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At least 19 recordsLinked to original sources
PubMed2002

Comparison of genetic services with and without genetic registers: knowledge, adjustment, and attitudes about genetic counselling among probands referred to three genetic clinics.

Genetic register services incorporating long term follow up and a proactive approach to at risk subjects have been recommended as a way of improving access to genetic counselling for families with dominant or X linked genetic disorders and chromosome translocations. The aims of the present study were to evaluate the psychosocial benefits and drawbacks of long term family contact, and to evaluate the attitudes of probands and their general practitioners towards proactive genetic counselling. We interviewed 192 people referred to three regional genetic clinics because of a family history of Duchenne or Becker muscular dystrophy, myotonic dystrophy, or chromosome translocations, and 43 of the referring GPs. Probands attending the centre using a genetic register approach were compared with those from the two centres offering the standard clinical genetic service. A very high proportion of probands in both groups were well informed about the genetic risks to themselves and their children, were satisfied with the service they had received from their local genetic clinic, and felt adequately prepared to discuss the family illness with their children. The register probands expressed approval of the ongoing contact and open access provided by the register service. Asked whether previously unaware relatives should be informed of their at risk status, 98% (188/192) said it was acceptable for this information to be disclosed by a family member, while three quarters of the probands (149/192) and just over half the GPs (27/43) thought it acceptable for the genetic service to approach them; a similar proportion of both GPs and probands also found it acceptable for GPs to do so. More than half the probands (107/190) thought it was the family's responsibility to pass on genetic risk information, but 43% said that either the genetic service or the GP should be responsible for this. The findings show that the genetic register approach incorporating long term follow up and a proactive approach to genetic counselling is highly acceptable to the families concerned, and although the register and non-register probands did not differ significantly on any of the main outcome measures used in this relatively short term study, it may be that the continuing contact associated with the register approach offers long term benefits, especially for those genetic conditions where medical surveillance may have an impact on the prognosis.

Adult↗
PubMed2002

Comparison of genetic services with and without genetic registers: access and attitudes to genetic counselling services among relatives of genetic clinic patients.

The pedigrees of 192 subjects at risk of Duchenne or Becker muscular dystrophy, myotonic dystrophy, or balanced chromosome translocations attending three regional genetic clinics were inspected to identify relatives who were themselves at high risk of these disorders. Of the 342 relatives eligible for inclusion, 43% (63/147) of the register relatives and 26% (50/195) of the non-register relatives had had contact with the clinical genetic services, a significant difference (p<0.02). Relatives from families with muscular dystrophy were significantly more likely to have been in contact with genetic services than those from BT families. Fifty-two relatives were interviewed about their experience and attitudes regarding genetic counselling. Almost all regarded knowledge about the family genetic disorder as helpful, and only one thought it unacceptable for relatives to be informed that they are at risk; 94% thought it was acceptable for this information to come from family members, 92% from general practitioners, and 90% from the clinical genetic service. A majority of relatives (53%) thought it was the family's responsibility to pass on genetic risk information, but 22% said the genetic service should be responsible and 18% thought it should be the GP. These data, together with the findings from the study of probands attending genetic clinics for these disorders, indicate that the genetic register approach incorporating long term follow up and a proactive approach to genetic counselling is acceptable to the families concerned and improves access to genetic services for at risk relatives.

Adult↗
PubMed2002

BMP 2--Genetics Institute/ Medtronic-Sofamor Danek/Integra. Bone morphogenetic protein 2--Genetics Institute/ Medtronic-Sofamor Danek/Integra, INFUSE Bone Graft, recombinant human bone morphogenetic protein 2--Genetics Institute/Medtronic-Sofamor Danek/Integra, RhBMP 2--Genetics Institute/Medtronic-Sofamor Danek/Integra.

