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PubMed1997

Physical mapping of the rice genome with BACs.

The development of genetics in this century has been catapulted forward by several milestones: rediscovery of Mendel's laws, determination of DNA as the genetic material, discovery of the double-helix structure of DNA and its implications for genetic behavior, and most recently, analysis of restriction fragment length polymorphisms (RFLPs). Each of these milestones has generated a huge wave of progress in genetics. Consequently, our understanding of organismal genetics now extends from phenotypes to their molecular genetic basis. It is now clear that the next wave of progress in genetics will hinge on genome molecular physical mapping, since a genome physical map will provide an invaluable, readily accessible system for many detailed genetic studies and isolation of many genes of economic or biological importance. Recent development of large-DNA fragment (> 100 kb) manipulation and cloning technologies, such as pulsed-field gel electrophoresis (PFGE), and yeast artificial chromosome (YAC) and bacterial artificial chromosome (BAC) cloning, has provided the powerful tools needed to generate molecular physical maps for higher-organism genomes. This chapter will discuss (1) an ideal physical map of plant genome and its applications in plant genetic and biological studies, (2) reviews on physical mapping of the genomes of Caenorhabditis elegans, Arabidopsis thaliana, and man, (3) large-insert DNA libraries: cosmid, YAC and BAC, and genome physical mapping, (4) physical mapping of the rice genome with BACs, and (5) perspectives on the physical mapping of the rice genome with BACs.

Animals↗
PubMed2002

Wright-Fisher revisited: the case of fertility correlation.

We study the non-genetic inheritance of fertility from parents to offspring. For this purpose, we propose an exchangeable extension of the Wright-Fisher model. This extension allows us to introduce non-genetic fertility correlation in the forward in time process and to study its effects on the genealogies of individuals (or genes) samples. Since it is independent of the gene considered, this effect is uniform on the genome, even in diploid populations. For values of fertility correlation observed in human populations, we show that coalescence times are strongly but inhomogenously reduced and that the shape of gene genealogies is markedly unbalanced. Despite the fact that our simulations concern stationary populations, the former non-genetic effect is very similar to what has been described for populations of variable size such as populations passing through demographic bottleneck. However, additional strong tree imbalance due to non-genetic causes is reported here for the first time.

Fertility↗
PubMed2003

Population genetic screening programmes: principles, techniques, practices, and policies.

This paper examines the professional and scientific views on the principles, techniques, practices, and policies that impact on the population genetic screening programmes in Europe. This paper focuses on the issues surrounding potential screening programmes, which require further discussion before their introduction. It aims to increase, among the health-care professions and health policy-makers, awareness of the potential screening programmes as an issue of increasing concern to public health. The methods comprised primarily the review of the existing professional guidelines, regulatory frameworks and other documents related to population genetic screening programmes in Europe. Then, the questions that need debate, in regard to different types of genetic screening before and after birth, were examined. Screening for conditions such as cystic fibrosis, Duchenne muscular dystrophy, familial hypercholesterolemia, fragile X syndrome, hemochromatosis, and cancer susceptibility was discussed. Special issues related to genetic screening were also examined, such as informed consent, family aspects, commercialization, the players on the scene and monitoring genetic screening programmes. Afterwards, these questions were debated by 51 experts from 15 European countries during an international workshop organized by the European Society of Human Genetics Public and Professional Policy Committee in Amsterdam, The Netherlands, 19-20, November, 1999. Arguments for and against starting screening programmes have been put forward. It has been questioned whether genetic screening differs from other types of screening and testing in terms of ethical issues. The general impression on the future of genetic screening is that one wants to 'proceed with caution', with more active impetus from the side of patients' organizations and more reluctance from the policy-makers. The latter try to obviate the potential problems about the abortion and eugenics issues that might be perceived as a greater problem than it is in reality. However, it seems important to maintain a balance between a 'professional duty of care' and 'personal autonomy'.

Ethics↗
PubMed2001

DNA quadruplexes and dynamical genetics.

In a recent paper, we have put forward the hypothesis that there exist smart purposive mechanisms - tandem repeat length managers - which regulate the length of some tandem repeat, or cause rearrangements, and are almost always driven by some variable number tandem repeat. We have called the framework in which such mechanisms act 'dynamical genetics'. The purpose of this paper is to contribute to lay the foundations of a molecular study of the above mechanisms, by proposing a hypothesis, based on various kinds of supporting evidence and plausibility arguments, about the special importance of DNA quadruplexes for dynamical genetics, and by considering the involved enzymes. This hypothesis states that a tandem repeat length manager acts almost always by monitoring a DNA tract that has the characteristics of being a variable number tandem repeat and/or forming a DNA quadruplex, and that it is almost always driven by at least one of them.

