58 Integrating Quantitative Genetics and Epidemiology: Why Selection Against Infectious Diseases Is More Promising Than We Think

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 31-32
Author(s):  
Piter Bijma ◽  
Piter Bijma
Keyword(s):  
Infectious Diseases ◽  
Genetic Parameters ◽  
Genetic Variance ◽  
Disease Status ◽  
Genetic Theory ◽  
Breeding Values ◽  
Quantitative Genetic ◽  
The Mean ◽  
Low Prevalence ◽  
Simple Average

Abstract Pathogens have profound effects on livestock. The low heritabilities of individual binary disease status suggest limited prospects for genetic improvement. However, a proper quantitative genetic theory for infectious diseases, including transmission dynamics, is currently lacking. Here we present a quantitative genetic theory for endemic infectious diseases, focussing on the genetic factors that determine the prevalence (P; the mean fraction of the population that is infected). We present simple expressions for breeding values and genetic parameters for the prevalence. Without genetic variation in infectiousness, breeding values for prevalence are a factor 1/P greater than the ordinary breeding values for individual binary disease status (0/1). Hence, even though prevalence is the simple average of individual binary disease status, breeding values for prevalence show much greater variation than our ordinary breeding values. This implies that the genetic variance that determines the potential response of prevalence to selection is largely due to indirect genetic effects (IGE), and thus hidden to ordinary genetic analysis and selection. Hence, the genetic variance that determines the potential of livestock populations to respond to selection must be much greater than currently believed, particularly at low prevalence. We evaluated this implication using simulation of endemics following standard methods in epidemiology. Results show that response of prevalence to selection increases very strongly when prevalence decreases, and is much greater than predicted by our ordinary breeding values. These results supports our theoretical findings, and show that selection against infectious diseases is much more promising than currently believed.

scholarly journals The quantitative genetics of the endemic prevalence of infectious diseases: Indirect Genetic Effects dominate heritable variation and response to selection

2021 ◽  
Author(s):  
Piter Bijma ◽  
Andries Hulst ◽  
Mart C. M. de Jong
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Disease Status ◽  
Host Population ◽  
Genetic Effects ◽  
Breeding Value ◽  
Response To Selection ◽  
Heritable Variation ◽  
Genetic Theory ◽  
Quantitative Genetic

AbstractPathogens have profound effects on life on earth, both in nature and agriculture. Despite the availability of well-established epidemiological theory, however, a quantitative genetic theory of the host population for the endemic prevalence of infectious diseases is almost entirely lacking. While several studies have demonstrated the relevance of the transmission dynamics of infectious diseases for heritable variation and response to selection of the host population, our current theoretical framework of quantitative genetics does not include these dynamics. As a consequence, we do not know which genetic effects of the host population determine the prevalence of an infectious disease, and have no concepts of breeding value and heritable variation for endemic prevalence.Here we propose a quantitative genetic theory for the endemic prevalence of infectious diseases. We first identify the genetic factors that determine the prevalence of an infectious disease, using an approach founded in epidemiological theory. Subsequently we investigate the population level effects of individual genetic variation on R0 and on the endemic prevalence. Next, we present expressions for the breeding value and heritable variation, for both prevalence and individual binary disease status, and show how these parameters depend on the endemic prevalence. Results show that heritable variation for endemic prevalence is substantially greater than currently believed, and increases when prevalence approaches zero, while heritability of individual disease status goes to zero. We show that response of prevalence to selection accelerates considerably when prevalence goes down, in contrast to predictions based on classical genetic models. Finally, we show that most of the heritable variation in the endemic prevalence of the infection is due to indirect genetic effects, suggestion a key role for kin-group selection both in the evolutionary history of current populations and for genetic improvement strategies in animals and plants.

