SEARCH · Search PubMed

Results for “Genetic Load”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed1998

Leukocyte differentials predict short-term clinical outcome following antipsychotic treatment in schizophrenia.

BACKGROUND: The majority of patients with schizophrenia and many of their unaffected siblings exhibit a relative granulocytosis and lymphopenia. To characterize these abnormalities better, we examined leukocyte differentials and organ nonspecific autoantibodies in relationship to intake phenomenology and short-term clinical outcome. METHODS: We studied patients with schizophrenia (n = 81) and their siblings (n = 18). At intake assessment, about one-half of the probands (n = 38) were neurolepticnaive first-episode patients; the remainder were medication-free for at least 2 weeks. Hematologic indices were obtained at intake assessment, and psychiatric symptomatology was assessed at baseline and following 6 months of clinically determined treatment. RESULTS: A relative granulocytosis and lymphopenia prospectively predicted poorer recovery in positive, but not negative, symptoms after 6 months of antipsychotic treatment. Abnormal leukocyte proportions were specific to patients who presented with clinically significant positive symptomatology at intake. In contrast, clinically significant negative symptoms were only evident in a small subgroup of patients who were positive for antinuclear autoantibodies and/or rheumatoid factor. CONCLUSIONS: Future research should further test the hypothesis that a relative granulocytosis and lymphopenia reflect genetic loading for the pathophysiologic determinants of positive symptoms. Future research also should determine the etiologic significance of organ nonspecific autoimmunity in predominantly negative symptom schizophrenia.

Adult↗

PubMed1987

Issues in the evaluation of chemical dependency treatment programs for adolescents.

To summarize, six issues have been identified in this article that need to be considered before adequate assessment of relative efficacy of treatment programs can be attempted, starting at the front door of treatment. First, the differential referral sources that bring these youngsters to treatment must be considered, with their differential perspectives and definitions of problem behavior. Second, the differential characteristics of the patient population must be assessed. This involves, primarily, systematic and thorough medical and psychiatric diagnosis, but it also includes careful assessment of genetic, familial, social, legal, and developmental characteristics that subcategorize these youngsters. As indicated, when this is done the typical adolescent referred for treatment is likely to have a lifetime diagnosis of attention deficit disorder, conduct disorder, some drug use diagnosis (most likely alcohol and marijuana), past legal problems, a family in turmoil (which has included personal, physical, and possibly sexual abuse to the youngster and also genetic loading for alcoholism), or some learning disability. Third, the differential characteristics of treatment programs must be adequately described and catalogued. No such assessment instruments currently exists. The differential characteristics based on philosophy, treatment strategies, personnel selection, patient admission criteria, treatment techniques employed, length and type of treatment, and length and type of aftercare, all must be assessed. Fourth, the presence or absence of differential treatment strategies responsive to the particular needs of individual adolescents must be categorized. In addition to the overall philosophic flexibility of the program, the capability of responding to particular issues such as the presence of major depressive disorder, learning disability, sexual abuse, or the need for a careful neurologic assessment for subtle temporal lobe issues, must be identified in the program. Fifth, the differential response of the youngster to the treatment process as it is progressing must be able to be assessed and considered as a variable. For example, the ability of the youngster to participate in group confrontational sessions and honestly review his or her past behavior is a measurable variable that to date is ignored in program evaluation. Essentially the only variable currently assessed is treatment completion or failure to complete treatment. Sixth, appropriate outcome variables need to be identified and used. While abstinence is a laudable theoretic goal of treatment, the reality falls somewhat short of that goal.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed2002

Ageing in plants.

