Revisiting FIS, FST, Wahlund Effects, and Null Alleles.
TL;DR: It is shown that, for organisms collected in a single sample, Wahlund effects and null alleles affect the values of both FIS and FST though in the opposite direction, and a determination key is proposed to interpret data with heterozygote deficits.
Abstract: Null alleles and Wahlund effects are well known causes of heterozygote deficits in empirical population genetics studies as compared to Hardy-Weinberg genotypic expectations. Some authors have theoretically studied the relationship of Wright's FIS computed from subsamples displaying a Wahlund effect and FST before the Wahlund effect, as can occasionally be obtained from populations of long-lived organisms. In the 2 subsample case, a positive relationship between these 2 parameters across loci would represent a signature of Wahlund effects. Nevertheless, for most organisms, getting 2 independent subsamples of the same cohort and population, one with a Wahlund effect and the other without, is almost never achieved and most of the time, empirical population geneticists only collect a single sample, with or without a Wahlund effect, or with or without null alleles. Another issue is that null allele increase FIS and FST altogether and thus may also create such correlation. In this article, I show that, for organisms collected in a single sample, which corresponds to the most common situation, Wahlund effects and null alleles affect the values of both FIS and FST though in the opposite direction. I also show that Wahlund effect produces no or weak positive correlation between the 2 F-statistics, while null alleles generate a strong positive correlation between them. Variation of these F-statistics is small and even minimized for FST under Wahlund effects as compared to null alleles. I finally propose a determination key to interpret data with heterozygote deficits.
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TL;DR: The coexistence of two highly divergent cryptic clades in the same sites is unveiled and separated analyses of the two clades suggest very small tsetse densities and relatively large dispersal.
Abstract: Population genetics is a convenient tool to study the population biology of non-model and hard to sample species. This is particularly true for parasites and vectors. Heterozygote deficits and/or linkage disequilibrium often occur in such studies and detecting the origin of those (Wahlund effect, reproductive system or amplification problems) is uneasy. We used new tools (correlation between the number of times a locus is found in significant linkage disequilibrium and its genetic diversity, correlations between Wright's FIS and FST , FIS and number of missing data, FIT and allele size and standard errors comparisons) for the first time on a real data set of tsetse flies, a vector of dangerous diseases to humans and domestic animals in sub-Saharan Africa. With these new tools, and cleaning data from null allele, temporal heterogeneity and short allele dominance effects, we unveiled the coexistence of two highly divergent cryptic clades in the same sites. These results are in line with other studies suggesting that the biodiversity of many taxa still largely remain undescribed, in particular pathogenic agents and their vectors. Our results also advocate that including individuals from different cohorts tends to bias subdivision measures and that keeping loci with short allele dominance and/or too frequent missing data seriously jeopardize parameter's estimations. Finally, separated analyses of the two clades suggest very small tsetse densities and relatively large dispersal.
21 citations
Cites background or methods or result from "Revisiting FIS, FST, Wahlund Effect..."
...This corresponds to "unshared" Wahlund effect and was shown to display similar behavior as compared to other kind of admixtures (De Meeûs, 2018)....
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...Technical problems, like null alleles, stuttering, short allele dominance or allele dropouts unevenly affects some loci, producing a positive FIS with an important variation across loci (De Meeûs, 2018)....
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...Population genetics is a convenient tool to study the population biology of non‐model, small and hard to sample species, where amplification problems, Wahlund effect and temporal heterogeneity of subsamples occur recurrently (De Meeûs, 2018; Waples, 2015, 2018)....
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...The recently published determination key (De Meeûs, 2018) to discriminate between amplification problems and Wahlund effect was here successfully used with the added information provided by CorLDHT....
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...In case of significant homozygote excess and linkage disequilibrium we have tried to discriminate demographic from technical causes with the determination key proposed by De Meeûs (De Meeûs, 2018)....
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TL;DR: The results argue for some caution in interpreting FIS × FST correlations under conditions where null alleles might be common and suggest that two-locus analyses might provide more robust assessments of Wahlund effects.
Abstract: Three published papers in this journal have considered the proposition that, under a Wahlund effect caused by population mixture, a positive correlation is expected between single-locus values of FIS for a sample from the mixture and FST between the populations contributing to the mixture. Two of the papers assumed unbiased samples to estimate FST but did not consider possible effects of null alleles; the other paper focused on effects of nulls but used biased samples that also included Wahlund effects to estimate FST. The result is an information gap regarding scenarios that include null alleles but have unbiased estimates of FST. Simulations were used to fill this information gap, with the following results: 1) converting ~10% of alleles to nulls substantially reduced apparent heterozygosity and substantially increased FIS, with few exceptions; 2) adding null alleles also increased FST at most loci, although the effect was much more modest; 3) null alleles generally degraded correlations between FIS and FST, but the relationship remained relatively strong for FST ≥ 0.06; and 4) null alleles had only a small effect on correlations between r2, a measure of linkage disequilibrium between pairs of loci, and the product of FST values for those loci. These results argue for some caution in interpreting FIS × FST correlations under conditions where null alleles might be common and suggest that two-locus analyses might provide more robust assessments of Wahlund effects.
