevier

Categories : Ethics and Law GeneticsTags :

‘Errant’ Human DNA can be Found Everywhere, Posing an Ethical Dilemma

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Source: Pixabay CC0

Researchers report in Nature Ecology and Evolution that human DNA traces can be found nearly everywhere, short of isolated islands and remote mountaintops. That ubiquity is both a scientific boon and an ethical dilemma, say the University of Florida researchers who sequenced this ‘errant’ DNA. The DNA was of such high quality that the scientists could identify mutations associated with disease and determine the genetic ancestry of nearby populations. They could even match genetic information to individual participants who had volunteered to have their errant DNA recovered.

David Duffy, the UF professor of wildlife disease genomics who led the project, says that ethically handled environmental DNA samples could benefit fields from medicine and environmental science to archaeology and criminal forensics. For example, researchers could track cancer mutations from wastewater or spot undiscovered archaeological sites by checking for hidden human DNA. Or detectives could identify suspects from the DNA floating in the air of a crime scene.

But this level of personal information must be handled extremely carefully. Now, scientists and regulators must grapple with the ethical dilemmas inherent in accidentally — or intentionally — sweeping up human genetic information, not from blood samples but from a scoop of sand, a vial of water or a person’s breath.

The paper by Duffy’s group outlines the relative ease of collecting human DNA nearly everywhere they looked.

“We’ve been consistently surprised throughout this project at how much human DNA we find and the quality of that DNA,” Duffy said. “In most cases the quality is almost equivalent to if you took a sample from a person.”

Because of the ability to potentially identify individuals, the researchers say that ethical guardrails are necessary for this kind of research. The study was conducted with approval from the institutional review board of UF, which ensures that ethical guidelines are adhered to during research studies.

“It’s standard in science to make these sequences publicly available. But that also means if you don’t screen out human information, anyone can come along and harvest this information,” Duffy said. “That raises issues around consent. Do you need to get consent to take those samples? Or institute some controls to remove human information?”

Duffy’s team at UF’s Whitney Laboratory for Marine Bioscience and Sea Turtle Hospital has successfully used environmental DNA, or eDNA, to study endangered sea turtles and the viral cancers they are susceptible to. They’ve plucked useful DNA out of turtle tracks in the sand, greatly accelerating their research program.

The scientists knew that human eDNA would end up in their turtle samples and probably many other places they looked. With modern genetic sequencing technology, it’s now straightforward to sequence the DNA of every organism in an environmental sample. The questions were how much human DNA there would be and whether it was intact enough to harbor useful information.

The team found quality human DNA in the ocean and rivers surrounding the Whitney Lab, both near town and far from human settlement, as well as in sand from isolated beaches. In a test facilitated by the National Park Service, the researchers traveled to part of a remote island never visited by people. It was free of human DNA, as expected. But they were able to retrieve DNA from voluntary participants’ footprints in the sand and could sequence parts of their genomes, with permission from the anonymous participants.

Duffy also tested the technique in his native Ireland. Tracing along a river that winds through town on its way to the ocean, Duffy found human DNA everywhere but the remote mountain stream where the river starts, far from civilization.

The scientists also collected room air samples from a veterinary hospital. They recovered DNA matching the staff, the animal patient and common animal viruses.

Now that it’s clear human eDNA can be readily sampled, Duffy says it’s time for policymakers and scientific communities to take issues around consent and privacy seriously and balance them against the possible benefits of studying this errant DNA.

“Any time we make a technological advance, there are beneficial things that the technology can be used for and concerning things that the technology can be used for. It’s no different here,” Duffy said. “These are issues we are trying to raise early so policy makers and society have time to develop regulations.”

Source: University of Florida

Categories : GeneticsTags :

DNA Analysis can Cut Adverse Drug Reactions by 30%

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Genetics
Image source: Pixabay

Patients can experience 30% fewer serious adverse reactions if their drugs are tailored to their genes, reports a study published in The Lancet. A European collaboration involving researchers from Karolinska Institutet suggests that a genetic analysis prior to drug therapy could significantly reduce suffering and healthcare costs.

 A significant proportion of patients experience adverse reactions to their medication. Since we each carry a unique set of genes, we react differently to the same drugs. For example, some people break them down faster, meaning that they require a higher dose to obtain the desired effect.  

DNA pass that fits in the wallet

To overcome this problem, researchers from Leiden University Medical Center in the Netherlands, Karolinska Institutet and other collaborating institutions have developed the principle for a “DNA pass” that has been clinically validated in the recently published study.

“It’s basically a credit card-sized card with a magnetic strip containing all the important genetic data on a particular patient,” explains one of the study’s co-authors Magnus Ingelman-Sundberg, professor of molecular toxicology at the Department of Physiology and Pharmacology at Karolinska Institutet. 

“When a patient’s card is scanned, doctors and pharmacists can work out the optimal dose of a drug for that particular individual.”

The study included almost 7 000 patients from seven European countries between March 2017 and June 2020 all of whom were genotyped with respect to variations in twelve specific genes of significance to drug metabolism, transport and side-effects. All participants then received their drugs either conventionally or with a genotype-based modification.

Twelve weeks after their drug regimen began, the patients were contacted by a specialist nurse about any adverse reactions, such as diarrhoea, pain or loss of taste. The study concluded that such adverse reactions to drugs can be greatly reduced by analysing the genes that code for enzymes that metabolise them.

