Human Heredity Research Articles

Large Scale Genetic Research on Neuropsychiatric Disorders in African Populations is Needed

Large Scale Genetic Research on Neuropsychiatric Disorders in African Populations is Needed

PVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation.

The von Hippel-Lindau (VHL) gene is a well-defined tumor suppressor linked to human heredity cancer syndromes. As a component of the VHL-elongin B/C E3 ligase complex, pVHL performs its tumor function by targeting proteins for proteasomal degradation. It is largely unknown whether pVHL functions in antiviral immunity. In this article, we identify that pVHL negatively regulates innate antiviral immunity, which acts mainly by inducing degradation of mitochondrial antiviral-signaling protein (MAVS, also known as Cardif, IPS-1, or VISA). Overexpression of pVHL abrogated the cellular response to viral infection, whereas knockdown of pVHL exerted the opposite effect. pVHL targeted the K420 residue of MAVS to catalyze the formation of K48-linked polyubiquitin chains, leading to proteasomal degradation of MAVS. After viral infection, Mavs levels remained low in wild type zebrafish embryos but became much higher in vhl-deficient (vhl(-/-)) zebrafish embryos. Higher MAVS levels correlated with a greatly exaggerated antiviral response. In this work, we demonstrate that pVHL exhibits a previously unknown role in innate antiviral immunity.

Helping Couples Fulfill the "Highest of Life's Goals": Mate Selection, Marriage Counselling, and Genetic Counseling in United States.

This article traces the history of modern genetic counseling to mate selection and marriage counselling practices of the early-20th century. Mate selection revolved around a belief that human heredity could be improved and genetic diseases eradicated through better breeding. Marriage counselling, though interested in reproduction, was also concerned with the emotional and psychological well-being of couples. These two practices coalesced most obviously in the work of well-known geneticist Sheldon Reed. Even as marriage and genetic counselling diverged in the post-WWII period, vestiges of these practices remain in contemporary counseling experiences with family planning and genetic screening programs. Emphasizing points of continuity between "positive" eugenic ideologies and modern genetic practices elaborates the diverse origins of genetic counseling. It also exposes how genetic counselors have become involved in genetic enterprises beyond standard clinical settings, and prods at key issues in the interaction between genetic science and social values.

Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan Africa.

CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa.

Constant or break? On the relations between human genetics and eugenics in the Twentieth Century

The history of human genetics has been a neglected topic in history of science and medicine for a long time. Only recently, have medical historians begun to pay more attention to the history of human heredity. An important research question deals with the interconnections between human genetics and eugenics. This paper addresses this question: By focusing on a Swiss case study, the investigation of the heredity of goiter, I will argue that there existed close but also ambiguous relations between heredity research and eugenics in the twentieth century. Studies on human heredity often produced evidence that challenged eugenic aims and ideas. Concurrently, however, these studies fostered visions of genetic improvement of human populations.

Neuron-based heredity and human evolution.

It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use) strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse) leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes in line with Neolamarckian concepts of evolution (Packard, 1901). Evidence is presented of bipartite evolutionary processes—Darwinian and Neolamarckian—driving human descent from a common ancestor shared with the great apes.

Stroke genomics in people of African ancestry: charting new paths: review article

One in six people worldwide will experience a stroke in his/her lifetime. While people in Africa carry a disproportionately higher burden of poor stroke outcomes, compared to the rest of the world, the exact contribution of genomic factors to this disparity is unknown. Despite noteworthy research into stroke genomics, studies exploring the genetic contribution to stroke among populations of African ancestry in the United States are few. Furthermore, genomics data in populations living in Africa are lacking. The wide genomic variation of African populations offers a unique opportunity to identify genomic variants with causal relationships to stroke across different ethnic groups. The Stroke Investigative Research and Educational Network (SIREN), a component of the Human Health and Heredity in Africa (H3Africa) Consortium, aims to explore genomic and environmental risk factors for stroke in populations of African ancestry in West Africa and the United States. In this article, we review the literature on the genomics of stroke with particular emphasis on populations of African origin.

Chromosome Photography and the Human Karyotype

In 1956, Joe Hin Tjio and Albert Levan published a paper in which they suggested that the number of human chromosomes was 46 and not 48. The story of the recount has been the subject of numerous studies and debates. In this essay I propose to revisit the 1956 paper and the questions surrounding it by considering the chromosome images it contained. Paying attention to the images, including especially the photomicrograph that has come to represent the new chromosome count, offers the opportunity to study the history of an iconic image of genetics. In the course of this history the image moved from proving the quality of Tjio and Levan’s preparations to becoming an object of contention, proof of authorship, example to emulate, manipulable object, recognizable icon, and historical object in its own right. More generally, the essay highlights the role of visual techniques and materials in shaping knowledge and staking claims in human heredity in the mid-twentieth century. The history of postwar cytogenetics has long been overshadowed by dominant accounts of molecular approaches in biology that developed rapidly at the same time. Yet the recognition that, well into the 1970s, chromosome pictures were the most recognizable images of genetics points to the need for new approaches to the historiography.

