[Somatic and genetic radiation load during the use of the photofluorographic camera "Jena 110" (Radiophotography) in extrathoracic roentgen diagnosis].
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Severe inbreeding depression in collared flycatchers (Ficedula albicollis).
The causes and magnitude of inbreeding depression are of considerable importance for a wide range of issues in evolutionary and conservation biology, but we have only a limited understanding of inbreeding depression in natural populations. Here, we present a study of inbreeding in a large wild population of collared flycatchers (Ficedula albicollis). Inbreeding was rare, to the extent that we detected only 1.04% of 2139 matings over 18 years that resulted in offspring with a non-zero inbreeding coefficient, f > 0. When it did occur, inbreeding caused a significant reduction in the egg-hatching rate, in fledgling skeletal size and in post-fledging juvenile survival, with the number of offspring being recruited to the breeding population from a nest of f = 0.25 being reduced by 94% relative to a non-inbred nest. A maximum-likelihood estimate of the number of lethal equivalents per gamete was very high at B = 7.47, indicating a substantial genetic load in this population. There was also a non-significant tendency for inbreeding depression to increase with the strength of selection on a trait. The probability of mating between close relatives (f = 0.25) increased throughout the breeding season, possibly reflecting increased costs of inbreeding avoidance. Our results illustrate how severe inbreeding depression and considerable genetic load may exist in natural populations, but detecting them may require extensive long-term datasets.
Animals↗
A population genetic model of selection that maintains specific trinucleotides at a specific location.
Periodic appearances of specific trinucleotides along the DNA sequence have been reported in the chicken core DNA, and the phenomenon has been suggested to be related to the supercoiling of DNA around nucleosomes. A population genetic model is constructed in which selection is operating to maintain specific trinucleotides at a specific location on the DNA sequence. Assuming low mutation rates, equilibrium probabilities of the appearances of respective trinucleotides were computed. Vague patterns appeared if the product of the effective size and the selection coefficient was 0.1-2.0. The genetic load and substitution rates in the equilibrium state were also computed. When the model was applied to the chicken DNA data, the product of the effective size and the selection coefficient was estimated to be 0.1-0.2. With this intensity of selection, the substitution rate was hardly different from that in the case without selection. However, the genetic load became fairly large. Considering the large number of times that DNA coils about nucleosomes, the number of trinucleotide sites must be very large, and thus the total load might be too large. Epistasis among these sites to reduce the total load is suggested to exist if selection is responsible for this periodic pattern observed in the chicken core DNA.
Alleles↗
Accelerated age-related decline of visual information processing in first-degree relatives of persons with schizophrenia.
A recent cross-sectional study suggested that persons with schizophrenia experience an accelerated age-related decline in performance on the Span of Apprehension task, a visual information processing paradigm. However, this study was not able to determine if such decline was primarily related to genetic loading for schizophrenia, as the decline may have been related to chronic neuroleptic use or other confounds found when studying persons with schizophrenia directly. To help address this question, the current study examined healthy first-degree relatives of persons with schizophrenia over a wide age range to investigate whether such age effects may be related to genetic loading for schizophrenia. Twenty-eight healthy first-degree relatives of persons with schizophrenia (ages 21-72) and 31 healthy controls (ages 19-75) were evaluated using the Span of Apprehension task with cross-sectional methodology. Results replicated and extended the earlier report examining persons with schizophrenia, as the data indicated a statistically significant accelerated age-related decline in performance in the relatives. While the study is limited by cross-sectional methodology, it suggests a genetically driven, age-related decline in visual information processing related to schizophrenia and informs future longitudinal studies that can more definitively address such a possibility.
Adult↗
Inbreeding and endangered species management: is New Zealand out of step with the rest of the world?
