Children diagnosed with autism spectrum disorder (ASD) have greater numbers of harmful mutations in their mitochondrial DNA than family members, report Zhenglong Gu of Cornell University in Ithaca, New York, and colleagues, in a study.

Increasingly, studies point to malfunctions in mitochondria — the powerhouses of the cell — as a cause of autism spectrum disorder, but the biological basis for this relationship is unclear. To see if a genetic link exists between mitochondrial malfunction and ASD, the scientists analysed mitochondrial DNA sequences from 903 children with ASD, along with their unaffected siblings and mothers. They discovered a unique pattern of heteroplasmic mutations, where both mutant and normal mitochondrial DNA sequences exist in a single cell. Children with ASD had more than twice as many potentially harmful mutations compared to unaffected siblings, and 1.5 times as many mutations that would alter the resulting protein. The researchers went on to show that these mutations can be inherited from the mother, or the result of spontaneous mutation during development.

The scientists noted that the risk associated with these mutations is most pronounced in children with lower IQ and poor social behaviour compared to their unaffected siblings. Carrying harmful mutations in mitochondrial DNA is also associated with increased risk of neurological and developmental problems among children with ASD. Because mitochondria play a central role in metabolism, these findings may help explain the metabolic disorders commonly associated with ASD and other neurodevelopmental disorders. Evaluating mutations in the mitochondrial DNA of high-risk families could help improve the diagnosis and treatment of these diseases.

Zhenglong Gu says ‘The result of our study synergizes with recent work on ASD, calling attention to children diagnosed with ASD who have one or more developmental abnormalities or related co-morbid clinical conditions for further testing on mitochondrial DNA and mitochondrial function. Since many neurodevelopmental disorders and related childhood disorders show abnormalities that converge upon mitochondrial dysfunction, and may have mtDNA defects as a common harbinger, future research is needed to elucidate the mitochondrial mechanisms underpinning to these diseases. Ultimately, understanding the energetic aspects of neurodevelopmental disorders may lead to entirely new kinds of treatments, and preventative strategies that would target mitochondria.’

ScienceDaily www.sciencedaily.com/releases/2016/10/161028161729.htm

Myopia, also known as short-sightedness or near-sightedness, is the most common disorder affecting the eyesight and it is on the increase. The causes are both genetic and environmental. The Consortium for Refractive Error and Myopia (CREAM) has now made important progress towards understanding the mechanisms behind the development of the condition. This international group of researchers includes scientists involved in the Gutenberg Health Study of the University Medical Center of Johannes Gutenberg University Mainz (JGU). The team has uncovered nine new genetic risk factors which work together with education-related behaviour as the most important environmental factor causing myopia to generate the disorder. The results of the study ‘Genome-wide joint meta-analyses of genetic main effects and interaction with education level identify additional loci for refractive error: The CREAM Consortium’ have recently been published in the scientific journal Nature Communications.
There has been a massive rise in the prevalence of short-sightedness across the globe in recent decades and this upwards trend is continuing. It is known from previous studies of twins and families that the risk of acquiring short-sightedness is determined to a large extent by heredity. However, the myopia-causing genes that had been previously identified do not alone sufficiently explain the extent to which the condition is inherited. In addition to the genetic causes of myopia there are also environmental factors, the most significant of which are education-related behaviour patterns. “We know from the Gutenberg Health Study conducted at Mainz that the number of years of education increases the risk of developing myopia,’ said Professor Norbert Pfeiffer, Director of the Department of Ophthalmology at the Mainz University Medical Center.

With the aim of identifying genetic mutations relating to myopia and acquiring better insight into the development of the condition, the international research group CREAM carried out a meta-analysis of data collected from around the world. The data compiled for this analysis originated from more than 50,000 participants who were analysed in 34 studies. The second largest group of participants was formed by the more than 4,500 subjects of the Gutenberg Health Study of the Mainz University Medical Center. ‘In the field of genetic research, international cooperation is of particular importance. This is also borne out by this study, to which we were able to make a valuable contribution in the form of data from our Gutenberg Health Study,’ continued Professor Norbert Pfeiffer. ‘And in view of the fact that a survey undertaken by the European Eye Epidemiology Consortium with the help of the Gutenberg Health Study shows that about one third of the adult population of Europe is short-sighted, it is essential that we learn more about its causes in order to come up with possible approaches for future treatments.’

