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A general frame of theory on genetic load.

Genetic load expresses the loss in mean fitness of a population because of the genetic variability present. The quantitative discussion of various genetic loads is provided with important meaning for research into evolution of species on realistic level. The past theory on genetic load starts off with equilibrium of population to investigate the evolution of species on realistic level. However, the evolution is a displacement on equilibrium of population. This is just made up of a contradiction between theory and praxis. We branch out the past theory on genetic load, and give out a general theoretic frame describing the various genetic loads. By the use of this theoretic frame the genetic loads in an equilibrium population can be represented, and the genetic loads in a non-equilibrium population and their change can also be simulated. Thus this theoretic frame overcomes the shortcoming of past theory on genetic loads, which can't describe non-equilibrium population and conflicts with praxis of biological evolution sometimes, and offers a sort of credible simulation methods for research into evolution of species.

Genetic Load↗

[Genetic load of hereditary diseases in populations of the Krasnodar Krai].

Medico-genetical study of populations living in Krasnodar district was carried out. The mean value of genetic load contributed by autosomal dominant diseases composed 0.92 +/- 0.06, this value being 0.56 +/- 0.04 for autosomal recessive and 0.36 +/- 0.05 for X-linked recessive disorders per one thousand. Comparative analysis of genetical load in urban and rural populations demonstrated that they had no differences in relation to genetical load contributed by autosomal recessive and X-linked recessive disorders. At the same time, significant differences were noted between the populations concerning genetic load contributed by autosomal-dominant disorders.

Genes, Dominant↗

Variability of genetic load with changing socio-cultural environment.

Variability in genetic load has been studied against their contrasting socioeconomic and cultural backgrounds in two endogamous populations, namely, the well-off Brahmins and the low income Jalaris of Visakhapatnam, India. The A (genetic and environmental damage) and B (hidden genetic damage) estimates are higher in Jalaris. Decreased A estimates indicate the better medical care in Brahmins; the value of B could be low since many of the deaths in consanguineous families due to infectious diseases are now rarer. The genetic load (B/A ratio) indicates that the average gamete carries 0.057 and 2.123 deleterious genes, respectively, in Brahmins and Jalaris, which, if made homozygous, would kill an individual before reproductive age. The load is 35 times higher in Jalaris; this may be due to their higher inbreeding level. Contrasting socioeconomic differences and meagre medical aid might add another bias towards relatively higher B/A in Jalaris. In general the observed genetic load in both populations are lower than in other studies which may be due to gradual elimination of deleterious genes by continued practice of inbreeding.

Consanguinity↗

The Effects of a Bottleneck on Inbreeding Depression and the Genetic Load.

We study the effects of a population bottleneck on the inbreeding depression and genetic load caused by deleterious mutations in an outcrossing population. The calculations assume that loci have multiplicative fitness effects and that linkage disequilibrium is negligible. Inbreeding depression decreases immediately after a sudden reduction of population size, but the drop is at most only several percentage points, even for severe bottlenecks. Highly recessive mutations experience a purging process that causes inbreeding depression to decline for a number of additional generations. On the basis of available parameter estimates, the absolute fall in inbreeding depression may often be only a few percentage points for bottlenecks of 10 or more individuals. With a very high lethal mutation rate and a very slow population growth, however, the decline may be on the order of 25%. We examine when purging might favor a switch from outbreeding to selfing and find it occurs only under very limited conditions unless population growth is very slow. In contrast to inbreeding depression, a bottleneck causes an immediate increase in the genetic load. Purging causes the load to decline and then overshoot its equilibrium value. The changes are typically modest: the absolute increase in the total genetic load will be at most a few percentage points for bottlenecks of size 10 or more unless the lethal mutation rate is very high and the population growth rate very slow.

bottlenecks↗

Genetic variation and genetic load due to the male reproductive component of fitness in Drosophila.

The genetic variation and genetic load due to virility, the male reproductive component of fitness, was measured in Drosophila melanogaster and D. pseudoobscura using males homozygous and heterozygous for the second chromosome of each species. Virility was determined in a female-choice, male mating competition experiment where both mating propensity and fertility were taken into account.--The mean virility of the homozygous D. melanogaster males relative to the heterozygous males was 0.50; the relative mean virility of the quasinormal homozygotes was 0.56. The mean virility of the homozygous D. pseudoobscura males relative to the heterozygous males was 0.70; the relative mean virility of the nonsterile homozygotes was 0.72, and of the quasinormal homozygotes, 0.68.--Depending on the species and chromosome sampled, fertile homozygous males had a mean virility 15 to 50% lower than the mean viability of individuals homozygous for a chromosome with quasinormal viability. The genetic load due to virility was also greater than that due to the female reproductive component. This higher level of hidden genetic variation (or genetic load) indicates that the results of Prout (1971a, b) and Bundgaard and Christian (1972), where the virility component of fitness dominated the dynamics of an artificial polymorphism, may be more general and that virility may dominate the dynamics of natural polymorphisms as well.