16 citations
06 Aug 2019
TL;DR: This is the first study to report on HLA allele and haplotype frequencies for umbilical cord blood units from the Barcelona Cord Blood Bank and the largest study to date involving two fields of HLA resolution typing of Spanish registry data.
Abstract: Allele-level HLA compatibility in cord blood transplantation has been associated with better transplant outcomes and is recommended as a selection criterion. It is also a crucial aspect for other therapeutic applications involving cord blood-derived cells. Determination of high-resolution HLA frequencies is an important step towards improving the quality of cord blood banks. We analyzed HLA-A, -B, -C, -DRB1, and -DQB1 allele frequencies in 5458 high-quality cord blood units from the Barcelona Cord Blood Bank and identified 275 class I and 121 class II HLA alleles. A*02:01, B*44:03, C*07:01, DRB1*07:01 and DQB1*03:01 were the most frequent alleles at each locus. We detected 26 novel alleles and were able to determine the presence or absence of some null alleles, including C*04:09N, in a large number of units. We also analyzed maternal HLA typing information for 1877 units to determine real haplotype frequencies and linkage disequilibrium. A*29:02-B*44:03-C*16:01-DRB1*07:01-DQB1*02:02 was the most frequent HLA haplotype and the DRB1-DQB1 gene pair contained the two-locus haplotypes with the strongest linkage disequilibrium values. Four of the 11 unique haplotypes identified in the HLA-homozygous cord blood units were the top-ranking haplotypes identified and were present in 18% of the cohort. This is the first study to report on HLA allele and haplotype frequencies for umbilical cord blood units from the Barcelona Cord Blood Bank and the largest study to date involving two fields of HLA resolution typing of Spanish registry data.
15 citations
TL;DR: Redundancy, partial redundancy, and multiple regression on distance matrices analyses revealed that both geographical distance and environmental factors interact to generate the structure observed across Australian P. monodon populations.
Abstract: Restrictions to gene flow, genetic drift, and divergent selection associated with different environments are significant drivers of genetic differentiation. The black tiger shrimp (Penaeus monodon), is widely distributed throughout the Indian and Pacific Oceans including along the western, northern and eastern coastline of Australia, where it is an important aquaculture and fishery species. Understanding the genetic structure and the influence of environmental factors leading to adaptive differences among populations of this species is important for farm genetic improvement programs and sustainable fisheries management. Based on 278 individuals obtained from seven geographically disparate Australian locations, 10,624 high-quality SNP loci were used to characterize genetic diversity, population structure, genetic connectivity, and adaptive divergence. Significant population structure and differentiation were revealed among wild populations (average FST = 0.001–0.107; p < 0.05). Eighty-nine putatively outlier SNPs were identified to be potentially associated with environmental variables by using both population differentiation (BayeScan and PCAdapt) and environmental association (redundancy analysis and latent factor mixed model) analysis methods. Clear population structure with similar spatial patterns were observed in both neutral and outlier markers with three genetically distinct groups identified (north Queensland, Northern Territory, and Western Australia). Redundancy, partial redundancy, and multiple regression on distance matrices analyses revealed that both geographical distance and environmental factors interact to generate the structure observed across Australian P. monodon populations. This study provides new insights on genetic population structure of Australian P. monodon in the face of environmental changes, which can be used to advance sustainable fisheries management and aquaculture breeding programs.
14 citations
TL;DR: This study confirms field-based censuses showing that recurrent-fire regimes give ecological opportunities to wall lizards that benefit from habitat openness and examines whether a recurrent fire regime may disrupt the spatial structure of populations.
Abstract: Socioeconomic and climatic factors are modifying fire regimes with an increase of fire frequency and extension. Unfortunately, the effects of recurrent fires on biological processes that ultimately affect the genetic diversity of animal populations are mostly unknown. We examined genetic patterns of diversity in the wall lizard Podarcis guadarramae in northern Portugal, one of the European regions with the highest percentage of burnt land. This species is a small saxicolous lizard as it inhabits natural outcrops and artificial stone walls, likely in recurrent-fire landscapes. We genotyped nine microsatellites from ten populations selected according to a gradient in fire recurrence, and compared genetic diversity indexes and demographic patterns among them. At the population level, we hypothesize that a high level of mortality and population bottlenecks are expected to reduce genetic heterozygosity in sampled localities affected by recurrent fires. Alternatively, genetic signatures are expected to be absent whether fire did not cause high mortality. Regardless of levels of mortality, we expect a gain in genetic diversity whether recurrent fires facilitate lizard dispersal and migration due to the increased quality of the habitat for wall lizards. At the regional level, we examine whether a recurrent fire regime may disrupt the spatial structure of populations. Our results showed an increase in genetic diversity in recurrently burnt populations, and a decline in longer-unburnt populations. We did not detect bottleneck effects in repeatedly-burnt populations. High genetic diversity in recurrent fire populations suggests a high dispersion rate between adjacent metapopulations and perhaps immigration from outside the fire boundary. At the regional level, lizard populations show low differentiation and weak genetic structure, suggesting no effects of fire. This study confirms field-based censuses showing that recurrent-fire regimes give ecological opportunities to wall lizards that benefit from habitat openness.