Genetics Institute (Wyeth) is collaborating with Medtronic-Sofamor Danek (which specialises in spinal reconstruction) and Integra Life Sciences to develop a BMP 2 product [INFUSE Bone Graft] for use in spinal reconstruction in North America. The INFUSE Bone Graft product has been approved for use in lumbar interbody spinal fusion procedures in the USA and is in phase III trials for use in lumbar posterolateral spinal fusion procedures. During the procedure, damaged disc is replaced with a collagen sponge (Integra's Absorbable Collagen Sponge) soaked with BMP 2, which is held in place within an implanted cage device (LT-CAGE Lumbar Tapered Fusion Devise); the fusion process subsequently requires several months to complete. However, the patient is able to leave hospital the day after the operation, whereas in conventional spinal surgery a longer recovery time is required. The procedure supersedes the use of autograft bone as it uses a recombinant human bone morphogenic protein, rhBMP-2, which induces the body to grow its own bone where required. Genetics Institute has cloned and expressed bone morphogenic proteins 1-7 and established manufacturing processes by recombinant DNA technology. Bone morphogenic proteins may be useful in the treatment of osteoporosis and orthopaedic trauma. BMP 2 is also being developed for bone regeneration as an implanted device and as an injectable formulation. Genetics Institute is also collaborating with Integra LifeSciences to develop a formulation of BMP 2 with Integra's absorbable collagen-based structures for fracture treatment, which is awaiting approval in the USA.

Bone Morphogenetic Protein 2↗
PubMed1999

Ionizing radiation and genetic risks. X. The potential "disease phenotypes" of radiation-induced genetic damage in humans: perspectives from human molecular biology and radiation genetics.

Estimates of genetic risks of radiation exposure of humans are traditionally expressed as expected increases in the frequencies of genetic diseases (single-gene, chromosomal and multifactorial) over and above those of naturally-occurring ones in the population. An important assumption in expressing risks in this manner is that gonadal radiation exposures can cause an increase in the frequency of mutations and that this would result in an increase in the frequency of genetic diseases under study. However, despite compelling evidence for radiation-induced mutations in experimental systems, no increases in the frequencies of genetic diseases of concern or other adverse effects (i.e., those which are not formally classified as genetic diseases), have been found in human studies involving parents who have sustained radiation exposures. The known differences between spontaneous mutations that underlie naturally-occurring single-gene diseases and radiation-induced mutations studied in experimental systems now permit us to address and resolve these issues to some extent. The fact that spontaneous mutations (among which are point mutations and DNA deletions generally restricted to the gene) originate through a number of different mechanisms and that the latter are intimately related to the DNA organization of the genes, are now well-documented. Further, spontaneous mutations include those that cause diseases through loss of function as well as gain of function of genes. In contrast, most radiation-induced mutations studied in experimental systems (although identified through the phenotypes of the marker genes) are predominantly multigene deletions which cause loss of function; the recoverability of an induced deletion in a livebirth seems dependent on whether the gene and the genomic region in which it is located can tolerate heterozygosity for the deletion and yet be compatible with viability. In retrospect, the successful mutation test systems (such as the mouse specific locus test) used in radiation studies have involved genes which are non-essential for survival and are also located in genomic regions, likewise non-essential for survival. In contrast, most of the human genes at which induced mutations have been looked for, do not seem to have these attributes. The inference therefore is that the failure to find induced germline mutations in humans is not due to the resistance of human genes to induced mutations but due to the structural and functional constraints associated with their recoverability in livebirths. Since the risk of inducible genetic diseases in humans is estimated using rates of "recovered" mutations in mice, there is a need to introduce appropriate correction factors to bridge the gap between these rates and the rates at which mutations causing diseases are potentially recoverable in humans. Since the whole genome is the "target" for radiation-induced genetic damage, the failure to find increases in the frequencies of specific single-gene diseases of societal concern does not imply that there are no genetic risks of radiation exposures: the problem lies in delineating the phenotypes of recoverable genetic damage that are recognizable in livebirths. Data from studies of naturally-occurring microdeletion syndromes in humans and those from mouse radiation studies are instructive in this regard. They (i) support the view that growth retardation, mental retardation and multisystem developmental abnormalities are likely to be among the quantitatively more important adverse effects of radiation-induced genetic damage than mutations in a few selected genes and (ii) underscore the need to expand the focus in risk estimation from known genetic diseases (as has been the case thus far) to include these induced adverse developmental effects although most of these are not formally classified as "genetic diseases". (ABSTRACT TRUNCATED)

Animals↗
PubMed2000

The ecology and genetics of fitness in Chlamydomonas. X. The relationship between genetic correlation and genetic distance.

