Determination of genetic relatedness from low‐coverage human genome sequences using pedigree simulations

We develop and evaluate methods for inferring relatedness among individuals from low‐coverage DNA sequences of their genomes, with particular emphasis on sequences obtained from fossil remains. We suggest the major factors complicating the determination of relatedness among ancient individuals are sequencing depth, the number of overlapping sites, the sequencing error rate and the presence of contamination from present‐day genetic sources. We develop a theoretical model that facilitates the exploration of these factors and their relative effects, via measurement of pairwise genetic distances, without calling genotypes, and determine the power to infer relatedness under various scenarios of varying sequencing depth, present‐day contamination and sequencing error. The model is validated by a simulation study as well as the analysis of aligned sequences from present‐day human genomes. We then apply the method to the recently published genome sequences of ancient Europeans, developing a statistical treatment to determine confidence in assigned relatedness that is, in some cases, more precise than previously reported. As the majority of ancient specimens are from animals, this method would be applicable to investigate kinship in nonhuman remains. The developed software grups (Genetic Relatedness Using Pedigree Simulations) is implemented in Python and freely available.     

THE MEANINGS OF KINSHIP AMONG THE ESE EJJA OF NORTHERN BOLIVIA

This article focuses on the construction of relatedness among an Amazonian people of northern Bolivia. In analysing the Ese Ejja's kinship terminology and practices, it engages with the widespread stress on the processual nature of relatedness encountered in Amazonian studies. The article shows that, for the Ese Ejja, kinship relations are made through shared practices, although in some important respects kinship is considered to be given at birth. Given kinship is considered fixed, whereas processual kinship is open to contestation. The article argues that processual and given aspects of kinship must be considered together in order to account for local understandings of relatedness. The data presented invite further investigation into Amazonian ideas about the sharing of substance through filiation. This has important implications for the understanding of the conceptualization of cross- and parallel cousins. The article also suggests that in Amazonia otherness is not always given, as has been extensively argued, and that, in the context of Ese Ejja kinship relations, it is created through marriage and it is constantly made and undone.     

Human ability to detect kinship in strangers' faces: effects of the degree of relatedness

The resemblance between human faces has been shown to be a possible cue in recognizing the relatedness between parents and children, and more recently, between siblings. However, the general inclusive fitness theory proposes that kin-selective behaviours are also relevant to more distant relatives, which requires the detection of larger kinship bonds. We conducted an experiment to explore the use of facial clues by ‘strangers’, i.e. evaluators from a different family, to associate humans of varying degrees of relatedness. We hypothesized that the visual capacity to detect relatedness should be weaker with lower degrees of relatedness. We showed that human adults are capable of (although not very efficient at) assessing the relatedness of unrelated individuals from photographs and that visible facial cues vary according to the degree of relatedness. This sensitivity exists even for kin pair members that are more than a generation apart and have never lived together. Collectively, our findings are in agreement with emerging knowledge on the role played by facial resemblance as a kinship cue. But we have progressed further to show how the capacity to distinguish between related and non-related pairs applies to situations relevant to indirect fitness.     

The efficiency of different search strategies in estimating parsimony jackknife,bootstrap, and Bremer support

Background  

For parsimony analyses, the most common way to estimate confidence is by resampling plans (nonparametric bootstrap, jackknife), and Bremer support (Decay indices). The recent literature reveals that parameter settings that are quite commonly employed are not those that are recommended by theoretical considerations and by previous empirical studies. The optimal search strategy to be applied during resampling was previously addressed solely via standard search strategies available in PAUP*. The question of a compromise between search extensiveness and improved support accuracy for Bremer support received even less attention. A set of experiments was conducted on different datasets to find an empirical cut-off point at which increased search extensiveness does not significantly change Bremer support and jackknife or bootstrap proportions any more.     

Genetic counseling in rare syndromes: a resampling method for determining an approximate confidence interval for gene location with linkage data from a single pedigree.

