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PubMed2001

Adoption in the age of reproductive technology.

The choice of adoption over genetic parenthood was investigated in 105 women retrospectively by questionnaire. Participants were divided into four groups: female/male subfertility; female subfertility; male subfertility; and female/male fertility. Half the sample (59/105) answered the question about the importance of a genetic link. Women who failed to adopt thought a genetic link was important, as did those who were less likely to disclose alternative reproductive conceptions to their child. First thoughts following diagnosis were more focused and actions more centered on adoption in the female/male subfertile group compared to the other groups. Communication of the child's origins was least prevalent in the female/male subfertile group, followed by the male subfertile group, although all groups would disclose adoption. The choice of adoption was determined by a number of factors, not all associated with infertility resolution. Although it is unlikely that resolution to infertility can be achieved in any population attempting to overcome infertility, the cognitive dissonance identified in this population is likely to be generalizable to those choosing other options to overcome infertility. Cultural and counselling acknowledgement of postmodern family theory principles is likely to ease cognitive consistency regarding the status of adoptive familyhood, and dispel the importance of reproductive options emphasizing a genetic link.

Adoption↗
PubMed1997

Reproductive toxicity, mutagenicity and antigenicity of pamiteplase (genetical recombination).

Pamiteplase (genetical recombination), YM866, is a novel recombinant modified human tissue-type plasminogen activator developed by Yamanouchi Pharmaceutical Co. Ltd., Tokyo, Japan. An intended route of administration in the clinical use of this drug is intravenous administration. We conducted an intravenous fertility and general reproduction studies of this drug in male and female rats and teratology study of this drug in rabbits at the dose levels of 0 (vehicle control), 0.1, 0.3 or 1 mg/kg/day. In the rat, no treatment-related abnormalities were observed up to the maximum dose in parental animals and their offspring. In the teratology study in rabbits, prolonged coagulation time at the injection site was observed at 0.3 mg/kg or more. One death and one abortion occurred at 1 mg/kg on days 22 and 23 of pregnancy, respectively. No toxic effects on the litters were observed up to the maximum dose. Results of evaluation of the mutagenicity of YM866 and its ability to induce chromosome aberrations using the L5178Y TK+/- mouse lymphoma assay, human lymphocyte chromosome aberration assay and the micronucleus assay in mice were negative. Evaluation of the immunogenicity of YM866 by repeated intravenous injection in chimpanzees elicited no confirmed antibody titers.

Abnormalities, Drug-Induced↗
PubMed1992

Reproductive decision making of aunts and uncles of a child with cystic fibrosis: genetic risk perception and attitudes toward carrier identification and prenatal diagnosis.

This paper evaluates the perceived genetic risk, the perceived burden, the impact on reproductive decision making, and the attitudes of aunts and uncles of a child with cystic fibrosis toward carrier identification, prenatal diagnosis, and pregnancy termination. A mailed questionnaire was sent to the aunts and uncles of 32 CF children (1) who attended the Paediatric Department of the University Hospital and (2) whose parents agreed to give the names and addresses of their sibs. The results for the 109 respondents aged less than 40 years are discussed. About one-fourth of them was aware of the "approximate" level of the risk to be a carrier of the CF gene and/or of the risk of having a CF child themselves. Nevertheless the subjective evaluation of the genetic risk has played a part in the reproductive decision-making process of at least 39% of the respondents. About three-fourths would (probably) make use of heterozygote detection and would (probably) ask for prenatal diagnosis should they become pregnant. It is striking that less than half of the group would interrupt the pregnancy should the fetus be affected. The intention to use prenatal diagnosis was significantly correlated with age and educational level while the acceptance of pregnancy interruption was significantly correlated with perceived burden, respondents' age, and health situation of the proband.

Adult↗
PubMed2005

Spare embryos: 3000 reasons to rethink the significance of genetic relatedness.

IVF laws in Victoria, Australia provide that human embryos must not remain in storage in excess of 5 years. Studies reviewing the fate of surplus human embryos reveal that close to 90% of couples choose to discard their excess embryos and that hundreds of embryos are disposed of annually. It has been argued that human embryos are a valuable resource and that there is a need to consider educational programmes to encourage couples to donate spare embryos to other infertile couples, rather than discard them. Surveys show that one reason that so few embryos are donated is that couples attach great significance to genetic parenthood. Advances in reproductive technology may necessitate a review of biological definitions of family and the importance of genetic relatedness. It can be argued that it is unreasonable to conclude that genetic ties are so significant that embryos should be discarded rather than donated and raised by non-genetically related parents. It is suggested that education programmes should encourage reflection on people's beliefs about the importance of genetic relatedness with regard to what makes a family. Open embryo donation or directed embryo donation programmes might cause couples to change their minds, or alleviate their anxiety about donating embryos to others.

