Applications In Population Genetics Research Articles

Genetic Diversity of Five Native Populations (Dusun, Rungus, Sonsogon, Murut and Sungai-Lingkabau Paitan) of North Borneo, East Malaysia based on 17 Y-chromosomal Short-Tandem Repeats Polymorphism

In this study, we typed 51 male individuals from North Borneo using 17 Y-chromosome STRs contained in the AmpFLSTR® Yfiler® kit (Applied Biosystems). These individuals constitute five indigenous ethnic populations representing the three major linguistic groups (Dusunic, Murutic and Paitanic): the Dusun ( n =7), Rungus ( n =12), Sonsogon ( n =12), Murut Paluan ( n =12), and Sungai Lingkabau Paitan ( n =8). A total of 37 haplotypes were identified, of which 30 individuals were represented by a single haplotype. The mean ± S.D. haplotype diversity was 0.600±0.181 and the discrimination capacity was 0.725. The results also showed that the haplotype H33 was the most frequent haplotype observed in the sampled male populations occurring exclusively in the Murut population. Comparative analysis between Y-haplotype populations of North Borneo and the ethnic populations (Bidayuh, Iban, and Melanau) of neighbouring Sarawak (East Malaysia) i.e. indicated that the Sungai Lingkabau Paitan was more closely associated with the Melanau with respect to Y-haplotype descent (RST=- 0.0023). In addition, the Multidimensional Scaling (MSD) analysis managed to clearly differentiate the eight groups from Borneo. We concluded that the 17 Y-chromosome STRs data of North Bornean populations are valuable resources in the applications of forensic and population genetics of the ethnic groups.

Genetic diversity and phylogenetic characteristics of Chinese Tibetan and Yi minority ethnic groups revealed by non-CODIS STR markers

Non-CODIS STRs, with high polymorphism and allele frequency difference among ethnically and geographically different populations, play a crucial role in population genetics, molecular anthropology, and human forensics. In this work, 332 unrelated individuals from Sichuan Province (237 Tibetan individuals and 95 Yi individuals) are firstly genotyped with 21 non-CODIS autosomal STRs, and phylogenetic relationships with 26 previously investigated populations (9,444 individuals) are subsequently explored. In the Sichuan Tibetan and Yi, the combined power of discrimination (CPD) values are 0.9999999999999999999 and 0.9999999999999999993, and the combined power of exclusion (CPE) values are 0. 999997 and 0.999999, respectively. Analysis of molecular variance (AMOVA), principal component analysis (PCA), multidimensional scaling plots (MDS) and phylogenetic analysis demonstrated that Sichuan Tibetan has a close genetic relationship with Tibet Tibetan, and Sichuan Yi has a genetic affinity with Yunnan Bai group. Furthermore, significant genetic differences have widely existed between Chinese minorities (most prominently for Tibetan and Kazakh) and Han groups, but no population stratifications rather a homogenous group among Han populations distributed in Northern and Southern China are observed. Aforementioned results suggested that these 21 STRs are highly polymorphic and informative in the Sichuan Tibetan and Yi, which are suitable for population genetics and forensic applications.

Molecular Markers- Characteristics and Applications in Animal Breeding

During the past three decades, the development of molecular genetics, especially DNA based markers has an important role in the field of animal genetics and breeding. Instead of conventional breeding program through selection alone, utilization of molecular genetic tools can ease us in optimizing the animal breeding program. Selection according to genotype has become an important tool in the breeding of farm animals. Molecular markers, revealing polymorphisms at the DNA level are the powerful tools to study the variation. These molecular markers have wide range of applications in population genetics, conservation biology and evolutionary biology. This review gives a brief summary on the characteristics of different molecular markers including hybridization and PCR-based markers.

Statistical Association Mapping of Population-Structured Genetic Data.

Association mapping of genetic diseases has attracted extensive research interest during the recent years. However, most of the methodologies introduced so far suffer from spurious inference of the associated sites due to population inhomogeneities. In this paper, we introduce a statistical framework to compensate for this shortcoming by equipping the current methodologies with a state-of-the-art clustering algorithm being widely used in population genetics applications. The proposed framework jointly infers the disease-associated factors and the hidden population structures. In this regard, a Markov Chain-Monte Carlo (MCMC) procedure has been employed to assess the posterior probability distribution of the model parameters. We have implemented our proposed framework on a software package whose performance is extensively evaluated on a number of synthetic datasets, and compared to some of the well-known existing methods such as STRUCTURE. It has been shown that in extreme scenarios, up to $10-15$10-15 percent of improvement in the inference accuracy is achieved with a moderate increase in computational complexity.

