News Article | April 12, 2016
Although it’s widely known that modern humans carry traces of Neanderthal DNA, a new international study led by researchers at the Stanford University School of Medicine suggests that Neanderthal Y-chromosome genes disappeared from the human genome long ago. The study was published April 7 in The American Journal of Human Genetics, in English and in Spanish, and will be available to view for free. The senior author is Carlos Bustamante, Ph.D., professor of biomedical data science and of genetics at the School of Medicine, and the lead author is Fernando Mendez, Ph.D., a postdoctoral scholar at Stanford. The Y chromosome is one of two human sex chromosomes. Unlike the X chromosome, the Y chromosome is passed exclusively from father to son. This is the first study to examine a Neanderthal Y chromosome, Mendez said. Previous studies sequenced DNA from the fossils of Neanderthal women or from mitochondrial DNA, which is passed to children of either sex from their mother. Other research has shown that the DNA of modern humans is from 2.5 to 4 percent Neanderthal DNA, a legacy of breeding between modern humans and Neanderthals 50,000 years ago. As a result, the team was excited to find that, unlike other kinds of DNA, the Neanderthal Y chromosome DNA was apparently not passed to modern humans during this time. “We’ve never observed the Neanderthal Y chromosome DNA in any human sample ever tested,” Bustamante said. “That doesn’t prove it’s totally extinct, but it likely is.” Why is not yet clear. The Neanderthal Y chromosome genes could have simply drifted out of the human gene pool by chance over the millennia. Another possibility, said Mendez, is that Neanderthal Y chromosomes include genes that are incompatible with other human genes, and he and his colleagues have found evidence supporting this idea. Indeed, one of the Y chromosome genes that differ in Neanderthals has previously been implicated in transplant rejection when males donate organs to women. “The functional nature of the mutations we found,” said Bustamante, “suggests to us that Neanderthal Y chromosome sequences may have played a role in barriers to gene flow, but we need to do experiments to demonstrate this and are working to plan these now.” Several Neanderthal Y chromosome genes that differ from those in humans function as part of the immune system. Three are "minor histocompatibility antigens," or H-Y genes, which resemble the HLA antigens that transplant surgeons check to make sure that organ donors and organ recipients have similar immune profiles. Because these Neanderthal antigen genes are on the Y chromosome, they are specific to males. Theoretically, said Mendez, a woman’s immune system might attack a male fetus carrying Neanderthal H-Y genes. If women consistently miscarried male babies carrying Neanderthal Y chromosomes, that would explain its absence in modern humans. So far this is just a hypothesis, but the immune systems of modern women are known to sometimes react to male offspring when there’s genetic incompatibility. When did we part ways? The Y chromosome data also shed new light on the timeline for the divergence of humans and Neanderthals. The human lineage diverged from other apes over several million years, ending as late as 4 million years ago. After the final split from other apes, the human lineage branched into a series of different types of humans, including separate lineages for Neanderthals and what are now modern Previous estimates based on mitochondrial DNA put the divergence of the human and Neanderthal lineages at between 400,000 and 800,000 years ago. The last common ancestor of Neanderthals and humans — based on the Y chromosome DNA sequenced in the study — is about 550,000 years ago. Scientists believe Neanderthals died out about 40,000 years ago. Sequencing the Neanderthal Y chromosome may shed further light on the relationship between humans and Neanderthals. One challenge for the research team is to find out whether the Y chromosome Neanderthal gene variants identified were indeed incompatible with human genes. The data for the study came from public gene sequencing databases. "We did not collect any data for this work," said Mendez. "It was all public data."