Attitude↗
PubMed1982

Evidence for the horizontal acquisition of murine AKR virogenes by recent horizontal infection of the germ line.

Several recent reports (8, 10, 11, 13) have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV(+) strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR strains by molossinus virus at 1;he strain's inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and molossinus, whereas the horizontal infection model does not. We have examined the polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci in 17 strains of mice including AKR, C58, BALB/c, Swiss, and molossinus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the "genetic distance" statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations have been reproductively isolated. The genetic distance computed between molossinus and AKR is large, nearly 5-10 times the distance between known related populations and strains (e.g., C57L vs. C57BL/6). Molossinus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV- positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from molossinus, AKR, and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of three AKR provirus sequences, Akv-1, Akv-2, and a third uncharacterized sequence, were not evident in molossinus cell DNA, which contained at least six different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and molossinus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the molossinus virus.

AKR murine leukemia virus↗
PubMed1982

Biological characteristics and host influence on a geographical isolate of Trichinella (wolverine: 55 degrees 00'N, 100 degrees 00'W, 1979).

Biological characteristics of Trichinella isolate (wolverine: 55 degrees 00'N, 100 degrees 00'W, 1979) were established in Crl: COBS CFW (SW) mice. Comparison of the wolverine isolate's biological characteristics with another Trichinella isolate (polar bear), both from closely related geographic areas, revealed there were stable and reproducible genetic differences between isolates. Differences were most pronounced for degree of infections causing a 50% mortality of mice, larval production by females in vitro, reproductive capacity indices, and survival of muscle larvae. Species and strain of host altered characteristics of the wolverine isolate such as worm position, sex ratios, % recovery, larval production by females in vitro, and reproductive capacity indices. Genetic differences between isolates of Trichinella and interaction with host genetics raises interesting questions on Trichinella speciation. Differences reported here, are best interpreted for the time being at least, as part of the normal biological variability of the species Trichinella spiralis.

Animals↗
PubMed2004

Yves Delage (1854-1920) as a forerunner of modern nuclear transfer experiments.

It is generally considered that animal cloning by nuclear transfer originated in proposals made by Hans Spemann (1936), following his experiments on delayed nucleation in the newt egg, which were preceded by similar attempts using the sea-urchin egg (Loeb, 1894). Briggs and King (1952) were the first to succeed in transplanting blastula and gastrula nuclei into the enucleated frog egg and in obtaining a significant number of normal tadpoles by means of this technique. We present evidence that much earlier (1895) Yves Delage (1854-1920), a French biologist, had clearly formulated the same experimental project of nuclear transfer, as a means to test Weismann's theory of cell differentiation during embryonic development. This was also Spemann's motivation. Both Delage and Spemann were aware of Loeb's experiments (1894), in which delayed nucleation in the sea-urchin egg was found to result in twin larvae. It is difficult to decide whether Delage's project was influenced by Loeb's findings. On the other hand, it seems that Spemann was not aware of Delage's proposal, since he did not express his own ideas on extended nuclear transfer before 1936. Finally, neither Delage nor Spemann imagined that nuclear transfer could be a means of obtaining groups of genetically identical animals (reproductive cloning).

Animals↗
PubMed2002

Eugenics or empowered choice? Community issues arising from prenatal testing.

The prevention of inherited disabilities is viewed in two contrasting ways--either as enhancing reproductive choice and improving population health, or as discriminating against disabled community members. We argue that modern clinical genetics, including preimplantation genetic diagnosis (PGD), reflects a persistent and defensible desire by the community to prevent disability, rather than as increasing discrimination or threatening to produce a 'new eugenic' society Screening should be presented as a distinct issue for decision-making about the prevention or acceptance of disability, rather than as a routinely accepted component of antenatal care. The community must improve its understanding of the experiences of those who manage disability, and continue to debate the issues of discrimination, selective genetic prevention and enhancement, reproductive freedom, and eugenics.

Australia↗
PubMed2006

Evaluating genetic containment strategies for transgenic plants.

One of the primary concerns about genetically engineered crop plants is that they will hybridize with wild relatives, permitting the transgene to escape into the environment. The likelihood that a transgene will spread in the environment depends on its potential fitness impact. The fitness conferred by various transgenes to crop and/or wild-type hybrids has been evaluated in several species. Different strategies have been developed for reducing the probability and impact of gene flow, including physical separation from wild relatives and genetic engineering. Mathematical models and empirical experimental evidence suggest that genetic approaches have the potential to effectively prevent transgenes from incorporating into wild relatives and becoming established in wild populations that are not reproductively isolated from genetically engineered crops.

