Prevention Of Genetic Disorders Research Articles

Beyond the Geneticization Thesis

In the last decade, preimplantation genetic testing (preimplantation genetic diagnosis [PGD] and preimplantation genetic screening [PGS]) have become widely used and in 2005 constituted 5 percent of all in vitro fertilization (IVF) cycles performed in Europe. Their diffusion, however, is not homogenous; while in some countries they are prohibited and in others hardly implemented, Spain performs 33 percent of all the PGD/PGS. While policy guidelines and mainstream bioethics address PGD from a patient choice perspective, disability studies insist on PGD’s potentiality for discrimination. Alternatively, other authors have explored PGD/PGS from the perspective of geneticization but little work has been done on how PGD/PGS are framed by the members of national regulatory bodies. Combining the analysis of juridical documents with semistructured interviews with members of the Spanish National Assisted Reproduction Committee (CNRHA), this study suggests that the remarkable diffusion of PGD/PGS in Spain may be largely due to the interaction between the growing momentum enjoyed by embryonic stem cell research and a vibrant expansion of IVF business along the Mediterranean coast. In this process, genetic issues per se seem to play a minor role, although the prevention of genetic diseases now constitutes the master narrative underpinning the extension of PGD from monogenic, early onset, diseases to polygenic, late-onset, ones.

GenEthics and religion

GenEthics and religion

English

A descriptive analysis of reported cases of sickle cell disease and the level of awareness about genetic counseling in 30 hospitals were carried out. Additionally, 150 individuals between ages 16 - 45 were randomly selected for evaluation of genetic counselling awareness.  The main tools for this study were questionnaires, which were taken to hospitals, and individuals completed the others. The numbers of reported cases of sickle cell disease recorded in private, public and teaching hospitals were 14 and 57; 143 and 89; 272 and 57 for the periods of 1995 - 2000 and 2001 – 2005, respectively.  A general informal genetic counselling took place mostly occasionally in the hospitals visited. 122 (86%) individuals have had the knowledge of genetic disease and only 43 (30.3%) individuals have been exposed to genetic counselling. 64% of individuals agreed that genetic counselling would help in the prevention of genetic disease.   Keywords: Sickle disease, genetic counseling, genetic testing, advocacy.

L'origine génétique des fentes labio-palatines non syndromiques.TWIST, gène candidat ? Protocole de recherche

Non syndromic cleft lip and palate (CLP) is the most frequent human malformation. CLP is of complex inheritance and at least twenty contributing chromosomal regions have been identified by linkage studies. On the other hand, mutations in several genes such as TWIST and FGFR2 result in syndromic cranio-facial abnormalities of highly variable range. It is our hypothesis that some mutations at TWIST might contribute to CLP in absence of other dysmorphic features. Thus, DNA biopsies of patients with non syndromic CLP are collected and prepared to search for allelic variations or mutations at TWIST. This study should contribute to improve the classification of facial malformations relative to gene, to help to a better understanding of the inheritance pattern of this pathology, to help to genetic counselling for some cases aiming at the prevention of genetic disease. This project is based on a close cooperation between the Orthodontic Department, the Paediatric Surgery Department and the Center for Clinical Investigation (University Hospital in Strasbourg), in a joint project with an academic research laboratory, expert in molecular biology and genetics.

Islamic ethical framework for research into and prevention of genetic diseases

Medical genetics involves the application of genetic knowledge and technology to specific clinical and epidemiologic concerns. Using genetics to benefit society requires that empirically verified knowledge be used within an ethical framework that combines appeal to written precedent with sensitivity to the options of individuals and families dealing with choices and necessities within the laws, norms and traditions of their society. Islamic bioethics is derived from a combination of principles, duties and rights, and to a certain extent a call to virtue, ihsan. It emphasizes prevention, and it teaches that the patient must be treated with respect and compassion and that the physical, mental and spiritual dimensions of the illness experience must be taken into account. Strategic planning for the prevention and care of genetic disorders, and for genomic research, within the context of Islamic religion and culture is promising and may provide lessons to the developed world. Islamic bioethics provides fundamental principles for genetic counseling, particularly in regard to consanguinity, which was part of the Arabian culture long before Islam but which was discouraged by the second Islamic khalifa. These fundamental principles are important for implementing many preventive and genomic research programs and for maintaining flexibility to respond to new biomedical technologies.