A necessary condition for the maintenance of genetic variation in heterogeneous environments is that the relative fitnesses of a collection of genotypes vary as conditions of growth change. This can be detected by estimating the amount of gene-by-environment interaction (G x E) when a range of types are tested across a range of conditions. However it is the sign and magnitude of the genetic correlation, which is a component of G x E, that governs the ultimate fate of variation. Whether genetic variation will be preserved, then, depends on how the genetic correlation changes as a function of the ecological differences among environments and the genetic differences among genotypes. To evaluate this, we assayed the performance of 15 chlorophyte species of known genetic relation in 20 environments. We found that the quantity of G x E increased as both the environmental variance across environments and the genetic distance increased. Moreover the genetic correlation declined as the environmental variance between pairs of environments and the genetic distance between pairs of genotypes increased. These results suggest that divergent selection will be more likely to maintain genetic variation when environments are strongly contrasted and genotypes widely divergent.

Animals↗
PubMedDate not supplied

Genetics and genomics in practice: the continuum from genetic disease to genetic information in health and disease.

This article reviews how the continuum and gradual shift from genetics (study of genes) to genomics (study of the whole genome) in medicine and public health will require reassessment of the traditional approach to delivery of genetic information, namely genetic services. A more general approach is needed to assess the value-added of genetic information for promoting health and for diagnosing, treating, predicting, and preventing all diseases, not only "genetic diseases." The article also discusses how family history can serve as a bridge from genetics to genomics in practice because it reflects the presence, not only of single-gene disorders, but also of shared genes, shared environments, and complex gene-environment interactions. Because of the expected volume of new genetic information, evidence-based practice should increasingly rely on scientific data on analytic performance of such information, its validity in predicting health outcomes, and its utility in improving health and preventing disease beyond approaches that do not use genetic information.

Environment↗
PubMedDate not supplied

Breast cancer genetics: family history, heterogeneity, molecular genetic diagnosis, and genetic counselling.

Between 5% and 10% of breast cancer cases can be traced to primary genetic factors. Before the discovery of the BRCA1 and BRCA2 genes, if a first-degree relative in direct genetic lineage had hereditary breast cancer or hereditary breast-ovarian cancer syndrome, the best estimate of family members' genetic risk for breast cancer was 50%. Now the lifetime cancer destiny of a patient who carries a BRCA1 or BRCA2 germ line mutation can be determined with an extraordinary degree of precision. However, a major concern facing clinicians is how to use this powerful genetic knowledge without harming the patient. This presentation focuses on the need for (a) compilation of a detailed family history of cancer of all anatomic sites; (b) understanding of the natural history of hereditary breast cancer and its heterogeneous forms and the pathobiology of hereditary breast cancer; and (c) preparation for performance of genetic counseling that is based on the results of DNA sequencing to detect genes related to cancer susceptibility. The discussion addresses the advantages of this molecular genetic movement, which include the abilities (a) to predict who is and who is not at inordinately high risk for cancer; (b) to provide opportunities for highly targeted disease surveillance and management; (c) to give patients the information they need to make appropriate long-term decisions about matters such as procreation; and (d) to give genetic counselors the information they need to appreciate the emotions patients may encounter, such as fear, anxiety, and apprehension, and the ordeal of being subjected to discrimination by insurance companies and employers.

Adult↗
PubMed2003

Genetic correlations between the maternal genetic effect on chick weight and the direct genetic effects on egg composition traits in a White Leghorn line.