Aging↗
PubMed1994

Fish oil and the prevention and regression of atherosclerosis.

Epidemiological studies in the seventies have put forward that dietary rather than genetic factors are responsible for the lower incidence of ischemic heart disease in Greenland Inuit and have generated a large body of both in vitro and in vivo experimental studies, exploring the putative favorable effects of fish (oil) on atherogenesis and its risk factors. The first part of this report reviews the in vivo animal studies, concentrating on the hypercholesterolemic models and the arterialized vein graft model. In the hypercholesterolemic animal studies, the results are inconclusive as the studies reporting a protective effect are matched by the number of studies showing no effect or an adverse effect. The diversity in species, dose of fish oil, duration of study, type of vessel studied and type of fish oil preparation (content of n-3 fatty acids, unesterified n-3 fatty acids, ethylesters or triglycerides) could all contribute. Furthermore, the definitions and criteria used in the literature to evaluate atherogenesis are diverse and it appears that while one parameter is affected, another is not necessarily modified in the same direction, stressing the importance of extending the analysis of the effects on atherogenesis to more than one parameter. We also believe that it is time to reach a consensus as to which animal model mimics most closely a particular human situation. Only in appropriate models, investigating more than one atherosclerosis variable, can the effects of a putative anti-atherogenic drug or diet be verified. In the veno-arterial autograft model, mimicking the patient after coronary bypass grafting, dietary fish oil has been consistently effective in preventing accelerated graft intima proliferation. It could therefore be of interest to evaluate the effects of fish oil on graft patency in patients after coronary bypass surgery after a period of years. The results from studies on restenosis after percutaneous transluminal angioplasty are also reviewed and it is concluded that the two large scale trials, that are currently underway, might reliably answer the question whether fish oil is effective as a non-pharmacological adjuvants in the prevention of restenosis. Lastly, the studies on the effects of fish oil on the regression of experimental atherosclerosis are reviewed. In view of the small number of studies (i.e., four) investigating the effects of fish oil on the regression of atherosclerosis, it is premature to draw any conclusion, and therefore further experimental work is required.

Animals↗
PubMed1994

Multifactorial interactions in the aetiopathogenesis of EPH-Gestosis--a hypothesis.

The aetiopathogenesis of EPH-Gestosis or pre-eclampsia-eclampsia is still not clear. Although many hypotheses implicating environmental, nutritional, immunological, and genetic factors have been put forward, no hypothesis provides the scientific basis for the early spiral arterial degenerative changes, and incomplete physiological trophoblastic invasion of the spiral arteries, leading to a high utero-placental resistance with reduced blood flow remains unexplained. To get an insight into the basic pathogenesis of EPH-Gestosis, the following hypothesis has been proposed. The hypothesis considers an abnormal proliferation of the spiral vessels as the key factor in the pathogenesis of the high uteroplacental resistance and the endothelial dysfunctions in EPH-Gestosis. Further it is proposed that this proliferation is on account of the enhanced polymerization of the deficient DNA triggered by the high steroidal level and relatively low micronutrient level in EPH-Gestosis during the early formative stages of the placental circulation. Steroidal hormone helps in polymerization of the DNA, micronutrients exert a controlling influence through DNA synthesis on cell proliferation. A critical balance of hormone-micronutrients such as vitamin A, B12, folic acid, etc., therefore, seems necessary for normal cellular proliferation. It appears therefore that there probably exists an imbalance with a high estrogen and a relatively low micro-nutrient level in EPH-Gestosis, triggering off a process of abnormal spiral vessel proliferation. These abnormal vessels with a deranged endothelial function may prevent the second wave of normal trophoblastic invasion assumed to be important for the establishment of the low resistance uteroplacental circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Predominant sensory Guillain-Barré syndrome in hereditary sensory neuropathy--case report of a three-year-old boy.

We observed a three-year-old boy with increasing ataxia over a period of two weeks, which cleared up completely within four months. The electroneurographic features and their course in the child and the father allow us to suspect the additional existence of a hereditary sensory neuropathy. The authors put forward the hypothesis that the genetic disturbance of the sensory nerves is responsible for this clinical variant of Guillain-Barré syndrome.

Child, Preschool↗
PubMed2003

New oral findings in Cohen syndrome.

