Couples who are undergoing pre-implantation genetic diagnosis (PGD) in order to avoid transmission of inherited diseases, such as Duchenne muscular dystrophy or cystic fibrosis, should also have their embryos screened for abnormal numbers of chromosomes at the same time, say Italian researchers.
By doing this, only embryos that are free not only of the genetic disease, but also of chromosomal abnormalities (aneuploidy), would be transferred to a woman’s womb, giving her the best chance of achieving a successful pregnancy, and avoiding the risk of implantation failure, miscarriage, or even live births that could be affected by conditions such as Down syndrome (in which there is an extra chromosome) or Turner syndrome (in which a girl has only one x chromosome rather than the normal two).
In a study reporting on the world’s largest series of double genetic tests the researchers carried out simultaneous PGD and pre-implantation genetic screening (PGS) on cells taken in a single biopsy.
They took between five and ten cells from the outer layer of 1122 blastocysts (the early collection of cells that begin to form about five days after an egg has been inseminated with sperm and which go on to develop into an embryo) and, after PGD and PGS, 218 blastocysts were transferred to the women’s wombs, resulting in 99 pregnancies and the birth of 70 healthy babies by January 2017, when the paper was written. This is a pregnancy rate of 49%, which is higher than the average clinical pregnancy rate of between 22-32% reported in the general population of couples undergoing in vitro fertilisation (IVF). At the time of writing the paper, 13 further pregnancies were ongoing and now 12 have resulted in the birth of healthy babies, while one miscarried. This gives a delivery rate of 38.6%. A total of 91 healthy blastocysts remain frozen awaiting transfer.
Dr Maria Giulia Minasi, laboratory director at the Centre for Reproductive Medicine, European Hospital, Rome, Italy, and first author of the study, said: “Importantly, we found that while 55.7% of the biopsied blastocysts did not carry a genetic disease or changes in the structures of chromosomes, only 27.5% of them also had the right number of chromosomes. Without performing pre-implantation genetic screening for aneuploidy, 316 blastocysts, which appeared to be healthy but had abnormal numbers of chromosomes, could have been transferred, leading to implantation failures, miscarriages or sometimes live births of babies affected by aneuploidy. For the couples involved, and particularly the women, these outcomes can be emotionally devastating.”
As a result of their findings, Dr Minasi and her colleagues believe that when couples undergo PGD, they should also have PGS.

The European Society of Human Reproduction and Embryology
www.eshre.eu/Press-Room/Press-releases-2017/Simultaneous-PGD-and-PGS-screening-on-cells-in-a-single-biopsy.aspx

Two types of testicular macrophages have recently been characterized by CNRS researchers at the Marseille-Luminy Immunology Center (CNRS / Inserm / Aix-Marseille University). A novel method of cellular tracing has enabled them to establish the origin, the development and the characteristics of these immune cells. This fundamental discovery is promising to understand some cases of infertility in men and to consider new treatments.
From the beginning of the individual’s life, the immune system learns to differentiate the cells belonging to the organism – the self – from other potentially pathogenic cells. However, since spermatozoa appear only at puberty, they are likely to be identified as foreign to the organism by some actors of the immune system. Special cells of the immunity, the testicular macrophages, are then mobilized to defend the spermatozoa. By emitting specific molecules, these fertility guardians prevent other actors of the immune system from entering the testicles.
If they are able to infiltrate infectious sites to phagocytate and destroy pathogens, Macrophages can also modulate the activity of the immune system to protect the functioning and regeneration of organs. These cells of immunity may be of embryonic origin or develop in the bone marrow in adults. Michael Sieweke’s team at the Marseille-Luminy Immunology Center (CNRS / Inserm / Aix Marseille University) was able to determine the profile of the two types of testicular macrophages.
The testicle is divided into two compartments. The first type of testicular macrophage described by the researchers is in the interstitial compartment, which also includes testosterone producing cells. The origin of these macrophages is embryonic: they are therefore present from the beginning of the life of the individual. The peritubular macrophages are located in the tubular compartment, around the seminiferous tubes which house the precursors of the spermatozoa. These two populations of macrophages have different cell markers.
Using a novel method of cell tracing, the researchers were able to follow the peritubular macrophages from the bone marrow into the testicles. The results showed that this type of macrophages only appeared two weeks after the birth of the mice, the equivalent of puberty in humans. Surprisingly, once established in the testes, the two populations of macrophages remain there all their lives.