The H3Africa policy framework: negotiating fairness in genomics

Human Heredity and Health in Africa (H3Africa) research seeks to promote fair collaboration between scientists in Africa and those from elsewhere. Here, we outline how concerns over inequality and exploitation led to a policy framework that places a firm focus on African leadership and capacity building as guiding principles for African genomics research.

操船者の可罰性 - 刑事過失と人間科学 -

Several human sciences for special qualities like as human's recognition, heredity or human factors have been wining development in recent years. According to those sciences, today, the one of the science knowledge which nobody as individual could do everything without any errors, attains academic common one. There are two standards for criminal negligence. The negligence is decided based on actual offender's conditions in accordance with standard of an act by an ordinary person when he would have been at the same position of offender. The said science knowledge might have an influence on offender's conditions and the standard as an ordinary person for that decision. Especially, it will become doubtful whether the concept of an ordinary person would keep the position as the above standard in the future. On this papers, the author would like to look for the problem on criminal negligence focusing on an ordinary person who shall be effected by science knowledge. And finally, the author may offer the repeal of slight and usual criminal negligence at least.

Pedigrees of madness: the study of heredity in nineteenth and early twentieth century psychiatry.

This article discusses the development of the statistical methods employed by psychiatrists to study heredity as a causative factor of mental diseases. It argues that psychiatric asylums and clinics were the first institutions in which human heredity became the object of systematic research. It also highlights the different concepts of heredity prevalent in the psychiatric community. The first of four parts traces how heredity became a central category of asylum statistics in the first half of the nineteenth century. The second part deals with attempts to introduce new methods of surveying in order to generate more precise data about psychopathological inheritance in the 1860s and 1870s. The third part discusses how, by the end of the nineteenth century, a widespread discontent with the results of asylum statistics led to an increasing interest in the use of family studies. Finally, the fourth part examines the impact of Mendelian theory on psychiatric statistics in the early twentieth century.

A tale of two papers.

Two papers published in HEREDITAS between 1921 and 1939 show how the attitude towards race biology changed in the course of the interwar period in the Nordic countries. In the early 1920s race biology was seen to constitute a legitimate science. Ordinary human genetics prevailed, however, over race biology already in the very beginning on the pages of HEREDITAS. Population thinking was introduced into the study of human heredity around the year 1930. It effectively contradicted the concept of the race. Interestingly, HEREDITAS does not carry a single paper on eugenics and sterilization. In 1939 we see a final repudiation of the doctrines on race. Times had changed and the National Socialists had usurped the doctrines of race in Germany.

Domesticating the Child: Maternal Responses to Hereditary Discourse in The Tenant of Wildfell Hall

This article examines the early nineteenth century connections between human, animal and plant by placing Erasmus Darwin’s The Botanic Garden (1791) and The Temple of Nature (1803) in conversation with Anne Brontë’s The Tenant of Wildfell Hall (1848). I argue that the Romantic versions of heredity described in Darwin’s poetry tended to reinscribe traditional gender roles. Brontë’s Tenant, on the other hand, revises earlier notions of heredity and motherhood via Helen Huntingdon, the wife of an alcoholic who tries to prevent her son from activating his genetic taint. By reconfiguring the supposedly natural connections between patriarchal inheritance of the land on the one hand and biological traits on the other, and by reclaiming and reinscribing popular metaphors of breeding, Anne Brontë’s female protagonist creates and attempts to implement a maternalist version of heredity while remaining entrenched within the nineteenth-century cult of motherhood. Whereas the Romantic and romanticized poetry of Erasmus Darwin and his contemporaries’ approach to natural history bestowed human characteristics on plants in order to make their reproduction more comprehensible, The Tenant of Wildfell Hall does the opposite. Without a satisfactory framework in place to express the anxieties surrounding human heredity, Brontë turns the tables on the metaphor and applies the language of breeding and agriculture to a human child. In doing so, she creates an alternate version of heredity based on maternal strength and power rather than one predicated upon patriarchal structures of kinship and economic inheritance.

Human heredity in the twentieth century

Human heredity in the twentieth century

Chromosome surveys of human populations: Between epidemiology and anthropology

It is commonly held that after 1945 human genetics turned medical and focussed on the individual rather than on the study of human populations that had become discredited. However, a closer look at the research practices at the time quickly reveals that human population studies, using old and new tools, prospered in this period. The essay focuses on the rise of chromosome analysis as a new tool for the study of human populations. It reviews a broad array of population studies ranging from newborn screening programmes to studies of isolated or ‘primitive’ people. Throughout, it highlights the continuing role of concerns and opportunities raised by the propagation of atomic energy for civilian and military uses, the collection of large data bases and computers, and the role of international organisations like the World Health Organisation and the International Biological Programme in shaping research agendas and carving out a space for human heredity in the postwar era.

