One hundred years of pleiotropy: a retrospective

Pleiotropy is defined as the phenomenon in which a single locus affects two or more distinct phenotypic traits. The term was formally introduced into the literature by the German geneticist Ludwig Plate in 1910, 100 years ago. Pleiotropy has had an important influence on the fields of physiological and medical genetics as well as on evolutionary biology. Different approaches to the study of pleiotropy have led to incongruence in the way that it is perceived and discussed among researchers in these fields. Furthermore, our understanding of the term has changed quite a bit since 1910, particularly in light of modern molecular data. This review traces the history of the term "pleiotropy" and reevaluates its current place in the field of genetics.     

The prevention and avoidance of genetic disease: summing up

The preceding papers have dealt with major advances in understanding and detecting the mutational basis of human disease. If these advances are to be of practical benefit, systems of effective, efficient and acceptable delivery of the technology to the relevant population groups will need to be planned. In these delivery systems, the key figure is likely to be the clinical geneticist, still a somewhat shadowy figure, difficult to define: a doctor among scientists, and a scientist among doctors. The clinical geneticist, among other duties, acts as a user-friendly interface between the public (including the medical profession) and the conceptually quite difficult fields of modern genetics. Few people in this age of transition to computer literacy will underestimate the importance of a user-friendly interface, without which even the most powerful analytical machines are underused, error prone, or even incomprehensible.     

Evaluation and treatment of BRCA-positive patients

The recent discovery of the breast cancer-associated genes BRCA1 and BRCA2 has now made it possible to identify individuals who are at a very high risk for the future development of breast cancer. To some extent, however, society has fallen victim to its molecular genetic technology. The significance of these discoveries to the detection, treatment, and prevention of breast cancer cannot be overstated. Nevertheless, the appropriate administration and interpretation of BRCA genetic testing and the treatment of BRCA-positive patients remain controversial issues. Complexities of BRCA testing require that such genetic screening be restricted to selected high-risk patients and that test results be interpreted by a knowledgeable molecular geneticist. Although no medical prophylaxis has been demonstrated to be of benefit in BRCA-positive patients, recent evidence suggests that a prophylactic mastectomy, with or without reconstruction, is a reasonable treatment option that substantially reduces cancer risk.     

Genetic counselling. I. Definition and present status (author's transl)]

Genetic counselling is a medical action which must be carried out by a M.D. specialized in genetics. Genetic counselling is peculiar in that couples rather than individuals are involved. Furthermore it is not concerned with the health of the consultants but with that of their expected children. Genetic counselling is not restricted to the statistical estimation of a risk; it raises important problems of psychology and behaviour. Finally, eugenic considerations about the diffusion of deleterious genes should not be taken into account in genetic counselling, which is given in the interest of individuals, not of the society. The increasing demand for genetic counselling is due to the change of the reproductive pattern. People do not want only to fix the size of their family, but also to avoid any accident of procreation.     

The duty to recontact: attitudes of genetics service providers

The term "duty to recontact" refers to the possible ethical and/or legal obligation of genetics service providers (GSPs) to recontact former patients about advances in research that might be relevant to them. Although currently this practice is not part of standard care, some argue that such an obligation may be established in the future. Little information is available, however, on the implications of this requirement, from the point of view of GSPs. To explore the opinions of genetics professionals on this issue, we sent a self-administered questionnaire to 1,000 randomly selected U.S. and Canadian members of the American Society of Human Genetics. We received 252 completed questionnaires. The major categories of respondents were physician geneticist (41%), Ph.D. geneticist (30%), and genetic counselor (18%); 72% of the total stated that they see patients. Respondents indicated that responsibility for staying in contact should be shared between health professionals and patients. Respondents were divided about whether recontacting patients should be the standard of care: 46% answered yes, 43% answered no, and 11% did not know. Those answering yes included 44% of physician geneticists, 53% of Ph.D. geneticists, and 31% of genetic counselors; answers were statistically independent of position or country of practice but were dependent on whether the respondent sees patients (43% answered yes) or not (54% answered yes). There also was a lack of consensus about the possible benefits and burdens of recontacting patients and about various alternative methods of informing patients about research advances. Analysis of qualitative data suggested that most respondents consider recontacting patients an ethically desirable, but not feasible, goal. Points to consider in the future development of guidelines for practice are presented.     

