scholarly journals Digenic traits under population admixture and inbreeding

2022 ◽  
Author(s):  
Reginald D Smith
Keyword(s):  
Population Genetics ◽  
Linkage Disequilibrium ◽  
Population Admixture ◽  
Combined Effects ◽  
Admixed Population ◽  
Medical Interest ◽  
Diploid Populations

The population genetics of digenic genotypes in diploid populations, genotypes based on alleles at two loci, have been studied theoretically for decades with relevant digenic traits of medical interest being known for over 25 years. Given the effects of linkage and linkage disequilibrium on two locus genotypes, it should be expected that these factors can change the expected frequencies of digenic genotypes in many, sometimes unexpected, ways. In particular, the combination of linkage disequilibrium and inbreeding can combine to increase the frequencies of double homozygotes and double heterozygotes significantly over outbred comparisons. Given the prevalence of linkage disequilibrium in recently admixed populations, this can lead to large shifts in trait prevalence such that it can sometimes exceed that of either original pre-admixed population with the combined effects of linkage disequilibrium and inbreeding. Here we investigate the frequencies of digenic genotypes under the combined effects of linkage, linkage disequilibrium, and inbreeding to analyze how these interact to increase or decrease the frequency of the genotypes across two loci.

scholarly journals mixIndependR: a R package for statistical independence testing of loci in database of multi-locus genotypes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Bing Song ◽  
August E. Woerner ◽  
John Planz
Keyword(s):  
Population Genetics ◽  
Linkage Disequilibrium ◽  
Genetic Markers ◽  
Software Package ◽  
Tandem Repeats ◽  
Population Data ◽  
Real Data ◽  
R Package ◽  
Nucleotide Polymorphisms ◽  
Mutual Independence

Abstract Background Multi-locus genotype data are widely used in population genetics and disease studies. In evaluating the utility of multi-locus data, the independence of markers is commonly considered in many genomic assessments. Generally, pairwise non-random associations are tested by linkage disequilibrium; however, the dependence of one panel might be triplet, quartet, or other. Therefore, a compatible and user-friendly software is necessary for testing and assessing the global linkage disequilibrium among mixed genetic data. Results This study describes a software package for testing the mutual independence of mixed genetic datasets. Mutual independence is defined as no non-random associations among all subsets of the tested panel. The new R package “mixIndependR” calculates basic genetic parameters like allele frequency, genotype frequency, heterozygosity, Hardy–Weinberg equilibrium, and linkage disequilibrium (LD) by mutual independence from population data, regardless of the type of markers, such as simple nucleotide polymorphisms, short tandem repeats, insertions and deletions, and any other genetic markers. A novel method of assessing the dependence of mixed genetic panels is developed in this study and functionally analyzed in the software package. By comparing the observed distribution of two common summary statistics (the number of heterozygous loci [K] and the number of share alleles [X]) with their expected distributions under the assumption of mutual independence, the overall independence is tested. Conclusion The package “mixIndependR” is compatible to all categories of genetic markers and detects the overall non-random associations. Compared to pairwise disequilibrium, the approach described herein tends to have higher power, especially when number of markers is large. With this package, more multi-functional or stronger genetic panels can be developed, like mixed panels with different kinds of markers. In population genetics, the package “mixIndependR” makes it possible to discover more about admixture of populations, natural selection, genetic drift, and population demographics, as a more powerful method of detecting LD. Moreover, this new approach can optimize variants selection in disease studies and contribute to panel combination for treatments in multimorbidity. Application of this approach in real data is expected in the future, and this might bring a leap in the field of genetic technology. Availability The R package mixIndependR, is available on the Comprehensive R Archive Network (CRAN) at: https://cran.r-project.org/web/packages/mixIndependR/index.html.

scholarly journals Population Admixture May Appear to Mask, Change or Reverse Genetic Effects of Genes Underlying Complex Traits

Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 1319-1323
Author(s):  
Hong-Wen Deng
Keyword(s):  
Population Genetics ◽  
False Positive ◽  
Complex Traits ◽  
Association Studies ◽  
Genetic Effects ◽  
Population Admixture ◽  
Reverse Genetic ◽  
Positive Identification ◽  
False Positive Identification

Abstract Association studies using random population samples are increasingly being applied in the identification and inference of genetic effects of genes underlying complex traits. It is well recognized that population admixture may yield false-positive identification of genetic effects for complex traits. However, it is less well appreciated that population admixture can appear to mask, change, or reverse true genetic effects for genes underlying complex traits. By employing a simple population genetics model, we explore the effects and the conditions of population admixture in masking, changing, or even reversing true genetic effects of genes underlying complex traits.

scholarly journals Polymorphic markers for identification of parasite population in Plasmodium malariae

2020 ◽  
Author(s):  
Vivek Bhakta Mathema ◽  
Supatchara Nakeesathit ◽  
Watcharee Pagornrat ◽  
Frank Smithuis ◽  
Nicholas J White ◽  
...  
Keyword(s):  
Population Genetics ◽  
Linkage Disequilibrium ◽  
Nucleotide Diversity ◽  
Gene Diversity ◽  
Repeat Unit ◽  
Plasmodium Malariae ◽  
Parasite Population ◽  
P Value ◽  
Indel Polymorphisms ◽  
Richness Index

Abstract Background Molecular genotyping in Plasmodium serves many aims including providing tools for studying parasite population genetics and distinguishing recrudescence from reinfection. Microsatellite typing, insertion-deletion (INDEL) and single nucleotide polymorphisms is used for genotyping, but only limited information is available for Plasmodium malariae, an important human malaria species. This study aimed to provide a set of genetic markers to facilitate the study of P. malariae population genetics. Methods Markers for microsatellite genotyping and pmmsp1 gene polymorphisms were developed and validated in symptomatic P. malariae field isolates from Myanmar (N=37). Fragment analysis was used to determine allele sizes at each locus to calculate multiplicity of infections (MOI), linkage disequilibrium, genetic richness index, heterozygosity and construct dendrograms. Nucleotide diversity (π), number of haplotypes, and genetic diversity (Hd) were assessed and a phylogenetic tree was constructed. Genome-wide microsatellite maps with annotated regions of newly identified markers were constructed. Results Six microsatellite markers were developed and tested in 37 P. malariae isolates which showed sufficient heterozygosity (0.530-0.922), genetic richness index (0.050-0.250) and absence of linkage disequilibrium (IAS = 0.03, p-value > 0.05)(N=37). In addition, a tandem repeat (VNTR)-based pmmsp1 INDEL polymorphisms marker was developed and assessed in 27 P. malariae isolates showing a nucleotide diversity of 0.0976, haplotype gene diversity of 0.698 and identified 14 unique variants. The size of VNTR consensus repeat unit adopted as allele was 27 base pairs. The markers Pm12_426 andpmmsp1 showed greatest diversity with heterozygosity scores of 0.920 and 0.835, respectively. Using six microsatellites markers, the likelihood that any two parasite strains would have the same microsatellite genotypes was 8.46 × 10-4 and was further reduced to 1.66 × 10-4 when pmmsp1 polymorphisms were included. Conclusions Six novel microsatellites genotyping markers and a set of pmmsp1 VNTR-based INDEL polymorphisms markers for P. malariae were developed and validated. Each marker could be independently or in combination employed to access genotyping of the parasite. The newly developed markers may serve as a useful tool for investigating parasite diversity, population genetics, molecular epidemiology and for distinguishing recrudescence from reinfection in drug efficacy studies.