There is growing evidence that inbreeding can negatively affect small, isolated populations. This contrasts with the perception in New Zealand, where it has been claimed that native birds are less affected by inbreeding depression than threatened species from continental regions. It has been argued that New Zealand's terrestrial birds have had a long history of small population size with frequent inbreeding and that this has 'purged" deleterious alleles. The rapid recovery of many tiny and inbred populations after introduced predators have been controlled, and without input from more genetically diverse populations, has further supported the view that inbreeding is not a problem. This has led to a general neglect of inbreeding as a factor in recovery programs for highly endangered species such as the Black Robin (Petroica traversi) and Kakapo (Strigops habroptilis). We examined the reasons for this situation and review the New Zealand evidence for genetic purging. Complete purging of the genetic load and elimination of inbreeding depression are unlikely to occur in natural populations, although partial purging may be more likely where small populations have become inbred over an extended period of time, such as on small isolated islands. Recent molecular data are consistent with the view that island endemics, including New Zealand's threatened birds, have low genetic variation and hence have possibly gone through longer periods of inbreeding than threatened species from continental regions. Nevertheless, results from recent field studies in New Zealand indicate that, despite the opportunity for purging, inbreeding depression is evident in many threatened species. Although inbreeding depression has not prevented some populations from recovering from severe bottlenecks, the long-term consequences of inbreeding and small population size--the loss of genetic variation--are potentially much more insidious. The degrees to which genetic factors reduce population viability generally remain unquantified in New Zealand. Although minimizing ecological risks (e.g., preventing reinvasion of islands by mammalian predators) will continue to receive high priority in New Zealand because of their much larger impacts, we advocate that genetic considerations be better integrated into recovery plans.
Animals↗
Familial versus mass selection in small populations.
We used diffusion approximations and a Markov-chain approach to investigate the consequences of familial selection on the viability of small populations both in the short and in the long term. The outcome of familial selection was compared to the case of a random mating population under mass selection. In small populations, the higher effective size, associated with familial selection, resulted in higher fitness for slightly deleterious and/or highly recessive alleles. Conversely, because familial selection leads to a lower rate of directional selection, a lower fitness was observed for more detrimental genes that are not highly recessive, and with high population sizes. However, in the long term, genetic load was almost identical for both mass and familial selection for populations of up to 200 individuals. In terms of mean time to extinction, familial selection did not have any negative effect at least for small populations (N< or =50). Overall, familial selection could be proposed for use in management programs of small populations since it increases genetic variability and short-term viability without impairing the overall persistence times.
Family↗
Psychopathology in the offspring of parents with bipolar affective disorders.
Thirty-nine children from intact families with a manic-depressive parent were evaluated by a semi-structured clinical interview and a number of rating scales for the presence or absence of psychopathology. This sample represents a larger one than in an earlier study, which showed minimal offspring psychopathology compared with reports of other investigators. The current study also examines the inter-relationships between the presence or absence of offspring psychopathology with both genetic loading and a number of psychosocial variables including measures of parental marital adjustment, severity and chronicity of proband parent illness and early exposure of children to parental illness. Nine of the thirty-nine children, (23%) received a positive DSM-III diagnosis, with depression of the dysthymic type being the most common. There was no significant correlation between genetic loading and offspring psychopathology. However, there were significant associations between children with psychopathology and paternal marital dissatisfaction and the age and chronicity of illness of the proband parent as compared with the children with no psychopathology.
Adolescent↗
[Clinical characteristics of unipolar and bipolar depression].
INTRODUCTION: In the last decades affective disorders were divided into unipolar and bipolar and this division has been generally accepted. The bipolar type is manifested by mania or by both mania and depression. On the other hand, unipolar affective disorders are manifested only by depression. In numerous investigations authors have noticed that there are very distinctive differences between these two types of depressive disorders such as: course of illness, personality disorders, sex, family history etc. Nevertheless, in practice it is often very difficult to make the right diagnosis. The bipolar type often starts with a few pure depressive episodes and sometimes mania occurs a few years later so only at that point the psychiatrist can make the right diagnosis and treat the patient correctly. MATERIAL AND METHODS: This investigation comprised 50 patients hospitalized at the Psychiatric Clinic in Novi Sad during 1992-1995. The experimental group consisted of 20 patients with a bipolar affective disorder (according to ICD-X), while the control group consisted of 30 patients with clinical diagnosis of unipolar depression (intensive, without psychiatric features). Both groups of patients were weekly evaluated by Hamilton Depression Rating Scale (HDRS), whereas the initial score for all patients had to be higher than 16. RESULTS: Patients suffering from unipolar depression were older than patients with bipolar depression and there were more females in this group. There were no differences in demographic characteristics (level of education, migration, etc.), but the experimental group had a greater genetic loading for affective disorders. Unipolar depressive patients had more agitation and they were more anxious than patients with bipolar depression. DISCUSSION AND CONCLUSION: The fact that unipolar depressive patients were older than bipolar is similar to most of the results gained in this kind of investigation. On the other hand, we did not find statistical differences in the intensity of disorders, and in the literature these results are contraindicating. Numerous investigators report that bipolar depressives had a stronger genetic loading for affective disorders and our study confirms the same. All these results can help us to make the right diagnosis of unipolar and bipolar affective disorders.
