Estimating kinship in admixed populations

Genome-wide association studies (GWASs) are commonly used for the mapping of genetic loci that influence complex traits. A problem that is often encountered in both population-based and family-based GWASs is that of identifying cryptic relatedness and population stratification because it is well known that failure to appropriately account for both pedigree and population structure can lead to spurious association. A number of methods have been proposed for identifying relatives in samples from homogeneous populations. A strong assumption of population homogeneity, however, is often untenable, and many GWASs include samples from structured populations. Here, we consider the problem of estimating relatedness in structured populations with admixed ancestry. We propose a method, REAP (relatedness estimation in admixed populations), for robust estimation of identity by descent (IBD)-sharing probabilities and kinship coefficients in admixed populations. REAP appropriately accounts for population structure and ancestry-related assortative mating by using individual-specific allele frequencies at SNPs that are calculated on the basis of ancestry derived from whole-genome analysis. In simulation studies with related individuals and admixture from highly divergent populations, we demonstrate that REAP gives accurate IBD-sharing probabilities and kinship coefficients. We apply REAP to the Mexican Americans in Los Angeles, California (MXL) population sample of release 3 of phase III of the International Haplotype Map Project; in this sample, we identify third- and fourth-degree relatives who have not previously been reported. We also apply REAP to the African American and Hispanic samples from the Women's Health Initiative SNP Health Association Resource (WHI-SHARe) study, in which hundreds of pairs of cryptically related individuals have been identified.     

Population correlation and population kinship

The processes of gene identity by descent and of allelic identities (or likenesses) between genes have been previously studied under a wide variety of migration and subdivision models of population evolution. Since the two processes follow probabilistically parallel paths, there has been a tendency to consider the two processes as equivalent, and to equate estimates of correlation of allele frequency with those of gene identity by descent. The adequacy of this procedure must depend upon the evolutionary history. Here, by distinguishing the processes and considering them jointly as a population evolves in time, we demonstrate the relationship between them in a simple situation, thus providing a basis for study of the extent to which observed allelic similarity between populations is a reflection of underlying gene identity.     

Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene‐flow populations

We combine kinship estimates with traditional F‐statistics to explain contemporary drivers of population genetic differentiation despite high gene flow. We investigate range‐wide population genetic structure of the California spiny (or red rock) lobster (Panulirus interruptus) and find slight, but significant global population differentiation in mtDNA (Φ_ST = 0.006, P = 0.001; D_{est_Chao} = 0.025) and seven nuclear microsatellites (F_ST = 0.004, P < 0.001; D_{est_Chao} = 0.03), despite the species’ 240‐ to 330‐day pelagic larval duration. Significant population structure does not correlate with distance between sampling locations, and pairwise F_ST between adjacent sites often exceeds that among geographically distant locations. This result would typically be interpreted as unexplainable, chaotic genetic patchiness. However, kinship levels differ significantly among sites (pseudo‐F_16,988 = 1.39, P = 0.001), and ten of 17 sample sites have significantly greater numbers of kin than expected by chance (P < 0.05). Moreover, a higher proportion of kin within sites strongly correlates with greater genetic differentiation among sites (D_{est_Chao}, R² = 0.66, P < 0.005). Sites with elevated mean kinship were geographically proximate to regions of high upwelling intensity (R² = 0.41, P = 0.0009). These results indicate that P. interruptus does not maintain a single homogenous population, despite extreme dispersal potential. Instead, these lobsters appear to either have substantial localized recruitment or maintain planktonic larval cohesiveness whereby siblings more likely settle together than disperse across sites. More broadly, our results contribute to a growing number of studies showing that low F_ST and high family structure across populations can coexist, illuminating the foundations of cryptic genetic patterns and the nature of marine dispersal.     

Estimating population trends using population viability analyses for the conservation ofCapra pyrenaica

Large herbivore populations can suffer important oscillations with considerable effects on ecosystem functions and services, yet our capacity to predict population fate is limited and conditional upon the availability of data. This study investigated the interannual variation in the growth rate of populations ofCapra pyrenaica Schinz, 1838, and its extinction risk by comparing the dynamics of populations that were stable for more than two decades (Gredos and Tortosa-Beceite), populations that had increased recently (Tejeda-Almijara), and populations that were in decline (Cazorla-Segura) or extinct (the Pyrenees population; hereafter, bucardo). To estimate quasi-extinction threshold assessments (50% of population extinct in this study), which have implications for the conservation of the species, we used empirical data and the predictions derived from several theoretical models. The results indicate that when variance of log population growth rate reaches a specific threshold, the probability of quasi-extinction increased drastically. ForC. pyrenaica, we recommend keeping population variance < 0.05, which will reduce the likelihood that the irruptive oscillations caused by environmental and demographic stochasticity will put the population at risk. Models to predict the dynamics ofC. pyrenaica populations should incorporate temporal stochasticity because, in this study, it strongly increased the likelihood that a population declined.     