INVITATION PAPER ANIMAL BREEDING TODAY — ITS DIMENSIONS AND ACCOMPLISHMENTS

1977 ◽  
Vol 19 (2) ◽  
pp. 193-210
Author(s):  
H. T. Fredeen
Keyword(s):  
Genetic Parameters ◽  
Genetic Variance ◽  
Animal Breeding ◽  
Practical Application ◽  
Genetic Theory ◽  
Testing Procedures ◽  
Effective Application ◽  
Quantitative Genetic ◽  
Animal Populations ◽  
Main Emphasis

Since its inception early in the present century, the science of animal breeding has been directed toward the effective application of quantitative genetic theory for improvement of animal populations. This has involved developing and refining biomedical techniques for estimating genetic parameters, designing mating systems for efficient utilization of additive and nonadditive genetic variance, developing criteria of net merit that have both genetic and economic relevance, and designing practical testing procedures for evaluating genetic differences in productive merit. While the main*** emphasis has been on quantitative inheritance, attention has also been given to qualitative genetics, specifically in respect of defective conditions and disease resistance, and to the implications of chromosomal aberrations. Controlled laboratory studies, designed to test genetic theory, have demonstrated the considerable potential that exists for improving animal productivity through manipulation of the genetic variability in animal populations. To date, relatively little of this potential has been utilized in commercial livestock populations and, while substantial genetic improvement has been achieved by the process of breed substitution, it is clear that the science of animal breeding has progressed far beyond its practical application. For this reason, the emphasis in the science has gradually shifted from refinement of theory to the more practical issues involved in effective application at the industry level.

scholarly journals The quantitative genetics of the prevalence of infectious diseases: hidden genetic variation due to Indirect Genetic Effects dominates heritable variation and response to selection

Genetics ◽  
2021 ◽  
Author(s):  
Piter Bijma ◽  
Andries D Hulst ◽  
Mart C M de Jong
Keyword(s):  
Genetic Variation ◽  
Infectious Diseases ◽  
Quantitative Genetics ◽  
Disease Status ◽  
Genetic Effects ◽  
Breeding Value ◽  
Response To Selection ◽  
Heritable Variation ◽  
Genetic Theory ◽  
Quantitative Genetic

Abstract Infectious diseases have profound effects on life, both in nature and agriculture. However, a quantitative genetic theory of the host population for the endemic prevalence of infectious diseases is almost entirely lacking. While several studies have demonstrated the relevance of transmission of infections for heritable variation and response to selection, current quantitative genetics ignores transmission. Thus, we lack concepts of breeding value and heritable variation for endemic prevalence, and poorly understand response of endemic prevalence to selection. Here we integrate quantitative genetics and epidemiology, and propose a quantitative genetic theory for the basic reproduction number R0 and for the endemic prevalence of an infection. We first identify the genetic factors that determine the prevalence. Subsequently we investigate the population level consequences of individual genetic variation, for both R0 and the endemic prevalence. Next, we present expressions for the breeding value and heritable variation, for endemic prevalence and individual binary disease status, and show that these depend strongly on the prevalence. Results show that heritable variation for endemic prevalence is substantially greater than currently believed, and increases strongly when prevalence decreases, while heritability of disease status approaches zero. As a consequence, response of the endemic prevalence to selection for lower disease status accelerates considerably when prevalence decreases, in contrast to classical predictions. Finally, we show that most heritable variation for the endemic prevalence is hidden in indirect genetic effects, suggesting a key role for kin-group selection in the evolutionary history of current populations and for genetic improvement in animals and plants.

Genetic and statistical analyses of strong selection on polygenic traits: what, me normal?

Genetics ◽  
1994 ◽  
Vol 138 (3) ◽  
pp. 913-941 ◽  
Author(s):  
M Turelli ◽  
N H Barton
Keyword(s):  
Allele Frequency ◽  
Genetic Variance ◽  
Gaussian Approximation ◽  
Selection Response ◽  
Disruptive Selection ◽  
Breeding Values ◽  
Central Moments ◽  
Linkage Disequilibria ◽  
The Mean ◽  
Frequency Changes