News Article | November 17, 2016
Some children suffer from completely tangled hair, which cannot be combed at all. In German, the phenomenon bears the apt name "uncombable hair syndrome" or even "Struwwelpeter syndrome." Researchers at the Universities of Bonn and Toulouse have identified mutations in three genes that are responsible for this. Scientists from a total of eight countries were involved in the work. The results were published in the American Journal of Human Genetics. Many parents know from their own experience that it is not always easy to comb children's hair. Yet with patience and nerves of steel, even the toughest of knots can usually be undone. In the case of "uncombable hair syndrome," brushes and combs don't stand even the hint of a chance. Those affected have extremely frizzy, dry, generally light blonde hair with a characteristic shine, which successfully resists any attempt to tame it. These symptoms are most pronounced in childhood and then ease over time. In adulthood, the hair can more or less be styled normally. Virtually nothing has so far been known about the causes -- particularly because the phenomenon is relatively rare. It was described in the specialist literature for the first time in 1973; since then, around one hundred cases have been documented worldwide. "However, we assume that there are much more people affected," explains Professor Regina Betz from the Institute for Human Genetics at the University of Bonn. "Those who suffer from uncombable hair do not necessarily seek help for this from a doctor or hospital." Nevertheless, it is known that the anomaly occurs more frequently in some families -- it thus appears to have genetic causes. Betz is a specialist for rare hereditary hair disorders. A few years ago, she was approached at a conference by a British colleague. He had recently examined a family with two affected children. The Bonn-based human geneticist's interest was piqued. "Via contact with colleagues from around the world, we managed to find nine further children," she explains. The scientists in Bonn sequenced all the genes of those affected. When comparing large databases, they thus came across mutations in three genes that are involved in forming the hair. The changed genes bear the identifiers PADI3, TGM3 and TCHH. The first two contain the assembly instructions for enzymes, while the third -- TCHH -- contains an important protein for the hair shaft. In healthy hair, the TCHH proteins are joined to each other with extremely fine strands of keratin, which are responsible for the shape and structure of the hair. During this process, the two other identified genes play an important role: "PADI3 changes the hair shaft protein TCHH in such a way that the keratin filaments can adhere to it," explains the lead author of the study, Dr. Fitnat Buket Basmanav Ünalan. "The TGM3 enzyme then produces the actual link." Together with colleagues from the University of Toulouse, the scientists in Bonn performed experiments in cell cultures. In these, they were able to show the importance of the identified mutations on the function of the proteins. If even just one of the three components is not functional, this has fundamental effects on the structure and stability of the hair. Mice in which the PADI3 or TGM3 gene is defective thus develop characteristic fur anomalies, which are very similar to the human phenotype. "From the mutations found, a huge amount can be learned about the mechanisms involved in forming healthy hair, and why disorders sometimes occur," says Professor Regina Betz, delighted. "At the same time, we can now secure the clinical diagnosis of 'uncombable hair' with molecular genetic methods." For people affected by hair disorders, this last point is good news: some hair anomalies are associated with severe concomitant diseases, which sometimes only become manifest in later life. However, Struwwelpeter syndrome generally occurs in isolation without any other health impairments. Uncombable hair may be tiresome and may also cause mental stress, says Betz. "However, those affected have no need to otherwise worry."
News Article | February 24, 2017
The genetic material of an organism encodes the instructions that guide its development. These codes are not written in stone; they can change or mutate any time during the life of the organism. Single changes in the code can occur spontaneously, as a mutation, causing developmental problems. Others, as an international team of researchers has discovered, are too numerous to be explained by random mutation processes present in the general population. When such multiple genetic changes occur before or early after conception, they may inform scientists about fundamental knowledge underlying many diseases. The study appears in Cell. "As a part of the clinical evaluation of young patients with a variety of developmental issues, we performed clinical genomic studies and analyzed the genetic material of more than 60,000 individuals. Most of the samples were analyzed at Baylor Genetics laboratories," said lead author Dr. Pengfei Liu, assistant professor of molecular and human genetics Baylor College of Medicine and assistant laboratory director of Baylor Genetics. "Of these samples, five had extreme numbers