13 citations
References
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TL;DR: MICRO - CHECKER estimates the frequency of null alleles and, importantly, can adjust the allele and genotype frequencies of the amplified alleles, permitting their use in further population genetic analysis.
Abstract: DNA degradation, low DNA concentrations and primer-site mutations may result in the incorrect assignment of microsatellite genotypes, potentially biasing population genetic analyses. MICRO - CHECKER is WINDOWS ®-based software that tests the genotyping of microsatellites from diploid populations. The program aids identification of genotyping errors due to nonamplified alleles (null alleles), short allele dominance (large allele dropout) and the scoring of stutter peaks, and also detects typographic errors. MICRO - CHECKER estimates the frequency of null alleles and, importantly, can adjust the allele and genotype frequencies of the amplified alleles, permitting their use in further population genetic analysis. MICRO CHECKER can be freely downloaded from http://www.microchecker.hull.ac.uk/.
9,953 citations
7,585 citations
TL;DR: It was found that there is no equilibrium in either case short of complete fixation locally, in spite of the linear increase in number of different ancestors with increasing number of ancestral generations, in contrast to systems (half first cousin or second cousin) in which this increase is more than linear and a steady state is rapidly attained with respect to heterozygosis.
Abstract: Kimura and Crow (1963b) have recently made an interesting comparison between two classes of systems of mating within populations of constant size: ones in which there is maximum avoidance of consanguine mating and ones in which all matings are between close relatives around an unbroken circle. These are illustrated in Figs. 1 and 2 in populations of eight. The rate of decrease of heterozygosis in the former class had, as they note, been found long before to approach 1/(4N) asymptotically with increasing size of population, N (Wright, 1921, 1933a). Two cases with patterns of mating similar to those of Kimura and Crow's second class, except that the matings were between neighbors along infinitely extended lines instead of around a circle, had also been considered in these papers. These systems consisted of exclusive mating of half-sibs or of first cousins, otherwise with a minimum of relationship. It was found that there is no equilibrium in either case short of complete fixation locally, in spite of the linear increase in number of different ancestors with increasing number of ancestral generations. This was in contrast to systems (half first cousin or second cousin) in which this increase is more than linear and a steady state is rapidly attained with respect to heterozygosis. Kimura and Crow were surprised to find that the limiting rates of decrease of heterozygosis in their circular systems are much less than under maximum avoidance approaching [v/(2N + 4)]2 in the case of half-sib matings and [7/ (N + 12)]2 under first-cousin matings with large N. Maxi-
3,305 citations
TL;DR: F(ST) estimation from corrected genotype frequencies performed well when restricted to visible allele sizes, and the use of the genetic distance of Cavalli-Sforza and Edwards (1967) corrected by the conventional method gave better estimates than those obtained without correction.
Abstract: Microsatellite null alleles are commonly encountered in population genetics studies, yet little is known about their impact on the estimation of population differentiation. Computer simulations based on the coalescent were used to investigate the evolutionary dynamics of null alleles, their impact on F(ST) and genetic distances, and the efficiency of estimators of null allele frequency. Further, we explored how the existing method for correcting genotype data for null alleles performed in estimating F(ST) and genetic distances, and we compared this method with a new method proposed here (for F(ST) only). Null alleles were likely to be encountered in populations with a large effective size, with an unusually high mutation rate in the flanking regions, and that have diverged from the population from which the cloned allele state was drawn and the primers designed. When populations were significantly differentiated, F(ST) and genetic distances were overestimated in the presence of null alleles. Frequency of null alleles was estimated precisely with the algorithm presented in Dempster et al. (1977). The conventional method for correcting genotype data for null alleles did not provide an accurate estimate of F(ST) and genetic distances. However, the use of the genetic distance of Cavalli-Sforza and Edwards (1967) corrected by the conventional method gave better estimates than those obtained without correction. F(ST) estimation from corrected genotype frequencies performed well when restricted to visible allele sizes. Both the proposed method and the traditional correction method have been implemented in a program that is available free of charge at http://www.montpellier.inra.fr/URLB/. We used 2 published microsatellite data sets based on original and redesigned pairs of primers to empirically confirm our simulation results.
2,470 citations
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