CNRS
www2.cnrs.fr/presse/communique/5151.htm

Research by Genevan scientists on gene expression and the non-coding genome is a significant breakthrough for the future of personalized medicine.
Geneticists have taken an important step towards true predictive medicine by exploring the links between disease and genetic activity in different tissues. They thus constructed a model, the first step in identifying sequences in the non-coding genome indicating a disease-related pathogenic effect. In a second study, they went even further by associating the risk of developing a disease – in particular schizophrenia, cardiovascular diseases or diabetes – with the variability of the activity of the genome in different types of cells. And their results brought some surprises. Their findings may well revolutionize how each of us, according to his genome, will take care of his health in the future.
These studies are based on data from the international GTEx project, for "Genotype-Tissue Expression", launched in 2010 and co-directed by Professor Emmanouil Dermitzakis, geneticist at the Faculty of Medicine of the University of Geneva (UNIGE) and director of the Health 2030 Genomics Center. The objective of this project was to collect as many tissues as possible from a large number of individuals to understand the effects of genes and their variations. The data published over the last 7 years have allowed scientists worldwide to make considerable progress in analysing genomic variations specific to each of these tissues and predispositions to diseases.
Examining different types of human tissue from hundreds of people has led to a better understanding of how genomic variants – those changes in the spelling of DNA code inherited from our parents – could control how, when, and how many genes are activated and deactivated in different tissues, increasing the risk of developing a wide range of diseases. One of the main discoveries of the GTEx consortium is that the same variant present in multiple tissues may have a different effect depending on the tissue involved. A variant that affects the activity of two genes associated with blood pressure will, for example, have a greater impact on the expression of these genes in the tibial artery, even if the activity of the genes is higher in other tissues. .
To evaluate the influence of variants on gene activity, the researchers perform an analysis called "eQTL". An eQTL – or quantitative locus of expression of the characters – consists of an association between a variant at a specific location of the genome and the level of activity of a gene in a particular tissue. By comparing the eQTLs of different tissues to the genes associated with diseases one can therefore determine which tissues are most related to a disease. But if we can associate a region of the genome with a phenotype (a disease, for example), scientists were not yet able to determine exactly which nucleotide – the bricks of our DNA – when it mutates, contributes to the phenotype. question. Emmanouil Dermitzakis emphasizes as follows: "We needed to design a model to precisely link variants to a particular disease. Our goal, to simplify, was to locate the exact nucleotide that, in case of mutation, increases the risk of a disease, rather than the associated region or gene.
To build a solid model, scientists performed eQTL analyzes of hundreds of samples and identified thousands of causal variations in the non-coding genome. Using this dataset, they began building models to recognize these variations from DNA sequences, without linking them to existing phenotypes. As described by Andrew A. Brown, assistant professor in the Department of Genetic Medicine and Development of UNIGE’s Faculty of Medicine and one of the first authors of these studies: "We wanted to recognize pathogenic variants without any other information than this. sequence. If our model is confirmed, we will solve one of the major problems of modern genomics: by simply reading non-coding DNA sequences, we will be able to identify their pathogenic effects. This is the real future of predictive medicine.

University of Geneva
www.unige.ch/medecine/fr/carrousel/la-lecture-des-variants-genomique-ouvre-la-voie-a-la-medecine-predictive/

Researchers led by Arizona State University (ASU) and the Translational Genomics Research Institute (TGen) have identified altered expression of a gene called ANK1, which only recently has been associated with memory robbing Alzheimer’s disease, in specific cells in the brain.
Using an extremely precise method of isolating cells called "laser capture microdissection," researchers looked at three specific cell types – microglia, astrocytes and neurons – in the brain tissue of individuals with a pathological diagnosis of Alzheimer’s disease, and compared them to brain samples from healthy individuals and those with Parkinson’s disease.
Following sequencing of each of these cell types, the ASU-TGen led team found that altered ANK1 expression originates in microglia, a type of immune cell found in the brain and central nervous system.
"Although previous genetic and epigenetic-wide association studies had shown a significant association between ANK1 and AD, they were unable to identify the class of cells that may be responsible for such association because of the use of brain homogenates. Here, we provide evidence that microglia are the source of the previously observed differential expression patterns in the ANK1 gene in Alzheimer’s disease," said Dr. Diego Mastroeni, an Assistant Research Professor at Biodesign’s ASU-Banner Neurodegenerative Disease Research Center, and the study’s lead author.
All three of the cell types in this study were derived from the hippocampus, a small looping structure shaped like a seahorse (its name derives from the Greek words for horse and sea monster).  The hippocampus resides deep inside the human brain and plays important roles in the consolidation of both short-term and long-term memory, and in the spatial memory that enables the body to navigate.
In Alzheimer’s disease – and other forms of dementia – the hippocampus is one of the first regions of the brain to suffer damage, resulting in short-term memory loss and disorientation. Individuals with extensive damage to the hippocampus are unable to form and retain new memories.
"Using our unique data set, we show that in the hippocampus, ANK1 is significantly increased four-fold in Alzheimer’s disease microglia, but not in neurons or astrocytes from the same individuals," said Dr. Winnie Liang, an Assistant Professor, Director of TGen Scientific Operations and Director of TGen’s Collaborative Sequencing Center, and one of the study’s authors. "These findings emphasize that expression analysis of defined classes of cells is required to understand what genes and pathways are dysregulated in Alzheimer’s."
Alzheimer’s features many signs of chronic inflammation, and microglia are key regulators of the inflammatory cascade, proposed as an early event in the development of Alzheimer’s, the study said.
Because the study found that ANK1 also was increased two-fold in Parkinson’s disease, "these data suggest that alterations in ANK1, at lease in microglia, may not be disease specific, but rather a response, or phenotype associated with neurodegeneration … more specifically, neuroinflammation."