Ageing in green plants differs in some fundamental ways from the process in animals. The seasonal cycle and persistence of a plant is governed by a combination of the determinate or indeterminate status of meristems (growth centres) and the cell death and disposal strategies employed by plants to generate well-adapted anatomies and morphologies. The degree of perenniality depends on the balance between exploratory growth and the wave of tissue death that succeeds it, and extremes of longevity can arise by relatively minor changes in the quantitative relationship between growth and death. The senescence and elimination of organs and tissues are related to the internal reallocation of resources but are programmed phases in the integrated development of the whole plant and do not represent a kind of ageing by stress or starvation. Meristems of long-lived plants accumulate genetic damage but selection mechanisms exist within the organism to control genetic load, and even to exploit somatic mutations that confer adaptive benefits. It is concluded that most plants do not age in the strict gerontological sense and that extremely long-lived forms like trees and clonal creeping perennials are sustained by selection and correction at the level of semi-autonomous cell lineages.

Aging↗

PubMed1998

Lithium and psychosis revisited.

1. Using differential response to medications may help in resolving the central problem of heterogeneity of the psychoses, 2. A distinct subgroup of patients with a lithium responsive, nonaffective psychosis has been shown to have their core psychotic (nonaffective) symptoms respond to lithium alone. 3. The family histories of patients with lithium responsive, nonaffective psychoses suggests that there is less genetic loading for this subgroup of patients. 4. Research on the prodromal adjustment of lithium responsive, nonaffective psychosis patients has not been reported. 5. Lithium responsive patients showed significantly fewer negative symptoms than did those patients with a nonaffective psychosis who did not respond to lithium. 6. Patients with lithium responsive, nonaffective psychoses showed more extreme in vitro lithium ratios in the red blood cells and significantly less of all types of phospholipid methylation. 7. Patients with lithium responsive, nonaffective psychoses showed significantly greater reduction in symptoms during a physostigmine challenge test, but results from apomorphine challenge tests could not be replicated. 8. Aside from differential response to lithium, research on difference in treatment response and outcome for this group has not been reported. 9. Preliminary evidence may suggest that lithium responsive, nonaffective psychosis is a phenocopy of other psychotic disorders that is not associated with ventriculomegaly but is associated with stimulant abuse. 10. Lithium's effects on acetylcholine as well as effects on dopamine and serotonin may explain its efficacy with this subgroup of patients. 11. This review supports the existence of a distinct subgroup of patients with nonaffective psychoses who may have a separate disorder, but further research is necessary. 12. Lithium responsive nonaffective psychosis appears to be a separate, distinct psychotic phenocopy.

Antipsychotic Agents↗

PubMed1997

The meaning of near-neutrality at coding and non-coding regions.

The nature of weak selection differs between coding and non-coding regions. Coding regions contain genetic information, whereas most non-coding regions do not have any information. Genetic information may be regarded as interaction systems, and the NK model of Kauffman was analysed. This model assumes that each amino acid makes a fitness contribution that depends on the amino acid and on K other amino acids among the N that make the protein. Through simulations, it was found that there are numerous nearly-neutral mutations under this model. Therefore, evolution is rapid in small populations, and slow in large populations. The variance of the evolutionary rate is not quite as large as data indicate under the model, and additional factors, such as environmental change or population-size fluctuation, need to be considered. Weak selection at non-coding regions may come from chromosome organization, and may be regional in character, which differs from that at coding regions. The problem of genetic load is thought to disappear in these circumstances.

Gene Frequency↗

PubMed1998

Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders.

One of the major neurobiological alterations in depressive disorders consists in a disturbed regulation of the hypothalamic-pituitary-adrenocortical (HPA) system. This is reflected by a pathological increase in the adrenocorticotropin (ACTH) and cortisol release after pretreatment with 1.5 mg dexamethasone (DEX) the previous night and a challenge with 100 micrograms corticotropin-releasing hormone (CRH) the next day. The changes evoked by this combined DEX-CRH test recede partially with an improvement of the psychopathological symptoms of depressed patients. It is still unclear, however, whether this long-lasting disturbance of the HPA system is due to acquired changes in the acute illness or whether it plays a causal role and could be considered as a trait or vulnerability marker for depression. In a previous study we have examined the HPA function of healthy probands with a high genetic load for affective disorders. We found that this group of high-risk probands (HRPs) showed abnormal DEX-CRH test results with a cortisol release that was between that of a control group and a group of patients with depression. In a follow-up study we now reexamined 14 of the 47 HRPs about 4 years after the index investigation and found surprisingly constant DEX-CRH test results, so that one of the requirements for a vulnerability marker is fulfilled.