Abstract We develop a general population genetic framework for analyzing selection on many loci, and apply it to strong truncation and disruptive selection on an additive polygenic trait. We first present statistical methods for analyzing the infinitesimal model, in which offspring breeding values are normally distributed around the mean of the parents, with fixed variance. These show that the usual assumption of a Gaussian distribution of breeding values in the population gives remarkably accurate predictions for the mean and the variance, even when disruptive selection generates substantial deviations from normality. We then set out a general genetic analysis of selection and recombination. The population is represented by multilocus cumulants describing the distribution of haploid genotypes, and selection is described by the relation between mean fitness and these cumulants. We provide exact recursions in terms of generating functions for the effects of selection on non-central moments. The effects of recombination are simply calculated as a weighted sum over all the permutations produced by meiosis. Finally, the new cumulants that describe the next generation are computed from the non-central moments. Although this scheme is applied here in detail only to selection on an additive trait, it is quite general. For arbitrary epistasis and linkage, we describe a consistent infinitesimal limit in which the short-term selection response is dominated by infinitesimal allele frequency changes and linkage disequilibria. Numerical multilocus results show that the standard Gaussian approximation gives accurate predictions for the dynamics of the mean and genetic variance in this limit. Even with intense truncation selection, linkage disequilibria of order three and higher never cause much deviation from normality. Thus, the empirical deviations frequently found between predicted and observed responses to artificial selection are not caused by linkage-disequilibrium-induced departures from normality. Disruptive selection can generate substantial four-way disequilibria, and hence kurtosis; but even then, the Gaussian assumption predicts the variance accurately. In contrast to the apparent simplicity of the infinitesimal limit, data suggest that changes in genetic variance after 10 or more generations of selection are likely to be dominated by allele frequency dynamics that depend on genetic details.

Male reproductive success and pedigree error in red spruce open-pollinated and polycross mating systems

2008 ◽  
Vol 38 (7) ◽  
pp. 1742-1749 ◽  
Author(s):  
T. K. Doerksen ◽  
C. M. Herbinger
Keyword(s):  
Reproductive Success ◽  
Mating Systems ◽  
Genetic Parameters ◽  
Genetic Variance ◽  
Red Spruce ◽  
Male Reproductive Success ◽  
Progeny Testing ◽  
Quantitative Genetic ◽  
Pedigree Errors ◽  
Quantitative Genetic Parameters

Open-pollinated and polycross mating systems are widely used in forest genetics and breeding to quickly, simply, and inexpensively generate progenies assumed to be related as half-sibs (coefficient of relationship, r = 0.25) from a random mating population. However, nonrandom mating, such as unequal male reproductive success (RS) or selfing, can increase the genetic correlation among offspring, and thus, genetic variance and heritability are overestimated. Conversely, pedigree errors will cause additive genetic variance and heritability to be underestimated. Unequal male reproductive success and three types of potential pedigree errors (volunteers, mishandled maternal identities, and foreign pollen) were detected in operational open-pollinated and polycross red spruce ( Picea rubens Sarg.) progeny tests, through paternity testing using microsatellite (simple sequence repeat) DNA markers. The potential impact of unequal RS and pedigree errors on quantitative genetic parameters is discussed. Paternity and parentage analyses could be used to reconstruct the pedigree of any plantation consisting of sibships, where candidate parents (e.g., members of seed orchard) can be identified. This offers an alternative to traditional progeny testing for estimation of quantitative genetic parameters.

scholarly journals Dissecting the genetic architecture of quantitative traits using genome-wide identity-by-descent sharing among full-sibs

2021 ◽  
Author(s):  
Antoine Fraimout ◽  
Zitong Li ◽  
Mikko J. Sillanpää ◽  
Pasi Rastas ◽  
Juha Merilä
Keyword(s):  
Natural Selection ◽  
Variance Components ◽  
Genetic Architecture ◽  
Quantitative Traits ◽  
Genetic Parameters ◽  
Genetic Variance ◽  
Identity By Descent ◽  
Quantitative Genetic ◽  
Genome Wide ◽  
Quantitative Genetic Parameters

ABSTRACTAdditive and dominance genetic variances underlying the expression of quantitative traits are important quantities for predicting short-term responses to selection, but they are notoriously challenging to estimate in most wild animal populations. Using estimates of genome-wide identity-by-descent (IBD) sharing from autosomal SNP loci, we estimated quantitative genetic parameters for traits known to be under directional natural selection in nine-spined sticklebacks (Pungitius pungitius) and compared these to traditional pedigree-based estimators. Using four different datasets, with varying sample sizes and pedigree complexity, we further assessed the performance of different Genomic Relationship Matrices (GRM) to estimate additive and dominance variance components. Large variance in IBD relationships allowed accurate estimation of genetic variance components, and revealed significant heritability for all measured traits, with negligible dominance contributions. Genome-partitioning analyses revealed that all traits have a polygenic basis and are controlled by genes at multiple chromosomes. The results demonstrate how large full-sib families of highly fecund vertebrates can be used to obtain accurate estimates quantitative genetic parameters to provide insights on genetic architecture of quantitative traits in non-model organisms from the wild. This approach should be particularly useful for studies requiring estimates of genetic variance components from multiple populations as for instance when aiming to infer the role of natural selection as a cause for population differentiation in quantitative traits.

scholarly journals What can genetic variation tell us about the evolution of senescence?