Multipoint linkage analysis is a powerful method for mapping a rare disease gene on the human gene map despite limited genotype and pedigree data. However, there is no standard procedure for determining a confidence interval for gene location by using multipoint linkage analysis. A genetic counselor needs to know the confidence interval for gene location in order to determine the uncertainty of risk estimates provided to a consultant on the basis of DNA studies. We describe a resampling, or "bootstrap," method for deriving an approximate confidence interval for gene location on the basis of data from a single pedigree. This method was used to define an approximate confidence interval for the location of a gene causing nonsyndromal X-linked mental retardation in a single pedigree. The approach seemed robust in that similar confidence intervals were derived by using different resampling protocols. Quantitative bounds for the confidence interval were dependent on the genetic map chosen. Once an approximate confidence interval for gene location was determined for this pedigree, it was possible to use multipoint risk analysis to estimate risk intervals for women of unknown carrier status. Despite the limited genotype data, the combination of the resampling method and multipoint risk analysis had a dramatic impact on the genetic advice available to consultants.     

Kin and kinship psychology both influence cooperative coordination in Yasawa,Fiji

Genes shared through common ancestry are among the oldest social bonds. Despite these ancient roots, humans often co-opt the psychology of genetic relatedness and extend it to genetically unrelated others through culturally-acquired kinship systems. We investigate how genealogical relatedness and kinship norms might mutually support or oppose each other within a known kin network in Yasawa, Fiji. Yasawans' reliance on intensive, kin-based cooperation for daily life makes Yasawan kinship an interesting test case to compare the effects of genealogy and kinship norms. Confirming qualitative ethnographic claims, we find that Yasawan kin terms can be described in two dimensions of respect/closeness and joking/authority. Individual players use different strategies for genealogical relatives and non-relatives by making economic game choices that are increasingly beneficial to partners who share a higher percentage of genes through common ancestry. However, pairs of players are most successful in coordinating their game choices despite conflicting self-interests based upon kinship norms relevant to hierarchy. Thus, while genealogical relatedness may boost generosity, the extra behavioral structuring from kinship norms facilitates more productive but difficult coordinated action even when communication is not possible.     

Reducing cryptic relatedness in genomic data sets via a central node exclusion algorithm

Cryptic relatedness is a confounding factor in genetic diversity and genetic association studies. Development of strategies to reduce cryptic relatedness in a sample is a crucial step for downstream genetic analyses. This study uses a node selection algorithm, based on network degrees of centrality, to evaluate its applicability and impact on evaluation of genetic diversity and population stratification. 1,036 Guzerá (Bos indicus) females were genotyped using Illumina Bovine SNP50 v2 BeadChip. Four strategies were compared. The first and second strategies consist on a iterative exclusion of most related individuals based on PLINK kinship coefficient (φij) and VanRaden's φij, respectively. The third and fourth strategies were based on a node selection algorithm. The fourth strategy, Network G matrix, preserved the larger number of individuals with a better diversity and representation from the initial sample. Determining the most probable number of populations was directly affected by the kinship metric. Network G matrix was the better strategy for reducing relatedness due to producing a larger sample, with more distant individuals, a more similar distribution when compared with the full data set in the MDS plots and keeping a better representation of the population structure. Resampling strategies using VanRaden's φij as a relationship metric was better to infer the relationships among individuals. Moreover, the resampling strategies directly impact the genomic inflation values in genomewide association studies. The use of the node selection algorithm also implies better selection of the most central individuals to be removed, providing a more representative sample.     