Cultural evolutionary theory: How culture evolves and why it matters

Human cultural traits—behaviors, ideas, and technologies that can be learned from other individuals—can exhibit complex patterns of transmission and evolution, and researchers have developed theoretical models, both verbal and mathematical, to facilitate our understanding of these patterns. Many of the first quantitative models of cultural evolution were modified from existing concepts in theoretical population genetics because cultural evolution has many parallels with, as well as clear differences from, genetic evolution. Furthermore, cultural and genetic evolution can interact with one another and influence both transmission and selection. This interaction requires theoretical treatments of gene–culture coevolution and dual inheritance, in addition to purely cultural evolution. In addition, cultural evolutionary theory is a natural component of studies in demography, human ecology, and many other disciplines. Here, we review the core concepts in cultural evolutionary theory as they pertain to the extension of biology through culture, focusing on cultural evolutionary applications in population genetics, ecology, and demography. For each of these disciplines, we review the theoretical literature and highlight relevant empirical studies. We also discuss the societal implications of the study of cultural evolution and of the interactions of humans with one another and with their environment.

Genetics in LGB Assisted Reproduction: Two Flipped Classroom, Progressive Disclosure Cases.

There have been several educational reforms calling for increasing lesbian, gay, bisexual, and transgender (LGBT) education materials, application of basic sciences to clinical medicine, and active engagement of students. While the amount of educational materials for LGBT clinical cases is increasing, this session for preclinical medical students uniquely combines basic science population genetics, cisgender lesbian, gay, and bisexual (LGB) cultural issues and reproductive endocrinology in a 1.5-hour flipped classroom session. Students were assigned a prediscussion video and reading. Facilitators attended a 1.5-hour training session prior to discussion. Each classroom of 30 students with small groups of six was led by a third- or fourth-year medical student facilitator who taught from a PowerPoint that included discussion questions. An audience response system was used to show aggregated, real-time anonymous responses to case questions, a pre- and postsurvey was used to analyze changes in student attitudes and knowledge of assisted reproduction services for same-sex couples, and course evaluations captured overarching student impressions. All first-year students (N = 180) attended this mandatory session. Audience response questions showed a high level of knowledge of population genetics concepts. Voluntary surveys showed a higher number of assisted reproduction recommendations for LGB patients compared to heterosexual patients before discussion, with this difference disappearing after the discussion. This may indicate a shift in student attitudes and knowledge of LGB patient barriers and assisted reproduction. Course evaluations showed appreciation of LGB material integration within the course. Educators will be able to successfully integrate the application of population genetics, assisted reproduction cases, and an examination of cultural barriers in health care for LGB patients with this session.

Twenty-nine SNP markers developed from the transcriptomics of rainbow clam Moerella iridescens and their application in population genetics

The rainbow clam Moerella iridescens is an ecologically important small marine clam located along China’s coastlines, as well as the Northwest Pacific coasts. Among 75 M. iridescens sequences from the total tissue transcriptome database, 29 show polymorphisms by the resolution melting (HRM) method. The observed and expected heterozygosity ranged from 0.1500 to 1.0000 and from 0.0526 to 0.5128, respectively. Ten loci were found to deviate significantly from the Hardy–Weinberg equilibrium (P < 0.01). These SNPs will be useful for future genetic diversity and population assessment and conservation studies of this species.

Genome-wide profiling of heritable and de novo STR variations.

Short tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases, population genetics applications, and forensic casework. However, STRs have proven problematic to genotype from high-throughput sequencing data. Here, we describe HipSTR, a novel haplotype-based method for robustly genotyping and phasing STRs from Illumina sequencing data and report a genome-wide analysis and validation of de novo STR mutations.

Development of Microsatellites for Population Genetic Analyses of the Granulate Ambrosia Beetle (Coleoptera: Curculionidae).