Selection can be a useful way to alter yolk proportion and thereby egg dry matter which, owing to its economic importance, is a trait of substantial importance for the egg-processing industry. However, the egg is primarily the chamber of embryonic development. The main purpose of this study was to estimate genetic correlations between the maternal effect on chick weight at hatching and the direct effect on different egg composition traits, in particular, yolk proportion. Additionally, genetic parameters were estimated for egg composition traits. To create a data set suitable for estimation of genetic parameters, a three-round selection experiment was set up. Birds were selected based on their predicted breeding values for the genetic maternal effect on chick weight and the direct genetic effect on yolk proportion according to the theory of elliptical selection. Genetic parameters were estimated using a multiple trait animal model and restricted maximum likelihood. The maternal heritability for chick weight was 0.5, whereas the direct heritability was dose to 0. The genetic correlations between the maternal effect on chick weight and the direct effect on yolk proportion, yolk weight, albumen weight, albumen dry matter concentration, and egg weight were 0.14, 0.76, 0.93, 0.14, and 0.99, respectively. The heritabilities for yolk proportion, yolk weight, albumen weight, albumen dry matter concentration, and egg weight were 0.33, 0.43, 0.57, 0.38, and 0.60, respectively. We conclude that breeding ought to be a useful way to increase egg dry matter with no expected unfavorable correlated effects on chick weight.

Analysis of Variance↗
PubMed1994

Complex genetic disease: can genetic strategies in Alzheimer's disease and new genetic mechanisms be applied to epilepsy?

Strategies used in molecular genetics have changed modern neurology. The gene or genes responsible for several major neurologic diseases have now been identified using "reverse" or positional genetics. Unexpected new genetic mechanisms have been discovered in human neurologic diseases, including (a) identical mutations of the prion protein gene in Creutzfeldt-Jakob disease and fatal familial insomnia with the phenotypic expression directed by an accompanying polymorphism; (b) stable duplications of chromosome 17 in Charcot-Marie-Tooth disease (type 1A) that involve many genes, only one of which appears to cause neuropathy; and (c) highly variable, dynamic mutations in myotonic dystrophy, fragile X syndrome, and Kennedy's syndrome that modulate variable expressivity in multiple tissues. There is growing recognition that neurologic diseases are often complex genetic diseases with multifactorial rather than simple modes of inheritance. For example, genetic association/linkage strategies have interacted with biochemistry and immunopathology studies to produce new insights into the disease mechanism of late-onset Alzheimer's disease. The role of apolipoprotein E in late-onset Alzheimer's disease is an example of how new analytical techniques of genetic disease can be applied to dissect multiple genes. Similar research strategies are suggested for the study of epilepsy as a complex disease.

Alleles↗
PubMed1999

The French school of genetics: from physiological and population genetics to regulatory molecular genetics.

French genetics had unusual beginnings. There are clear indications that the French biological establishment resisted Mendelian genetics strenuously from about 1910 to 1940. From about 1930 to 1950 several unconventional research programs with a strongly physiological orientation paved the way for the full entrance of French biology into genetics after World War II. This review examines some salient features of this history to clarify the strengths, weaknesses, and distinctive features of French genetics until about 1965. We suggest that after that data French genetics slowly merged into the international mainstream as genetics has become a largely molecular discipline.

Animals↗
PubMed1994

Reverse genetics of the mouse central nervous system: targeted genetic analysis of neuropeptide function and reverse genetic screens for genes involved in human neurodegenerative disease.