Epidemic population structure of clinical Klebsiella aerogenes inferred by multilocus sequence typing

2019 ◽  
Author(s):  
Sheng Chen ◽  
Yu Wang ◽  
Lijun Zeng ◽  
Wenbo Luo ◽  
Wei Feng ◽  
...  
Keyword(s):  
Population Genetics ◽  
Population Structure ◽  
Linkage Disequilibrium ◽  
Homologous Recombination ◽  
Key Words ◽  
Multilocus Sequence Typing ◽  
Bacterial Population ◽  
Purifying Selection ◽  
Klebsiella Aerogenes ◽  
Sequence Types

Abstract Background: Multilocus sequence typing (MLST) act as an accurate approach to characterize bacterial population genetics, phylogeny and epidemiology, and has not yet been applied to Klebsiella aerogenes. Results: A MLST scheme was established for a collection of 213 isolates of K. aerogenes. These strains exhibited considerable sequence diversity under purifying selection, and could be assigned into 135 sequence types, which were further divided into 8 clonal complexes and a lot of doubletons and singletons scatterred in the population snapshot. Five separately clustering lineages were presented in the population, which displayed evident homologous recombination occurred within and across lineages, with a tendency of linkage disequilibrium. Conclusions: K. aerogenes shows an epidemic population structure displaying high levels of recombination occurring more frequently than point mutation. Key words: Klebsiella aerogenes; multilocus sequence typing; sequence types; purifying selection; linkage disequilibrium; population structure

scholarly journals Population Admixture: Detection by Hardy-Weinberg Test and Its Quantitative Effects on Linkage-Disequilibrium Methods for Localizing Genes Underlying Complex Traits

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 885-897 ◽  
Author(s):  
Hong-Wen Deng ◽  
Wei-Min Chen ◽  
Robert R Recker
Keyword(s):  
Linkage Disequilibrium ◽  
Error Rate ◽  
Population Differentiation ◽  
False Positive ◽  
Complex Traits ◽  
Type I Error ◽  
Association Studies ◽  
Type I ◽  
Population Admixture ◽  
Random Samples

Abstract In association studies searching for genes underlying complex traits, the results are often inconsistent, and population admixture has been recognized qualitatively as one major potential cause. Hardy-Weinberg equilibrium (HWE) is often employed to test for population admixture; however, its power is generally unknown. Through analytical and simulation approaches, we quantify the power of the HWE test for population admixture and the effects of population admixture on increasing the type I error rate of association studies under various scenarios of population differentiation and admixture. We found that (1) the power of the HWE test for detecting population admixture is usually small; (2) population admixture seriously elevates type I error rate for detecting genes underlying complex traits, the extent of which depends on the degrees of population differentiation and admixture; (3) HWE testing for population admixture should be performed with random samples or only with controls at the candidate genes, or the test can be performed for combined samples of cases and controls at marker loci that are not linked to the disease; (4) testing HWE for population admixture generally reduces false positive association findings of genes underlying complex traits but the effect is small; and (5) with population admixture, a linkage disequilibrium method that employs cases only is more robust and yields many fewer false positive findings than conventional case-control analyses. Therefore, unless random samples are carefully selected from one homogeneous population, admixture is always a legitimate concern for positive findings in association studies except for the analyses that deliberately control population admixture.

scholarly journals Polymorphic markers for identification of parasite population in Plasmodium malariae

2019 ◽  
Author(s):  
Vivek Bhakta Mathema ◽  
Supatchara Nakeesathit ◽  
Watcharee Pagornrat ◽  
Frank Smithuis ◽  
Nicholas J White ◽  
...  
Keyword(s):  
Population Genetics ◽  
Linkage Disequilibrium ◽  
Nucleotide Diversity ◽  
Gene Diversity ◽  
Repeat Unit ◽  
Parasite Population ◽  
P Value ◽  
Limited Information ◽  
Indel Polymorphisms ◽  
Richness Index