The politics of human heredity in the USSR, 1920-1940

After the Bolshevik revolution of 1917, Iurii Filipchenko (in Petrograd) and Nikolai Koltsov (in Moscow) created centers of genetic research where eugenics prospered as a socially relevant part of the new "experimental" biology. The Russian Eugenics Society, established in 1920, was dominated by research-oriented professionals. However, Bolshevik activists in the movement tried to translate eugenics into social policies (among them, sterilization) and in 1929, Marxist geneticist Alexander Serebrovsky was stimulated by the forthcoming Five-Year Plan to urge a massive eugenic program of human artificial insemination. With the advent of Stalinism, such attempts to "biologize" social phenomena became ideologically untenable and the society was abolished in 1930. Three years later, however, a number of eugenicists reassembled in the world's first institute of medical genetics, created by Bolshevik physician Solomon Levit after this return from a postdoctoral year in Texas with H.J. Muller. Muller himself moved to the Soviet Union in 1933, where he agitated for eugenics and wrote Stalin in 1936 to urge an artificial insemination program. Shortly thereafter, Muller left Russia, several of his colleagues were shot, and the Institute of Medical Genetics was disbanded. During the next three decades, Lysenkoists regularly invoked the Soviet eugenic legacy to claim that genetics itself was fascist.     

Conceptual and ethical problems in the epistemology of genetic information

My thesis will be that the identification of genetic features and their medical interpretation follow at least partially from reductionist premises: “Genes are charging the gun, life(-style) will trigger it.” This simplistic metaphor illustrates a problem of genetic diagnosis: from the viewpoint of philosophy of science, concepts of the gene and the genome are vague and confused. Until now these concepts have not been defined satisfactorily. Partly on account of this there is an additional problem in applying genetic tests in medical diagnostics. The epistemic status of predictive genetic diagnosis in many cases can justifiably be called “opaque.” But a predictive genetic test is designed to reveal genetic knowledge of and for a client on the basis of scientific research. Methodologically the diagnosis of the scientific problem in genetics as a science is developed philosophically as an epistemological argument. The problem of genetics as applied science in medicine and society is the danger of irrationality due to reductionist premises of science. This problem is to be revealed by philosophical analysis. The major result of the argument is that the assessment of applications of basic research in genetics should include considerations from epistemology and philosophy of science. The epistemological status of scientific concepts and reasonableness of advice are interrelated. My thesis is that at the interface between theory of science in genetics and reasonableness of “genetic advice” is the responsibility of the researchers for concepts of their science.     

Attitude of the pediatric surgeon to antenatal diagnosis of a malformation

To have found by prenatal ultrasonography a fetal severe malformation implies a complete collaboration between paediatric surgery who must take a decision and the echographist , the obstetrician, the geneticist. The information they give to the parents is a delicate and necessary step. Four kinds of decisions are discussed (termination, provoked delivery, in utero surgery, secondary neo-natal surgery) at the light of medical, psychological, ethical and juridical data.     

At the Revolution with Fred Sherman

Fred Sherman was a prominent yeast geneticist and my mentor in graduate school. Fred passed away in September 2013 at the age of 81. In this minireview, I describe what it was like to know Fred and be in his lab from 1977 to 1982, the extraordinarily exciting time when the recombinant DNA revolution hit yeast genetics.     

Problems of value in medicine and the humanities, or will the real doctor please stand up?