Animals↗

Effects of a change in the level of inbreeding on the genetic load.

"The effects of inbreeding may not be as noticeable in the first generation as the invigoration immediately apparent after crossing". This statement, published in 1919, has received little attention, and has apparently never been tested empirically, although the reduction of the genetic load of populations by inbreeding is well known in theoretical terms. Because inbreeding increases homozygosity, and hence the effectiveness of selection against recessive or partially recessive detrimental alleles, changes in levels of inbreeding can lead to a reduction in the frequencies of such mutant alleles. This results in equilibration at higher population mean fitness and is referred to as 'purging' populations of their genetic load. Severe inbreeding can also reduce genetic load due to overdominant alleles, provided selection coefficients are not symmetrical at all loci, because alleles giving lower fitness will be reduced in frequency at equilibrium. With either fitness model, however, reduction in genetic load takes time, and the initial effect of an increase in inbreeding is reduced fitness due to homozygosity. There are few data relating to the extent to which fitness is reduced during inbreeding in a set of lines and to how long the reduction lasts before increasing again to the initial level, or higher. Inbreeding experiments involving sib mating in mice and Drosophila subobscura, and successive bottlenecks in house flies have yielded some evidence consistent with the purging hypothesis. Here, we report results of an experiment demonstrating a prolonged time-course of recovery of mean fitness under self-fertilization of a naturally outcrossing plant, and also compare our results with expectations derived by computer calculations. Our results show that the genetic load present in an outcrossing population can be explained only with a high mutation rate to partially recessive deleterious alleles, and that inbreeding purges the population of mutant alleles.

Animals↗

Population size and the nature of genetic load in Gentianella germanica.

Theory predicts a significant relationship between the size of a population and the magnitude and composition of its genetic load, but few natural populations have been investigated. We examined the magnitude of genetic load due to recessive deleterious alleles (GL) both segregating and fixed within Gentianella germanica populations of varying size by selfing and reciprocally crossing plants within and between natural populations according to a partial diallel design and by comparing the performance of the experimental progeny in a common-garden experiment. The results show that GL for total fitness in small populations (fewer than 200 plants) was mainly due to fixed recessive deleterious alleles, whereas GL for total fitness in larger populations (more than 200 plants) appeared to be mainly due to segregating deleterious recessive alleles. The total fitness of selfed plants increased with decreasing population size, indicating some purging of deleterious alleles associated with declining population sizes. The magnitudes of GL due to fixed deleterious alleles in small populations and segregating deleterious alleles in large populations, however, were overall similar, suggesting that purging selection was an insignificant force when compared to genetic drift in determining the magnitude of GL in small natural populations in this species. The results of this study highlight the importance of population size in determining the dynamics of genetic loads of natural populations and are overall in line with a large body of theoretical work indicating that small populations may face higher extinction risks due to the fixation and accumulation of deleterious alleles of small effect.

Alleles↗

Genetic loading in familial migraine with aura.

Migraine with aura (MA) arises from a combination of genetic and environmental factors. The sibling risk, age at onset, and aura type were compared in 54 MA probands categorised by family history of MA. Three family types were ascertained each having an MA proband and: (1) an MA parent and MA offspring (three generation; n=15), (2) either an MA parent or an MA offspring (two generation; n=20), and (3) neither an MA parent nor an MA offspring (one generation; n=19). The crude recurrence risk to siblings of probands was 2.7-fold higher in three generation compared with two generation MA families (chi(2)=6.24, p=0.0125) and 4.8-fold higher in three generation compared with one generation MA families (chi(2)=9.95, p<0.002). The mean age at onset decreased with an increase in genetic load. The MA probands from three generation families were significantly younger than probands from the one generation families (F=5.14, p=0.030). MA probands from three generation families were more likely to report more than one type of aura than MA probands from two generation families (chi(2)=4.44, p=0.035). The significant difference in genetic loading and the earlier age at onset in the three generation families add further evidence for a genetic basis for MA and the difference in sibling risks demonstrates that the MA population is heterogeneous.