of genetic changes that could not be explained by random events alone." The researchers looked at a type of genetic change called copy number variants, which refers to the number of copies of genes in human DNA. Normally we each have two copies of each gene located on a pair of homologous chromosomes. "Copy number variants in human DNA can be compared to repeated or missing paragraphs or pages of text in a book," said senior author Dr. James R. Lupski, Cullen Professor of Molecular and Human Genetics at Baylor. "For instance, if one or two pages are duplicated in a book it could be explained by random mistakes. On the other hand, if 10 different pages are duplicated, you have to suspect that it did not happen by chance. We want to understand the basic mechanism underlying these multiple new copy number variant mutations in the human genome." A rare, early and transitory phenomenon that can affect human development The researchers call this phenomenon multiple de novo copy number variants. As the name indicates, the copy number variants are many and new (de novo). The latter means that the patients carrying the genetic changes did not inherit them from their parents because neither the mother nor the father carries the changes. In this rare phenomenon, the copy number variants are predominantly gains - duplications and triplications - rather than losses of genetic material, and are present in all the cells of the child. The last piece of evidence together with the fact that the parents do not carry the alterations suggest that the extra copies of genes may have occurred either in the sperm or the egg, the parent's germ cells, and before or very early after fertilization. "This burst of genetic changes happens only during the early stages of embryonic development and then it stops," Liu said. "Interestingly, despite having a large number of mutations, the young patients present with relatively mild neurological problems." The researchers are analyzing more patient samples looking for additional cases of multiple copy number variants to continue their investigation of what may trigger this rare phenomenon. "We hope that as more researchers around the world learn about this and confirm it, the number of cases will increase," Liu said. "This will improve our understanding of the underlying mechanism and of why and how pathogenic copy number variants arise not only in developmental disorders but in cancers." "A new era of clinical genomics-supported medicine and research" This discovery has been possible in great measure thanks to the breadth of genetic testing performed and genomic data available at Baylor Genetics laboratory. "The diagnostics lab Baylor Genetics is one of the pioneers in this new era of clinical genomics-supported medical practice and disease gene discovery research," Lupski said. "They are developing the clinical genomics necessary to foster and support the Precision Medicine Initiative of the National Institutes of Health, and generating the genomics data that further drives human genome research." Using state-of-the art technologies and highly-trained personnel, Baylor Genetics analyzes hundreds of samples daily for genetic evaluation of patients with conditions suspected to have underlying genetic factors potentially contributing to their disease. Having this wealth of information and insight into the genetic mechanisms of disease offers now the possibility of advancing medicine and basic research in ways that were not available before. "There is so much that both clinicians and researchers can learn from the data generated in diagnostic labs," Liu said. "Clinicians receive genomic information that can aid in diagnosis and treatment of their patients, and researchers gather data that can help them unveil the mechanisms underlying the biological perturbations resulting in the patients' conditions." Other contributors to this work include Bo Yuan, Claudia M.B. Carvalho, Arthur Wuster, Klaudia Walter, Ling Zhang, Tomasz Gambin, Zechen Chong, Ian M. Campbell, Zeynep Coban Akdemir, Violet Gelowani, Karin Writzl, Carlos A. Bacino, Sarah J. Lindsay, Marjorie Withers, Claudia Gonzaga-Jauregui, Joanna Wiszniewska, Jennifer Scull, Pawel Stankiewicz, Shalini N. Jhangiani, Donna M. Muzny, Feng Zhang, Ken Chen, Richard A. Gibbs, Bernd Rautenstrauss, Sau Wai Cheung, Janice Smith, Amy Breman, Chad A. Shaw, Ankita Patel and Matthew E. Hurles. The researchers are affiliated with one of more of the following institutions Baylor, Wellcome Trust Sanger Institute in the U.K., Fudan University in China, the University of Texas MD Anderson Cancer Center Houston, the Clinical Institute of Medical Genetics in Slovenia and the Medical Genetics Center in Germany. This work was supported in part by grants from the US National Institute of Neurological Disorders and Stroke (R01NS058529), the National Human Genome Research Institute (U54HG003273), a joint NHGRI/National Heart Blood and Lung Institute grant (U54HG006542) to the Baylor Hopkins Center for Mendelian Genomics, and the BCM Intellectual and Developmental Disabilities Research Center, IDDRC Grant Number 5P30HD024064-23, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The work was also partially supported by the Wellcome Trust (WT098051).