After a general discussion of the need for physicians to concern themselves with questions of human ethics, this paper considers genetics, the population explosion, abortion, curing patients of psychological problems which are perfectly normal (such as masturbation), and behavior modification. The population explosion is the outgrowth of the understandable desire to reduce disease and death. Now births must be reduced immediately or the world will eliminate starvation among infants only to have starvation among adults. The 2nd problem is preventing births. Contraception is not caught up in moral problems but abortion pits 1 set of ethics against another. Here, again, the physician must have a broad world view. The humanist theory holds that procedures that enhance human freedom are both natural and desirable while procedures that suppress it are unnatural and undesirable. This also applies to medical procedures. An understanding of the humanist point of view is important to the physician in his work.     

Syndrome mit dem Leitsymptom Großwuchs

Syndromic conditions with overgrowth as the cardinal clinical sign are a relevant problem in human genetics and pediatrics. Overgrowth is defined as a length/height of more than two standard deviations above the mean, i.e. a body length above the 97^th centile. Overgrowth syndromes relevant in the clinical daily routine of the geneticist or pediatrician are described here: Marfan, Beckwith-Wiedemann, Sotos, Weaver, Simpson-Golabi-Behmel and Proteus syndromes. The characteristic clinical signs, diagnostic criteria, molecular bases, modes of inheritance, prevention programs—where necessary—as well as differential diagnoses are presented here.     

How Important is Genetics for an Understanding of Evolution?

SYNOPSIS. The contributions of modern genetics to the understandingof evolution have been threefold. First, it has documented theextent of genetic variation that exists in populations as abasis for future evolution. In particular it has shown thatnatural selection has not destroyed all variation, as mightbe predicted, so that there must be mechanisms for the maintenanceandorigin of new selectable variation that balance the homogenizingforces of selection. Second, it has begun to provide a mechanismof the origin of genetic novelties which must be at the basisof the major features of the history of life. In doing so, ithas shown how selection fornew features is at all times historicallycontingent and that evolution is at all times at riskof fallinginto genetic dead-ends. Third, modern genetics has greatly enrichedthe diversity ofmechanisms known to cause evolutionary change.All of these mechanisms involve the conversion of variationbetween individuals into variation between populations in timeand space, but many are non-selective or even counter-selective.Natural selection is not the only mechanism of evolution.     

Internet resources for the human geneticist

The Internet is a massive expanding body of information, which is likely to play a significant role for clinicians and researchers across the world. Since its inception in December 1969 the Internet has grown rapidly and is anticipated to expand 1,000% in the coming next few years. Various useful databases on human genetics are already in 'the Net' and many more are being added constantly. The future of human geneticist is in handling of information. In this review of Internet and compilation of important web site addresses we expect to stimulate and instruct human geneticists in navigating the Net. The list of web sites provided in this article is expected to facilitate their search.     

The economics of clinical genetics services. IV. Financial impact of outpatient genetic services on an academic institution.

Those clinical genetic services that do not involve laboratory tests or procedures--i.e., the "cognitive" services such as diagnosis, management, and counseling--are labor-intensive, time-consuming, and not self-supporting. However, as a result of an evaluation at a genetics clinics, a patient will often receive other services at the same medical center. The full economic impact of the genetics clinic may be underappreciated. Therefore, at one medical center we examined (a) three settings that delivered genetics services and (b) two specialty clinics providing services to children with genetics conditions; and we calculated charges and payments for an unselected, consecutive group of outpatients. The results showed that cognitive genetics services accounted for a variable, but generally low, percentage of both the professional (generally physicians') and total charges accumulated by patients as a consequence of their visit to the genetics clinic. With laboratory and procedural charges included, patients seen in general genetics clinics (or their insurance plans) paid up to three times as much to the medical center and to its health professionals as to the genetics professional. These data confirm that clinical genetics services, while not generating enough income to cover their own costs, bring considerable revenue to the medical center. This fact alone should prove useful to the director of clinical genetics programs when they are negotiating finances with institutional administrators.     