Aware that environmental effects and hereditary factors reinforce one another in the development of myopia, the scientists devised a novel research concept for their investigations. They used a statistical analysis technique that takes into account both the effects of the environmental and hereditary factors and does so in equal measure and simultaneously. Their efforts were crowned with success as they were able to classify nine previously unknown genetic risk factors.

Risk-associated gene involved in the development of short-sightedness
These newly discovered genetic variants are associated with proteins which perform important functions when it comes to the transmission of signals in the eye. One of these genes is of particular interest because it plays a major role in the transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the eye. Previous studies have shown that there is greater activation of the gene in question in eyes that are myopic. The results of current research substantiate this conclusion. The CREAM researchers interpret this as evidence that this newly discovered risk-related gene is actually involved in the development of short-sightedness. This represents significant initial headway towards understanding how genetic causes interact with the level of education as an environmental factor to produce the heterogeneity of myopia. Further research will be needed to clarify the details of how the mechanisms actually work and interact with one another.

The spread of short-sightedness is a worldwide phenomenon. Particularly in South East Asia the incidence of myopia in school children has increased notably over the last decades. This is likely due to an improvement in educational attainment. People who read a great deal also perform a lot of close-up work, usually in poor levels of daylight. The eye adjusts to these visual habits and the eyeball becomes more elongated than normal as a result. But if it becomes too elongated, the cornea and lens focus the image just in front of the retina instead of on it so that distant objects appear blurry. The individual in question is then short-sighted.

Johannes Gutenberg University Mainz
www.uni-mainz.de/presse/20232_ENG_HTML.php

Scientists at the Wellcome Trust Sanger Institute and their collaborators have discovered genetic markers in malaria parasites linked with resistance to the anti-malarial drug piperaquine. This research will allow health officials to monitor the spread of resistance, and help doctors and public health officers decide where the treatment is most likely to be effective.

Resistance to this key anti-malarial drug has recently emerged in Cambodia, leading to complete treatment failure there, threatening global efforts to treat and eliminate malaria.

Malaria is caused by Plasmodium parasites and in 2015, the World Health Organisation estimated that more than 200 million people were infected and nearly half a million people died worldwide from the disease. Children under the age of five made up 70 percent of these deaths. Malaria is a treatable disease when caught early enough, but is a huge problem in many areas due to drug resistance.

Piperaquine is a powerful drug, which is used in combination with another anti-malarial, artemisinin, as a first-line treatment in many areas of the world. Resistance to artemisinin emerged more than seven years ago in South East Asia, but until recently the combination of the drugs still successfully killed the malaria parasites there.  Now, the development of piperaquine resistance has led to complete failure of treatment in Cambodia.

Researchers carried out a genome-wide association study on approximately 300 Plasmodium falciparum samples from Cambodia to study the genetic basis behind piperaquine resistance. They looked at thousands of variations in the DNA sequence of the parasites, comparing these across samples with different levels of resistance to piperaquine.

“By studying the genomes of these parasites we found two genetic markers that are linked with piperaquine resistance. Not only can we now use these markers to monitor the spread of the drug resistant malaria, they will also help towards understanding as much as possible about the biology and evolution of the parasite.”

Dr Roberto Amato, lead author from the Wellcome Trust Sanger Institute
The scientists found that extra copies of the genes encoding two proteins of a family called plasmepsin, were linked with piperaquine resistance. Plasmepsins are part of a biological pathway that is targeted by other anti-malarial drugs, so this marker could also help the researchers understand the mechanism of the drug resistance. In addition to this, a mutation on chromosome 13 was found to be a second genetic marker linked with the resistance. Both markers were observed in parasites infecting patients who were not responding to treatment.

“The emergence of piperaquine resistance in these Cambodian parasites has led to complete treatment failure there. These malaria parasites are now resistant to both drugs, and since they are no longer being killed, resistance to both drugs will spread. This will threaten global attempts to eliminate malaria.”

