Defects of blastogenesis.

One of the most perplexing questions in clinical genetics is why patients with identical gene mutations oftentimes exhibit radically different clinical features. This inconsistency between genotype and phenotype is illustrated in the malformation spectrum of holoprosencephaly (HPE). Family members carrying identical mutations in sonic hedgehog (SHH) can exhibit a variety of facial features ranging from cyclopia to subtle midline asymmetries. Such intrafamilial variability may arise from environmental factors acting in conjunction with gene mutations that collectively reduce SHH activity below a critical threshold. We undertook a series of experiments to test the hypothesis that modifying the activity of the SHH signaling pathway at discrete periods of embryonic development could account for the phenotypic spectrum of HPE. Exposing avian embryos to cyclopamine during critical periods of craniofacial development recreated a continuum of HPE-related defects. The craniofacial malformations included hypotelorism, midfacial hypoplasia, and facial clefting and were not the result of excessive crest cell apoptosis. Rather, they resulted from molecular reprogramming of an organizing center whose activity controls outgrowth and patterning of the mid and upper face. Collectively, these data reveal one mechanism by which the variable expressivity of a disorder such as HPE can be produced through temporal disruption of a single molecular pathway.

Schizophrenia is a common disorder that may frequently be encountered when taking family histories in the genetics clinic, whether or not the referral is for a psychiatric indication. Like in other common disorders, the provision of recurrence risks for schizophrenia is a complex clinical issue because empiric recurrence risks (while reasonably well established) can rarely be used without individual tailoring. This review seeks to identify and detail some pertinent issues surrounding the clinical utility of empiric recurrence risks for schizophrenia, and to provide an overview of important factors to consider when tailoring empiric risks for individual patients.

Purpose Genetics, a discipline of biology, is one of the most recent and rapidly advancing disciplines in science. This study aims to present a bibliometric analysis of the genetics research output of Iranian authors, map the intellectual structure of these studies and investigate the development path of this literature and the interrelationships among the main topics. Design/methodology/approach This study searched the Web of Science database for documentation of Iranian-published genetics research published up to 2020. Further, this study used HistCite software to profile and analyze the most cited articles and references and to draw their historiographies. Findings A database search revealed 21,329 documents that created the study population. The highest cited publications based on the Global Citation Score (GCS) and Local Citation Score (LCS) achieved scores of 602 and 47, respectively. The publication growth rate study demonstrated consistent expansion over time. The scientific maps based on LCS and GCS had five and four clusters, respectively. Furthermore, journal articles emerged as the predominant type of publication. Practical implications The significance of this study is in its contribution to understanding the genetics research position in Iran, informing policymakers and researchers, helping scientific collaboration and its impact on public attitudes and quality of life. The results of the present study, with benefits for various groups of communities, such as policymakers, academic groups and public society, can bridge the gap between theoretical research and practical implications. Social implications The results of this study, by helping future advancement in health care, medical genetics and disease prevention, may have a direct and indirect positive influence on the quality of life. Furthermore, it may lead to more informed discussions on health care and biotechnology as well as influencing public attitudes and perceptions. Originality/value Ultimately, this study concludes that despite the proliferation of publications in terms of quantity and complexity, especially in areas such as disease diagnosis, prevention and treatment, there remains a need for more attention to other facets of genetics such as biology and biotechnology. Iranian publications are most related to population genetics, human genetics, molecular genetics, medical genetics, genomics, developmental genetics and evolutionary genetics out of 10 branches of genetics. This study reveals patterns in scientific outputs and authorship collaborations and plays an alternative and innovative role in revealing Iranian research trends in genetics.