Adolescent↗
Effect of genetic risk load defined by HLA-DQB1 polymorphism on clinical characteristics of IDDM in children.
Clinical and autoimmune characteristics of 150 diabetic children of mean age 7.8 years (SD 4.1 years) were recorded at clinical manifestation and during the first 2 years of IDDM in order to investigate whether subjects with high risk HLA-DQB1 genotypes differ from those without these risk markers. When comparing subjects with the DQB1*0302/0201, DQB1*0302/x, DQB1*0201/x, or other DQB1 genotypes (x = no protective allele), no differences were found in the age of the subjects at diagnosis, the duration of hyperglycaemic symptoms, or the length of clinical remission. The frequency of islet cell antibodies (ICA) and quantitative serum levels of these antibodies were of the same magnitude in all four groups. During the initial 2 years of IDDM serum C-peptide concentrations were observed to be inversely related to the degree of genetic risk (P < 0.001 in two-way analysis of variance for repeated measures), the lowest C-peptide levels being observed in the group of DQB1*0302/0201 heterozygotes (P < 0.001 vs. DQB1*0201/x; P < 0.01 vs. DQB1*0302/x; P = 0.05 vs. others). On the other hand, the subjects with the DQB1*0201 genotype had the highest serum C-peptide concentrations, the levels being even higher than those of the patients carrying neutral or protective DQB1 genotypes (P < 0.01). These subjects also had lower daily insulin doses and blood glycated haemoglobin A1 (HbA1) levels over the initial 2 years of the disease when compared with the DQB1*0302/0201 heterozygotes (P < 0.05 and P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Five reasons why inbreeding may have considerable effect on post-reproductive human health.
As the genetic architecture of common complex diseases of late onset is emerging through intensive research, it is intriguing to assess the predicted effect of inbreeding on those diseases. In this paper, we propose five reasons why we believe inbreeding may have a considerable effect on post-reproductive human health. (i) The joint effect of inbreeding depression on all polygenic quantitative phenotypes that confer risk for late-onset diseases is predicted to be multiplicative rather than additive. (ii) The "genetic load" of rare "Mendelian" variants with large deleterious effects in post-reproductive adults is unknown, but could be much greater than expected as these variants were invisible to selection through human history. (iii) Deleterious effects resulting from autozygosity in hundreds of affected rare recessive variants of small effect under common disease/rare variant (CD/RV) hypothesis could result in epistatic effects that could jointly impair capacity to compensate against environmental risks. (iv) Heterozygote advantage in loci under balancing selection could be reduced by inbreeding. (v) Published empirical evidence in animals and humans consistently report large inbreeding effects on late-onset traits. Since inbreeding is common in many populations and the effects of inbreeding depression could substantially contribute to disease burden and reduced life expectancy we believe there is now a clear need for further genetic epidemiological research in humans to investigate this issue.
Animals↗
Disturbed frontal gyrification within families affected with schizophrenia.