Cohen syndrome is a hereditary disorder transmitted as an autosomal-recessive trait. Approximately 100 cases have been reported in the genetic and pediatric literature. Despite the fact that oral alterations are often observed in these cases, only 1 work has been published addressing this specific topic, and it tended to concentrate on periodontal abnormalities. The present study details 2 new patients, 2 brothers (8 and 11 years old), and mainly consists of an analysis of the dentomaxillary anomalies that until now have not been studied in depth. In this study, the mandible, characterized as hypoplastic in Cohen syndrome, appears to be in a normal position; what really exists is a maxillary hyperplasia of genetic origin. We also put forward an observation hitherto undescribed in the literature: dental agenesis.

Cephalometry↗
PubMed1995

LGANN: a parallel system combining a local genetic algorithm and neural networks for the prediction of secondary structure of proteins.

In this work we describe a parallel system consisting of feed-forward neural networks supervised by a local genetic algorithm. The system is implemented in a transputer architecture and is used to predict the secondary structures of globular proteins. This method allows a wide search in the parameter space of the neural networks and the determination of their optimal topology for the predictive task. Different neural network topologies are selected by the genetic algorithm on the basis of minimal values of mean square errors on the testing set. When the alpha-helix, beta-strand and random coil motifs of secondary structures are discriminated, the maximal efficiency obtained is 0.62, with correlation coefficients of 0.35, 0.31 and 0.37 respectively. This level of accuracy is similar to that previously attained by means of neural networks without hidden layers and using single protein sequences as input. The results validate the neural network topologies used for the prediction of protein secondary structures and highlight the relevance of the input information in determining the limit of their performance.

Algorithms↗
PubMed2001

Medical ethos and social responsibility in clinical medicine.

The medical profession will face many challenges in the new millenium. As medicine looks forward to advances in molecular genetics and the prospect of unprecedented understanding of the causes and cures of human disease, clinicians, scientists, and bioethicists may benefit from reflection on the origins of the medical ethos and its relevance to postmodern medicine. Past distortions of the medical ethos, such as Nazism and the Tuskegee Syphilis Study, as well as more recent experience with the ethical challenges of employer-based, market-driven managed care, provide important lessons as medicine contemplates the future. Racial and ethnic disparities in health status and access to care serve as reminders that the racial doctrines that fostered the horrors of the Holocaust and the Tuskegee Syphilis Study have not been removed completely from contemporary thinking. Inequalities in health status based on race and ethnicity, as well as socioeconomic status, attest to the inescapable reality of racism in America. When viewed against a background of historical distortions and disregard for the traditional tenets of the medical ethos, persistent racial and ethnic disparities in health and the prospect of genetic engineering raise the specter of discrimination because of genotype, a postmodern version of "racist medicine" or of a "new eugenics." There is a need to balance medicine's devotion to the well-being of the patient and the primacy of the patient-physician relationship against the need to meet the health care needs of society. The challenge facing the medical profession in the new millennium is to establish an equilibrium between the responsibility to ensure quality health care for the individual patient while effecting societal changes to achieve "health for all."

Black or African American↗
PubMed1975

[The association of diabetic disease with Friedreich's disease in members of the same family].

Friedreigh's disease is only rarely associated with diabetes mellitus and only few cases are to be found in the literature, especially as regards siblings. Three cases of this association in members of two different families are reported. Two of the patients died from cardiovascular complication; the third case is that of a 32-yr-old woman who was able to complete a pregnancy. The pathogenesis of the association is discussed and a number of theories are put forward. The most generally accepted genetic hypothesis makes it possible to explain under a common metabolic denominator neurological disturbances and those in other systems. The association is not a purely casual event but is perhaps dependent on either two different genes or on a single gene with pleitropic effect. Heart signs are frequent in Friedreich's disease and brief mention is made of these.

Adult↗
PubMed2001

The medical ethos and social responsibility in clinical medicine.

The medical profession will face many challenges in the new millennium. As medicine looks forward to advances in molecular genetics and the prospect of unprecedented understanding of the causes and cures of human disease, clinicians, scientists and bioethicists may benefit from reflection upon the origins of the medical ethos and its relevance to postmodern medicine. Past distortions of the medical ethos, such as Nazism and the Tuskegee Syphilis Study, as well as more recent experience with the ethical challenges of employer-based market driven managed care, provide important lessons as medicine contemplates the future. Racial and ethnic disparities in health status and access to care serve as a reminders that the racial doctrines that fostered the horrors of the Holocaust and the Tuskegee Syphilis Study have not been completely removed from contemporary thinking. Inequalities in health status based on race and ethnicity, as well as socioeconomic status, attest to the inescapable reality of racism in America. When viewed against a background of historical distortions and disregard for the traditional tenets of the medical ethos, persistent racial and ethnic disparities and health and the prospect of genetic engineering raise the specter of discrimination because of genotype, a postmodern version of "racist medicine" or of a "new eugenics." There is a need to balance medicine's devotion to the wellbeing of the patient and the primacy of the patient-physician relationship against with the need to meet the health care needs of society. The challenge facing the medical profession in the new millennium is to establish an equilibrium between the responsibility to assure quality health care for the individual patient while affecting societal changes to achieve "health for all."