Historically, Ontario has lagged well behind other jurisdictions in Canada in its ability to survey congenital anomalies within the province. Birth defect registries or programs exist in several provinces, namely, British Columbia, Alberta, Manitoba, Prince Edward Island, Nova Scotia and Newfoundland. While Ontario does track cases of Down syndrome, neural tube defects (NTDs) and trisomy 18 through its Maternal Serum Screening database, it has not had a province-wide program to survey birth defects until recently. Therefore, Dr Kim and other members of the Fetal Alert Network (FAN) (1) of Ontario are to be applauded for taking the first step in developing a birth defects registry that goes beyond the traditional model, by aiming to track anomalies detected before birth and linking them to postnatal outcomes. This approach recognizes the huge advances in prenatal detection and diagnosis of birth defects that have taken place in recent years. Fetal anomaly data will be critical in analyzing the effectiveness of various modalities that result in either a reduction in the incidence of birth defects or an improvement in health outcomes. Analysis of birth defect data without comparable data from prenatally diagnosed cases may lead to some false conclusions. A case in point: efforts to determine the relative contributions of primary versus secondary prevention of NTDs in British Columbia have shown that the declining birth rate of NTDs in the late 1990s was not primarily due to prenatal folic acid supplementation and food fortification, as might have been assumed before the study. Instead, the data showed that enhanced detection of NTDs by maternal serum screening and prenatal ultrasound was responsible for the decline (2). Surveys of prenatally diagnosed cases will also aid in determining prognostic factors for many congenital anomalies, as well as the effectiveness of various fetal medical and surgical therapeutic interventions, and the impact of mode, timing and location of delivery on morbidity for infants with birth defects. Similarly, the data could be used to track risk factors such as maternal age, health, ethnic background and socioeconomic status, exposure to teratogens, family history and other risk categories. Why track birth defects? Congenital anomalies are major contributors to paediatric morbidity and mortality, accounting for approximately one in 10 paediatric hospitalizations (3) and 30% of infant deaths (4). The rise in prominence of birth defects in infant mortality statistics appears to be related to a decline in deaths due to other causes, specifically, sudden infant death syndrome, respiratory distress syndrome, sepsis and asphyxia, as a result of public health campaigns and improvements in perinatal care. At the same time, overall infant mortality rates have declined sharply over the past 15 years, primarily due to advances in prenatal diagnosis and pregnancy termination of congenital anomalies (4). Ontario is Canada’s most populous province, with approximately 40% of the country’s annual births. Clearly, without data from Ontario, Canada-wide statistics would not be possible. While most of the population consists of urbanites, a substantial proportion live in rural settings in geographically diverse regions of the province. As in other areas of the country, prenatal health care providers vary from academic obstetricians in ‘downtown’ teaching hospitals to family doctors in small towns to nurse practitioners in remote nursing units in the far north. Increasingly, midwives are also providing obstetrical care. Data derived from the FAN will allow comparisons with other provinces and countries, as well as highlighting regional variations within the province. Such data may be used to determine, for example, if the incidence of specific anomalies varies with geographical location. These data will be critical in planning appropriate resources to allow optimal access to health care, both diagnostic and therapeutic, for the obstetrical patient population. One of the primary goals of the FAN is to gather data on all birth defects in the province. To date, collection of data has been restricted to patients referred to one of five regional perinatal centres, in which the FAN database is housed. The relatively recent introduction of perinatal centres in major centres has provided an important tertiary level service for complex maternal-fetal problems. However, a significant proportion of pregnancies with fetal anomalies are managed outside the perinatal centres. Genetics play a key role in the etiology of congenital anomalies in almost all cases. Whether it is the dominant factor as in chromosomal anomalies and single gene disorders, or one of a series of factors in single birth defects such as cleft lip and palate or congenital heart defects, understanding genetics is necessary to understanding birth defects. Clinical geneticists and genetic counsellors have and will continue to have a primary role in prenatal diagnosis and management of fetal anomalies. Through a network of clinics, both in major centres as well as outreach clinics in small communities throughout Ontario, the genetics community has provided prenatal genetics services for at least 30 years. It will, therefore, be critical for the FAN to access data from each of the genetics centres and clinics to come close to collecting data on the majority of prenatally detected anomalies. Another of the FAN’s primary goals is to improve access and coordination of health care service delivery for pregnant women whose babies have birth defects. To achieve this plan, a Web site with contact information for each of the five perinatal centres, complete with downloadable referral forms, is provided. Similar referral forms could be provided for each of the listed genetic centres and clinics as well. In addition, it would be helpful if providers were given guidance on which referrals are best directed to genetics clinics and which referrals should be sent to maternal-fetal medicine clinics. In relation to the access issue, a somewhat surprising finding in the FAN study was the late average gestation time for detection of fetal anomaly (21 weeks) and the even later average gestational age when patients were first assessed (24.7 weeks). At most genetics clinics, fetal anomalies are usually referred before 20 weeks and are seen immediately after referral. Little data are given about the spectrum of anomalies in the study group or whether the almost four-week lag time between first detection of the anomaly and consultation in a perinatal centre is due to a delay in referral or a problem with wait times. The FAN provides an exciting opportunity to survey congenital anomalies, both prenatally and after birth. The FAN will bring together a wide range of experts, all of whom have special knowledge and skills in diagnosing and treating congenital anomalies. In addition to experts in genetics, paediatrics and maternal-fetal medicine, surgeons, radiologists and paediatric pathologists will all undoubtedly play an important role. We look forward to the next phase of the project where attempts will be made to capture the majority of all birth defects identified in pregnancies and newborns in Ontario.