News Article | February 22, 2017
CINCINNATI - Scientists propose in Nature blocking a molecule that drives inflammation and organ damage in Gaucher and maybe other lysosomal storage diseases as a possible treatment with fewer risks and lower costs than current therapies. An international research team led by Cincinnati Children's Hospital Medical Center, which also included investigators from the University of Lübeck in Germany, report their data Feb. 22. The study was conducted in mouse models of lysosomal storage disease and in cells from blood samples donated by people with Gaucher disease. Current treatments for Gaucher and other lysosomal storage diseases (LSDs) include enzyme replacement therapy or substrate reduction therapy. These break down or prevent the accumulation of certain fatty molecules and other waste particles that clog cells to cause inflammation, cell and organ damage and, in some cases, death. People with LSDs lack enzymes that break down used-up proteins and other spent particles, preventing their cells from shedding these waste materials and functioning normally. Individually, the 50 genetic diseases characterized as LSDs are considered rare. But collectively they have a frequency of one in 8,000 births, making LSDs a major challenge for the health care system, according to information from the National Institutes of Health. Study authors stress there is a need for new therapies. "Current enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of malignancies and Parkinson's disease," says Manoj Pandey, PhD, study first author and a scientist in the Division of Human Genetics at Cincinnati Children's. "We suggest that targeting a molecule called C5aR1 may serve as a viable treatment option for patients with Gaucher disease and possibly other LSDs." Pandey is co-corresponding author on the paper along with Jörg Köhl, MD, director of the Institute for Systemic Inflammation Research at the University of Lübeck, and adjunct professor in the Division of Immunobiology at Cincinnati Children's. In laboratory mouse models and human cells, researchers show that C5aR1 is a critical part of a molecular pathway that drives pro-inflammatory processes in Gaucher disease, which is initiated by mutations of a gene known as GBA1. GBA1 encodes the lysosomal enzyme glucocerebrosidase (GCase), which degrades the fatty molecule glucosylceramide (GC). C5aR1 is a receptor for a small peptide (a protein component) that is derived from the complement system (part of the immune system) called C5a, which drives inflammation in several different types of immune cells. The disease process starts by GBA1 mutation driving extensive accumulation of glucosylceramide in immune cells. Before the current study, the molecular process that connects glucosylceramide accumulation to inflammation was unknown, as was the role of inflammation in disease development. Pandey and colleagues show inflammatory glucosylceramide accumulation in spleen, liver, lung and bone marrow immune cells in Gaucher mouse models drives the induction of auto-antibodies against glucosylceramide, which form immune complexes. These immune complexes promote the production of C5a and activation of its receptor C5aR1. In organ tissues from disease mouse models, the researchers found evidence of abundant and active C5aR1, which fuels glucosylceramide accumulation through its control of an enzyme that produces the fatty molecule. According to the authors, C5aR1 activation is what tips the balance between glucosylceramide formation and its degradation. The researchers also found similar evidence of C5aR1 and related pro-inflammatory molecules in cells from the donated blood samples of Gaucher patients. Based on evidence of C5aR1's involvement in the Gaucher disease process, the researchers decided to test targeting the molecule pharmacologically in laboratory mouse models. Taking advantage of a C5aR antagonist (C5aRA) developed by Köhl (patent owned by Cincinnati Children's), the scientists injected C5aRA into the peritoneal cavities of mice. The infiltration of pro-inflammatory immune cells (macrophages) was substantially reduced in the lungs, livers and spleens of mice, and glucosylceramide accumulation was almost completely abolished, as was overall disease burden, the authors report. Because the current project was conducted in mouse models and human blood cells, Pandey and his colleagues stress that additional study is needed before determining whether targeting C5aR1 would be effective and safe enough to test in human patients. Pandey said researchers will continue testing the C5aRA molecule used in the mouse study (which is effective in targeting human and mouse C5aR). They also will test a commercially available anti-C5 monoclonal antibody called eculizumab, which is produced by Alexion Pharmaceuticals (which helped fund the current study). This will allow the researchers to test these compounds as a novel adjunctive therapeutic approach for human patients with Gaucher, and as a possible therapy for other lysosomal storage diseases. Funding support for the study came from Division of Human Genetics at Cincinnati Children's, the German Research Foundation (EXC 306/2, CL XII, IRTG 1911) and the Alexion Rare Disease Innovation Fund (31-91910-584000).