Preventive effects of lupeol on DMBA induced DNA alkylation damage in mouse skin

Mutations that occur through DNA strand breaks are the precursors of the variety of genetic disorders including cancer. Life style and dietary habits are considered as major determinants in causation and prevention of genetic diseases. Epidemiological and laboratory studies suggest that plant derived compounds have the potential to prevent a number of genetic diseases. Therefore, use of nutraceuticals can be an important and convenient tool for chemoprevention. Polyphenolic phytochemicals such as epigallocatechin gallate flavonoids quercetin, genistein, curcumin and resveratrol constitute a class of nutraceuticals with notable efficacy in preclinical models of carcinogenesis. Lupeol, a pentacyclic triterpene present in mango, is a biologically active compound that has been reported to possess a number of pharmacological properties in the in vivo and in vitro studies. In the present study, we investigated the effects of lupeol on 7,12-dimethylbenz[ a]anthracene (DMBA), induced DNA strand breaks in mouse skin, using an alkaline unwinding assay. Increasing doses of lupeol (50–200 μg/mouse) were given topically, prior or after the single topical application of DMBA (100 μg/mouse) with the sampling time of 24, 48, 72 and 96 h, respectively. Both pre and post treatment of lupeol showed significant ( p < 0.001) preventive effects in DMBA induced DNA strand breaks in dose and time dependent manner. The pre-treatment of lupeol at the dose of 200 μg/mouse showed 56.05% prevention, and post-treatment at the same dose showed 43.26% prevention, at 96 h time interval, against DMBA induced DNA strand breakage. The results suggest preventive effects of lupeol on DMBA induced DNA alkylation damage in Swiss albino mice.

Sperm Abnormalities in Heterozygous Acid Sphingomyelinase Knockout Mice Reveal a Novel Approach for the Prevention of Genetic Diseases

Acid sphingomyelinase knockout mice are a model of the inherited human disorder types A and B Niemann-Pick disease. Herein, we show that heterozygous (ASMKO(+/-)) mice have two distinct sperm populations resembling those found in normal and mutant animals, respectively, and that these two populations could be distinguished by their morphology, ability to undergo capacitation or the acrosome reaction, and/or mitochondrial membrane potential (MMP). The abnormal morphology of the mutant sperm could be normalized by demembranation with detergents or by the addition of recombinant acid sphingomyelinase to the culture media, and the corrected sperm also had an enhanced fertilization capacity. Methods were then explored to enrich for normal sperm from the mixed ASMKO(+/-) population, and flow cytometric sorting based on MMP provided the best results. In vitro fertilization was performed using ASMKO(+/-) oocytes and sperm before and after MMP sorting, and it was found that the sorted sperm produced significantly more wild-type pups than nonsorted sperm. Sperm sorting is much less invasive and more cost-effective than egg isolation, and offers several advantages over the existing assisted reproduction options for Niemann-Pick disease carrier couples. It therefore could have a major impact on the prevention of this and perhaps other genetic diseases.

The future of preimplantation genetic diagnosis

Preimplantation genetic diagnosis (PGD) is one of the current options for prevention of genetic disorders and the practical means, in assisted-reproduction technology (ART), to improve in vitro fertilization (IVF) effectiveness. Available PGD evidence for chromosomal disorders shows that at least half of the embryos obtained from IVF patients of advanced reproductive age are aneuploid, suggesting that PGD has clinical relevance for ART. It is also obvious that couples at genetic risk should be provided with information regarding the option of PGD so that they can make their own choices regarding the possibility of avoiding the birth of children with inherited disorders. This article will describe the future of PGD for genetic and chromosomal disorders. We shall demonstrate that PGD may soon not only be an integral part and a required standard of IVF and genetic practices, but will also improve access to human leukocyte antigen identical stem cell transplantation and contribute to the development of cellul...