Abstract Background Molecular genotyping in Plasmodium serves many aims including providing tools for studying parasite population genetics and distinguishing recrudescence from reinfection. Microsatellite typing, insertion-deletion (INDEL) and single nucleotide polymorphisms is used for genotyping, but only limited information is available for P. malariae , an important human malaria species. This study aimed to provide a set of genetic markers to facilitate the study of P. malariae population genetics. Methods Markers for microsatellite genotyping and pmmsp1 gene polymorphisms were developed and validated in symptomatic P. malariae field isolates from Myanmar (N=37). Fragment analysis was used to determine allele sizes at each locus to calculate multiplicity of infections (MOI), linkage disequilibrium, genetic richness index, heterozygosity and construct dendrograms. Nucleotide diversity (π), number of haplotypes, and genetic diversity ( H d ) were assessed and a phylogenetic tree was constructed. Genome-wide microsatellite maps with annotated regions of newly identified markers were constructed. Results Six microsatellite markers were developed and tested in 37 P. malariae isolates which showed sufficient heterozygosity (0.530-0.922), genetic richness index (0.050-0.250) and absence of linkage disequilibrium ( I A S = 0.03, p-value > 0.05 ) (N=37). In addition, a tandem repeat (VNTR)-based pmmsp1 INDEL polymorphisms marker was developed and assessed in 27 P. malariae isolates showing a nucleotide diversity of 0.092, haplotype gene diversity of 0.698 and identified 14 unique variants. The size of VNTR consensus repeat unit adopted as allele was 27 base pairs. The markers Pm12_426 and pmmsp1 showed greatest diversity with heterozygosity scores of 0.920 and 0.835, respectively. Using six microsatellites markers, the likelihood that any two parasite strains would have the same microsatellite genotypes was 8.46 × 10 -4 and was further reduced to 1.66 × 10 -4 when pmmsp1 polymorphisms were included. Conclusions Six novel microsatellites genotyping markers and a set of pmmsp1 VNTR-based INDEL polymorphisms markers for P. malariae were developed and validated. Each marker could be independently or in combination employed to access genotyping of the parasite. The newly developed markers may serve as a useful tool for investigating parasite diversity, population genetics, molecular epidemiology and for distinguishing recrudescence from reinfection in drug efficacy studies.

scholarly journals Polymorphic markers for identification of parasite population in Plasmodium malariae

2019 ◽  
Author(s):  
Vivek Bhakta Mathema ◽  
Supatchara Nakeesathit ◽  
Watcharee Pagornrat ◽  
Frank Smithuis ◽  
Nicholas J White ◽  
...  
Keyword(s):  
Population Genetics ◽  
Linkage Disequilibrium ◽  
Nucleotide Diversity ◽  
Gene Diversity ◽  
Repeat Unit ◽  
Parasite Population ◽  
P Value ◽  
Limited Information ◽  
Indel Polymorphisms ◽  
Richness Index

Abstract Background Molecular genotyping in Plasmodium serves many aims including providing tools for studying parasite population genetics and distinguishing recrudescence from reinfection. Microsatellite typing, insertion-deletion (INDEL) and single nucleotide polymorphisms is used for genotyping, but only limited information is available for P. malariae, an important human malaria species. This study aimed to provide a set of genetic markers to facilitate the study of P. malariae population genetics. Methods Markers for microsatellite genotyping and merozoite surface protein 1 (pmmsp1) gene polymorphisms were developed and validated in symptomatic P. malariae field isolates from Myanmar (N=37). Fragment analysis was used to determine allele sizes at each locus to calculate multiplicity of infections (MOI), linkage disequilibrium, genetic richness index, heterozygosity and construct dendrograms. Nucleotide diversity (π), number of haplotypes, and genetic diversity (Hd) were assessed and a phylogenetic tree was constructed. Genome-wide microsatellite maps with annotated regions of newly identified markers were constructed.Results Six microsatellite markers were developed and tested in 37 P. malariae isolates which showed sufficient heterozygosity (0.530-0.922), genetic richness index (0.050-0.250) and absence of linkage disequilibrium (IAS = 0.03, p-value > 0.05) (N=37). In addition, a tandem repeat (VNTR)-based pmmsp1 INDEL polymorphisms marker was developed and assessed in 27 P. malariae isolates showing a nucleotide diversity of 0.092, haplotype gene diversity of 0.698 and identified 14 unique variants. The size of VNTR consensus repeat unit adopted as allele was 27 base pairs. The markers Pm12_426 and pmmsp1 showed greatest diversity with heterozygosity scores of 0.920 and 0.835, respectively. Using six microsatellites markers, the likelihood that any two parasite strains would have the same microsatellite genotypes was 8.46 × 10-4 and was further reduced to 1.66 × 10-4 when pmmsp1 polymorphisms were included.Conclusions Six novel microsatellites genotyping markers and a set of pmmsp1 VNTR-based INDEL polymorphisms markers for P. malariae were developed and validated. Each marker could be independently or in combination employed to access genotyping of the parasite. The newly developed markers may serve as a useful tool for investigating parasite diversity, population genetics, molecular epidemiology and for distinguishing recrudescence from reinfection in drug efficacy studies.