Chimera↗
PubMed2005

On the verge of extinction: genetics of the critically endangered Iberian plant species, Borderea chouardii (Dioscoreaceae) and implications for conservation management.

Borderea chouardii is a relictual and dioecious, strictly sexually reproducing, long-living geophyte of the Dioscoreaceae family. Previous biological and demographic studies have indicated the existence of a uniformly distributed panmictic population of this taxon at the southernmost Spanish pre-Pyrenean mountain ranges where it occurs in rather inaccessible crevices of a single limestone cliff. However, individuals of B. chouardii are spatially subdivided into two subpopulations located, respectively, on the upper and lower parts of the cliff, and vertically separated 150 m. Because of its extreme rarity, B. chouardii was the first Iberian taxon to have a specific conservation plan and has been included in several red lists under the category of critically endangered (CR). However, no previous attempts have been conducted to analyse the fine scale evolutionary mechanisms involved in its present microspatial distribution. Genetic diversity and population structure have been investigated through the analysis of neutral hypervariable markers such as simple sequence repeats (SSRs) and randomly amplified polymorphic DNAs (RAPDs) to unravel the impact of life history traits in the differentiation of the two subpopulations. Both types of molecular markers were unequivocal in distinguishing two genetically distinct groups of individuals corresponding to their spatial separation. However, SSRs detected a higher level of subpopulation differentiation (F(ST) = 0.35, R(ST) = 0.32) than RAPDs (F(ST) = 0.21). SSR data indicated significant deviation from random dispersal of genes and genotypes between the two groups, suggesting that mating occurs mainly among individuals within subpopulations, thus, favouring the divergence between the two groups. This microevolutionary differentiation scenario might have been caused by a coupled effect of past genetic drift and reproductive isolation, as a result of strong glacial age bottlenecks and inefficient dispersal system of pollen and seeds, respectively. The identification of such genetic structure in this narrow endemic prompts a modification of the management strategies of its single extant population.

Conservation of Natural Resources↗
PubMed1998

The long view: how genetic discoveries will aid healthcare reform.

This article addresses social and ethical priorities on the agenda for women's health research in the next century. Specifically, the relevance of genetic discoveries for healthcare reform and why both topics ought to be among these priorities are discussed. If the present gap between diagnosis and treatment of genetic diseases could be bridged, especially in such common diseases as cancer and heart disease, arguments for universal access to healthcare would be vastly strengthened. Important scientific and ethical problems are involved in bridging the gap, including volatile issues of research with human embryos and fetuses. Other issues deserve high priority on the women's health research agenda: adequate funding for biomedical research, maintaining an equitable number of women in clinical trials, and creating a knowledge base in gender-based biology. Progress in genetic research is clearly relevant to women's health for understanding and treating common diseases, as well as for reproductive decisions. Until recently, genetic services have been aimed exclusively at reproductive choices, including counseling, prenatal diagnosis, and carrier screening. However, the meaning of the term needs to be vastly broadened to include the uses of genetic information in mainstream medicine. Through genetic testing and DNA technology, it will be increasingly possible for physicians to have access to family history and a reliable profile of each patient's genetic health risks. Drugs will be designed that will be responsive to individual genetic variability and risks for disease. If scientific and ethical obstacles are overcome, there may also be effective human gene therapy to correct mutations and prevent lifelong harm. In my view, linking the agenda for women's health research with the unfinished social task of ensuring access to adequate primary and preventive care, which foreseeably will include genetic services and human gene therapy, strengthens the agenda and promotes solidarity with the needs of the majority of Americans. This link will help to prevent political and moral isolation of women's health research.

Bioethics↗
PubMed1997

Fisher's fundamental theorem of natural selection revisited.

W. J. Ewens, following G. R. Price, has stressed that Fisher's fundamental theorem of natural selection about the increase in mean fitness is of general validity without any restrictive assumptions on the mating system, the fitness parameters, or the numbers of loci and alleles involved, but that it concerns only a partial change in mean fitness. This partial change is obtained by replacing the actual genotypic fitnesses by the corresponding additive genetic values and by keeping these values fixed in the change of the mean with respect to changes in genotype frequencies. We propose an alternate interpretation for this partial change which uses partial changes in genotype frequencies directly consequent on changes in gene frequencies, the fitness parameters being kept constant. We argue that this interpretation agrees more closely with Fisher's own explanations. Moreover, this approach leads to a decomposition for the total change in mean fitness which explains, unifies, and extends previous decompositions. We consider a wide range of models, from discrete-time selection models with nonoverlapping generations to continuous-time models with overlapping generations and age effects on viability and fecundity, which is the original framework for Fisher's fundamental theorem.

Age Factors↗

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