Celebrating the career and contributions of Dr Henry T. Lynch (1928–2019)

This article celebrates the career of Dr Henry Lynch and his contributions to cancer genetics through his extensive research, clinical practice and his passion for personalising care by using a patient's genetic profile to determine management and treatment. Dr Lynch's contributions were momentous and continue to have relevance to medical practice, in particular in the fields of clinical genetics, medical oncology and gastroenterology.     

Reno-endocrinal disorders: A basic understanding of the molecular genetics

The successful management of endocrine diseases is greatly helped by the complete understanding of the underlying pathology. The knowledge about the molecular genetics contributes immensely in the appropriate identification of the causative factors of the diseases and their subsequent management. The fields of nephrology and endocrinology are also interrelated to a large extent. Besides performing the secretory functions, the renal tissue also acts as target organ for many hormones such as antidiuretic hormone (ADH), atrial natriuretic peptides (ANP), and aldosterone. Understanding the molecular genetics of these hormones is important because the therapeutic interventions in many of these conditions is related to shared renal and endocrine functions, including the anemia of renal disease, chronic kidney disease, mineral bone disorders, and hypertension related to chronic kidney disease. Their understanding and in-depth knowledge is very essential in designing and formulating the therapeutic plans and innovating new management strategies. However, we still have to go a long way in order to completely understand the various confounding causative relationships between the pathology and disease of these reno-endocrinal manifestations.     

Recent advances in diagnosis,treatment, and outcome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal-recessive disease causing cortisol deficiency, aldosterone deficiency and hyperandrogenism. Diagnosis of 21-OHD is confirmed by steroid analysis in newborn screening or later on. Standard medical treatment consists of oral glucocorticoid and mineralocorticoid administration in order to suppress adrenal androgens and to compensate for adrenal steroid deficiencies. However, available treatment is far from ideal, and not much is known about the long-term outcome in CAH as trials in patients in adulthood or old age are rare. Here we briefly describe the pathophysiology, clinical picture, genetics and epidemiology of 21-OHD. This is followed by a comprehensive review of the recent advances in diagnosis, treatment and outcome. Novel insights have been gained in the fields of newborn screening, specific steroid measurement utilizing mass spectrometry, genetics, glucocorticoid stress dosing, additive medical therapy, prenatal treatment, side-effects of medical treatment, adrenomedullary involvement, metabolic morbidity, fertility and gender identity. However, many issues are still unresolved, and novel questions, which will have to be answered in the future, arise with every new finding.     

Cancer vaccines: accomplishments and challenges

Advancements in knowledge in diverse fields of science, including genetics, cell biology, molecular biology and biochemistry, have shed light on the origins of cancer and cell intrinsic properties that allow it to grow, invade and metastasize. Many therapies currently in use or under development are based on this knowledge. Advances in immunology, on the other hand, have shed light on how the host responds to these malignant properties of cancer. Based on that knowledge, immunotherapy, in particular vaccines directed at improving the host response against cancer, is being developed as an alternative therapeutic approach. In this review, we address main issues that have driven development of cancer vaccines and the challenges that have been met and/or are anticipated.     

Bioinorganic chemistry in the postgenomic era

Genome sequencing has revolutionized all fields of life sciences. Bioinorganic chemistry is certainly not immune to this influence, which is presenting unprecedented challenges. A new goal for bioinorganic chemistry is the investigation of the linkages between inorganic elements and genomic information. This requires new advancements andor the development of new expertise in fields such as bioinformatics and genetics but also provides a driving force to push forward the exploitation of traditional analytical techniques and spectroscopic tools. The "case study" of metal homeostasis in cells is discussed to provide a flavor of the current evolution of the field.     

Genetic alterations in prostate cancer

Prostate cancer is the number one malignancy among men. The search for causative factors has proven to be difficult and, accordingly, treatment options for advanced prostate cancer remain limited. However, technologic breakthroughs in the fields of genetics and molecular biology have advanced our understanding of the mechanisms involved in prostate carcinogenesis. The aim of this article is to review the most recent evidence for the role of various genetic insults at specific steps in tumor formation and to suggest potential therapeutic targets.     

Vaccines and vaccine adjuvants as biological response modifiers

Vaccines have been used successfully for many years to prevent death and morbidity from infectious diseases. In the last two decades major advances in the fields of genetics and immunology have allowed a significant increase in the use of immunomodulatory drugs in a broad range of pathologic conditions. This article reviews several uses of immunomodulating properties of vaccines, both old and new, with a focus on cancer and autoimmune diseases. Special emphasis is placed on the historical aspects and current applications of the bacillus Calmette-Guérin vaccine, the first vaccine to be used in cancer immunotherapy.     