News Article | February 27, 2017
The genetic material of an organism encodes the instructions that guide its development. These codes are not written in stone; they can change or mutate any time during the life of the organism. Single changes in the code can occur spontaneously, as a mutation, causing developmental problems. Others, as an international team of researchers has discovered, are too numerous to be explained by random mutation processes present in the general population. When such multiple genetic changes occur before or early after conception, they may inform scientists about fundamental knowledge underlying many diseases. The study appears in Cell. "As a part of the clinical evaluation of young patients with a variety of developmental issues, we performed clinical genomic studies and analyzed the genetic material of more than 60,000 individuals. Most of the samples were analyzed at Baylor Genetics laboratories," said lead author Pengfei Liu, assistant professor of molecular and human genetics Baylor College of Medicine and assistant laboratory director of Baylor Genetics. "Of these samples, five had extreme numbers of genetic changes that could not be explained by random events alone." The researchers looked at a type of genetic change called copy number variants, which refers to the number of copies of genes in human DNA. Normally we each have two copies of each gene located on a pair of homologous chromosomes. "Copy number variants in human DNA can be compared to repeated or missing paragraphs or pages of text in a book," said senior author James R. Lupski, Cullen Professor of Molecular and Human Genetics at Baylor. "For instance, if one or two pages are duplicated in a book it could be explained by random mistakes. On the other hand, if 10 different pages are duplicated, you have to suspect that it did not happen by chance. We want to understand the basic mechanism underlying these multiple new copy number variant mutations in the human genome." The researchers call this phenomenon multiple de novo copy number variants. As the name indicates, the copy number variants are many and new (de novo). The latter means that the patients carrying the genetic changes did not inherit them from their parents because neither the mother nor the father carries the changes. In this rare phenomenon, the copy number variants are predominantly gains – duplications and triplications – rather than losses of genetic material, and are present in all the cells of the child. The last piece of evidence together with the fact that the parents do not carry the alterations suggest that the extra copies of genes may have occurred either in the sperm or the egg, the parent's germ cells, and before or very early after fertilization. "This burst of genetic changes happens only during the early stages of embryonic development and then it stops," Liu said. "Interestingly, despite having a large number of mutations, the young patients present with relatively mild neurological problems." The researchers are analyzing more patient samples looking for additional cases of multiple copy number variants to continue their investigation of what may trigger this rare phenomenon. "We hope that as more researchers around the world learn about this and confirm it, the number of cases will increase," Liu said. "This will improve our understanding of the underlying mechanism and of why and how pathogenic copy number variants arise not only in developmental disorders but in cancers." This discovery was made possible in great measure thanks to the breadth of genetic testing performed and genomic data available at Baylor Genetics laboratory. "The diagnostics lab Baylor Genetics is one of the pioneers in this new era of clinical genomics-supported medical practice and disease gene discovery research," Lupski said. "They are developing the clinical genomics necessary to foster and support the Precision Medicine Initiative of the National Institutes of Health, and generating the genomics data that further drives human genome research." Using state-of-the art technologies and highly-trained personnel, Baylor Genetics analyzes hundreds of samples daily for genetic evaluation of patients with conditions suspected to have underlying genetic factors potentially contributing to their disease. Having this wealth of information and insight into the genetic mechanisms of disease offers now the possibility of advancing medicine and basic research in ways that were not available before.
