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PubMed2004

Levels of inbreeding depression over seven generations of selfing in the androdioecious clam shrimp, Eulimnadia texana.

Androdioecy (mixtures of males and hermaphrodites) is a rare mating system in both plants and animals. Theory suggests that high levels of inbreeding depression can maintain males in androdioecious populations if hermaphrodites commonly self-fertilize. However, if inbreeding depression (delta) can be 'purged' from selfing populations, maintaining males is more difficult. In the androdioecious clam shrimp, Eulimnadia texana, delta is estimated to be as high as 0.7. Previous work suggests that this high level is maintained in the face of high levels of inbreeding due to an associative overdominance of fitness-related loci with the sex-determining locus. Such associative overdominance would make purging of inbreeding depression difficult to impossible. The current experiment was designed to determine if delta can be purged in these shrimp by tracking fitness across seven generations in selfing and outcrossing treatments. Evidence of purging was found in one of four populations, but the remaining populations demonstrated a consistent pattern of delta across generations. Although the experimental design allowed ample opportunity for purging, the majority of populations were unable to purge their genetic load. Therefore, delta in this species is likely due to associative overdominance caused by deleterious recessive alleles linked to the sex determining locus.

Analysis of Variance↗

PubMed2002

[Genetic analysis on diversity of reproductive modes of silver crucian carp inferred by transferrin and isozyme markers].

Silver crucian carp (Carassius auratus gibelio) has been known for its gynogenetic reproduction. In this paper, eggs from clone F of gynogenetic silver crucian carp were inseminated respectively by sperms of clone D, clone A and common carp, and polymorphic patterns of transferrin and isozymes of the produced three offspring FD, FA and FL were studied comparatively to explore the diversity in reproductive modes of silver crucian carp. As control, zymograms of FL progenies exhibited a maternally clonal inheritance, and gynogenesis was reconfirmed. However, differentiation of morphs and electrophoretic patterns was both observed among the FD progenies, and detection of bands specific for the clone F or clone D in some FD individuals urged the occurrence of recombination. Furthermore, extreme linkage disequilibrium for different protein loci suggested that linkage groups composed of different genes might function as the fundamental unit in the recombination. With respect to FA group, phenotypes of parental clones were both detected in the F2 generation (FA x FA progenies) while only maternal phenotypes were detected in the F1 generation. It appeared that both the parental chromosome sets could be transmitted to the offspring but expression of paternal genes were fundamentally upset in the F1 generation because of incompatibility of the parental genes. Generally, genetic analysis of FD and FA offspring primarily exhibited a particular syngamy for silver crucian carp. Besides the clonal reproduction of gynogenesis, syngamy could provide opportunities of recombination for silver crucian carp, which might remove some genetic loads from the genome and introduce new genotypes. Diversity in reproductive modes might play an important role in ecological adaptation of silver crucian carp.

Animals↗

PubMed2004

Mutation and epimutation load in haploid and diploid life forms.

Epigenetic differentiation is the potentially heritable changes in levels of gene expression not caused by DNA sequence changes. Here, a classification scheme of mutations and epimutations is introduced, enabling a simple analysis of mutation and epimutation load in haploid and diploid organisms. It is found that the deleterious effect of epimutations is mainly determined by epimutation rate and degree of reversibility. Inherited epimutations have the same fitness consequences as inherited mutations. With complete reversibility and no inheritance, then epimutations have the same fitness consequences as somatic mutations. It is argued that organisms with somatic inheritance may experience more genetic load than organisms without somatic inheritance due to inherited epimutations in the former. This may partly explain the maintenance of soma/germ differentiation in many life forms. It is also argued that masking of deleterious somatic mutations may not necessarily explain the evolution of diploidy in life forms with inherited epimutations.

Animals↗

PubMed1988

Time for acquiring a new gene by duplication.