The development of gene targeting technology in mouse embryonic stem cells allows reverse genetics to be used to investigate the function of any cloned gene in the developing and adult brain. Promoter-trap, replacement and insertion vector strategies can be used to generate defined mutations in the chromosomal copy of a cloned gene in embryonic stem cells. These cells can be used to make chimaeric mice, some of which transmit the in vitro mutation via the germline to transgenic offspring. The phenotype of complete loss-of-function mutations (gene knock-outs) can be studied at molecular, cell biological, neurophysiological and behavioural levels, and allows inferences about gene function to be made. Precise small mutations can also be made using integrative vector or two-step replacement vector strategies, allowing specific questions to be asked about regulation and protein structure-function relationships. Reverse genetics can therefore be used as an alternative or additional approach to pharmacology for the study of molecular functions in the central nervous system. Reverse genetic studies of the involvement of particular molecules in neurological disease syndromes may be superior to pharmacological studies to the extent that the syndrome is determined by genetic predisposition. The general ways in which reverse genetics of the mouse can be used to ask questions about molecules in the central nervous system are illustrated by examples from ongoing work of this laboratory. Neuropeptides are an important class of transmitters in the brain, but only in very few cases have specific CNS functions been assigned to a particular neuropeptide. Targeted mutation of neuropeptide precursor and receptor genes offers a rapid way to learn about neuropeptide function. Complete loss-of-function mutations will provide information on any developmental roles of a neuropeptide and on overall behavioural and physiological effects of loss-of-function. More specific targeted mutations allow dissection of the individual roles of multiple neuropeptides that derive from a common precursor protein, and allow in vivo studies of the functional importance of particular amino acids. Experimental progress towards targeted mutation of the neurotensin receptor is described as an example. Recent technological improvements makes targeted mutation of a number of genes possible. This allows reverse genetic screening to be undertaken for genes involved in particular neurobiological phenomena: genes are identified on the basis of molecular criteria (e.g. expression pattern), and gene-targeting used to check their relevance to a phenotype. Neurodegenerative disease is an important aspect of the human phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1986

[Genetic and ecological study of aboriginal populations of northeastern Siberia. II. Polymorphic blood systems, immunoglobulin allotypes and other genetic markers in asian eskimos. Genetic structure of Bering sea eskimos].

Blood groups, immunoglobulin allotypes, serum proteins and red cell enzymes were tested in four populations of Asiatic Eskimos. 12 of 16 gene loci studied were found to be polymorphic. Analysis of covariance and variance matrices for gene frequencies of 8 Bering Sea populations revealed major aspects of regional genetic structure. Regression of average heterozygosity on genetic distance from centroid permitted us to interpret it in the light of counterbalancing action of systematic and non-systematic pressure. Analysis of R matrix containing gene frequencies for both Eskimo and Chukchi populations revealed two different clusters - more heterogeneous Eskimo cluster and less heterogeneous Chukchi cluster. Good fit was observed between regional genetic structure, history and geography.

Blood Group Antigens↗
PubMed1988

[The genetics of breast cancer. A genetic dispersion analysis and the genetic heterogeneity of breast cancer].

The multifactorial nature of breast cancer was established based on population and family study, the contribution of genetic factors being 52% (premenopausal--62 and postmenopausal--39%). Genetic heterogeneity of different coefficients of inheritance of breast cancer with the portion of common genes was shown to be 53%. The analysis of breast cancer interaction with other malignant neoplasms revealed that the development of other malignant neoplasms was the result of the influence of partially common genes. On the basis of data obtained in this study, the tables of repeated risk for the relatives have been worked out which may be used for medico-genetic consultations.

Breast Neoplasms↗
PubMedDate not supplied

[From genetic privacy to the right to genetic data protection. Basic protection of genetic data in Spanish law (regarding SSTC290/2000 and 292/2000, of November 30) (II)]].

In the second part the author examines the repercussions of constitutional case law on the legal protection of genetic information. He then considers the special nature of genetic information and addresses the corresponding need for special treatment thereof in law. A specific model is suggested for the legal status of such information. This model is based on the Spanish Constitution and the European Convention on Human Rights and Biomedicine. The article then casts a critical eye over data protection legislation in Spain (in particular Law 15/1999 of 13 December) concentrating on five principles, four of which are substantive and the fifth procedural: 1) consent; 2) purpose; 3) confidentiality; 4) quality; 5) proportionality. Lastly, the article gives examples of areas in which the model might be applied (for instance in employment contracts, insurance, access to information by family members).

Confidentiality↗
PubMed2001

The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. This is the most frequent form of monogenic parkinsonism so far identified. The associated phenotypical spectrum encompasses early onset, levodopa-responsive parkinsonism (average onset in the early 30s in Europe), and it overlaps with dopa-responsive dystonia in cases with the earliest onset, and with clinically typical Parkinson's disease in cases with later onset. Despite clinical features, Lewy bodies are not found at autopsy in brains of patients with parkin mutations. The parkin protein possesses ubiquitin ligase activity, which is abolished by the pathogenic mutations.

Age of Onset↗