Background selection and FST: Consequences for detecting local adaptation

Background selection is a process whereby recurrent deleterious mutations cause a decrease in the effective population size and genetic diversity at linked loci. Several authors have suggested that variation in the intensity of background selection could cause variation in F_ST across the genome, which could confound signals of local adaptation in genome scans. We performed realistic simulations of DNA sequences, using recombination maps from humans and sticklebacks, to investigate how variation in the intensity of background selection affects F_ST and other statistics of population differentiation in sexual, outcrossing species. We show that, in populations connected by gene flow, Weir and Cockerham's (1984; Evolution, 38 , 1358) estimator of F_ST is largely insensitive to locus‐to‐locus variation in the intensity of background selection. Unlike F_ST, however, d_XY is negatively correlated with background selection. Moreover, background selection does not greatly affect the false‐positive rate in F_ST outlier studies in populations connected by gene flow. Overall, our study indicates that background selection will not greatly interfere with finding the variants responsible for local adaptation.     

A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information

A general approach to family-based examinations of association between marker alleles and traits is proposed. The approach is based on computing p values by comparing test statistics for association to their conditional distributions given the minimal sufficient statistic under the null hypothesis for the genetic model, sampling plan and population admixture. The approach can be applied with any test statistic, so any kind of phenotype and multi-allelic markers may be examined, and covariates may be included in analyses. By virtue of the conditioning, the approach results in correct type I error probabilities regardless of population admixture, the true genetic model and the sampling strategy. An algorithm for computing the conditional distributions is described, and the results of the algorithm for configurations of nuclear families are presented. The algorithm is applicable with all pedigree structures and all patterns of missing marker allele information.     

Estimating ancestral population sizes and divergence times

This article presents a new method for jointly estimating species divergence times and ancestral population sizes. The method improves on previous ones by explicitly incorporating intragenic recombination, by utilizing orthologous sequence data from closely related species, and by using a maximum-likelihood framework. The latter allows for efficient use of the available information and provides a way of assessing how much confidence we should place in the estimates. I apply the method to recently collected intergenic sequence data from humans and the great apes. The results suggest that the human-chimpanzee ancestral population size was four to seven times larger than the current human effective population size and that the current human effective population size is slightly >10,000. These estimates are similar to previous ones, and they appear relatively insensitive to assumptions about the recombination rates or mutation rates across loci.     

Dispersal,kinship and inbreeding in an island population of the Great Tit

We investigated the kinship structure of an island population of the Great Tit (Parus major). Kinship of birds could be inferred by comparing their family trees. Dispersal was also studied to explain the observed pattern of kinship. On the island of Vlieland the tits breed in several wooded areas. Both males and females preferred to breed in their natal area; males did so more strongly than females. Hence gene flow between the areas is restricted. However, within the largest wooded area females showed random dispersal, while males showed a slight tendency to breed near their natal site. The degree of kinship of neighbouring birds is a suitable control group for the relatedness of partners that takes into account the effects of dispersal. In the largest wooded area, birds were on average equally related to their partner and to their neighbours. Moreover, the mean coefficient of kinship between male and female neighbours was equal to the average kinship in this part of the population. We conclude that mating is random with respect to kinship. There is no evidence for avoidance of inbreeding. It is unlikely that kin recognition plays an important role in the process of mate choice in this population of Great Tits. We suggest that ecological factors are the main causes for the observed patterns of dispersal and mating. On the island more female than male immigrants enter the population each year. Incidental data indicate an exchange of birds between the population studied and surrounding populations. Ancestries of immigrants are not known, and indeed a first analysis of all birds, including immigrants, showed that males were more closely related than females. However, differential immigration could not fully explain the observed difference in kinship. The presence of local adaptation in males is suggested as a possible additional cause.     

Microsatellites and kinship

Many evolutionary studies, particularly kinship studies, have been limited by the availability of segregating genetic marker loci. Microsatellites promise to alleviate these problems. Microsatellite loci are segments of DNA with very short sequence motifs repeated in tandem; their often numerous alleles differ in the number of these repeat units. They are very common in eukaryotic DNA and can be amplified by the polymerase chain reaction, which allows the use of minute or degraded DNA samples. The alleles can be scored consistently and compared unambiguously, even across different gels.     

STR markers for kinship analysis

The analysis of short tandem repeats is a widely used method to estimate relatedness between closely related populations or individuals. The AmpFlSTR PCR Amplification Kit has 15 highly variable autosomal markers of tetranucleotide repeats and is principally made to identify individuals and first- or second-degree relatives. However, in many studies one is searching for individuals who are related through more than one generation. We wanted to test whether the amplification kit can also be used to identify more distantly related individuals. Therefore we compared 16 different methods that calculate genetic distance with regard to each method's ability to cluster more distantly related individuals from two test families. Among all the tested methods Nei et al.'s (1983) DA distance performed well in clustering family members within a group of unrelated individuals for a broad range of scenarios. However, second-degree relatives were difficult to cluster with any of the examined methods when other family members were absent. With a simulation we further estimated how many markers would actually be needed to detect a certain degree of relatedness. According to this simulation, one would need at least 123 independent microsatellite markers to detect third-degree relatives with 90% probability. In conclusion, the 15 STR markers in the amplification kit are suitable for detecting only very closely related individuals or entire families.     