In view of the widespread occurrence of gene families in eukaryotic genomes that suggests the importance of gene duplication in evolution, a population genetic model incorporating unequal crossing-over was formulated. By using this model, the time needed for acquiring a new gene is investigated by an approximate analytical method and by computer simulations. The model assumes that natural selection favors those chromosomes with more beneficial genes than other chromosomes in the population, as well as random genetic drift, mutation, and unequal crossing-over. Starting from a single gene copy, it is found that the time for acquiring another gene with a new function is dependent on the rates of occurrence of unequal crossing-over and mutation. Within a realistic range of parameter values, the required time was at least several times 4N generations, where N is the effective population size. Interchromosomal unequal crossing-over at meiosis is more effective than intrachromosomal (between sister chromatids) unequal crossing-over for obtaining a new gene, provided that other parameters are the same. However, the genetic load for acquiring a gene is larger under the model of interchromosomal crossing-over. The relevance of this finding to the advantage of sexual reproduction is discussed.

Alleles↗

PubMed2001

Examining the comorbidity of ADHD-related behaviours and conduct problems using a twin study design.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD) frequently co-occur, the underlying mechanisms for this comorbidity are not well understood. AIMS: To examine whether ADHD and conduct problems share common risk factors and whether ADHD+CD is a more heritable variant of ADHD. METHOD: Questionnaires were sent to 2846 families. Parent-rated data were obtained for 2082 twin pairs and analysed using bivariate genetic analysis and a liability threshold model approach. RESULTS: The overlap of ADHD and conduct problems was explained by common genetic and non-shared environmental factors influencing both categories. Nevertheless, the two categories appeared to be partly distinct in that additional environmental factors influenced conduct problems. It appeared that ADHD+CD was a genetically more severe variant of ADHD. CONCLUSIONS: Conduct problems and ADHD share a common genetic aetiology; ADHD+CD appears to be a more severe subtype in terms of genetic loading as well as clinical severity.

Adolescent↗

PubMed2003

Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents.

Selection against deleterious mutations imposes a mutation load on populations because individuals die or fail to reproduce. In vertebrates, estimates of genomic rates of deleterious mutations in protein-coding genes imply the existence of a substantial mutation load, but many functionally important regions of the genome are thought to reside in noncoding DNA, and the contribution of noncoding DNA to the mutation load has been unresolved. Here, we infer the frequency of deleterious mutations in noncoding DNA of rodents by comparing rates of substitution at noncoding nucleotides with rates of substitution at the fastest evolving intronic sites of adjacent genes sampled from the whole genome sequences of mouse and rat. We show that the major elements of selectively constrained noncoding DNA are within 2,500 bp upstream and downstream of coding sequences and in first introns. Our estimate of the genomic deleterious point mutation rate for noncoding DNA (0.22 per diploid per generation) is similar to that for coding DNA. Mammalian populations therefore experience a substantial genetic load associated with selection against deleterious mutations in noncoding DNA. Deleterious mutations in noncoding DNA have predominantly quantitative effects and could be an important source of the burden of complex genetic disease variation in human populations.

Animals↗

PubMed1994

Role of genetic factors in human sexual behavior based on studies of Tourette syndrome and ADHD probands and their relatives.

Most significant variations in the expression of human sexuality are considered to be the result of learned behavior or psychological problems. Tourette syndrome (TS) is a common, hereditary tic and disinhibition disorder sometimes associated with compulsive use of obscene words (coprolalia) and previously reported to be occasionally associated with exhibitionism. To further explore the relationship between the Gts genes and sexual behavior, questions concerning a wide range of such behaviors were administered to 1,040 subjects, 14 years of age or older, consisting of 358 TS probands, 101 non-proband relatives with TS, 359 non-TS first degree relatives, 79 attention deficit hyperactivity disorder (ADHD) probands, 70 unaffected relatives of the ADHD probands, and 73 controls. The behaviors included magnitude of sex drive, sex orientation, exhibitionism, transvestitism, transsexualism, sadism, masochism, pedophilia, fetishism, aversion to being touched, and aversion to sex. While most of these behaviors occurred in a distinct minority of TS subjects, there was a significant positive correlation between each behavior examined and the degree of genetic loading for the Gts gene(s). The nature of these behaviors and their association with TS suggests many are variants of obsessive-compulsive disorder. Studies in animals indicate that changes in serotonin and dopamine play a significant role in the sexual behavior and many lines of evidence are consistent with the hypothesis that TS is due to genetic changes in serotonin and dopamine metabolism. These studies suggest that genetic factors play a much greater role in a wide range of forms of sexual expression than previously thought.