Limited male dispersal and local mating in ambrosia beetles are expected to result in extreme inbreeding and highly structured populations. In this study, we developed microsatellite markers for the granulate ambrosia beetle, Xylosandrus crassiusculus (Motschulsky), for use in future studies into population and family structure of this invasive pest species. We employed de novo next-generation sequencing to generate whole genome shotgun sequences for the characterization of microsatellite loci. Approximately 6% of the 84,024 contigs generated from Hi-Seq Illumina 2x250bp sequencing contained microsatellites with at least four repeats of di-, tri-, tetra-, penta-, and hexamers. Primers were synthesized for 40 microsatellite loci with trimer repeat units. Twenty-four primer pairs yielded consistent PCR products of unique loci and were validated for population genetic application using three sample groups each containing 20 X. crassiusculus individuals from Mississippi. Thirteen loci were found to be polymorphic with up to five alleles per population. The two beetle sample groups from Pearl River County (Poplarville and McNeill) belonged genetically to the same population. The population from Lamar County (Purvis) was genetically distinct, separated by a moderate genetic distance (FST = 0.11) and five unique alleles (with >5% frequency). Consistent with the perceived mating structure (incest of females with flightless males), the populations showed homozygote excess at most loci, as indicated by the coefficients of inbreeding (FIT = 0.45 and FIS = 0.37) and high mean relatedness among individuals (r = 0.15).

Genetic polymorphisms of 54 mitochondrial DNA SNP loci in Chinese Xibe ethnic minority group

We analyzed the genetic polymorphisms of 54 mitochondrial DNA (mtDNA) variants in Chinese Xibe ethnic minority group. A total of 137 unrelated healthy volunteers from Chinese Xibe group were the objects of our study. Among the selected loci, there were 51 variable positions including transitions and transversions, and single nucleotide transitions were common (83.93%) versus transversions. These variations defined 64 different mtDNA haplotypes exclusive of (CA)n and 9 bp deletion variation. The haplotype diversity and discrimination power in Xibe population were 0.9800 ± 0.004 and 0.9699, respectively. Besides, we compared Xibe group with 18 other populations and reconstructed a phylogenetic tree using Neighbor-Joining method. The result revealed that Xibe group was a close to Xinjiang Han and Yanbian Korean groups. Our data also indicated that Xibe group has a close relationship with Daur and Ewenki groups, which is reflected by the history that Xibe was influenced by Daur and Ewenki groups during the development of these groups. In conclusion, the variants we studied are polymorphic and could be used as informative genetic markers for forensic and population genetic application.

How meso-scale pollen dispersal and its gene flow shape gene conservation decisions

Pine pollen dispersal has been well-studied over a century due to its ubiquity, robust shape and unusual longevity; this knowledge can be brought to bear on forest population genetics applications and gene conservation programs for pines and other high-latitude wind-pollinated species. Dispersal models are shifting towards meso-scale transport processes so I assert here that this shift in transport scale is important to population genetics assumptions inherent to gene conservation decision-making. Support comes from the following: (1) aerodynamic properties for pollen is more akin to spores than seeds. (2) Gradient-free dispersal is typical of pollen transported at meso-scale distances. (3) Importance of vertically uplifted pollen on meso-scale transport has been overlooked and its interaction with atmospheric processes is not yet understood. (4) A fraction of pine pollen retains its capacity for germination and seed fertilization after meso-scale transport. These findings raise the question of whether forest fragmentation aligns with genetics theory of small populations; this question shapes ex situ and in situ collections. The shift to meso-scale transport of pine pollen can re-shape forest gene conservation decision-making about ex situ and in situ collection strategies.

Eigenfunctions and the Dirichlet Problem for the Classical Kimura Diffusion Operator

We study the classical Kimura diffusion operator defined on the $n$-simplex, $\operatorname{L^{Kim}}=\sum_{1\leq i,j\leq n+1}x_i(\delta_{ij}-x_j)\partial_{x_i}\partial_{x_j},$ which has important applications in population genetics. Because it is a degenerate elliptic operator acting on a singular space, special tools are required to analyze and construct solutions to elliptic and parabolic problems defined by this operator. The natural boundary value problems are the “regular” problem and the Dirichlet problem. For the regular problem, one can only specify the regularity of the solution at the boundary. For the Dirichlet problem, one can specify the boundary values, but the solution is then not smooth at the boundary. In this paper we give a computationally effective recursive method to construct the eigenfunctions of the regular operator in any dimension, and a recursive method to use them to solve the inhomogeneous equation. As noted, the Dirichlet problem does not have a regular solution. We give an e...