Reviewed by: Heredity under the Microscope: Chromosomes and the Study of the Human Genome by Soraya de Chadarevian Miguel García-Sancho Soraya de Chadarevian. Heredity under the Microscope: Chromosomes and the Study of the Human Genome. Chicago: University of Chicago Press, 2020. 272 pp. Ill. $37.50 (978-0-226-68511-3). In Heredity under the Microscope, Soraya de Chadarevian complements the picture of post-World War II biomedicine that she uncovered in her previous book, Designs for Life: Molecular Biology after World War II.1 Unlike in her earlier monograph, here she focuses on chromosomes as spaces of convergence of several lines of inquiry. This focus on research objects rather than disciplinary developments leads her to investigate a variety of practices that life scientists deployed to visualize and [End Page 466] interpret human chromosomes. The diversity of disciplinary backgrounds of these scientists and the multiplicity of uses to which their chromosome practices were put enable the author to expand the historiographical boundaries of both molecular biology and genetics research. Firstly, de Chadarevian disentangles “the study of postwar human heredity from the predominant concern about continuities with eugenic practices” (p. 5). The book does not limit itself to documenting the invention of karyotyping techniques to represent and detect anomalies in human chromosomes; it follows their standardization and spread, including their use as evidence of safe levels of radiation in the workplace (chapter 1) or sex assignment in the Olympic games (chapter 3). The emphasis on these uses, departed as they were from scientific theories about population improvement, displaces eugenics as the dominant interpretative framework of the history of human genetics. Secondly, the book presents chromosomes as showing “historical commonalities” (p. 177) between two approaches that have been traditionally considered as separate: molecular genetics and microscope-assisted chromosome observations. De Chadarevian stresses how these two approaches emerged as a consequence of the key role that nuclear research had played during World War II and the search of peacetime applications. Radioactive isotopes decisively fostered molecular biology, while the investigation of the effects of radiation was a crucial concern of human and medical geneticists using chromosome observations (chapter 1). Both molecular biologists and chromosome researchers also attempted to apply computers to their investigations, the former as an aid to the structural study of proteins and DNA, and the latter to automate the interpretation of karyotype images (chapter 4). However, whereas molecular biologists focused on simpler organisms, chromosome researchers engaged with both human populations and patients in the clinic. Radiation-induced leukemia was their first focus for then rapidly shifting to other conditions (especially those affecting mental abilities and sex identity) and larger-scale epidemiological studies (chapters 2 and 4). The 1960s, a decade that historians have dubbed the golden age of molecular biology,2 was also a time of expansion of chromosome observations. From the mid-1970s onward, molecular biologists turned to human subjects in order to realize the medical promise of the new recombinant DNA techniques. It is at this point when the intersection with chromosome research becomes more visible and de Chadarevian wonders “whose turn” this represents in history, a molecularization of human genetics or a humanization of molecular biology (pp. 171–76). Although subsequent success stories have put the emphasis on molecular biology, chapter 5 shows the importance of chromosome research as a key tool for gene mapping and the emergence of the human genome as an object of study. Even in the so-called post-genomic era, chromosome observations are [End Page 467] essential to clinically interpret the molecular sequence data derived from the Human Genome Project. Overall, the book offers a most welcomed framework to address the coexistence of chromosome observations and molecular biology, and their importance in genomics research. Understanding this is a pressing historiographical problem, given the dominance of molecular biologists in existing narratives and the apparent revival of chromosome research. There is yet still work to do in exploring specific overlaps between the visual and molecular approaches to the genome. A potential candidate is Victor McKusick, a main actor in de Chadarevian’s account and a co-author of the article in which Celera Genomics presented one of the draft sequences of the human...