Adolescent↗

PubMed1981

[Genetics of diabetes mellitus].

Diabetes is genetically heterogeneous. The subdivision of idiopathic diabetes should better be performed according to the necessity of treatment (dependence on insulin) than according to the age in the primary manifestation. Up to now only few genetic entities are clinically defined, and a coordination to certain types is often difficult in the individual case. Altogether the genetic load is clearly smaller in the insulin-dependent diabetes. The risk for children of insulin-dependent diabetics is only about 1-2%. Since the risk of disease for children of young non-insulin-dependent diabetics is about 50%, a clear clinical diagnostics of the mothers within the consultation is important. However, there are no reliable genetic markers for an exact subdivision into types in the individual case. The association of certain HLA-types with insulin-dependent diabetes is theoretically of great interest and refers to the participation of autoimmunological phenomena in the development of this type of diabetes. However, the estimation of HLA is not helpful for the consideration of individual cases, also within a genetic consultation. the existing heterogenias within the non-insulin-dependent diabetes are not yet sufficiently clarified. This type is altogether much more genetically determined, particularly when it appears in younger age and when it is not associated with adiposity.

Adolescent↗

PubMed2003

Maintenance of aphid clonal lineages: images of immortality?

Artificial cloning and ancient asexuals have impacted upon both scientific and lay thinking in applied and theoretical fields as diverse as medicine and evolution. Hence, this is an opportune time to promote debate and discussion on what maintains a clonal lineage. The genetic fidelity of a clone has been discussed in detail elsewhere [Genet. Res. 79 (2002) 1; Biol. J. Linnean Soc. 79 (2003) 3]. In this paper, we focus on the lineage integrity (=longevity), or physiological lifespan of a clone with respect to senesce in relation to factors controlling telomere functioning. Aspects of cell line research pertinent to eukaryotic clonal lineages are discussed and, in particular, we try to extrapolate aspects of this research and apply it to apomictic (=mitotic) aphid lineages to suggest how they may be maintained. Analogies are made between single cells and individual aphids that senescence through a generation, whilst the respective lineages persist for finite periods, unless that is, compensatory mechanisms have evolved allowing immortality in the one and ancient asexuality in the other. Such comparison may allow fresh insights into the mechanisms of clonal lineage maintenance and evolution. We hypothesise that: (1). the cause of extinction in eukaryotic clonal lineages is due to deleterious effects on key regions of the genome, the chromosomal telomere being one such site; (2). recombination acts as a common mechanism to reset telomere functioning, perhaps more fundamental than its utility to reduce genetic load and maintain adaptability; and (3). ancient lineages persist through time as a function of group-specific compensatory mechanisms that maintain telomere integrity.

Aging↗

PubMed1976

Comparative field cage tests of the population suppressing efficiency of three genetic control systems for Aedes Aegypti.

Cycling populations of Aedes aegypti were set up in cages and managed in such a way that the populations had a maximum of threefold recovery potential in response to control measures. Into three such populations daily releases were made of males which had been chemosterilised, or were double translocation heterozygotes (T1T3) or T1T3 with sex ration distortion (DT1T3). Eradication of the populations was achieved with all cases, but the rate of suppression was markedly slower with T1T3 than the other two systems, with which the rates were similar. T1T3 and DT1T3 releases introduced considerable inherited genetic loads into the target populations. The results were in general agreement with computer predictions.

Aedes↗

PubMed2026

Population history rather than tree age contributes to the evolutionary importance of ancient trees in an endangered conifer.