OBJECTIVE: Recently, in a post-mortem and a subsequent structural MR study, a significantly increased gyrification index (GI) was demonstrated in the frontal lobe in individuals with schizophrenia. To examine whether frontal lobe hypergyria is region-specific and whether this might be a suitable endophenotype in the search for the genetic basis of schizophrenia, the frontal as well as parieto-occipital GI were determined in MRI scans of families affected with schizophrenia. METHOD: In the MRI scans of 48 subjects suffering from schizophrenia, in 82 of their first-degree relatives and in 41 control subjects, the GI was determined in three sections anterior to the genu of the corpus callosum and three sections posterior to the splenium, thus allowing for a selective determination of this measure in the frontal as well as the parietal lobe. Outer and inner contours constituting the GI was determined in each section by manual tracing. Statistical analysis was performed using MANOVA with factors diagnostic group and intervening factors from preliminary analyses. RESULTS: The frontal, but not parieto-occipital GI was significantly higher in schizophrenic patients as well as unaffected relatives compared with control subjects (right: 7%, F=13.24, df=3, 155, p<0.0005, left: 6%, F=8.92, df=3, 155, p<0.0005). There was no overall difference between affected and unaffected family members. On the left side however, there was a significant interaction between diagnostic group and genetic loading (F=4.68, df=2, 101, p=0.01): significantly higher GI was found in affected compared with unaffected family members only in uniaffected and not multiaffected families. CONCLUSIONS: These results support our primary finding of hypergyria in the frontal lobe in schizophrenic patients. Compared to the parietal lobe, hypergyria seems to affect the frontal lobe selectively and serves as a suitable neurodevelopmental, possibly even an endophenotypic marker.
Adult↗
A hypertensive father, but not hypertensive mother, determines blood pressure in normotensive male offspring through body mass index.
This investigation was to assess the role of genetic loading of hypertensive parents in the determination of blood pressure (BP) in their normotensive offspring. The medical check-up data from 7279 Japanese university students aged 19.22 +/- 0.01 years were analysed of which 641 students had only one hypertensive parent with or without hypertensive grandparents, and from this number 609 cases were available for the present analysis. The BP in the students having only one hypertensive parent were in the normotensive range, but was significantly higher than in those students without hypertensive relatives. Analyses of the data from the students having only one hypertensive parent revealed that systolic BP (SBP) and body mass index (BMI) were higher in the male than in the female students. In addition, there were no differences in BP and BMI between the male students with a hypertensive father and the male students having a normotensive father. However, multivariate analyses revealed that BMI was an independent predictor of SBP solely in the male students having a hypertensive father, but not in the male students having a normotensive father. Such a relationship between BMI and BP determination was not observed in the female students with one hypertensive parent. It is suggested that there are different mechanisms for the determination of BP in normotensive offspring of hypertensive parents, and genetic loading of a hypertensive father plays a critical role in the determination of BP through BMI.
Adolescent↗
Reduced bovine leukaemia virus proviral load in genetically resistant cattle.
The bovine leukaemia virus (BLV) is an exogenous retrovirus that is closely related to the human T cell leukaemia viruses. Genetic resistance and susceptibility to persistent lymphocytosis (PL), an advanced subclinical stage of infection characterized by a polyclonal expansion of the infected B cell population, have been mapped to structural motifs in bovine MHC DRB3 (class II) alleles. To determine whether alleles of DRB3 influence the number of BLV-infected B cells in peripheral blood, seven pairs of Holstein cows naturally infected with BLV were matched on the basis of DRB3 genotype (resistance or susceptibility to PL), age, and year of seroconversion. Flow cytometry was used to separate B cell populations that then were tested for the presence of provirus by a single-cell PCR methodology. Animals with the PL-resistance associated DRB3.2*11 allele had significantly fewer BLV-infected B cells than did age- and seroconversion-matched cows with DRB3 alleles associated with susceptibility to PL. Our results demonstrate that DRB3 or a closely linked gene may play a direct role in controlling the number of BLV-infected peripheral B cells in vivo. Association of MHC class II alleles with resistance to disease progression in cattle naturally infected with BLV provides a unique immunogenetic model for the study of host resistance to human and other animal retroviral infections.
Aging↗
Relation between cerebrospinal fluid, gray matter and white matter changes in families with schizophrenia.