2009 ◽  
Vol 276 (1665) ◽  
pp. 2271-2278 ◽  
Author(s):  
Jacob A. Moorad ◽  
Daniel E.L. Promislow
Keyword(s):  
Genetic Variation ◽  
Variance Components ◽  
Genetic Parameters ◽  
Genetic Variance ◽  
Mutation Accumulation ◽  
Antagonistic Pleiotropy ◽  
Age Classes ◽  
Dominance Variance ◽  
Quantitative Genetic ◽  
Genetic Techniques

Quantitative genetic approaches have been developed that allow researchers to determine which of two mechanisms, mutation accumulation (MA) or antagonistic pleiotropy (AP), best explain observed variation in patterns of senescence using classical quantitative genetic techniques. These include the creation of mutation accumulation lines, artificial selection experiments and the partitioning of genetic variances across age classes. This last strategy has received the lion's share of empirical attention. Models predict that inbreeding depression (ID), dominance variance and the variance among inbred line means will all increase with age under MA but not under those forms of AP that generate marginal overdominance. Here, we show that these measures are not, in fact, diagnostic of MA versus AP. In particular, the assumptions about the value of genetic parameters in existing AP models may be rather narrow, and often violated in reality. We argue that whenever ageing-related AP loci contribute to segregating genetic variation, polymorphism at these loci will be enhanced by genetic effects that will also cause ID and dominance variance to increase with age, effects also expected under the MA model of senescence. We suggest that the tests that seek to identify the relative contributions of AP and MA to the evolution of ageing by partitioning genetic variance components are likely to be too conservative to be of general value.

scholarly journals Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed

Genetics ◽  
2021 ◽  
Author(s):  
Andries D Hulst ◽  
Mart C M de Jong ◽  
Piter Bijma
Keyword(s):  
Infectious Diseases ◽  
Herd Immunity ◽  
Genetic Selection ◽  
Disease Status ◽  
Response To Selection ◽  
Feedback Effects ◽  
Feedback Mechanisms ◽  
Quantitative Genetic ◽  
The Common ◽  
Selection For

Abstract Genetic selection for improved disease resistance is an important part of strategies to combat infectious diseases in agriculture. Quantitative genetic analyses of binary disease status, however, indicate low heritability for most diseases, which restricts the rate of genetic reduction in disease prevalence. Moreover, the common liability threshold model suggests that eradication of an infectious disease via genetic selection is impossible because the observed-scale heritability goes to zero when the prevalence approaches zero. From infectious disease epidemiology, however, we know that eradication of infectious diseases is possible, both in theory and practice, because of positive feedback mechanisms leading to the phenomenon known as herd immunity. The common quantitative genetic models, however, ignore these feedback mechanisms. Here we integrate quantitative genetic analysis of binary disease status with epidemiological models of transmission, aiming to identify the potential response to selection for reducing the prevalence of endemic infectious diseases. The results show that typical heritability values of binary disease status correspond to a very substantial genetic variation in disease susceptibility among individuals. Moreover, our results show that eradication of infectious diseases by genetic selection is possible in principle. These findings strongly disagree with predictions based on common quantitative genetic models, which ignore the positive feedback effects that occur when reducing the transmission of infectious diseases. Those feedback effects are a specific kind of Indirect Genetic Effects; they contribute substantially to the response to selection and the development of herd immunity (i.e., an effective reproduction ratio less than one).