Mutations in Soviet public health science: Post-Lysenko medical genetics, 1969–1991

This paper traces the integration of human genetics with Soviet public health science after the Lysenko era. For nearly three decades, USSR biology pursued its own version of anti-bourgeois, Soviet ‘creative Darwinism’, departing from western, post-WWII scientific developments. After Lysenko was suspended, research niches of immunology, biophysics and mutation research formed the basis of new departments at the Institute of Medical Genetics, which was founded in 1969 as part of the Soviet Academy of Medical Sciences. Focussing on early research activities and collaborations at the institute, I show how the concept of mutagenesis, a pivotal issue during the Cold War, became mobilized from Drosophila genetics to human heredity and to society as a whole. This mode of scaling up and down through population studies shaped not only Soviet human biology and genetics; it also brought about changes in clinical practice and public health as well as in the monitoring and regulation of mutagenic agents in the environment.

From Mummies to Modern Man: Genomic Research to Advance Human Heredity and Health

From Otzi, the Tyrolean Iceman, to the royal mummies of pharaohs Akhenaten and Tutankhamun, genetic and genomic analyses of ancient deoxyribonucleic acid have shed light on the social and environmental influences on life and longevity, population dynamics, migratory patterns, dietary habits, putative and actual causes of death, and the susceptibility to congenital and acquired diseases during life more than 5,000 years ago [1–3]. For example, detailed analysis of the Otzi genome demonstrated the presence of several single nucleotide polymorphisms associated with increased risk for coronary heart disease, ischemic stroke, sudden cardiac death, and general atherosclerosis [4]. The full impact and clinical manifestations of these genetic variants were likely not experienced because of the short life expectancy at that time. Several articles in this issue of Global Heart on mummies provide intriguing details on the value of genomic analyses and correlates in atherosclerosis and other diseases in ancient humans. [5–10] For modern man, genomic analyses can also provide a unique opportunity to further explore gene-gene and gene-environment interactions that have the potential to greatly inform the prevention, detection, diagnostic valuation, treatment, and control of heritable diseases and traits. In particular, the current ability to link genetic variation to disease susceptibility, at least in rare variants and Mendelian disorders, provides an opportunity for genetic counseling and appropriate behavioral and lifestyle interventions to reduce the risk of specific diseases. However, more is known today about the genomes of Akhenaten, Tutankhamun, and their pharaonic lineage that lived more than 3,500 years ago than those of present-day Egyptians. Additionally, biomedical research in genetics and genomics involving African scientists has been limited [11]. Considering that modern human populations originated in Africa, and that genetic diversity is most profound on that continent, much can be gained by investments in this arena. This perspective presents investments made by the U.S National Institutes of Health (NIH) and the U.K.-based Wellcome Trust to advance the field of human heredity and health in Africa.

THU0472 Amino Acid Position 10 in the HLA-DRB1 Protein Associates with Radiological Erosions in Early Active RA

BackgroundAdvances in imputation methods have enabled association studies of HLA protein amino acid polymorphisms and rheumatoid arthritis (RA) susceptibility. A recent meta-analysis of this region has attributed most of its...

H3Africa: a tipping point for a revolution in bioinformatics, genomics and health research in Africa.

BackgroundA multi-million dollar research initiative involving the National Institutes of Health (NIH), Wellcome Trust and African scientists has been launched. The initiative, referred to as H3Africa, is an acronym that stands for Human Heredity and Health in Africa. Here, we outline what this initiative is set to achieve and the latest commitments of the key players as at October 2013.FindingsThe initiative has so far been awarded over $74 million in research grants. During the first set of awards announced in 2012, the NIH granted $5 million a year for a period of five years, while the Wellcome Trust doled out at least $12 million over the period to the research consortium. This was in addition to Wellcome Trust’s provision of administrative support, scientific consultation and advanced training, all in collaboration with the African Society for Human Genetics. In addition, during the second set of awards announced in October 2013, the NIH awarded to the laudable initiative 10 new grants of up to $17 million over the next four years.ConclusionsH3Africa is poised to transform the face of research in genomics, bioinformatics and health in Africa. The capacity of African scientists will be enhanced through training and the better research facilities that will be acquired. Research collaborations between Africa and the West will grow and all stakeholders, including the funding partners, African scientists, scientists across the globe, physicians and patients will be the eventual winners.

Comparing the Hub-and-Spoke Model Practices of the LifeLines Study in the Netherlands and the H3Africa Initiative

Biobank sample storage is critical in population health and epidemiology studies. Biobanks bridge two very different worlds: they connect to the participants and patients at an individual level, but they also aggregate information and represent the cutting edge of scientific discovery. In this brief report, we describe how the LifeLines study in the Netherlands manages its resources for communication and services, and how it can serve as a model for the Human Heredity and Health in Africa Initiative (H3Africa Initiative).