Quality and quantity of genetic relatedness data affect the analysis of social structure

Kinship plays a fundamental role in the evolution of social systems and is considered a key driver of group living. To understand the role of kinship in the formation and maintenance of social bonds, accurate measures of genetic relatedness are critical. Genotype‐by‐sequencing technologies are rapidly advancing the accuracy and precision of genetic relatedness estimates for wild populations. The ability to assign kinship from genetic data varies depending on a species’ or population's mating system and pattern of dispersal, and empirical data from longitudinal studies are crucial to validate these methods. We use data from a long‐term behavioural study of a polygynandrous, bisexually philopatric marine mammal to measure accuracy and precision of parentage and genetic relatedness estimation against a known partial pedigree. We show that with moderate but obtainable sample sizes of approximately 4,235 SNPs and 272 individuals, highly accurate parentage assignments and genetic relatedness coefficients can be obtained. Additionally, we subsample our data to quantify how data availability affects relatedness estimation and kinship assignment. Lastly, we conduct a social network analysis to investigate the extent to which accuracy and precision of relatedness estimation improve statistical power to detect an effect of relatedness on social structure. Our results provide practical guidance for minimum sample sizes and sequencing depth for future studies, as well as thresholds for post hoc interpretation of previous analyses.     

Cultural relatedness under oblique and horizontal transmission rules

The concept of genetic relatedness is central to the sociobiological theory of kinship altruism. Genes which code for altruistic acts toward closely related genetic kin can overcome selection pressures favoring self-interested behavior. But genetic relatedness declines rapidly as kinship becomes more distant, thereby restricting genetically-based altruism to very close kin. This paper extends these notions to cultural relatedness, arguing that oblique and horizontal transmission can yield high levels of cultural relatedness in larger groups. A mathematical model of cultural transmission is proposed, and equilibria for several special cases are investigated. For all models, the equilibrium level of relatedness is critically dependent on the influence of exogenous sources. In models with equal influence of nonparents, the level of relatedness varies inversely with group size. On the other hand, when nonparental influence is concentrated on a single individual, the level of relatedness does not vary with group size.     

A comparison of two methods for making statistical inferences on Nei's measure of genetic distance

The delta and jackknife methods can be used to estimate Nei's measure of genetic distance and calculate confidence intervals for this estimate. Computer stimulations were used to study the bias and variance of each estimator and the accuracy of the corresponding approximate 95% confidence intervals. The simulations were conducted using 3 sets of data and several sample sizes. The results showed: (1) the jackknife reduced bias; (2) in 8 out of 9 cases the variance and mean square error of the jackknife estimator were less; (3) a second order jackknife reduced the bias the most but suffered a corresponding increase in variance; (4) both the first order jackknife and delta methods yielded intervals whose confidence levels were approximately equal but less than 95%.     

Power and Effective Study Size in Heritability Studies

Correlation between study units in quantitative genetics studies often makes it difficult to compare important inferential aspects of studies. Describing the relatedness between study units is critical to capture features of pedigree studies involving heritability, including power and precision of heritability estimates. Blangero et al. (Adv Genet 81:1–31, 2012) showed that in pedigree studies the power to detect heritability is a function of the true heritability and the eigenvalues of the kinship matrix. We extend this to a more general setting which allows statements about expected precision of heritability estimates. Using two different Taylor series approximations, we summarize the relatedness in a study design by one or two parameters. These relatedness summary parameters (RSPs) are functions of the eigenvalues or log-eigenvalues of the kinship matrix. Using the RSPs based on the log-eigenvalues, we accurately approximate the expectation of the likelihood ratio test and expected confidence interval widths. We define an effective sample size of a target study as one which has the equivalent power and precision to a reference design. Using unrelated sibpairs as the reference design provides very accurate assessments of power. RSPs and effective sample sizes provide new tools for comparing studies and communicating information about relatedness in heritability studies.     

Multilocus estimation of pairwise relatedness with dominant markers

Estimators for pairwise relatedness designed for dominant markers are derived, based on a genetic model that accounts for the full structure of pairwise relatedness between two individuals at a diploid locus with dominance. They jointly estimate 'relatedness' and 'fraternity', in which case the estimators are inherently multilocus, as at least two loci of differing gene frequency are required. Extensions to cases of zero fraternity and isolation by distance (inbreeding) are also examined. Properties of estimators are examined by simulation and compared to the estimator of Hardy. The most statistical power for pairwise relatedness occurs when roughly half of individuals are the recessive phenotype. Estimation procedures are implemented in the computer program mark.     