Adrenocorticotropic Hormone↗

PubMed1997

Effects of inbreeding on reproductive losses in Kota tribe.

Sanghvi's hypothesis on long term effects of inbreeding was tested in Kotas. Kota is a numerically small tribal population in the Nilgiri district, Tamil Nadu State, India. Consanguineous marriages are common in this tribe. A total of 95 couples were taken for this study and necessary data were collected on a set proforma. Of the 95 couples, 28 (29.5%) were consanguineously related. The inbreeding coefficient for autosomal genes is 0.022 and for sex-linked genes is 0.03. Inbreeding effects on reproductive losses were examined through an exponential regression model. Although the regression coefficient B values are positive, they are insignificant, suggesting no consistent relationship between degree of consanguinity and the reproductive losses. The estimates of genetic load is 1.8 lethal equivalents per gamete and the average B/A ratio is 5. These findings empirically support the Sanghvi's contention.

Ethnicity↗

PubMed1985

Genetic factors in the sex ratio of major depression.

A twofold increase in the prevalence of depression among women has been consistently observed. Several possible explanations, including methodological, endocrine, psychosocial, and genetic factors, have been proposed for the increased rates of depression among women. This paper describes the analysis of data from a family-genetic study of depressed probands to examine whether genetic factors can explain the preponderance of depressed females. Our data indicate that the excess of females with major depression cannot be attributed to increased genetic loading for depression in women. Other factors which may explain increased rates of major depression in women are discussed.

Alcoholism↗

PubMed2005

Saccadic distractibility is elevated in schizophrenia patients, but not in their unaffected relatives.

BACKGROUND: Saccadic distractibility, as measured by the antisaccade task, has attracted attention as a putative endophenotypic marker for schizophrenia. Some studies have suggested that this measure is elevated in the unaffected relatives of schizophrenia patients. However, recent studies have called this into question and the topic remains controversial. METHOD: Saccadic distractibility was measured in 53 patients with DSM-IV schizophrenia, 80 unaffected first-degree relatives and 41 unaffected controls.Results. Schizophrenia patients performed worse than relatives and controls combined (p<0.00001), but relatives did not differ significantly from controls. Performance in multiply affected families was no worse than that in singly affected families. Relatives with a high presumed genetic risk for schizophrenia performed no worse than other relatives. The performance of the patients did not predict that of their relatives. CONCLUSIONS: These results demonstrate that saccadic distractibility is strongly associated with disease status but not with genetic loading for schizophrenia. We conclude that saccadic distractibility is unlikely to be useful as an endophenotypic marker in schizophrenia.

Adult↗

PubMed2006

Mechanisms and evolution of deceptive pollination in orchids.