Genetic disorders presenting as “schizophrenia”. Karl bonhoeffer's early view of the psychoses in the light of medical genetics

There is overwhelming empirical evidence for the influence of genetic factors in the etiology of schizophrenic psychoses. An appreciable and still increasing number of exogenous factors have been known for decades that are capable of inducing psychoses that present as "schizophrenia" or are more or less similar to it. In this article, genetic disorders--chromosomal abnormalities and Mendelian diseases--are summarized that may be associated with such psychoses. These disorders frequently but not necessarily exhibit additional physical symptoms. Although the majority of schizophrenic psychoses can so far not be explained by exogenous factors or well-defined genetic disorders, the proportion of these etiologies among all cases may be higher than presumed so far, because they evade detection. Data from the literature are discussed in the light of Karl Bonhoeffer's early concept of exogenous reaction types and modern medical genetics.     

Nikolaĭ Vladimirovich Timofeev-Resovskiĭ (1900-1981). (Essay on his life and works)

The article contains a brief review of the basic works (1925-1981) written by Nikolay V. Timofeeff-Ressovsky--one of the famous geneticist of the elapsing century, the founder of radiobiology and radiation genetics, biocenology and radioecology, a prominent evolutionary biologist. In genetics, his name is associated with the development of fundamental problems of population genetics, phenogenetics, gene interaction and investigations of the role of environmental and genetic factors in expression of different characters. Timofeeff-Ressovsky classical works on mutagenesis process and especially, radiation mutagenesis, promoted penetration of methods and approaches applied in molecular physics and chemistry, into genetic analysis, and accelerated forming of the modern molecular genetics. A special place in the development of population genetics is occupied by the hypothesis of microevolutionary process developed by Nikolay V. Timofeeff-Ressovsky along with other famous biologists in the end of the 30-ies. This hypothesis connected Darwin's evolutionary theory with rapidly developing concepts of genetics. In the last years of his life, Timofeeff-Ressovsky was especially interested in a global problem which was called by him "The Biosphere and Humanity". Here was especially strikingly shown the broadness of his approach to the analysis of the biosphere phenomena in the best traditions of the Russian natural science. In the course of time, the wealth of Nikolay V. Timofeeff-Ressovsky's scientific heritage not only remains valuable, but also takes on more profundity and value.     

An ethnomedicine study among women in Uremia (North-West Iran)

During the recent years, ethomedicine has attracted a great deal of attention among the investigators throughout the world. Although ethnomedicine seeks, in the first place, to compensate for a biological need through providing cures for disorders, it, however, is of a cultural nature, too, in that it investigates people's behaviors and reactions toward health and the issues related to it. Consequently, traditional health must be counted as a component of a society's culture. Investigations of people's views toward traditional medicine are capable of throwing light on acquaintance with their conducts, customs, traditions and behaviors, as well as the social-economic conditions prevailing in their environment. In addition, such investigations of public medicine bring about familiarities with gradual developments in traditional medical methodologies as introduced by culture, economic, or social factors, first into the society, then medicine. Familiarizations with cultural diversities in relation to medicine are the end results. The present paper comprise an anthropological approach toward investigation of ethnomedical practiced by women of Uremia (North-West, Iran).     

微卫星标记及其在动物遗传育种中的应用

微卫星标记技术一出现,就以其独特的优点引起了动物遗传育种学家的广泛关注,显示出较好的应用前景。本文就微卫星标记的特点及其在动物遗传育种中的应用作以综述。     

遗传检测综述

目前,遗传检测正在更多的国家、更广泛的范围内被采用。然而,在中国人们还不大熟悉遗传检测的原理、类型、技术、对社会的益处以及国内或国际是如何对它进行管理的。随着遗传检测的广泛使用,正确的监督显得相当必要。对近年来遗传检测所取得的进展进行了粗略的回顾,这将帮助我们对人类遗传学和分子医学革命的新时代有更多的了解。