Ancient trees are in global decline and face increasing conservation challenges. Their exceptional longevity has fostered the view that they are genetic reservoirs, yet whether old age is synonymous with unique genetic variation remains unclear. Here we assembled a ~8-Gb chromosome-level reference genome for the critically endangered conifer Glyptostrobus pensilis, now largely restricted to southern China with scattered populations in Vietnam and Laos, and resequenced 147 individuals, including 64 ancient (>100 years old and persisting in human-dominated landscapes), 33 wild and 50 recently cultivated individuals. Ancient individuals comprised both likely natural relics and historically introduced individuals and formed two deeply divergent lineages and one ancestral-admixed group, each with distinct demographic histories of prolonged contraction and genomic erosion. Lineage identity explained more variation in genome-wide diversity, inbreeding and genetic load than the three conservation types, despite broad differences in age structure. Rare-allele analyses revealed pronounced heterogeneity among ancient trees: only relic and ancestral-origin individuals from high-diversity lineages contributed substantial unique variation, much of which is poorly represented in wild and cultivated populations. Together, our findings suggest that ancient trees are not uniformly genetically irreplaceable and that, at least in this conifer, evolutionary importance is shaped more strongly by population history than by age alone.

Endangered Species↗

PubMed2003

Site-specific selfish genes as tools for the control and genetic engineering of natural populations.

Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.

Animals↗

PubMed1984

Familial incidence of congenital anorectal anomalies.

We describe two families with pedigrees over three and two generations with nine members affected with anorectal malformations. Both pedigrees are compatible with autosomal dominant inheritance with variable penetrance and expression or with multifactorial inheritance with a high genetic load. The recurrence risk is thought to be in the range of 10% to 20% for first degree relatives of affected members.

Adolescent↗

PubMed1987

Simulating evolution by gene duplication.

By considering the recent finding that unequal crossing over and other molecular interactions are contributing to the evolution of multigene families, a model of the origin of repetitive genes was studied by Monte Carlo simulations. Starting from a single gene copy, how genetic systems evolve was examined under unequal crossing over, random drift and natural selection. Both beneficial and deteriorating mutations were incorporated, and the latter were assumed to occur ten times more frequently than the former. Positive natural selection favors those chromosomes with more beneficial mutations in redundant copies than others in the population, but accumulation of deteriorating mutations (pseudogenes) have no effect on fitness so long as there remains a functional gene. The results imply the following: Positive natural selection is needed in order to acquire gene families with new functions. Without it, too many pseudogenes accumulate before attaining a functional gene family. There is a large fluctuation in the outcome even if parameters are the same. When unequal crossing over occurs more frequently, the system evolves more rapidly. It was also shown, under realistic values of parameters, that the genetic load for acquiring a new gene is not as large as J.B.S. Haldane suggested, but not so small as in a model in which a system for selection started from already redundant genes.

Alleles↗

PubMed1981

The genetics and biochemistry of paranoid schizophrenia and other paranoid psychoses.

Genetic and biochemical findings in paranoid schizophrenia and other paranoid psychoses are reviewed. Although the data suggesting a lower genetic loading for schizophrenia in paranoid versus nonparanoid schizophrenia are unclear, paranoid schizophrenia does, to a limited extent, breed true within families. Monozygotic twins concordant for schizophrenia tend to be either both paranoid or both nonparanoid schizophrenics. In all studies, the risk for schizophrenia in the relatives of patients with paranoid psychosis is close to that found in the normal population. Genetic studies provide no evidence for a link between affective illness and either paranoid schizophrenia or paranoid psychosis. Although reports of low platelet monoamine oxidase activity in paranoid schizophrenia have not been confirmed, recent results suggest that brain norepinephrine levels may be higher in paranoid than in nonparanoid schizophrenics. Genetic and biochemical findings suggest some differences between paranoid and nonparanoid schizophrenia, but definitive clarification of the relationship between these two syndromes must await future research. From a genetic perspective, paranoid psychosis appears to bear little relationship to schizophrenia.