Estimating the unbiased estimator theta for population genetic survey data

We consider a method of approximating Weir and Cockerham's theta, an unbiased estimator of genetic population structure, using values readily available from published studies using biased estimators (Wright's F(ST) or Nei's G(ST)). The estimation algorithm is shown to be useful for both model populations and real-world avian populations. However, the correlation between Wright's F(ST) and Weir and Cockerham's theta is strong when compared among 39 empirical avian datasets. Thus, the advantage of approximating an unbiased estimator is unclear considering the small actual effect of theta's bias-removing power on empirical datasets.     

Microsatellite DNA markers for delineating population structure and kinship among the endangered Kirtland's warbler (Dendroica kirtlandii)

We document the isolation and characterization of 23 microsatellite DNA markers for the endangered Kirtland's warbler (Dendroica kirtlandii), a Nearctic/Neotropical migrant passerine. This suite of markers revealed moderate to high levels of allelic diversity (averaging 7.7 alleles per locus) and heterozygosity (averaging 72%). Genotypic frequencies at 22 of 23 (95%) markers conformed to Hardy–Weinberg equilibrium expectations, and no linkage disequilibrium was observed in blood samples taken from 14 warblers found on the wintering grounds in the Bahamas archipelago. Multilocus genotypes resulting from this suite of markers should reduce the amount of resources required for initiating new genetic studies assessing breeding structure, parentage, demographics, and individual‐level ecological interactions for D. kirtlandii.     

Estimating animal population density using passive acoustics

Reliable estimation of the size or density of wild animal populations is very important for effective wildlife management, conservation and ecology. Currently, the most widely used methods for obtaining such estimates involve either sighting animals from transect lines or some form of capture‐recapture on marked or uniquely identifiable individuals. However, many species are difficult to sight, and cannot be easily marked or recaptured. Some of these species produce readily identifiable sounds, providing an opportunity to use passive acoustic data to estimate animal density. In addition, even for species for which other visually based methods are feasible, passive acoustic methods offer the potential for greater detection ranges in some environments (e.g. underwater or in dense forest), and hence potentially better precision. Automated data collection means that surveys can take place at times and in places where it would be too expensive or dangerous to send human observers. Here, we present an overview of animal density estimation using passive acoustic data, a relatively new and fast‐developing field. We review the types of data and methodological approaches currently available to researchers and we provide a framework for acoustics‐based density estimation, illustrated with examples from real‐world case studies. We mention moving sensor platforms (e.g. towed acoustics), but then focus on methods involving sensors at fixed locations, particularly hydrophones to survey marine mammals, as acoustic‐based density estimation research to date has been concentrated in this area. Primary among these are methods based on distance sampling and spatially explicit capture‐recapture. The methods are also applicable to other aquatic and terrestrial sound‐producing taxa. We conclude that, despite being in its infancy, density estimation based on passive acoustic data likely will become an important method for surveying a number of diverse taxa, such as sea mammals, fish, birds, amphibians, and insects, especially in situations where inferences are required over long periods of time. There is considerable work ahead, with several potentially fruitful research areas, including the development of (i) hardware and software for data acquisition, (ii) efficient, calibrated, automated detection and classification systems, and (iii) statistical approaches optimized for this application. Further, survey design will need to be developed, and research is needed on the acoustic behaviour of target species. Fundamental research on vocalization rates and group sizes, and the relation between these and other factors such as season or behaviour state, is critical. Evaluation of the methods under known density scenarios will be important for empirically validating the approaches presented here.     

Estimating the size of a transient population

Migratory populations often stop over for short periods of time at predictable sites along their migration routes. These staging areas can be heavily used and are potentially critical to the survival of the migrants. This paper presents a method for estimating the number of individuals using such an area and their average residence time. The estimator is based on daily population estimates and records of repeat sightings of identifiable individuals. Its application is illustrated with observations on a population of migrating birds, some of which could be identified from bands that were readable from a distance.     

Estimating incident population distribution from prevalent data

A prevalent sample consists of individuals who have experienced disease incidence but not failure event at the sampling time. We discuss methods for estimating the distribution function of a random vector defined at baseline for an incident disease population when data are collected by prevalent sampling. Prevalent sampling design is often more focused and economical than incident study design for studying the survival distribution of a diseased population, but prevalent samples are biased by design. Subjects with longer survival time are more likely to be included in a prevalent cohort, and other baseline variables of interests that are correlated with survival time are also subject to sampling bias induced by the prevalent sampling scheme. Without recognition of the bias, applying empirical distribution function to estimate the population distribution of baseline variables can lead to serious bias. In this article, nonparametric and semiparametric methods are developed for distribution estimation of baseline variables using prevalent data.