Archaeological and genetic insights into the origins of domesticated rice

Rice (Oryza sativa) is one of the most important cereal grains in the world today and serves as a staple food source for more than half of the world’s population. Research into when, where, and how rice was brought into cultivation and eventually domesticated, along with its development into a staple food source, is thus essential. These questions have been a point of nearly continuous research in both archaeology and genetics, and new information has continually come to light as theory, data acquisition, and analytical techniques have advanced over time. Here, we review the broad history of our scientific understanding of the rice domestication process from both an archaeological and genetic perspective and examine in detail the information that has come to light in both of these fields in the last 10 y. Current findings from genetics and archaeology are consistent with the domestication of O. sativa japonica in the Yangtze River valley of southern China. Interestingly, although it appears rice was cultivated in the area by as early 8000 BP, the key domestication trait of nonshattering was not fixed for another 1,000 y or perhaps longer. Rice was also cultivated in India as early as 5000 BP, but the domesticated indica subspecies currently appears to be a product of the introgression of favorable alleles from japonica. These findings are reshaping our understanding of rice domestication and also have implications for understanding the complex evolutionary process of plant domestication.     

日本血吸虫种群的遗传标志应用研究进展

日本血吸虫种群遗传结构的研究有助于更好地理解日本血吸虫病的传播和感染途径，这对于血吸虫病的监控与防治以及对其疫苗的发展都将具有重要的意义。近年来，随着分子遗传学理论与实验技术的发展，在日本血吸虫种群遗传学上取得了一些重大的研究进展。多种遗传标志如：限制性片段长度多态性、线粒体DNA、微卫星等在日本血吸虫种群遗传学上均得到了很好的应用，该文就应用于日本血吸虫的种群遗传学上主要的遗传标志作一综述。     

Genetics of coronary artery disease – A clinician's perspective

Coronary artery disease (CAD) is the major cause of fatality and disability among all cardiovascular diseases (CVD). Intricate interactions of genes and environment dictate the outcomes of CAD. Technological advances in the different fields of genetics including linkage studies (LS), candidate gene studies (CGS) and genome-wide association studies (GWA studies) have augmented the knowledge of pathogenesis of CAD. LS were more successful in identifying genetic variants among monogenic disease. GWA studies were relatively popular in identification of variation in polygenic disease. Until now, GWA studies recognized about 50 loci determining around 6% of the heritability in CAD. Clinical utility of the above knowledge would result in better CAD management, but validation of the variants in native population is warranted for active adoption into the clinic. The major aim of this review is to provide an adequate perspective of our current understanding and advances of genetics in CAD.     

Etiopathogenesis of inflammatory bowel disease: the importance of the pediatric perspective

Inflammatory bowel disease (IBD) is now recognized as a common chronic disease affecting children and adolescents. This article will review recent advances made in the fields of genetics, epidemiology, gut ecology, and immunology regarding the etiopathogenesis of IBD, with particular emphasis on the contributions made by pediatric studies. Areas where further study of the pediatric age group would be beneficial will be highlighted.     

Experimental research on ageing in Russia

An analysis of the current situation in Russian biogerontology is presented in this paper. There are several active groups in Russia pursuing research in biogerontology capable of producing results publishable in international journals of high repute. The main directions of research on the biology of ageing in this country are prevention of premature ageing, the role of free radicals and of the endocrine system (in particular, the pineal gland) in the mechanisms of ageing, carcinogenesis and ageing and population genetics of ageing. Several groups are conducting fruitful research on the theoretical aspects of the biology of ageing. Only a few teams are focusing on molecular biology and the genetics of ageing. In the past few years, many more researchers in fields highly relevant to gerontology have been attracted by issues in gerontological research. In Russia, the most basic problem facing researchers in biogerontology and other relevant areas is an almost complete absence of support from the State and other decision makers.     

Sex with two SOX on: SRY and SOX9 in testis development.

Although gonads are not required for development or survival, defects in gonadal development undoubtedly have a profound influence on affected individuals. Recent complementary studies in the fields of cytology, biochemistry and molecular genetics have revealed that normal gonad development involves an exquisitely regulated network of gene expression and protein-protein interactions. The initial event of gonadogenesis, in both males and females, involves the formation of a bipotential primordium. A Y chromosome then activates the male-specific pathway. The demonstration that mutations in the SOX proteins, SRY and SOX9, are responsible for disorders associated with male-to-female sex reversal showed dramatically that SRY and SOX9 have an essential role in male sex differentiation. This was emphasized when it was shown that female mice carrying transgenes that encode these proteins developed as males. SRY and SOX9 proteins have been characterized extensively and aspects of their function and regulation are now known.     

epiPATH: an information system for the storage and management of molecular epidemiology data from infectious pathogens

Background  

Most research scientists working in the fields of molecular epidemiology, population and evolutionary genetics are confronted with the management of large volumes of data. Moreover, the data used in studies of infectious diseases are complex and usually derive from different institutions such as hospitals or laboratories. Since no public database scheme incorporating clinical and epidemiological information about patients and molecular information about pathogens is currently available, we have developed an information system, composed by a main database and a web-based interface, which integrates both types of data and satisfies requirements of good organization, simple accessibility, data security and multi-user support.     