Adolescent↗

PubMed2006

Enhanced acquisition of cocaine self-administration by increasing percentages of C57BL/6J genes in mice with a nonpreferring outbred background.

RATIONALE: Individual differences in the propensity to acquire drug self-administration may have a substantial genetic basis. OBJECTIVES: To study the genetic contribution to cocaine self-administration by comparing hybrids of cocaine preferring (C57BL/6J) and nonpreferring (ICR) mice. METHODS: ICR and C57BL/6J parental strains were compared to hybrids with 75% ICR:25% C57BL/6J, 50% ICR:50% C57BL/6J, and 25% ICR:75% C57BL/6J genetic backgrounds for acquisition of sucrose pellet and intravenous cocaine self-administration in 1-h test sessions. Mice that acquired cocaine self-administration were subsequently tested in a between-session self-administration dose-response procedure. RESULTS: Increasing presence of C57BL/6J genes increased the percentage of mice that acquired sucrose pellet self-administration in the first test session. In lever-trained mice, only 19% of ICR mice met acquisition criteria for cocaine self-administration after 15 sessions, whereas 76% of C57BL/6J mice met acquisition criteria, although both strains initially sampled a similar number of cocaine injections. Increasing the percentage of C57BL/6J genes in the nonpreferring ICR background to 50 and 75% led to increasing percentages of mice that met acquisition criteria to 31 and 52%, respectively. In mice that acquired self-administration, only mice with 75% C57BL/6J genes showed a typical inverted U-shaped self-administration dose-response curve, whereas the curve was flat across doses for mice with < or = 50 and 100% C57BL/6J genes. CONCLUSIONS: The findings are consistent with a genetically based dose-dependent enhancement of cocaine reinforcement by C57BL/6J genes. These results suggest that heritable traits impart a substantial genetic load that facilitates the propensity for cocaine addiction among individuals in outbred populations.

Animals↗

PubMed2000

Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey.

Previous studies examining an association with other autoimmune diseases have suggested the existence of a generalized autoimmune diathesis in patients with multiple sclerosis. We investigated the prevalence of autoimmune disease in first-degree relatives of probands with multiple sclerosis using a case-control method. The results show an excess of autoimmune disease within these families, but no significant association was seen with non-autoimmune diseases. The higher risk in multiplex than simplex families suggests an effect of genetic loading. While the increase in risk applies to each autoimmune disease, autoimmune thyroid disease (and Graves' disease in particular) contributes disproportionately to the excess risk. There was no increase in autoimmune disease within patients with multiple sclerosis themselves when compared with the index controls or population data. We conclude that autoimmune disease is more common in first-degree relatives of patients with multiple sclerosis and hypothesize that common genetic susceptibility factors for autoimmunity co-exist with additional disease specific genetic or environmental factors, which determine clinical phenotype in the individual.

Adolescent↗

PubMed2000

The genetic heterogeneity of "schizophrenia".

The main reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conformity. This has not changed markedly following the introduction of modern operational diagnostic systems. Taking schizophrenia as a disease entity or assuming schizophrenia spectrum psychoses to represent a continuum of diseases without any clear dividing lines, the results of family and twin studies point to a multifactorial etiology based on a polygenic mode of transmission. Further, then it has to be assumed a familial continuum from schizophrenia to affective psychosis and other spectrum disorders. However, in family and twin studies based on Leonhard's classification, there is clearcut evidence that schizophrenic spectrum psychoses have to be divided into clinical and etiological subgroups with a completely different genetic background. For example, systematic catatonia is, for the most part, a sporadic disease, whereas periodic catatonia aggregates in families in a manner consistent with a major gene effect. Further, the results indicate that schizophrenic spectrum psychoses consist of three main valid categories: cycloid psychoses, unsystematic schizophrenias and systematic schizophrenias. In the case of cycloid psychosis and systematic schizophrenias, genetic loading seem to be very low, while "environmental" factors, for example, birth complications, may play an important etiological role. Unsystematic schizophrenias, however, are predominantly inherited and "environmental" factors are not very prominent.

Adult↗