Adult↗

Inbreeding depression and genetic load in laboratory metapopulations of the butterfly Bicyclus anynana.

We investigated the effects of inbreeding on various fitness components and their genetic load in laboratory metapopulations of the butterfly Bicyclus anynana. Six metapopulations each consisted of four subpopulations with breeding population sizes of N = 6 or N = 12 and migration rate of m = 0 or m = 0.33. Metapopulations were maintained for seven generations during which coancestries and pedigrees were established. Individual inbreeding coefficients at the F7 were calculated and ranged between 0.01 and 0.51. Even though considerable purging had occurred during inbreeding, the genetic load remained higher than that of many outbreeding species: approximately two lethal equivalents were detected for egg sterility, one for zygote survival, one for juvenile survival, and one for longevity. Severe inbreeding depression occurred after seven generations of inbreeding, which jeopardized the metapopulation survival. This finding suggests that the purging of genetic load by intentional inbreeding cannot be recommended for the genetic conservation of species with a high number of lethal equivalents.

Animals↗

Genetic load and coadaptation of chromosomal inversions. II. O-chromosomes in Drosophila subobscura populations.

We have analysed the inversion polymorphism and genetic load of O-chromosomes in three populations of D. subobscura from southeastern Europe. As expected for a central populations the inversion polymorphism was extensive. In a like fashion, the genetic load, in particular the frequency of lethals, was heavy in all three populations. There were significant differences in the frequency of moderately deleterious genes. These differences in viability can be attributed to balancing selection. A comparison of these two kinds of genetic polymorphism indicates that there are differences in mean viability among different gene arrangements of O-chromosomes in the three populations. The differences observed are due to an unequal distribution of various viability classes among O-chromosome gene arrangements. We here show for the first time a specific distribution of lethal genes among these arrangements within the Palearctic distribution area of D. subobscura. The lethal allelism test showed lethals are non-randomly associated with the Ost gene arrangement. The amount of genetic load is heavy in gene arrangements with a high frequency, in comparison with the ones with a low frequency. Lethal genes may be protected in combinations of low and moderate frequency gene arrangements that harbor more lethal genes, as the Ost in the one population. Some arrangements that are less protected against recombination have a higher load than ones that are more protected against recombination. This can be taken as evidence for coadaptation.

Animals↗

Human genetic studies in areas of high natural radiation. VIII. Genetic load not related to radiation.

The genetic load disclosed by inbreeding has been analyzed in a multiple regression model for a population involving several localities in the state of Espírito Santo, Brazil. The inbreeding load has been estimated for number of pregnancies, abortions, stillbirths, children born alive, anomalies in general, sex ratio, infant mortality, post-infant mortality, and sterility and infertility of the couple. There was no evidence of either maternal or paternal inbreeding effects on the variables analyzed. The effect of inbreeding of the zygote was significant only for anomalies in general (B = 2.29 +/- 0.45) and infant mortality (B = 3.19 +/- 1.39). The latter result must be accepted with caution because of the many environmental causes affecting infant mortality. The B/A ratio suggested a predominantly mutational load for anomalies in general (B/A = 25), but with respect to infant mortality (B/A = 6), the ratio is regarded as an underestimate because of the environmental contribution to A and therefore not supportive of the segregational interpretation.

Abnormalities, Radiation-Induced↗

The Wilhelmine E. Key 1986 invitational lecture. Fifty years of genetic load.

The author's involvement with and his successive reactions to the genetic load concept [whose beginning is identified with Haldane's paper. The effect of variation on fitness] is presented in the form of a personal odyssey. The major change in attitude involved the realization that the density- and frequency-independent selection discussed by most population geneticists has little bearing on events transpiring within natural populations; instead, natural selection should be viewed primarily as a density- and frequency-dependent phenomenon. Under this view, the culling of a large number of young zygotes to the considerably smaller number of adults that can be sustained by the environment is an essential process enabling any population's continued existence; to the extent that genetic variation facilitates culling, a genetic load (in direct opposition to the early view) can enhance a population's persistence through time.

Animals↗

Population on the verge of a mutational meltdown? Fitness costs of genetic load for an amphibian in the wild.