Translational Genomics Research Institute
tgen.org/home/news/2017-media-releases/asu-tgen-find-source-of-alzheimers-gene.aspx#.WWqRu_-GP5Y

EKF Diagnostics, the global in vitro diagnostics company, has published a guide to ‘Diabetes and HbA1c testing’ which can be found at EKF’s new Diabetes Portal (www.ekfdiagnostics.com/diabetes-portal.html). This new educational guide draws on EKF’s expertise in the diagnosis and monitoring of diabetes and associated conditions. It provides an overview of the global diabetes ‘epidemic’, symptoms and complications, through to discussion on methods for diagnosis and monitoring using both glucose and HbA1c testing, with consideration given to factors influencing their measurement.
Diabetes is a growing issue, particularly in developing countries, with five million people dying from diabetes related complications in 2015 alone. Although not an ‘epidemic’ in the conventional sense, there are currently 415 million people living with diabetes and this is predicted to grow to 642 million by 2040. Approximately 46% of people living with diabetes are doing so without a full and proper diagnosis with subsequent complications, and associated healthcare costs.
There are multiple options for the diagnosis of diabetes, most of which involve measuring the level of glycemic control a person exhibits. In addition to methods such as fasting plasma glucose and two-hour plasma glucose, another option is to use glycated hemoglobin (HbA1c) which reflects average plasma glucose over an 8-12 week period. As well as lab-based testing, WHO has approved HbA1c for diabetes diagnosis with a Point of-Care-Testing (POCT) device, providing the test is undertaken by a trained professional adhering to an appropriate External Quality Assurance scheme and using a methodology traceable to the IFCC reference method. POCT HbA1c testing gives a strong indication of both diabetes and pre-diabetes within a timeframe that enables immediate intervention.
Since it is not impacted by the same issues as blood glucose monitoring, HbA1c testing is fast becoming the preferred technique for diabetes and pre-diabetes diagnosis and monitoring. There are situations where use of HbA1c is not appropriate though. EKF’s new Guide includes discussion on both glucose and HbA1c testing and where factors may influence measurement of both diagnostic markers.
“The often ‘low to no’ maintenance approach to disease management of diabetes is not only dangerous but can also significantly contribute to ongoing healthcare costs. At present, approximately 12% of global health expenditure is spent on diabetes, and without significant changes to the way patients and health systems monitor glycemic control this will surely rise,” said Gavin Jones, Global Product Manager for Diabetes Care at EKF Diagnostics. “To enhance patient outcomes and reduce the cost for long-term healthcare of the diabetic and pre-diabetic population, we aim to improve patient access to diabetes care techniques, whatever their location. This can be achieved by providing affordable, easy-to-use POCT analysers and chemistry assays for both diabetes diagnosis and monitoring.”
EKF’s expertise and product range cover all aspects of diabetes care, from research and hospital laboratories to diabetes clinics, emergency rooms and GP surgeries. Products include the Biosen C-Line glucose analyser, which uses chip sensor technology to provide low cost, fast and lab accurate glucose results. Quo-Test and Quo-Lab point-of-care HbA1c analysers that deliver results meeting NGSP and IFCC POC requirements in four minutes. And lastly, to aid the diagnosis and monitoring of diabetes related conditions such as ketoacidosis, EKF offers Beta-Hydroxybutyrate LiquiColor Reagent and the handheld STAT-Site M β-HB strip-based analyser.
www.ekfdiagnostics.com