The orchid family is renowned for its enormous diversity of pollination mechanisms and unusually high occurrence of non-rewarding flowers compared to other plant families. The mechanisms of deception in orchids include generalized food deception, food-deceptive floral mimicry, brood-site imitation, shelter imitation, pseudoantagonism, rendezvous attraction and sexual deception. Generalized food deception is the most common mechanism (reported in 38 genera) followed by sexual deception (18 genera). Floral deception in orchids has been intensively studied since Darwin, but the evolution of non-rewarding flowers still presents a major puzzle for evolutionary biology. The two principal hypotheses as to how deception could increase fitness in plants are (i) reallocation of resources associated with reward production to flowering and seed production, and (ii) higher levels of cross-pollination due to pollinators visiting fewer flowers on non-rewarding plants, resulting in more outcrossed progeny and more efficient pollen export. Biologists have also tried to explain why deception is overrepresented in the orchid family. These explanations include: (i) efficient removal and deposition of pollinaria from orchid flowers in a single pollinator visit, thus obviating the need for rewards to entice multiple visits from pollinators; (ii) efficient transport of orchid pollen, thus requiring less reward-induced pollinator constancy; (iii) low-density populations in many orchids, thus limiting the learning of associations of floral phenotypes and rewards by pollinators; (iv) packaging of pollen in pollinaria with limited carry-over from flower to flower, thus increasing the risks of geitonogamous self-pollination when pollinators visit many flowers on rewarding plants. All of these general and orchid-specific hypotheses are difficult to reconcile with the well-established pattern for rewardlessness to result in low pollinator visitation rates and consequently low levels of fruit production. Arguments that deception evolves because rewards are costly are particularly problematic in that small amounts of nectar are unlikely to have a significant effect on the energy budget of orchids, and because reproduction in orchids is often severely pollen-, rather than resource-limited. Several recent experimental studies have shown that deception promotes cross-pollination, but it remains unknown whether actual outcrossing rates are generally higher in deceptive orchids. Our review of the literature shows that there is currently no evidence that deceptive orchids carry higher levels of genetic load (an indirect measure of outcrossing rate) than their rewarding counterparts. Cross-pollination does, however, result in dramatic increases in seed quality in almost all orchids and has the potential to increase pollen export (by reducing pollen discounting). We suggest that floral deception is particularly beneficial, because of its promotion of outcrossing, when pollinators are abundant, but that when pollinators are consistently rare, selection may favour a nectar reward or a shift to autopollination. Given that nectar-rewardlessness is likely to have been the ancestral condition in orchids and yet is evolutionarily labile, more attention will need to be given to explanations as to why deception constitutes an 'evolutionarily stable strategy'.

Biological Evolution↗

PubMed2001

Differential expression of diacylglycerol kinase iota and L18A mRNAs in the brains of alcohol-preferring AA and alcohol-avoiding ANA rats.

Ethanol preference and behavioral disinhibition in AA (alcohol accepting) animals is a behavioral constellation similar to that seen in human type II alcoholism, for which considerable genetic loading has been shown. In search of novel neural substrates for this phenotype, we compared gene expression in the cerebral cortex of the AA rat with two groups of control animals, the ANA (alcohol non-accepting) line and heterogeneous Wistar animals, by differential display RT-PCR. We identified two transcripts, ribosomal protein L18a mRNA and diacyglycerol kinase iota mRNA, which are differentially expressed between AA and ANA rats. Ribosomal protein L18A mRNA is evenly expressed throughout the brain, but strongly reduced in cortex of AA rats vs controls. Diacylglycerol kinase iota is exclusively found in the brain, and expressed in a distinct regional pattern. Its cortical expression is about 25% higher in AA than ANA rats. Differential display RT-PCR seems to provide a feasible strategy to identify previously unknown genes whose differential expression correlates with behavioral phenotypes related to dependence.

Alcohol Drinking↗

PubMed2001

High levels of diploid male production in a primitively eusocial bee (Hymenoptera: Halictidae).

Under single locus complementary sex determination (sl-CSD), diploid males are produced from fertilized eggs that are homozygous at the sex-determining locus. Diploid males are effectively sterile, and thus their production generates a costly genetic load. Using allozyme electrophoresis, a large number of diploid males were detected in natural populations of the primitively eusocial bee, Halictus poeyi Lepeletier collected in southern and central Florida during May 2000. Estimates for the proportion of diploids that are male ranged from 9.1% to 50%, while the frequency of matched matings ranged from 18.2% to 100%. The effective number of alleles at the sex-determining locus ranged from two to 11, with an average of five alleles. The effective population size of Halictus poeyi was estimated to be 19.6 +/- 2.5 SE. These data are interpreted in the light of the biogeographic history of Florida and the social biology/population dynamics of H. poeyi.