scholarly journals Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with multiple exponential functions

2015 ◽  
Author(s):  
Ying Zhou ◽  
Kai Yuan ◽  
Yaoliang Yu ◽  
Xumin Ni ◽  
Pengtao Xie ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Exponential Functions ◽  
Dynamic Changes ◽  
Multiple Wave ◽  
Flow Parameters ◽  
Genome Wide ◽  
Complex Population ◽  
Genome Wide Data ◽  
Admixed Population ◽  
Source Populations

Admixture-introduced linkage disequilibrium (LD) has recently been introduced into the inference of the histories of complex admixtures. However, the influence of ancestral source populations on the LD pattern in admixed populations is not properly taken into consideration by currently available methods, which affects the estimation of several gene flow parameters from empirical data. We first illustrated the dynamic changes of LD in admixed populations and mathematically formulated the LD under a generalized admixture model with finite population size. We next developed a new method, MALDmef, by fitting LD with multiple exponential functions for inferring and dating multiple-wave admixtures. MALDmef takes into account the effects of source populations which substantially affect modeling LD in admixed population, which renders it capable of efficiently detecting and dating multiple-wave admixture events. The performance of MALDmef was evaluated by simulation and it was shown to be more accurate than MALDER, a state-of-the-art method that was recently developed for similar purposes, under various admixture models. We further applied MALDmef to analyzing genome-wide data from the Human Genome Diversity Project (HGDP) and the HapMap Project. Interestingly, we were able to identify more than one admixture events in several populations, which have yet to be reported. For example, two major admixture events were identified in the Xinjiang Uyghur, occurring around 27???30 generations ago and 182???195 generations ago, respectively. In an African population (MKK), three recent major admixtures occurring 13???16, 50???67, and 107???139 generations ago were detected. Our method is a considerable improvement over other current methods and further facilitates the inference of the histories of complex population admixtures.

scholarly journals Linkage disequilibrium, genetic distance and evolutionary distance under a general model of linked genes or a part of the genome

1982 ◽  
Vol 39 (1) ◽  
pp. 63-77 ◽  
Author(s):  
Naoyuki Takahata
Keyword(s):  
Population Genetics ◽  
Linkage Disequilibrium ◽  
Genetic Distance ◽  
Dna Sequence ◽  
General Model ◽  
Diffusion Equations ◽  
A Genome ◽  
Molecular Population Genetics ◽  
Neutral Mutations ◽  
Made In

SummaryA general model of linked genes or a part of a genome is proposed which enables us to study various problems in molecular population genetics in a unified way. Several formulae with special reference to the linkage disequilibrium and genetic distance are derived for neutral mutations in finite populations, based on the method of diffusion equations. It is argued that the model and formulae are useful particularly when observations are made in terms of DNA sequence.

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