Genetics and Genomics of Coronary Artery Disease

Coronary artery disease (or coronary heart disease), is the leading cause of mortality in many of the developing as well as the developed countries of the world. Cholesterol-enriched plaques in the heart’s blood vessels combined with inflammation lead to the lesion expansion, narrowing of blood vessels, reduced blood flow, and may subsequently cause lesion rupture and a heart attack. Even though several environmental risk factors have been established, such as high LDL-cholesterol, diabetes, and high blood pressure, the underlying genetic composition may substantially modify the disease risk; hence, genome composition and gene-environment interactions may be critical for disease progression. Ongoing scientific efforts have seen substantial advancements related to the fields of genetics and genomics, with the major breakthroughs yet to come. As genomics is the most rapidly advancing field in the life sciences, it is important to present a comprehensive overview of current efforts. Here, we present a summary of various genetic and genomics assays and approaches applied to coronary artery disease research.     

Current approaches to the molecular and physiological basis of cystic fibrosis

Cystic fibrosis (CF) is the most common disease caused by a single gene abnormality within the caucasian population. Its severity of expression in homozygotes varies widely, and the disease involves multiple organ systems. During the past few years, major advances in CF research have been made. These advances have occurred primarily in the fields of physiology and molecular genetics. As a result of these advances, it is now generally accepted that the basic defect in CF is the inability of an epithelial chloride channel to respond to adrenergic stimulation in affected organs. The recent major breakthrough in CF research is the localization of the CF gene and identification of the mutation responsible for the majority of cases of CF. In this article, the evidence which has led to this conclusion, as well as possible mechanisms by which a mutation in a single codon can produce the CF defects are reviewed. Finally, new approaches to the characterization of the CF gene by complementation of the defect in immortal cell lines displaying the transport phenotype associated with CF are discussed.     

Genetic rat models of hypertension: Relationship to human hypertension

Experimental models of human disease are frequently used to investigate the pathophysiology of disease as well as the mechanisms of action of therapeutics. However, as long as models have been used there have been debates about the utility of experimental models and their applicability for human disease on the phenotypic and genomic level. The recent advances in molecular genetics and genomics have provided powerful tools to study the genetics of multifactorial diseases, such as hypertension. However, studies of such diseases in humans remain challenging in part due to lack of statistical power and genetic heterogeneity within patient populations. For hypertension, various rat models have been developed and used for the identification of susceptibility loci for genetic hypertension. With the advent of "comparative genomics," the application of genetic studies to both human and animal model systems allows for a new paradigm, where comparative genomics can be used to bridge between model utility and clinical relevance. This review discusses recent approaches in genetics to facilitate gene discovery for polygenic disorders with specific focus on how comparative mapping can be used to select target regions in the human genome for large-scale association studies and linkage disequilibrium testing in clinical populations.     

Update on the molecular diagnosis of endocrine tumors: toward -omics-based personalized healthcare?

Genetic advances in endocrine neoplasia provided the paradigm for the practice of clinical cancer genetics: germline RET mutations in multiple endocrine neoplasia type 2. In the last 14 yr, both genetics and -omics advances have occurred, almost exponentially in the last 5 yr. The time has come to reevaluate recent advances in genomic medicine's promise to revolutionize personalized healthcare in the context of endocrine neoplasias. This update focuses on two examples of endocrine neoplasias, those of the thyroid and of the adrenal, and discusses recent advances in germline and somatic genetics and genomics, as they relate to clinical application.     

Net energy of cellulosic ethanol from switchgrass

Perennial herbaceous plants such as switchgrass (Panicum virgatum L.) are being evaluated as cellulosic bioenergy crops. Two major concerns have been the net energy efficiency and economic feasibility of switchgrass and similar crops. All previous energy analyses have been based on data from research plots (<5 m2) and estimated inputs. We managed switchgrass as a biomass energy crop in field trials of 3-9 ha (1 ha = 10,000 m2) on marginal cropland on 10 farms across a wide precipitation and temperature gradient in the midcontinental U.S. to determine net energy and economic costs based on known farm inputs and harvested yields. In this report, we summarize the agricultural energy input costs, biomass yield, estimated ethanol output, greenhouse gas emissions, and net energy results. Annual biomass yields of established fields averaged 5.2-11.1 Mg x ha(-1) with a resulting average estimated net energy yield (NEY) of 60 GJ x ha(-1) x y(-1). Switchgrass produced 540% more renewable than nonrenewable energy consumed. Switchgrass monocultures managed for high yield produced 93% more biomass yield and an equivalent estimated NEY than previous estimates from human-made prairies that received low agricultural inputs. Estimated average greenhouse gas (GHG) emissions from cellulosic ethanol derived from switchgrass were 94% lower than estimated GHG from gasoline. This is a baseline study that represents the genetic material and agronomic technology available for switchgrass production in 2000 and 2001, when the fields were planted. Improved genetics and agronomics may further enhance energy sustainability and biofuel yield of switchgrass.