COANCESTRY: a program for simulating, estimating and analysing relatedness and inbreeding coefficients

The software package COANCESTRY implements seven relatedness estimators and three inbreeding estimators to estimate relatedness and inbreeding coefficients from multilocus genotype data. Two likelihood estimators that allow for inbred individuals and account for genotyping errors are for the first time included in this user-friendly program for PCs running Windows operating system. A simulation module is built in the program to simulate multilocus genotype data of individuals with a predefined relationship, and to compare the estimators and the simulated relatedness values to facilitate the selection of the best estimator in a particular situation. Bootstrapping and permutations are used to obtain the 95% confidence intervals of each relatedness or inbreeding estimate, and to test the difference in averages between groups.     

Kin Preference and Partner Choice

This paper presents a comparison of social kinship (patrilineage) and biological kinship (genetic relatedness) in predicting cooperative relationships in two different economic contexts in the fishing and whaling village of Lamalera, Indonesia. A previous analysis (Alvard, Human Nature 14:129-163, 2003) of boat crew affiliation data collected in the village in 1999 found that social kinship (patrilineage) was a better predictor of crew affiliation than was genetic kinship. A replication of this analysis using similar data collected in 2006 finds the same pattern: lineage is a better predictor than genetic kinship of crew affiliation, and the two together explain little additional variance over that explained by lineage alone. However, an analogous test on food-sharing relationships finds the opposite pattern: biological kinship is a better predictor of food-sharing relationships than is social kinship. The difference between these two cooperative contexts is interpreted in terms of kin preferences that shape partner choice, and the relative autonomy with which individuals can seek to satisfy those preferences. Drawing on stable matching theory, it is suggested that unilineal descent may serve as a stable compromise among multiple individuals' incongruent partner preferences, with patriliny favored over matriliny in the crew-formation context because it leads to higher mean degrees of relatedness among male cooperators. In the context of food-sharing, kin preferences can be pursued relatively autonomously, without the necessity of coordinating preferences with those of other households through the institution of lineage.     

Relatedness and Social Behaviors in <Emphasis Type="Italic">Cercopithecus solatus</Emphasis>

Inclusive fitness and kin selection theories predict that organisms will evolve biased behavior toward kin when the inclusive fitness benefits outweigh the costs of such behaviors. Researchers have long observed that primates bias their behavior toward relatives, particularly maternal kin. We examined the effect of kinship on social behaviors in a semifree-ranging colony of Cercopithecus solatus, a poorly studied forest guenon species. We used microsatellite loci and paternity analyses to determine the degree of relatedness between individuals, as well as kinship. Individuals biased some of their behavior according to relatedness. Specifically, related individuals are more spatially associated and less aggressive toward each other. When we replaced the relatedness coefficients with defined kin categories, Cercopithecus solatus seemed to behave preferentially toward maternal kin versus paternal kin. Even though the setting of the colony and the small sample size limit our conclusions, we discuss the potential implications of our finding for the study of the impact of kin selection in primate social relationships.     

Fluctuating populations and kin interaction in mammals

Kin selection in animals favors less aggressive interaction among related individuals. If the genetic relatedness among neighbors changes with population structure and density, behavioral interaction may also change according to the population structure. Charnov and Finerty proposed a hypothesis that kin selection in voles causes population cycles if the relatedness among neighbors decreases as density increases. Field experiments have recently tested this hypothesis. Furthermore, field studies of social interaction in voles have increased in number, so that the effects of kinship on reproductive success can be reviewed. These studies indicate that although kin interaction might be an important factor affecting social behavior and reproductive success in voles, the relationships both between kinship and degree of amicable behavior or reproductive rate, and between relatedness among neighbors and population density, are far less simple than had been supposed.     