Animals↗

PubMed2003

Antidepressant-induced mania: an overview of current controversies.

OBJECTIVE: The prevalence, characteristics, and possible risk factors associated with antidepressant-induced mania remain poorly described. The present review sought to identify published rates of antidepressant-induced mania and describe risk factors for its emergence. METHODS: A MedLine search was conducted of journals that focused on mania or hypomania associated with recent antidepressant use. Data from published reports were augmented with relevant findings from recent clinical trials presented at scientific conferences. RESULTS: Antidepressant-induced manias have been reported with all major antidepressant classes in a subgroup of about 20-40% of bipolar patients. Lithium may confer better protection against this outcome when compared with other standard mood stabilizers, although switch rates have been reported with comparable frequencies on or off mood stabilizers. Evidence across studies most consistently supports an elevated risk in patients with (i) previous antidepressant-induced manias, (ii) a bipolar family history, and (iii) exposure to multiple antidepressant trials. CONCLUSION: About one-quarter to one-third of bipolar patients may be inherently susceptible to antidepressant-induced manias. Bipolar patients with a strong genetic loading for bipolar illness whose initial illness begins in adolescence or young adulthood may be especially at risk. Further efforts are needed to better identify high-vulnerability subgroups and differentiate illness-specific from medication-specific factors in mood destabilization.

Affect↗

PubMed1990

[Predictors of the course of schizophrenia--a review of the literature].

As the course of schizophrenia shows a large variability, a prognosis of outcome is extremely difficult. The search for valid predictors shows that there exist numerous predictors with variable predictive significance for distinct outcome criteria and also for different phases of the illness. The indications in the literature are accordingly variable or even inconsistent. The following statements seem us to be proved: A good premorbid social adjustment, a harmonious premorbid personality, and an acute onset of the illness predict a better course, whereas an insidious onset and a development of marked negative symptoms correspond to a poorer outcome. A combination of several factors improves the predictive significance. The importance of the following indicators remains questionable: Genetic loading, neuropathological findings, positive symptoms, and age at onset of the illness. Equally open are these questions: How are the various indicators interrelated and for what span of time have they a predictive power? Psychosocial indicators have more predictive significance than the so far known biological variables. Probably the difficulties in finding valid predictors are not only related to unsolved methodological problems, but above all to intrinsic characteristics of the illness itself.

Female↗

PubMedDate not supplied

Parental effects on offspring longevity--evidence from 17th to 19th century reproductive histories.

BACKGROUND: Family studies provide support for a modest genetic influence on offspring life span, although the magnitude of these correlations is small. AIM: The study aimed to clarify the relative contributions of parental age at birth and overall parental longevity on offspring lifespan, and to identify the biological and cultural mechanisms. SUBJECTS AND METHODS: Information was derived from two village genealogies (1650-1927) encompassing 9979 births (5315 males, 4664 females). Data selection was guided by the inclusion of information about parental age at birth and lifespan, offspring lifespan and cohort-specific life expectancy. RESULTS: Parental age at reproduction displayed a negative association with offspring survivability, which was caused by a host of biological as well as environmental factors. In contrast, parental lifespan was positively associated with offspring age at death. These effects differed by parent's and child's sex. CONCLUSION: The maternal age effect on female progeny is thought to be indicative of a preferential genetic load. From an evolutionary point of view, direct selection for maternal lifespan may be an adaptive strategy to enhance child survival prospects.

Cohort Studies↗

PubMed2000

The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia.