The fitness costs of high genetic load in wild populations have rarely been assessed under natural conditions. Such costs are expected to be greatest in small, bottlenecked populations, including those occurring near range edges. Britain is at the northwesterly range limit of the natterjack toad Bufo calamita. We compared fitness attributes in two populations of this amphibian with very different recent histories. Key larval fitness attributes in B. calamita, notably growth rate and metamorph production, were substantially higher in the large outbreeding population (Ainsdale) than in the small and isolated one (Saltfleetby). These differences were manifest under seminatural conditions, when larvae were reared in mesh cages within breeding ponds at the site of the small population, and were exacerbated by high stress treatments. The results indicate that genetic load effects can be sufficiently severe enough to predispose extinction over relatively short time frames, as predicted by extinction vortex models.

Animals↗

Perspective: purging the genetic load: a review of the experimental evidence.

Inbreeding depression, the reduction in fitness that accompanies inbreeding, is one of the most important topics of research in evolutionary and conservation genetics. In the recent literature, much attention has been paid to the possibility of purging the genetic load. If inbreeding depression is due to deleterious alleles, whose effect on fitness are negative when in a homozygous state, then successive generations of inbreeding may result in a rebound in fitness due to the selective decrease in frequency of deleterious alleles. Here we examine the experimental evidence for purging of the genetic load by collating empirical tests of rebounds in fitness-related traits with inbreeding in animals and plants. We gathered data from 28 studies including five mammal, three insect, one mollusc, and 13 plant species. We tested for purging by examining three measures of fitness-component variation with serial generations of inbreeding: (1) changes in inbreeding depression, (2) changes in fitness components of inbred lines relative to the original outbred line, and (3) purged population (outcrossed inbred lines) trait means as a function of ancestral outbred trait means. Frequent and substantial purging was found using all three measures, but was particularly pronounced when tracking changes in inbreeding depression. Despite this, we found little correspondence between the three measures of purging within individual studies, indicating that the manner in which a researcher chooses to estimate purging will affect interpretation of the results obtained. The discrepancy suggests an alternative hypothesis: rebounds in fitness with inbreeding may have resulted from adaptation to laboratory conditions and not to purging when using outcrossed inbred lines. However, the pronounced reduction in inbreeding depression for a number of studies provides evidence for purging, as the measure is likely less affected by selection for laboratory conditions. Unlike other taxon-specific reviews on this topic, our results provide support for the purging hypothesis, but firm predictions about the situations in which purging is likely or the magnitude of fitness rebound possible when populations are inbred remain difficult. Further research is required to resolve the discrepancy between the results obtained using different experimental approaches.

Animals↗

Influence of genetic loading, obstetric complications and premorbid adjustment on brain morphology in schizophrenia: a MRI study.

Cerebrospinal fluid (CSF) space enlargement in schizophrenia is a prominent finding. This study was initiated to examine the influence of genetic loading, obstetric complications and premorbid adjustment on the extent of this enlargement. The sample of this MRI study consisted of 40 schizophrenic patients, 24 psychiatric and 40 healthy family members from 10 uniaffected and 19 multiple affected families with schizophrenia, such as 27 control subjects from non-affected families. The ventricle-to-brain-ratio (VBR), and the areas of the third ventricle, sylvian fissure, temporal horn and interhemispheric fissure at the slice where these structures reached their maximum were examined relatively to the corresponding total brain areas. The sum of CSF areas was calculated as a parameter for global atrophy. From MANCOVA adjusted for intervening variables the right VBR and the sum of CSF areas revealed significant differences between diagnostic groups. For these areas schizophrenic patients showed an increase compared to control subjects and family members with psychiatric disorder. Genetic loading influenced the interhemispheric fissure, enlarged in multiple affected compared to uniaffected families, and the temporal horn asymmetry, which was right sided (right > left) in control subjects and multiple affected families, but inverted in uniaffected families. Neonatal obstetric complications influenced only the size of the VBR, while premorbid adjustment predicted various CSF areas. In conclusion, schizophrenic subjects from multiple and uniaffected families showed a global atrophy, which was most pronounced in the VBR. Genetic loading seems to have an impact on frontal regions as the interhemispheric fissure and on the temporal horn.

Adolescent↗

Genetic load among four Andhra caste populations.

The effect of inbreeding on mortality is assessed through genetic load estimates among four caste populations, the Chakali, Kummari, Mangali, and Madiga of Andhra Pradesh, India. The regression coefficient "B" is positive and statistically not significant except in the Mangali where reduced fetal wastage with increased inbreeding coefficient is noted. The B/A values of the majority of populations suggest that the genetic load is mainly segregational. It is suggested that among the Kummari, the load is predominantly mutational for prereproductive mortality. Relatively higher values of intercept "A" are observed in the present study for low socioeconomic caste groups.

Consanguinity↗