Kin structure and social organization in the spotted eagle ray,Aetobatus narinari,off coastal Sarasota,FL

Observations of elasmobranchs in groups suggest sociality in sharks and rays. However we currently lack a strong understanding of social structure and the role kinship has in structuring group organization in cartilaginous fishes. The spotted eagle ray, Aetobatus narinari (Euphrasen, 1790) frequents the shallow waters near Sarasota, FL, often in pairs or groups suggesting a social component to their behavior. In the present study, eight eagle ray-specific microsatellite markers were used to investigate relatedness in A. narinari groups, and used to determine if kin structure contributed to group organization. Using regression-based and maximum-likelihood approaches, relatedness was quantified and compared within and among groups of juveniles, and adults in mixed sex and same sex groups. Results showed a lack of kin-structured sociality in A. narinari, suggesting factors apart from relatedness shape social interactions among spotted eagle rays in the near-shore waters of Sarasota, FL. Our results add to the limited amount of published literature on elasmobranch kinship, which are important for understanding implications of anthropogenic disturbance on genetic variability for coastal populations.     

Amazonian horticulturalists live in larger,more related groups than hunter–gatherers

The relatedness of human groups has important ramifications for kin (group) selection to favor more collective action and invites the potential for more exploitation by political leaders. Endogamous marriages among kin create intensive kinship systems with high group relatedness, while exogamous marriages among nonrelatives create extensive kinship with low group relatedness. Here, a sample of 58 societies (7,565 adults living in 353 residential groups) shows that average group relatedness is higher in lowland horticulturalists than in hunter–gatherers. Higher relatedness in horticulturalists is remarkable given that village sizes are larger, harboring over twice the average number of adults than in hunter–gatherer camps. The relatedness differential between subsistence regimes increases for larger group sizes. Large and dense networks of kin may have favored an increased propensity for some forms of in-group cooperation and political inequality that emerged relatively recently in human history, after the advent of farming.     

Resampling measures of group support: a reply to Grant and Kluge

Grant and Kluge (2003) associated resampling measures of group support with the aim of evaluating statistical stability, confidence, or the probability of recovering a true phylogenetic group. This interpretation is not necessary to methods such as jackknifing or bootstrapping, which are better interpreted as measures of support from the current dataset. Grant and Kluge only accepted the absolute Bremer value as a measure of group support, and considered resampling methods as irrelevant to phylogenetic inference. It is shown that under simple circumstances resampling indices better reflect the degree of support than Bremer values. Grant and Kluge associated the resampling methods (and the use of measures of group support in general) with what they call a “verificationist agenda”, where strongly supported groups are first detected, and then protected against additional testing. They propose that identifying weakly supported groups, and then concentrating additional tests on them, will better serve science. Both programs are actually equivalent, and inert as to the selection of methods to estimate group support. The ranking of groups under a range of resampling strength is proposed as an additional criterion to evaluate resampling methods. A reexamination of the slope of symmetric resampling frequency as a function of resampling strength suggest that slopes can be problematic as well as a measure of group support. © The Willi Hennig Society 2005.     

Detecting instability in animal social networks: genetic fragmentation is associated with social instability in rhesus macaques

The persistence of biological systems requires evolved mechanisms which promote stability. Cohesive primate social groups are one example of stable biological systems, which persist in spite of regular conflict. We suggest that genetic relatedness and its associated kinship structure are a potential source of stability in primate social groups as kinship structure is an important organizing principle in many animal societies. We investigated the effect of average genetic relatedness per matrilineal family on the stability of matrilineal grooming and agonistic interactions in 48 matrilines from seven captive groups of rhesus macaques. Matrilines with low average genetic relatedness show increased family-level instability such as: more sub-grouping in their matrilineal groom network, more frequent fighting with kin, and higher rates of wounding. Family-level instability in multiple matrilines within a group is further associated with group-level instability such as increased wounding. Stability appears to arise from the presence of clear matrilineal structure in the rhesus macaque group hierarchy, which is derived from cohesion among kin in their affiliative and agonistic interactions with each other. We conclude that genetic relatedness and kinship structure are an important source of group stability in animal societies, particularly when dominance and/or affilative interactions are typically governed by kinship.