BACKGROUND: Gray matter reduction and ventricular enlargement belong to the best replicated findings in schizophrenia. Brain morphologic changes were also found in non-schizophrenic family members (FM). The intention of this study was to examine whether non-psychotic first-degree relatives reveal similar morphologic changes as schizophrenic patients and how state of genetic loading contribute to these abnormalities. METHODS: Forty-nine schizophrenic patients, 71 non-schizophrenic FM and 48 control subjects took part in this volumetric MRI study. All subjects were between 18 and 59 years old. Dependent variables were gray matter, white matter and total cerebrospinal fluid (CSF) volume, determined by SPM99 segmentation algorithm. As an important part of CSF lateral ventricle volume was determined manually by removing surrounding CSF areas. RESULTS: In schizophrenic patients compared to controls and non-schizophrenic FM total CSF volumes and lateral ventricles were increased. Gray and, to a lesser degree, white matter volumes were decreased as well. For CSF, gray and white matter there was no significant difference between uni- and multiple affected families. CSF correlated significantly negative with gray matter (r=-0.78) and, less intensive, with white matter (r=-0.40). There were negative correlations between gray and white matter volume as well (r=-0.26). These correlations were not significantly different between the diagnostic groups. CONCLUSION: CSF enlargement and gray matter reductions in schizophrenic patients compared to controls and non-affected FM seem to be interdependent findings. However, this correlation is independent of the factor diagnosis and is therefore not specific for schizophrenia.
Adult↗
The load of genetic and partially genetic disorders in man. I. Congenital anomalies: estimates of detriment in terms of years of life lost and years of impaired life.
This paper represents an attempt to estimate quantitatively, the detriment associated with spontaneously arising congenital anomalies in man. The system used in the International Classification of Diseases (Chapter XIV, entries 740-759) has been followed to classify the congenital anomalies. Detriment was assessed using estimates of the years of life lost, years of life potentially impaired and years of life actually impaired, as indicators. The data on birth prevalences for the various conditions were derived from several epidemiological surveys carried out in Hungary and from the Hungarian Congenital Malformation Registry. Most of the information on mortality profiles was obtained from the records of the Hungarian Central Statistical Office, Budapest. An overall comparison of the prevalence figures in Hungary with those for the U.S. (this study aimed at complete ascertainment) and for the Canadian province of British Columbia (in this study, ascertainment is believed to be incomplete) showed that, in Hungary, at least certain classes of congenital anomalies, particularly some of the less severe ones, have been under-ascertained. Since detriment estimates are heavily dependent on accurate estimates of birth prevalences, we believe that the estimates of detriment arrived at using the Hungarian data may also be underestimates. In Hungary, the total birth prevalence of all isolated major congenital anomalies is of the order of about 600/10(4). Our calculations show that these congenital anomalies may cause, per 10(4) livebirths, about 4800 years of life loss, about 37000 years of potentially impaired life and about 4500 years of actually impaired life. In these calculations, it has been assumed that the average life-expectancy at live birth for the general population is 70 years. These estimates are considerably higher than those made by Carter for detriment associated with spontaneously arising monogenic disorders.
British Columbia↗
The load of genetic and partially genetic diseases in man. III. Mental retardation.
This paper summarizes estimates of detriment associated with different etiologic categories of mental retardation (MR) in Hungary. The basic data derive from an earlier study carried out in Budapest on 1276 school-age mentally retarded children (with some etiologic reclassification based on recent studies). Detriment associated with these different categories of MR is expressed in terms of years of lost and impaired life. About 30 per 10(3) school-age children in Hungary are mentally retarded (mild + severe MR), one-tenth of whom have severe MR (IQ less than or equal to 50); 50% of the latter are institutionalized. The breakdown on the basis of etiology is as follows: gene mutations and chromosomal abnormalities, about 4 per 10(3); 'familial' (multifactorial) causes, 12 per 10(3); adverse pre-, peri- and post-natal causes, 11 per 10(3); and 'causes as yet unknown', the remainder. The estimates of mean number of years of lost life range from 42 to 68 (depending on the etiologic category), with an overall mean of 58. The total number of years of lost life is about 36,000 per 10(4) live births of which over 70% is due to pre-, peri- and post-natal causes, 18% due to 'familial' causes and the remainder due to Mendelian and chromosomal diseases. The total number of years of impaired life is about 7300 per 10(4) livebirths, 50% of which is due to 'familial' causes. While admittedly approximate, these estimates suggest that detriment associated with MR-related causes is not inconsiderable. Additionally, they provide some indication of causes of MR which are minimizable.
Adolescent↗
The load of genetic and partially genetic disease in man. IV. Severe visual handicaps and profound childhood deafness in Hungarian school-age children.