Sanger Institute www.sanger.ac.uk/news/view/genetic-marker-found-resistance-malaria-treatment-cambodia

Researchers from the Fraunhofer Institute have developed a new prototype lab-on-a-chip platform for the easy and versatile detection of molecular pathogens.
Nuclear amplification testing is commonly used for pathogen detection; however, the process is currently manually intensive and complex, and requires dedicated equipment. This prevents its use in some settings, and pathogen detection in individual samples.
In a bid to solve these issues, Natalia Sandetskaya and colleagues at the Fraunhofer Institute for Cell Therapy & Immunology (Leipzig, Germany) have developed a prototype lab-on-a-chip platform capable of automating the process in a single instrument.
“We were motivated by the existing need for making the molecular analysis of complex samples much simpler for the users,” commented Sandetskaya. “Our particular applied interest is the detection of the pathogens in blood; for instance in sepsis, when only a few microorganisms must be rapidly found in a large volume of blood.”
The chip utilizes microfluidics and integrates sample volume transition, lysis, nucleic acid isolation, amplification (PCR or LAMP), and real-time fluorescence detection. As a single instrument, it could enable diagnostics in situations not previously feasible.
The researchers go on to demonstrate its proof-of-concept in the detection of E. coli and Salmonella bacterial species.
“Although our current prototype of the platform will need further development for this application, we have already demonstrated a high level of integration of very diverse processes without making the system overly complex,” noted Sandetskaya.
The team is now planning experiments to evaluate the platform in real-world samples and perfect its design.

Future Science OA
www.future-science-group.com/new-lab-on-a-chip-platform-seeks-to-improve-pathogen-detection/

Royal Philips and LabPON, the first clinical laboratory to transition to 100% histopathology digital diagnosis, recently announced its plans to create a digital database of massive aggregated sets of annotated pathology images and big data utilizing Philips IntelliSite Pathology Solution. The database will provide pathologists with a wealth of clinical information for the development of image analytics algorithms for computational pathology and pathology education, while promoting research and discovery to develop new insights for disease assessment, including cancer.
Deep learning algorithms have the potential to improve the objectivity and efficiency in tumour tissue diagnosis. In recent years, ‘deep learning’ techniques for image analysis have quickly become the state of the art in computer vision and has surpassed human performance in a number of tasks. The challenge for executing deep learning techniques is having access to a database with sufficient high volume and high quality data from which to develop the algorithms. As one of the largest pathology laboratories in the Netherlands, LabPON will contribute its repository of approximately 300,000 whole slide images (WSI) they prospectively create each year to the database. This will contain de-identified datasets of annotated cases that are manually commented by the pathologist, and will comprise of a wide variety of tissue and disease types, as well as other pertinent diagnostic information to facilitate deep learning.
“Deep learning focuses on the development of advanced computer programs that automatically understand and digitally map tissue images in considerable detail: The more data available, the more refined the computer analysis will be.” Said Peter Hamilton, Group Leader Image Analytics at Philips Digital Pathology Solutions. “Together, LabPON and Philips have the competence and skills to realize this.”
During a time where the pathologist shortage is mounting and cancer caseloads are increasing, the accurate diagnosis and grading of cancer has become increasingly complex, placing significant pressures on pathology services. Technologies such as computational pathology, could help pathologists with tools to work in the most efficient way possible.
“The role of the pathologist remains important by making the definitive diagnosis, which has a high impact on the patient’s treatment. Software tools could help to relieve part of the pathologists’ work such as identifying tumour cells, counting mitotic cells or identifying perineural and vaso-invasive growth, as well as carrying out measurements in a more accurate and precise way,” said Alexi Baidoshvili, pathologist at LabPON. “This ultimately could help to improve the quality of diagnosis and make it more objective.”
Next to the development of computational algorithms for diagnostic use, Philips intends to make available the database to research institutions and other partners through its translational research platform. This could enable selected parties to interrogate and combine massive datasets with the goal to discover new insights that ultimately could be translated into new personalized treatment options for patients.
www.philips.com/digitalpathology