Evidence for work-related musculoskeletal disorders.

Purpose and scopeThe aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing...

As Bluetongue virus (BTV) spread in Italy following its first incursion in 2000, it soon became apparent that, besides Culicoides imicola, additional species of the subgenus Avaritia were involved as vectors, namely one or more of the species that belong to the so-called 'Culicoides obsoletus group', which comprises C. dewulfi, C. chiopterus, C. obsoletus sensu stricto, C. scoticus and C. montanus; the three last named species are considered generally as forming the Obsoletus complex. This study presents the findings made over the last decade and more, within the Italian entomological surveillance program for Bluetongue. It describes the integrated morphological and molecular approach used to identify the species of the 'C. obsoletus group', maps in detail their relative abundances and geographic ranges in Italy, clarifies the hitherto unknown comparative seasonal abundances of C. obsoletus s.s. and C. scoticus in a site in Central Italy, and provides further details on the potential vector status of five species of the 'C. obsoletus group', with emphasis on C. obsoletus s.s., C. scoticus and C. montanus. Unlike the situation in Northern Europe, Culicoides dewulfi and C. chiopterus are uncommon to rare in Italy. In contrast, the Obsoletus complex occurs abundantly throughout Italy, with C. obsoletus s.s. being the most prevalent and ecologically adaptive of the three species making up the complex. A longitudinal study conducted at a site in Central Italy revealed that: (i) species of the Obsoletus complex prefer horses to sheep; (ii) their parity rates range from 10% (March) to 56% (November); (iii) throughout the year C. scoticus is consistently more abundant than C. obsoletus s.s.; (iv) abundances in both, C. obsoletus s.s. and C. scoticus, peak in May-June, with the peak of the latter species being more evident. Bluetongue virus was first isolated from wild caught midges of the Obsoletus complex in 2002. Thereafter, pools of selected parous midges collected across Italy, and during multiple outbreaks of BT, have been found consistently PCR-positive for the virus. More recently, viral RNA has been detected in field specimens of C. dewulfi, C. obsoletus s.s., C. scoticus and C. montanus.

The active learning student-centered teaching approach process-oriented guided inquiry learning (POGIL) is a stimulating peer-based pedagogical method gaining momentum based on reported students’ outcomes that align with STEM undergraduate goals and objectives and job market competencies. Specific advanced topics in biology are intractable to many undergraduate students and require innovative, collaborative methods to produce desired learning outcomes. Chemistry instructors originally designed POGIL, and while biology-based POGILs are present in the literature, there is a limited amount of POGILs available in molecular biology. Thus, the current article illustrates a POGIL exercise that explores the central dogma, a fundamental principle in molecular biology. The central dogma of molecular biology provides a framework for gene expression processes and describes the flow of genetic information in living organisms. The central dogma describes how DNA nucleotides are transcribed into RNA nucleotides and translated into proteins. This seminal concept of molecular biology is critical to student understanding in introductory and advanced biological sciences courses. The POGIL exercise is organized based on the learning cycle model associated with inquiry-focused teaching techniques. The learning cycle model promotes gradual concept comprehension and real-world utilization. An increase in molecular biology POGIL exercises is required to improve student understanding and course grades in molecular biology or related disciplines. Examining the efficacy of using the current molecular biology POGIL exercise is necessary from the perspectives of undergraduate students and biology faculty to fortify POGIL usage at colleges and universities.