A history of medical genetics in pediatrics.

Medical genetics emerged from a basic science only one half century ago. Scientists and physicians housed in a variety of basic science and clinical departments have accomplished many of the major advances in the study of genetic diseases in children. A scientific approach to human genetics emerged in 1948 with the establishment of the American Society of Human Genetics. Even before the use of modern laboratory techniques, Pediatric departments spearheaded the clinical description of simple genetic disorders, syndromes, and major malformations. The burgeoning of medical genetics as a specialty and its tremendous growth in departments of pediatrics was stimulated by major technological advances, such as the ability to visualize human chromosomes, the development of methods to study biochemical variations in blood and urine, cell culture, somatic cell hybridization, and molecular technology, all of which allowed for the diagnosis, treatment, and prevention of genetic disorders in children. Many pediatricians sought training in genetics, and training programs in medical genetics flourished in departments of pediatrics. The explosion of knowledge concerning the metabolic and molecular causes of genetic disease and understanding of their pathogenesis has led to a variety of specific diagnostic, preventive, and therapeutic approaches for alleviating the symptoms or preventing the complications of many of these disorders. Medical genetics is now recognized as a distinct medical specialty with its own American Board of Medical Specialties approved board (American Board of Medical Genetics) and clinical specialty college (American College of Medical Genetics).

Community-Based Program for the Diagnosis and Prevention of Genetic Disorders in Cuba

The author’s experience of 20 years as director of the medical genetic services program in Cuba is presented. The setting of the infrastructure for equipment and the training of personnel for the medical genetic program began in 1981 in the city of Havana, and was progressively extended to cover the whole country in 1988. Between 1982 and 2002, 2.8 million pregnant women were tested for sickle cell carrier status, 96,000 carriers and 4,786 couples at risk were detected and offered genetic counseling and prenatal diagnosis. In the same period, the combination of maternal serum α-fetoprotein screening and fetal ultrasound led to the prenatal diagnosis of anomalies in several thousand fetuses. The accessibility to legal abortion, and the autonomous decisions by the majority of couples to terminate abnormal pregnancies reduced the prevalence of neural tube defects and sickle cell disease at birth by 90 and 65%, respectively, by 2002. In the span of approximately 20 years, 22,690 pregnant women at risk received prenatal chromosomal diagnosis. Newborn screening for phenylketonuria and congenital hypothyroidism was established. Genetic counseling was offered to every detected person or family at risk for genetic conditions. The network of medical genetic services established in the country received a very positive acceptance by the population. A very successful connection with the primary health care level was established.

Rights and Responsibilities in the New Genetics Era

This article critically explores the distribution of rights and responsibilities associated with recent developments in genetic testing and DNA donation. The author identifies two key discourses in various accounts of genetics in the clinical and policy domains: patients' rights to informed choice and the public's right to involvement in policy decisions. However, other discourses among professionals, patients and members of the public around responsibilities for supporting genetic research and testing and managing their social implications are also present. The author goes on to argue that these discourses undermine the case for a dramatic difference between past eugenics and present genetics, as the prevention of genetic disease remains of paramount importance. This suggests that `new genetic citizenship' is not so new after all.