Black People↗
PubMed2004

[Molecular neurogenetics of sensory behaviors in the hematode C. elgans].

The molecular mechanisms of neural plasticity, learning and memory are still poorly understood. The nematode Caenorhabditis elegans is capable of responding to a variety of environmental changes through its nervous system, consisting of only 302 neurons. C. elegans is an ideal model organism to elucidate neural plasticity, learning and memory at molecular, cellular and neuronal network levels. Thermotaxis behavior is particularly amenable to dissect learning and memory at all these levels. After cultivation at a certain temperature with food, C. elegans migrates to the cultivation temperature on a temperature gradient. By contrast, cultivation in food-deprived condition induces cultivation temperature avoidance behavior on a temperature gradient. We have been conducting forward as well as reverse genetic approaches to identify molecules, neurons and neuronal networks that are responsible for aspects of learning and memory in thermotaxis behavior.

Animals↗
PubMed1994

Myotonic disorders and periodic paralysis.

The myotonias are a diverse set of diseases, variable in presentation, often difficult to diagnose and, until now, treated with only a limited degree of success. Recent genetic advances have pinpointed many of the mutations that underlie these disorders and have demonstrated that there may be different causative genetic mutations underlying the same phenotype. This chapter summarizes the genetic data currently available for these disorders and attempts to link these to their clinical features. In some instances this is conceptually relatively straightforward but in others, particularly DM, the manner in which the mutation leads to the observed phenotype is very unclear and can be used as a paradigm for some of the more puzzling aspects of modern human genetics. Some suggestions are put forward on how the unusual mutation seen in DM can lead to highly variable symptoms between individual patients, and how the mutation can be transmitted unstably through a pedigree.

Humans↗
PubMed1975

Genetic and physiological characterization of met15 mutants of Saccharomyces cerevisiae: a selective system for forward and reverse mutations.

One hundred and thirty-three spontaneous and induced mutants of the met15 locus in Saccharomyces cerevisiae were characterized with respect to temperature sensitivity, osmotic remediability, interallelic complementation, and suppressibility by amber and ochre suppressors. Forty mutants are osmotic remedial; 17 of these, and no others, are also temperature-sensitive. Seven of 133 mutations are suppressible by an amber suppressor and 11 are suppressible by an ochre suppressor. Seventy percent of the mutants exhibited interallelic complementation, suggesting that the functional gene product of the met15 gene is a multimeric protein. Relative map positions of 30 met15 were estimated from the frequencies of X-ray-induced mitotic reversion of various heteroallelic diploids. All complementing nonsense mutations are located near one end of the gene in contrast to other nonsense mutations which span most of the gene, thus relating the direction of translation of the mRNA with respect to the fine-structure map. Recombination studies indicated that two of 30 mutants contained deletions of the entire met15 locus. -- It was established that a variety of mutational types, including missense, nonsense, and deletions, are recovered with this unique system in which both forward and reverse mutations can be selected on the basis of methyl mercury resistance and methionine requirement of the met15 mutants.

Alleles↗
PubMed1994

I-J revisited: is the I-J genetic restriction in downregulation due to an endogenous superantigen analogous to mammary tumour virus (Mtv)-encoded endogenous superantigen?

This article puts forward the hypothesis that the I-J genetic restriction observed between certain downregulatory (suppressor) T cells and antigen presenting cells is due to an endogenous superantigen analogous to the mouse mammary tumour virus (Mtv) products encoded by the open reading frames in the 3' long terminal repeat (LTR) of mtv's. In its weak form this hypothesis asserts that the I-J genetic restriction is due to an endogenous superantigen ligand on antigen presenting cells, which crosslinks the V beta and/or V alpha chains of certain T cell receptors (TCR) with major histocompatibility complex (MHC) class II, and that MHC together with this superantigen ligand causes positive selection of T cells bearing the appropriate I-J+ TCR in the thymus. In the periphery these T cells recognize peptide/MHC complex in the presence of the superantigen. In its strong form the hypothesis states that this superantigen ligand for TCR and MHC is encoded by integrated virus genome, e.g. Mtv. These possibilities can now be approached experimentally and their exploration may uncover one of the ways in which T cells are assigned to different functions, including downregulation.

Animals↗