News Article | December 15, 2016
Britain's fertility regulator has approved controversial techniques allowing doctors to create babies using DNA from three people - what it called a "historic" decision to help prevent a small number of children from inheriting potentially fatal diseases from their mothers. The regulator's chair, Sally Chesire, on Thursday described it as a "life-changing" moment for families who might benefit from the treatment. "Parents at very high risk of having a child with a life-threatening mitochondrial disease may soon have the chance of a healthy, genetically related child," she said in a statement. The new procedures are intended to fix problems linked to mitochondria, the energy-producing structures outside a cell's nucleus. Faulty mitochondria can result in conditions including muscular dystrophy, major organ failure and severe muscle weakness. Last year, Britain changed its law to permit scientists to modify eggs or embryos before they are transferred into women, becoming the first country to legally approve the techniques. In September, U.S.-based doctors announced they had created the world's first baby using such techniques, after traveling to Mexico to perform the methods, which have not been approved in the United States. To help women with mitochondria problems from passing them down to their children, scientists remove the nucleus DNA from the egg of a prospective mother and insert it into a donor egg from which the donor DNA has been removed. That can happen before or after fertilization. The resulting embryo ends up with nucleus DNA from its parents but mitochondrial DNA from a donor. The DNA from the donor amounts to less than 1 percent of the resulting embryo's genes. But Britain's decision to approve using the new methods will not open the floodgates to genetically modified babies. Clinics will need to apply to Britain's fertility regulator for permission to use the techniques on a case-by-case basis. The decision was made after five years of reviewing the development, safety and efficacy of the procedures. Newcastle University said it was planning to apply for a license to use the new fertility techniques and was aiming to treat up to 25 patients a year. "It is enormously gratifying that our many years of research in this area can finally be applied to help families affected by these devastating diseases," said Mary Herbert, a professor of reproductive biology at Newcastle University. But critics charged the decision will put people at unnecessary risk of an untested procedure and said women with faulty mitochondria should opt simply to use egg donors. "This decision opens the door to the world of (genetically modified) designer babies," said David King, director of the Human Genetics Alert group. "Allowing mitochondrial replacement means that there is no logical basis for resisting GM babies."
News Article | December 8, 2016
NovogeneAIT Singapore and the Genome Institute of Singapore Forge Public-Private Partnership to Establish Whole Genome Sequencing Centre in Singapore Novogene, a leading commercial provider of genomic services and solutions with cutting edge next-generation sequencing and bioinformatics expertise; AITbiotech Pte Ltd, a Singapore biotechnology company; and the Genome Institute of Singapore (GIS) announced today that NovogeneAIT Genomics Singapore (NovogeneAIT) - a new joint venture between Novogene and AITbiotech - will establish a joint whole genome sequencing (WGS) centre at Biopolis, Singapore. The new centre will provide Illumina HiSeq X based whole genome sequencing and bioinformatics analysis of human, plant and animal samples for biomedical and agricultural researchers. The centre will devote a major portion of its sequencing capability to support public research projects and empower super scale sequencing initiatives in Singapore and the region. In addition, NovogeneAIT will collaborate with GIS to develop new applications of next-generation sequencing, such as WGS solutions for cancer diagnosis and stratified cancer treatment. "I am very excited and pleased to announce this significant new initiative with the Genome Institute of Singapore," stated Dr. Ruiqiang Li, CEO of Novogene. "The centre is the first major project for NovogeneAIT and is an important milestone for our company. We look forward to providing high-quality sequencing services in Singapore and to advancing important research initiatives that can benefit humanity." "We are delighted to work with a local biotech company," said Prof. Ng Huck Hui, Executive Director of GIS. "Such public-private partnerships will prove to be highly beneficial as it leverages the strengths of both parties to advance genomic science and medicine in Singapore, as well as to create successful local biotech companies." About Novogene Corporation Novogene is a leading provider of genomic services and solutions with cutting edge NGS and bioinformatics expertise and one of the largest sequencing capacities in the world. Novogene utilizes scientific excellence, a commitment to customer service and unsurpassed data quality to help our clients realize their research goals in the rapidly evolving world of genomics. With 1,300 employees, multiple locations around the world, 43 NGS related patents, and over 200 publications in top tier journal such as Nature and Science, the company has rapidly become a world-leader in NGS services. For more information, visit http://en.novogene.com. NovogeneAIT, a