In Hungary, the school-age prevalences of severe visual handicaps and of profound childhood deafness have been estimated to be about 6/10(4) and 10/10(4), respectively. Most of these conditions have onset at birth or in early childhood and are aetiologically heterogeneous. Severe visual handicaps are grouped under 11 aetiological categories, their relative contributions to the prevalence being: perinatal damage syndrome (20%; half of this is due to retinopathy of premature infants), cataracts (15%), choroidoretinal degenerations (15%), congenital abnormalities of the eye (15%), syndromes (10%), high myopia +/- retinal detachment (7%), postnatal causes (5%), nystagmus (5%), optic atrophy (4%), bilateral retinoblastoma (2%) and prenatal causes (2%). Overall, Mendelian conditions (included under many of the above) account for about 50% with relatively more autosomal dominant than autosomal recessive and sex-linked entities, and acquired causes account for about 40% of the cases studied. No aetiology could be assigned in 10% of the cases. For profound childhood deafness, the rank order of the aetiological categories is: autosomal recessive entities (34%), postnatal causes (22%), perinatal causes (19%), autosomal dominant entities (17%), prenatal causes (5%) and unknown causes (3%). Severe childhood visual handicaps are responsible for about 60 years of loss of life per 10(4) live births and about 400 years of impaired life per 10(4) live births. Genetic causes account for one-quarter of lost life years and three-quarters of impaired life years. The comparable estimates for profound childhood deafness are: about 240 years of life loss per 10(4) live births (again, about one-quarter due to genetic causes) and about 640 years of impaired life per 10(4) live births (about one-half due to genetic causes). In all these calculations, it has been assumed that the average life expectancy at birth for an individual in the population is 70 years.
Adolescent↗
The load of genetic and partially genetic diseases in man. II. Some selected common multifactorial diseases: estimates of population prevalence and of detriment in terms of years of lost and impaired life.
This paper presents epidemiological data on the prevalence of 26 common (i.e., having a lifetime prevalence of more than 1 per 10(4) individuals in the population) multifactorial diseases in Hungary and estimates of detriment associated with them. The detriment is expressed using 3 indicators, namely years of lost life (LL), potentially impaired life (PIL) and actually impaired life (AIL). The total prevalence of these diseases in Hungary has been estimated to be about 6500 per 10(4) individuals in the population. This estimate is in agreement with published data for other parts of the world. On the basis of clinical severity, these diseases have been split into 3 groups, namely (1) very severe (schizophrenia, multiple sclerosis, epilepsy, acute myocardial infarction and related conditions, and systemic lupus erythematosus); (2) moderately severe and/or episodal or seasonal (15 entities including Graves' disease, diabetes mellitus, gout, affective psychoses, essential hypertension, peptic ulcers, asthma, etc.); and (3) less severe than those in the first 2 groups (varicose veins, allergic rhinitis, atopic dermatitis, Scheuermann disease and adolescent idiopathic scoliosis). The essential clinical and genetic aspects of these diseases are briefly discussed. With the exception of epilepsy, none of the diseases included in our list causes mortality between ages 0 and 19. However, they are among the leading causes of death between ages 20 and 69 and thereafter. A sizeable proportion of those with essential hypertension, diabetes mellitus, rheumatoid arthritis, etc. survive to 70 years and beyond, as do those with gout, glaucoma, allergic rhinitis, psoriasis, etc. Overall, about 16% of all deaths that occur in Hungary every year (all age groups) can be attributed to these diseases. The mean number of years of PIL covers a wide range (about 20-40, 12-70 and 40-60 for groups 1, 2 and 3, respectively), the overall mean being about 24 years. However, the nature and degree of impairment and the impact on the life quality of those afflicted differ for the different diseases. Likewise, the mean number of years of AIL (for which the interval between the mean age at premature retirement and mean age at death was used as a rough index) also spans a wide range from 16 to 45, and the overall mean is about 20 years. At the population level, the diseases considered in this paper cause about 2700 years of LL, 96,000 years of PIL and about 5800 years of AIL per 10(4) individuals in the population. Relative to Mendelian diseases as a whole, these multifactorial diseases are associated with much greater detriment (LL: 1.4 X; PIL: 30 X and AIL: 3.9 X).
Biometry↗