Biotechnologies. Conséquences socio-économiques

The actual technological revolution is largely sustained by developments in biotechnology. The rapid acquisition of knowledge in biological sciences, coupled with the advancement in robotics and computer sciences and with the multiplication of bio-industries, have caused a worldwide disruption of socio-economical conditions. Some remarks on these consequences are emphasized here, with respect to agribusiness, health and the environment. Agriculture now depends on upstream related industries and food producers are under increasing pressure from food transformers and distributors. In this situation, genetically modified organisms are introduced on the market. Both their advantages (e.g., extensive production, enlargement of the distribution areas of species, lowering the use of pesticides, synthesis of micronutrients and pharmaceutical essences, materials for interspecies transplant) and risks (e.g., deepening of the N-S rupture, settlement of farming, health and environment hazards) are stressed. In the health field biotechnologies are involved in the research for the improvement of fitness and lifetime primarily for those living in rich countries, in the increasing cost of public health care, in the situation of senior citizens. Biotechnologies are also at the basis of health problems (listeriose, diseases due to animal feeding diet). In the environmental field, challenges are the increasing shortage of water resources, pollutions of different nature, and the global warming of the earth. At the entry of the xxi century, will biotechnologies allow the development of small farms, with the agricultural practice based on science of “functional food”? Does the knowledge of genome expressions and the development of proteomic analyses allow the prediction and the prevention of genetic diseases and certain forms of cancer? Does the discovery of new vaccines allow the eradication of parasitoses such as flu, AIDS, malaria and various incoming viral diseases? In the genome therapy will conclusive recovery be achieved? All these results could be obtained in the context of the need for an universal health right and an appropriate control of health cost? Will biotechnologies help discover the sources of pollutions and facilitate their eradication and decontamination? Will their applications in energetic industries (biofuels, biogases) become profitable? Will the necessary regulation of the conditions of the new markets meet success? The granting of patents is one of the difficulties to deal with. Will the oligarchic powers of the economical actors be able to keep in balance with the political powers? In democracy, all citizens have to participate in the decisions concerning their way of life. Are they interested? Is it possible to democratically regulate the controlable effects of biotechnologies? These are the questions which are to be dealt with in this paper.

Potential usefulness of preimplantation genetic diagnosis in the control and prevention of genetic diseases

Prenatal diagnosis of molecular mutations can be of immense value, since diagnosis followed by genetic counselling provides the most appropriate approach to genetic diseases control and prevention. However, ethical, psychosocial and religious considerations hamper adoption of prenatal diagnosis in communities where termination of a pregnancy may not be acceptable. Recently, preimplantation genetic diagnosis has attracted considerable interest. This involves in vitro fertilization, followed by genetic disorder diagnosis using polar bodies or cells extracted from a blastomere stage. The normal blastomere is implanted in the womb and pregnancy proceeds naturally. If an abnormality is diagnosed, the blastomere is not implanted, thus preventing pregnancy with the affected fetus. This paper outlines the potential usefulness of preimplantation genetic diagnosis in the control and prevention of genetic disease in our part of the world.

Sex selection and preimplantation genetic diagnosis

Sex selection and preimplantation genetic diagnosis

Awareness and use of prenatal diagnosis among Greek women: a national survey

The prevention of genetic diseases through prenatal diagnosis depends to a large extent on the awareness and acceptance of available methods by the public. A national survey was conducted among Greek women in order to explore their attitudes towards and their use of prenatal diagnosis in relation to their lifestyle. The survey was originally addressed to 3000 Greek women 18–65 years of age. Using as a criterion having a child 5 years old or younger, 350 women were eligible for the study. It was noted that 52 per cent of the respondents were adequately informed, while 48 per cent had either superficial knowledge of the subject or no knowledge at all. Amniocentesis was the method that most women were familiar with. The majority said that they were informed by their doctors and the media, and 13 per cent of the participants had prenatal diagnosis during a previous pregnancy. Twenty-two per cent of those who were not tested were over 35 years of age at the time of pregnancy. There was a significant positive correlation between awareness and acceptance of prenatal diagnosis, on the one hand, and the social, educational and financial profile of the women, on the other. Women aware of prenatal diagnosis adhered more closely to a healthy lifestyle and lived a family-centred life. © 1998 John Wiley & Sons, Ltd.