newly formed joint venture between Novogene and AITbiotech announced in September 2016, provides Illumina HiSeq X based NGS services to the Association of Southeast Asia Nations (ASEAN) and other Asian regions. About AITbiotech AITbiotech is a leading Genomic Services and MDx company based in Singapore. Founded by Alex Thian in 2008, it has a core molecular services and R&D laboratory in Singapore managed by a team of experienced biotechnologists. It provides a complete suite of Genomic Services including Capillary Sequencing, Next-generation Sequencing Services, Bioinformatics Services and customized molecular services to the research, healthcare and biomedical industries in Singapore and Asia. AITbiotech is also an ISO 13485 certified company which manufactures and distributes its own line of real-time PCR pathogen detection assays branded as abTESTM in the Asian and European markets. For more information, please visit our website: www.aitbiotech.com. About A*STAR's Genome Institute of Singapore (GIS) The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards academic, economic and societal impact. The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Regenerative Biology, Cancer Stem Cell Biology, Computational and Systems Biology, and Translational Research. The genomics infrastructure at the GIS is utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact. For more information about GIS, please visit www.gis.a-star.edu.sg Media contacts: Mr Alex Thian AITbiotech +65 6778 6822 www.aitbiotech.com Joyce Peng, Ph.D. Global Marketing Director and General Manager Novogene Corporation +1-626-222-5584 Joyce Ang Senior Officer, Office of Corporate Communications Genome Institute of Singapore, A*STAR +65 6808 8101
News Article | February 17, 2017
When a child is conceived, he or she receives DNA from both parents. The child's own genome thus consists of a maternal and a paternal genome. However, some genes -- about 100 out of the 20,000 encoded genes-- are exclusively expressed either from the maternal or from the paternal genome, with the other copy of the gene remaining silent. We know that these imprinted genes are more likely to lead to serious genetic diseases, such as Prader-Willi or Angelman syndrome. Researchers at the University of Geneva (UNIGE), Switzerland, have devised a new technique, based on a combination of biology and bioinformatics, to quickly and accurately detect the imprinted genes expressed in each of the cell types that constitute the human organs. This major breakthrough will improve our understanding and diagnosis of genetic diseases. The study can be read in full in the American Journal of Human Genetics. The research team, led by Professor Stylianos Antonarakis from the Department of Genetic Medicine and Development in the Faculty of Medicine at UNIGE, focused on genomic imprinting. This is a set of genes exclusively expressed from the genetic code inherited either from the father (the paternal allele) or from the mother (maternal allele). Why is there so much interest in the identification of the imprinted genes? Because if a deleterious mutation affects the functional allele, it cannot be compensated by the expression of the second silent allele, likely causing a serious genetic disease. The goal, therefore, is to determine the imprinted genes in all cell types of human body tissues that are liable to cause these kind of diseases. Until recently, millions of cells were analysed together without distinction. «We have now developed a new technique with a better resolution, known as Human Single-Cell Allele-Specific Gene Expression," explains Christelle Borel, UNIGE researcher. "The process can be used to simultaneously examine the expression of the two alleles, paternal and maternal, of all known genes in each individual cell. The method is fast and can be carried out on thousands of single cells with the utmost precision using next-generation sequencing technology." The heterogeneity of each tissue of the body is thus analysed in detail while searching for imprinted genes in disease-relevant tissue. The individual's genome is sequenced, as is the genome of both parents, in order to identify the parental origin of the alleles transcribed in the person's single cell. Federico Santoni, first author of the study and researcher at UNIGE and HUG (Geneva University Hospitals) further explains, "We establish the profile of the allelic expression for thousands of genes in each single cell. We then process this data with a novel computational and statistical framework to identify the specific signature of each imprinted gene, enabling us to accurately record them." This new technique redefines the landscape of imprinted genes by examining all cell types, and can be applied to all tissues affected by diseases, such as cardiac and brain tissue. Moreover, the scientists have discovered novel imprinted genes and demonstrated that some were restricted to certain tissues or cell types. This technique focuses on the specific characteristics of each individual by treating each cell as a single entity. This concept, called Single-cell Genomics, is part of an emerging field that is assuming an all-important role at UNIGE, which sees it as the future of medicine that will be personalised rather than generalised. Thanks to the technique pioneered by UNIGE researchers, it will be possible to identify new disease causing genes and to adapt a specific and targeted treatment for individual patients.