CNS Cancer Models

Molecular ecology is a recently developed discipline in biology. During the midtwentieth century, ecology and molecular biology occupied almost opposite positions in biological studies. Molecular biology is the study of organisms at the molecular level mainly for DNA, RNA and proteins. The disconnection between ecology and molecular biology may have been due to the differences in the size of objects being studied and investigative procedures. Molecular biologists seldom studied individual organisms in the field and most ecologists were not aware of DNA in their studies; however, the improvement of molecular techniques and advances in theoretical studies in evolutionary ecology and population genetics enable both disciplines to be combined.

Websites of note

Objective Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences. Topics general biochemistry pathobiochemistry structural biology molecular and cellular biology genetics and epigenetics molecular medicine cancer research virology immunology plant molecular biology and biochemistry novel experimental methodologies Article formats Research Articles, Short Communications, Reviews and Minireviews Reviews are published by invitation only, but suggestions to the Editor-in-Chief are welcome. The journal is associated with the German Society for Biochemistry and Molecular Biology (GBM).

Medical Genetics at a Glance, 2nd edn Edited by Dorian J. Pritchard and Bruce R. Korf . ( 168 pp . ISBN 978-1-4051-4846-7 ; paperback ; £23.99 ) Singapore : Wiley Blackwell . 2007 . This book states that ‘the complex field of medical genetics is simplified’ within its covers, and is aimed at medical students and other students of genetics and genetic counselling. The first edition was criticised due to its lack of clinical examples, and the authors have tried to address this problem with the new edition. It is laid out in an attractive format, common to other titles in this series, with diagrams on one page and explanatory text on the facing page. The first section of the book, ‘Cellular, Molecular and Developmental Biology’, is very well thought-out. Topics such as DNA replication, transcription and translation are given a double-page spread each, and the clear diagrams will ensure that this information can be retained by students. It is also reassuring to see that topics such as mitosis and meiosis are included – these are often omitted from such texts as the knowledge is assumed. In an effort to include more clinical examples there are short paragraphs on each page, giving examples of some genetic diseases. This does appear a little contrived, however, and omission of these examples would not detract from the value of the content. The more clinical chapters devoted to medical genetics are generally well done, with good diagrams and clear explanations. I would have preferred to see some photographs of affected individuals included, as most other texts of this nature do include these, and students report that they find them useful. In my opinion, the biochemical genetics chapter loses sight of the aims of the book, as there are several pages of densely packed text with no illustrations. This will, I am sure, be a good reference resource, but I cannot envisage students finding this part of the book user-friendly. The laboratory techniques chapters are extremely well done, with clear illustrations. My greatest reservation about this book is that it fails to address the important topic of cancer genetics adequately. Families with a history of cancer now comprise around 50% of referrals to UK Clinical Genetics Departments, with the vast majority being suspected of having mutations in the BRCA genes or of having Lynch Syndrome. It is simply not acceptable to confine explanation of BRCA1 and BRCA2 mutations to a 5-line paragraph that fails to give the lifetime risk of breast cancer in women with such mutations. Finally, an attempt is made to draw the chapters together and explain how Clinical Genetics Departments work. This is a vitally important chapter for the medical students for whom the book has been written. Sadly for UK medical students, however, this chapter seems to reflect US practice, and there is no detailed discussion of predictive testing, which forms one of the cornerstones of UK cancer genetics practice. In summary, therefore, the initial section of this book, covering molecular biology, is extremely good, as are the sections on laboratory techniques. For UK students seeking an overview of Clinical Genetics as applied to Medicine, however, there are some serious shortfalls, and I would not recommend it.

Essential roles of sensory nerve in maintenance of cornea-phenotype in mice.