“The patients who’d received genotype-driven treatment had, on average, 30 per cent fewer adverse reactions than the controls,” says Professor Ingelman-Sundberg.  

Now sufficiently compelling data

Professor Ingelman-Sundberg, a long-standing expert at the European Medical Agency on the development of this method, believes that there is now sufficiently compelling data to warrant the widespread use of the DNA pass.

“I think we’ve come to the point where a genetic pass like this will be useful,” he says. 

Globally, the problem of adverse reactions is considerable. In the EU, they cause up to 128 000 fatalities a year and up to 9% of all hospital admissions, a figure that more than doubles to 20% in over 70s.

“Our results strongly suggest that an initial genotyping of the patients will deliver significant savings to society,” says Professor Ingelman-Sundberg. “The genotyping itself need only be done once per patient at a maximum cost of 6,000 SEK. The general introduction of this predictive system could therefore go a long way towards reducing public healthcare costs.”

Source: Karolinska Institutet

Categories : GeneticsTags :

Genetic Radiation Damage Passed down Through Fathers

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Chromosomes. Source: NIH

Whether radiation exposure of fathers can have consequences on their children is one of the most long-standing questions in radiation biology. Using the nematode Caenorhabditis elegans as a model, University of Cologne researchers reported in the journal Nature that radiation damage to mature sperm cannot be repaired but is instead passed on to the offspring.

Female eggs with radiation damage either accurately repair it or, if the damage is too severe, are eliminated and no damage is passed on. However, when the egg is fertilised with a radiation-damaged sperm, the maternal repair proteins that are provided by the egg try to repair the paternal DNA.

For this purpose, a highly error-prone repair mechanism is used and fuses the broken DNA pieces randomly. These random fusions of the breaks then lead to structural changes in the paternal chromosomes. The resulting offspring now carry the chromosome damage and in turn their offspring show severe developmental defects. The work done on C. elegans lays the foundation for a better understanding of the mechanisms for the heritable effects of paternal radiation exposure.

This work has now been published under the title ‘Inheritance of paternal DNA damage by histone-mediated repair restriction’ in 

The offspring that results from male animals that have been exposed to radiation and healthy female worms carry on the so-called structural variations – random connections of chromosome parts. In the offspring, these aberrations lead to recurrent breaks but this damage can no longer be repaired. Instead, the damaged chromosomes are shielded from accurate repair by proteins, so-called histones, that densely pack the long strands of DNA. In the densely packed DNA, the breaks can no longer be reached by the repair proteins. The packed DNA structures are held tightly together by the specific histone proteins, HIS-24 and HPL-1. When those histone proteins are removed, the paternally inherited damage is completely eliminated and viable offspring can be produced. The finding that histone proteins govern the accessibility of DNA for repairs could provide effective therapeutic targets for treating radiation damage.

Adding to the work on nematodes, the team detected the same structural variants, or randomly assembled chromosomes, in humans. Also here, the chromosome aberrations were specifically passed on from the fathers but not the mothers. For this, the scientists analysed various data sets from the 1000 Genome Project that contains genetic data from more than a thousand people and the Islandic deCODE project with genetic data from the respective mothers, fathers and children.

“Genome aberrations, especially structural variations in chromosomes, which develop in the paternal germline, are thought to increase the risk of disorders like autism and schizophrenia,” study leader Professor Dr Björn Schumacher said. This means that also in humans, mature sperm needs to be especially protected from radiation damage, and damaged mature sperm should not be used for conception. He added, “Such damage could potentially be inflicted during radiotherapy or chemotherapy and thus pose a risk in the two months that it takes to generate new sperm to replace the damaged one.” This is because in contrast to mature sperm, newly generated sperm have the capacity to accurately repair the damage.

Interestingly, the scientists found those structural variations in the chromosomes also in nematodes in the wild and in the human population. These results suggest that damage to mature sperm and the inaccurate repair of paternal DNA in the zygote could be major drivers for genetic diversity during evolution and might be responsible for genetic diseases in humans.

Source: University of Cologne

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Scientists Uncover Three Genes Linked to Multiple Sclerosis

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Genetics
Image source: Pixabay

New research published in the Annals of Clinical and Translational Neurology has identified three genes and their expressed proteins that may be involved in the pathogenesis of multiple sclerosis.

By comparing information on the genes and proteins expressed in the brains of thousands of individuals with and without multiple sclerosis, investigators discovered different expression levels of the SHMT1, FAM120B, and ICA1L genes (and their proteins) in brain tissues of patients versus controls.

Protein abundance alteration in human brain has linked to MS. For instance, protein abundance of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP)3 and thymosin β-46 was dysregulated in lesions from MS patients’ brain, and these proteins have been used for disease severity prediction and targeted therapy lately. In addition, compared to bodily fluid samples like cerebrospinal fluid and plasma, human brain tissue directly reflects the pathophysiology changes of MS and has become increasingly important in disease biomarker identification. However, few studies focused on specific subregions of the brain, ignoring the possible differences in protein types and abundance between subregions with distinct functions.

Studying the functions of these genes may uncover new information on the mechanisms involved in the development and progression of multiple sclerosis. “Our findings shed new light on the pathogenesis of MS and prioritised promising targets for future therapy research,” the authors wrote.

Source: Wiley