The influence of genetic counselling in the era of DNA testing on knowledge, reproductive intentions and psychological wellbeing

Subjects of reproductive age at risk of having an affected child with a severe single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis (CF) were surveyed to ascertain: their views on genetic counselling and antenatal testing; their knowledge of their risk of having an affected child; and their psychological wellbeing. Questionnaires were posted to 209 individuals at 130 addresses; a 65% response rate was achieved. The majority of those surveyed were under 40 years of age (91%), half of them had received genetic counselling only once and for 47% the first encounter was after the diagnosis of their affected child. Most patients expressed their intention to use prenatal testing. However, less than 50% of those counselled knew their risk of having an affected child. Knowledge of risk was associated with the type of disease in the family (p<0.001) (inheritance of DMD was poorly understood by relevant subjects) and was positively associated with the participant's level of education (p<0.05). We did not detect a significant association between the number of intended children and the risk of having an affected child. In terms of family relations, genetic counselling appears to be beneficial for the nuclear family, the couple and their children, but some counsellees reported a detericration in relations with other relatives. The results indicate that couples at risk of having a child with a severe genetic disorder value the counselling provided, but many of them do not remember important facts in relation to their risk status.     

Gene Therapy: The Potential Applicability of Gene Transfer Technology to the Human Germline

The theoretical possibility of applying gene transfer methodologies to the human germline is explored. Transgenic methods for genetically manipulating embryos may in principle be applied to humans. In particular, microinjection of retroviral vector appears to hold the greatest promise, with transgenic primates already obtained from this approach. Sperm-mediated gene transfer offers potentially the easiest route to the human germline, however the requisite methodology is presently underdeveloped. Nuclear transfer (cloning) offers an alternative approach to germline genetic modification, however there are major health concerns associated with current nuclear transfer methods. It is concluded that human germline gene therapy remains for all practical purposes a future possibility that must await significant and important advances in gene transfer technology.     

The Origin and Evolution of Human T-Cell Lymphotropic Virus Types I and II

Studies on human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) are briefly reviewed from the viewpoint of molecular evolution, with special reference to the evolutionary rate and evolutionary relationships among these viruses. In particular, it appears that, in contrast to the low level of variability of HTLV-I among different isolates, individual isolates form quasispecies structures. Elucidating the mechanisms connecting these two phenomena will be one of the future problems in the study of the molecular evolution of HTLV-I and HTLV-II.     

Alkaptonuria in the Trenčín District of Czechoslovakia

For several years the Clinical Genetics Research Laboratory at Martin, Czechoslovakia, has been studying alkaptonuria (AU) in the northern part of the District of Tren?ín in Slovakia. These affected individuals are part of a group of 103 alkaptonurics originated mostly in the mountainous parts of Slovakia. We report results of pedigree analyses; population and affected-family biochemical urine screening; estimation of inbreeding coefficient, of exogamy rate and of average marital distance and of calculation of the frequency of the AU allele, and of homozygotes and jeterozygotes in this portion of the Tren?ín District. Twelve homozygotes were found, but seven originated from a single hamlet in which a founder effect – genetic drift and inbreeding – are thought to account for the high prevalance of AU.     

Reproductive genetic counselling in non-mosaic 47,XXY patients: implications for preimplantation or prenatal diagnosis: Case report and review

With an incidence of approximately 1 in 500 male newborns, the 47,XXY genotype is one the most common sex chromosome anomalies. It is also the most frequent genetic cause of human infertility. Some non-mosaic 47,XXY patients have sperm production which allows infertility treatment to be offered by ICSI. Therefore, the risk of transmitting a chromosome anomaly to the next generation is an important problem in reproductive genetic counselling of these patients. Here, we report on a twin pregnancy where two karyotypically normal neonates 46,XX and 46,XY were born after the use of ICSI in assisted reproduction of a patient with a non-mosaic 47,XXY syndrome. To date, only 38 evolving pregnancies including the present cases, have been reported after ICSI using sperm from non-mosaic 47,XXY patients. Although these data are scarce, they suggest that the risk of chromosome anomaly in the offspring of these patients is low; hence, their reproductive genetic counselling can be reassuring, and management of the pregnancy can proceed with caution.     

Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic

In a sample of 5483 adults who had been legally adopted early in life by persons not biologically related to them, 33 were identified, from mental hospital records, for whom a diagnosis of definite schizophrenia (chronic, latent, or acute) could be agreed upon by four raters. An equal number of matched controls were selected from the sample of adopted individuals who had never been admitted to a mental hospital. Ninety percent of the living parents, siblings, and half-siblings, biological and adoptive, cooperated in an extensive psychiatric interview permitting a consensus diagnosis by three blind raters. Schizophrenia and uncertain schizophrenia were found to be significantly concentrated in the population genetically related to the schiziphrenic adoptees. Their adoptive relatives did not differ from the control populations in the prevalence of schizophrenic illness.This was presented at the Annual Meeting of the American Society of Human Genetics, Portland. Oregon, October 18, 1974.     

Seven generations of genetic selection for ethanol dependence in mice

An animal model of alcohol dependence is being produced by selecting mice for differences in severity of ethanol withdrawal seizures. Replicate lines of high-dependence (HA), low-dependence (LA), and control (CA) mice are being developed by within-family selection. After seven generations both (replicate) HA and LA lines have separated significantly. Some of the difference between the replicate pairs of HA and LA in the early generations was due to differences in ethanol consumption. This difference in consumption may be attributable to a difference in metabolic rate or activity level rather than to a difference in ethanol preference. Females are more susceptible to seizures than males; this appears to be due partly to their higher consumption of ethanol during treatment.This research was supported in part by Grant AA-03527 from the National Institute of Alcohol Abuse and Alcoholism to the University of Colorado Alcohol Research Center.     

Scanning electron microscopy of teeth in dominant osteogenesis imperfecta: Support for genetic heterogeneity

Scanning electron microscopic studies were performed on 25 deciduous and permanent teeth from members of 7 kindreds with dominant nonlethal osteogenesis imperfects (OI). Two families had normal teeth on clinical and radiological examination; five familes had blue or brown opalescent teeth with specific radiologic findings. Enamel surfaces and prism organization were normal on all teeth. On fractured surfaces, the dentin tubules of normal teeth from patients with OI were evenly distributed and coursed regularly to the dentin-enamel junction. Opalescent teeth had few tubules and those present were short, narrow, and tortuous. Dentin calcification fronts of normal teeth were composed of many nodules with regularly spaced openings on their surfaces. Calcification fronts of opalescent teeth were composed of irregularly spaced, small nodules, which varied greatly in size and the nodules lacked tubule openings on their surfaces. The results of this study support the concept that at least two dominant forms of OI exist – one in which all individuals with IO have normal teeth, and the other in which all with OI have blue or brown opalescent teeth with characteristic changes on SEM.     

早期鼠胚简化双针取样法

为建立早期胚胎活检的动物模型，以安全高效地开展人类的植入前遗传学诊断，应用显微操作技术，对发育到8细胞期的小鼠胚胎进行了透明带溶洞吸取单个卵裂球的研究。结果表明：简化组的胚胎活检时间显著缩短，而胚胎完整率及单个卵裂球的完整率与传统组无明显差别。对照和两实验组胚胎在体外培养过程中均出现不同程度的胚胎发育延迟现象。活检后胚胎桑椹胚的发育率较对照组显著降低，但三组胚胎的出生率和生后三周仔鼠的体重无显著性差别，提示简化组的胚胎活检是安全而高效的，因而为开展人类的早期胚胎活检提供了方法学的参考。