Work-related musculoskeletal disorders in highway sanitary workers

2015 ◽  
Author(s):  
Happiness Anulika Aweto ◽  
Oluwatoyosi Babatunde Owoeye ◽  
Korede Sunday Adegbite
Keyword(s):  
Musculoskeletal Disorders ◽  
Body Part ◽  
Sudden Onset ◽  
Work Related ◽  
Significant Relationships ◽  
Lower Back ◽  
Gradual Onset ◽  
Work Related Musculoskeletal Disorders ◽  
The Mean ◽  
Low Prevalence

Background: Highway sanitary workers are exposed to various health hazards in the course of duty. This study investigated the prevalence of work-related musculoskeletal disorders (WMSDs) among highway sanitary workers in Lagos Waste Management Authority (LAWMA), Lagos, Nigeria.Method: Two hundred fifty highway sanitary workers (46 males and 204 females) of LAWMA selected from four Local Government Areas of Lagos State, Nigeria completed a 26-item questionnaire that collected information on WMSDs.Results: The 12-month prevalence of WMSDs among the workers was 24.8%. The most commonly affected body part was the lower back (22.0%). Thirty-seven (59.7%) of the respondents reported gradual onset of musculoskeletal disorders (MSDs) while 25 (40.3%) reported sudden onset. The mean years of working experience was 3.22 + 0.23 years with 111 (44.4%) of the respondents having worked for 4 years and 7 (2.8%) having worked for 1year. The three major job risk factors identified were: continuing to work when injured (87.2%), working in the same position for long periods (53.6%) and lifting heavy materials (52.4%). Pearson’s Product Moment Correlation Coefficient analysis showed that there were significant relationships between prevalence of WMSDs and age (r = 0.42, p = 0.001*) and years on the job (r = 0.17, p = 0.01*).Conclusion: There was a low prevalence of WMSDs among highway sanitary workers of LAWMA. The most commonly affected body part was the lower back. Increasing age and years of working experience are significant factors that can contribute to the development of WMSDs among these workers.

PERIODONTAL DISEASE STATUS, KNOWLEDGE, ATTITUDE, PRACTICE AND TREATMENT NEEDS OF PREGNANT WOMEN

2018 ◽  
Vol 8 (6) ◽  
pp. 138-144
Author(s):  
Thien Nguyen Duc ◽  
Tai Tran Tan
Keyword(s):  
Periodontal Disease ◽  
Pregnant Women ◽  
Oral Hygiene ◽  
Disease Status ◽  
Incidence Rates ◽  
Gestation Period ◽  
Treatment Needs ◽  
Cross Sectional ◽  
Mean Values ◽  
The Mean

Background: Periodontal disease is a prominent and important issue of public health, especially in pregnant women. The objective of this study is to describe the clinical characteristics; learn knowledge, attitudes, practice oral hygiene and assess the need for treatment of periodontal disease in pregnant women. Subjects and Methods: A cross-sectional study of 210 pregnant women who visited the Department of Obstetrics and Gynecology at the Hue University of Medicine and Pharmacy Hospital. Clinical examination and interview questions on knowledge, attitudes and practice of oral care for all subjects. Results: The incidence of gingivitis was 100%, with mild gingivitis of 4,3% and moderate gingivitis of 95.7%. There was a difference in incidence rates of gingivitis in the gestational period (p<0.001). The incidence of periodontitis is 17.6% and there is no difference in gestational age (p>0.05). The mean values of GI and BOP indices differed by gestation period (p<0.05) and PD, OHI-S, PlI have statistically significant relationship with gestation period (p>0.05). The incidence of periodontal disease is 80.5%; The percentage of pregnant women who abstain from brushing their teeth after birth is 61.4%. Prevalence of brushing once a day: 7.1%; Twice a day: 70.5% and 3 times daily: 22.4%; The mean values of GI, PD, BOP, OHI-S and PlI were inversely proportional to the number of brushing (p<0.001). The rate of dental hygiene is just 3.3%; The rate of oral hygiene, dental plaque and plaque removal was 94,3%; The proportion of subjects required for intensive treatment is 2.4%. Conclusion: Periodontal disease, especially for pregnant women, is high. It is necessary to educate the knowledge, attitudes and practice of proper oral hygiene and to better meet the demand for periodontal disease treatment for pregnant women. Key words: Periodontal disease, pregnant women, knowledge, attitude, practice for oral hygiene, treatment needs

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