Awareness and use of prenatal diagnosis among Greek women: a national survey

The prevention of genetic diseases through prenatal diagnosis depends to a large extent on the awareness and acceptance of available methods by the public. A national survey was conducted among Greek women in order to explore their attitudes towards and their use of prenatal diagnosis in relation to their lifestyle. The survey was originally addressed to 3000 Greek women 18-65 years of age. Using as a criterion having a child 5 years old or younger, 350 women were eligible for the study. It was noted that 52 per cent of the respondents were adequately informed, while 48 per cent had either superficial knowledge of the subject or no knowledge at all. Amniocentesis was the method that most women were familiar with. The majority said that they were informed by their doctors and the media, and 13 per cent of the participants had prenatal diagnosis during a previous pregnancy. Twenty-two per cent of those who were not tested were over 35 years of age at the time of pregnancy. There was a significant positive correlation between awareness and acceptance of prenatal diagnosis, on the one hand, and the social, educational and financial profile of the women, on the other. Women aware of prenatal diagnosis adhered more closely to a healthy lifestyle and lived a family-centred life.

Clinical experience with preimplantation genetic diagnosis and intracytoplasmic sperm injection.

Preimplantation genetic diagnosis (PGD) is a novel procedure whose use may be considered to obtain a very early prenatal diagnosis for couples at risk for transmitting genetic diseases. Using the polymerase chain reaction (PCR) or fluorescence in-situ hybridization (FISH) the genotype or the sex of biopsied cleavage-stage embryos obtained after in-vitro fertilization can be determined and selected embryos can then be transferred. In-vitro fertilization with intracytoplasmic sperm injection is the method of choice to obtain embryos to be analysed through PCR to reduce contamination by residual sperm DNA. In our series of 61 PGD cycles for 29 couples at risk over a period of 4 years the ongoing pregnancy rate per cycle was 15%, per transfer 19% and per patient 31%. One of the six morphologically normal children born, who is still alive and doing well, weighed 850 g after birth at 25 weeks following a complicated triplet pregnancy. More experience is needed to correctly evaluate the efficiency and safety of this novel technique as well as to determine its place in the prevention of genetic disease.

Empowering individuals in the prevention of genetic disease.

As the International Human Genome Project nears the term of a long gestation, the ethical and social implications of complex new genetic technologies will require a new breed of clinicians for a safe delivery. Clinical genetic care has been time intensive as performed by medical specialists. Empowering individuals to take advantage of new opportunities for genetic testing to prevent disease will require clinician education and decision support in the context of individual values.

Tay-Sachs disease carrier screening: a model for prevention of genetic disease.

Tay-Sachs disease (TSD) is an autosomal-recessive, progressive, and ultimately fatal neurodegenerative disorder. Within the last 30 years, the discovery of the enzymatic basis of the disease, namely deficiency of the enzyme hexosaminidase A, made possible both enzymatic diagnosis of TSD and heterozygote identification. In the last decade, the cloning of the HEXA gene and the identification of more than 80 associated TSD-causing mutations has permitted molecular diagnosis in many instances. TSD was the first genetic condition for which community-based screening for carrier detection was implemented. As such, the TSD experience can be viewed as a prototypic effort for public education, carrier testing, and reproductive counseling for avoiding fatal childhood disease. More importantly, the outcome of TSD screening over the last 28 years offers convincing evidence that such an effort can dramatically reduce incidence of the disease.

Lowering the burden of hereditary diseases in a traditional, inbred community: ethical aspects of genetic research and its application.

The remarkable progress in modern genetic technology enables the identification of genes causing devastating diseases and thereby the development of tools for prenatal diagnosis and carrier detection. To implement the results of genetic research in traditional societies, where genetic diseases are more prevalent due to inbreeding, necessitates a culturally appropriate approach that also promotes traditional and societal values important to the relevant community. This paper presents our experience with implementing the results of modern genetic research among the traditional community of the Negev Bedouin of Israel. Although the benefit of using those results for the prevention of genetic diseases seems obvious, successful implementation relies on a carefully designed educational program aimed at changing culturally related attitudes and perceptions. Such a program should attend to the needs of the community and be sensitive to its traditional values.