News Article | February 27, 2017
Also publishes five additional immunology, virology and microbiology books CAMBRIDGE, MA--(Marketwired - February 27, 2017) - Elsevier, a world-leading provider of scientific, technical and medical information products and services, today announced the publication of an updated edition of its valuable reference, Genetics and Evolution of Infectious Diseases, edited by Michel Tibayrenc. This book is aimed at controlling and preventing neglected and emerging worldwide diseases that are a major cause of global morbidity, disability and mortality. Using an integrated approach, the book discusses the constantly evolving field of infectious diseases and their continued impact on the health of populations, especially in resource-limited areas of the world. At the same time, Elsevier announced five additional immunology, virology and microbiology books. Genetics and Evolution of Infectious Diseases, Second Edition looks at the worldwide human immunodeficiency virus (HIV) pandemic, increasing antimicrobial resistance, and the emergence of many new bacterial, fungal, parasitic and viral pathogens. With contributions from leading authorities, the book includes developments in the field of infectious disease since it was last published in 2010. It demonstrates how the economic, social and political burden of infectious diseases is most evident in developing countries which must confront the dual burden of death and disability due to infectious and chronic illnesses. Learn more about infectious disease genomics in this sample chapter. Michel Tibayrenc, M.D., Ph.D., has worked on the evolution of infectious diseases for more than 35 years. He is a director of research emeritus at the French Institut de Recherche pour le Développement (IRD) Montpellier, France, and the founder and principal organizer of the international congresses MEEGID (molecular epidemiology and evolutionary genetics of infectious diseases). The author of more than 200 international papers, Dr, Tibayrenc has been the head of the unit of research "genetics and evolution of infectious diseases" at the IRD research center for 20 years. With his collaborator, Jenny Telleria, he is the founder and scientific adviser of the Bolivian Society of Human Genetics. Dr. Tibayrenc has won the prize of the Belgian Society of Tropical Medicine (1985), and the medal of the Instituto Oswaldo Cruz, Rio de Janeiro (2000), for his work on Chagas disease. A fellow of the American Association for the Advancement of Science, he is the founder and editor-in-chief of the Elsevier journal, "Infection, Genetics and Evolution." The six new immunology, virology and microbiology titles are: In order to meet content needs in immunology, virology and microbiology, Elsevier uses proprietary tools to identify the gaps in coverage of the topics. Editorial teams strategically fill those gaps with content written by key influencers in the field, giving students, faculty and researchers the content they need to answer challenging questions and improve outcomes. These new books, which will educate the next generation of immunologists and virologists, and provide critical foundational content for information professionals, are key examples of how Elsevier is enabling science to drive innovation. Note for Editors E-book review copies of the new books are available to credentialed journalists upon request. Contact Jelena Baras at firstname.lastname@example.org. About Elsevier Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions - among them ScienceDirect, Scopus, Research Intelligence and ClinicalKey - and publishes over 2,500 journals, including The Lancet and Cell, and more than 35,000 book titles, including a number of iconic reference works. Elsevier is part of RELX Group, a world-leading provider of information and analytics for professional and business customers across industries. www.elsevier.com
News Article | October 26, 2016
Kuwait plans to scale down, and may ultimately revoke, a law forcing all its citizens and visitors to provide samples of their DNA. Reportedly introduced as a measure to combat terrorism, it is the first law of its kind worldwide, and has been criticised for being unconstitutional, undermining privacy rights and as being unlikely to prevent terrorist attacks. In the wake of a legal challenge last month, and an appeal from the emir of Kuwait, the Kuwait parliament has now agreed to change the law so that only suspected criminals will need to give their DNA. “Public authorities in Kuwait have agreed collectively on the flaws of the current DNA law,” says Adel Abdulhadi, the Kuwait-based lawyer behind the legal challenge lodged in September on constitutional grounds. This was followed on 19 October by a request from the Emir that the law be revised in a way that would “safeguard people’s privacy”. The parliament’s revised plans have been praised internationally. “This is a wise and responsible decision,” said Olaf Rieß, president of the European Society of Human Genetics, in a statement. “The law as originally proposed was disproportionate and likely to be ineffectual in tackling the problem of terrorism, and would have had negative consequences not just for Kuwaiti society, but also for medical science and research.”