While genetic influences in schizophrenia are substantial, the disorder's molecular genetic basis remains elusive. Progress has been hindered by lack of means to detect nonpenetrant carriers of the predisposing genes and by uncertainties concerning the extent of locus heterogeneity. One approach to solving this complexity is to examine the inheritance of pathophysiological processes mediating between genotype and disease phenotype. Here we evaluate whether deficits in neurocognitive functioning covary with degree of genetic relationship with a proband in the unaffected MZ and DZ co-twins of patients with schizophrenia. Twin pairs discordant for schizophrenia were recruited from a total population cohort and were compared with a demographically balanced sample of control twin pairs, on a comprehensive neuropsychological test battery. The following four neuropsychological functions contributed uniquely to the discrimination of degree of genetic loading for schizophrenia and, when combined, were more highly correlated within MZ pairs than within DZ pairs, in both discordant and control twins: spatial working memory (i.e., remembering a sequence of spatial locations over a brief delay), divided attention (i.e., simultaneous performance of a counting and visual-search task), intrusions during recall of a word list (i.e., "remembering" nonlist items), and choice reaction time to visual targets. Together with evidence from human and animal studies of mediation of these functions by partially distinct brain systems, our findings suggest that there are multiple independently inherited dimensions of neural deficit in schizophrenia and encourage a search for genes contributing to quantitative variation in discrete aspects of disease liability. On tests of verbal and visual episodic memory, but not on the liability-related measures, patients were more impaired than their own MZ co-twins, suggesting a preferential impact of nongenetic influences on long-term memory systems.

Adult↗

PubMed2000

Investigations into the Genetic Variation, Population Structure, and Breeding Systems of the Fern Asplenium trichomanes subsp. quadrivalens.

The genetic structure of five populations of the tetraploid fern Asplenium trichomanes subsp. quadrivalens in northern Switzerland was analyzed. Asplenium trichomanes subsp. quadrivalens is one of the most common and most widespread ferns in Europe. In this study we have combined genetic investigations, spatial autocorrelation, and breeding experiments to investigate in detail five populations from natural rock faces. Enzyme electrophoresis revealed very low genetic variability within and among the populations. The small amount of variation was partitioned mainly among the localities, indicated by high Fst values up to 0.764. Overall means of the proportion of polymorphic loci (P=0.076), the mean number of alleles per locus (A=1.086), and the mean expected heterozygosity (H=0.018) were low compared with other ferns (e.g., Kirkpatrick et al. 1990). Very few heterozygous individuals were found. Values of the fixation index (F) were high, ranging between 0.732 and 1.000 and indicating substantial inbreeding. Spatial autocorrelation showed different patterns of substructure in populations of A. trichomanes subsp. quadrivalens with a tendency for patches in short distances (up to 1.5 m). The breeding experiments with isolated prothalli and prothalli pairs showed that a mean of 56.4% of the isolated prothalli were successful in sporophyte formation. The highest rate in one population was 83.3%. We conclude that genetic load must be low in A. trichomanes subsp. quadrivalens. Sporophyte formation was statistically more successful in the experiments with gametophyte pairs than in isolates, indicating that additional cross-fertilization occurred. The latter agreed with the occurrence of few heterozygote samples and the small number of multilocus phenotypes found in natural habitats. Asplenium trichomanes subsp. quadrivalens is shown to be a highly inbreeding taxon with the capability of single spore colonization and subsequent founding of new populations. Such features can be hypothesized to have contributed to the postglacial colonization and the widespread distribution of this taxon in Europe.

Journal Article↗

PubMed2004

Familial clustering of classic Kaposi sarcoma.

It is widely accepted that there is a causal association between Kaposi sarcoma-associated herpesvirus (KSHV) and Kaposi sarcoma (KS). However, the majority of individuals infected with KSHV never develop KS. Here, we present a unique familial case of classic KS, in which the disease occurs in 4 siblings who have no recognized underlying immunodeficiency. We examine risk factors that could play a role in this condition, including KSHV infection, KSHV DNA load, genetic variants of KSHV, infection with additional viruses, interleukin-6-promoter polymorphism, and HLA genotype. We hypothesize that a genetic susceptibility to KS, in combination with KSHV infection, may play an important role in the presented familial case.

Adult↗