On the notion of dispersion: from dispersion to diversity

Summary Dispersion and diversity are two variants of the notion of biological variation that are often not properly distinguished even though they address intrinsically disparate aspects. Dispersion focuses on the assessment of (variable) differences among individuals or types, while diversity focuses on the assessment of numbers of distinct types. Here, ‘type’ is a proxy for biological entities such as species, genotype and phenotype culminating in individuals at the highest level of resolution. The present paper bridges the apparent gap between dispersion and diversity by showing how numbers of types and individuals can be treated as a dispersion characteristic (the number‐characteristic). Drawing from the general concept of effective quantities, it is shown that the contribution of difference arrays to dispersion measures can always be summarized in terms of an effective difference. If the number‐characteristic is realized in addition, numbers of types (of individuals) can be determined that are effectively distinct at specified levels of difference. Whereas measures of diversity that replace abundances of types by differences of each type from other types can also be considered as numbers of effectively different types, they do not explicitly involve levels of distinctness among types. By contrast, dispersion effective numbers of types gain their sole validity from explicit reference to the degree to which types effectively differ from each other. In particular, dispersion effective numbers obey the diversity criterion only at levels of distinctness equal to or greater than the effective difference in that they do not exceed the actual number of types and become equal to that number only for uniform type distributions. The corresponding ‘proper dispersion effective number’ thus sets an upper limit to the effective number of types in a community and meets the characteristics of a diversity effective number. Examples are outlined that have broader application in phylogenetics, population genetics and ecology.

Dealing with paralogy in RADseq data: in silico detection and single nucleotide polymorphism validation in Robinia pseudoacacia L.

The RADseq technology allows researchers to efficiently develop thousands of polymorphic loci across multiple individuals with little or no prior information on the genome. However, many questions remain about the biases inherent to this technology. Notably, sequence misalignments arising from paralogy may affect the development of single nucleotide polymorphism (SNP) markers and the estimation of genetic diversity. We evaluated the impact of putative paralog loci on genetic diversity estimation during the development of SNPs from a RADseq dataset for the nonmodel tree species Robinia pseudoacacia L. We sequenced nine genotypes and analyzed the frequency of putative paralogous RAD loci as a function of both the depth of coverage and the mismatch threshold allowed between loci. Putative paralogy was detected in a very variable number of loci, from 1% to more than 20%, with the depth of coverage having a major influence on the result. Putative paralogy artificially increased the observed degree of polymorphism and resulting estimates of diversity. The choice of the depth of coverage also affected diversity estimation and SNP validation: A low threshold decreased the chances of detecting minor alleles while a high threshold increased allelic dropout. SNP validation was better for the low threshold (4×) than for the high threshold (18×) we tested. Using the strategy developed here, we were able to validate more than 80% of the SNPs tested by means of individual genotyping, resulting in a readily usable set of 330 SNPs, suitable for use in population genetics applications.

Natural Selection, Adaptive Topographies and the Problem of Statistical Inference: The Moraba scurra Controversy Under the Microscope.

This paper gives a detailed narrative of a controversial empirical research in postwar population genetics, the analysis of the cytological polymorphisms of an Australian grasshopper, Moraba scurra. This research intertwined key technical developments in three research areas during the 1950s and 1960s: it involved Dobzhansky's empirical research program on cytological polymorphisms, the mathematical theory of natural selection in two-locus systems, and the building of reliable estimates of natural selection in the wild. In the mid-1950s the cytologist Michael White discovered an interesting case of epistasis in populations of Moraba scurra. These observations received a wide diffusion when theoretical population geneticist Richard Lewontin represented White's data on adaptive topographies. These topographies connected the information on the genetic structure of these grasshopper populations with the formal framework of theoretical population genetics. As such, they appeared at the time as the most successful application of two-locus models of natural selection to an empirical study system. However, this connection generated paradoxical results: in the landscapes, all grasshopper populations were located on a ridge (an unstable equilibrium) while they were expected to reach a peak. This puzzling result fueled years of research and triggered a controversy attracting contributors from Australia, the United States and the United Kingdom. While the original problem seemed, at first, purely empirical, the subsequent controversy affected the main mathematical tools used in the study of two-gene systems under natural selection. Adaptive topographies and their underlying mathematical structure, Wright's mean fitness equations, were submitted to close scrutiny. Suspicion eventually shifted to the statistical machinery used in data analysis, reflecting the crucial role of statistical inference in applied population genetics. In the 1950s and 1960s, population geneticists were not simply in search for new generalizations about the evolutionary process and for new evidence about genetic variation: struggling against statistical artifacts, they were searching for reliable tests and descriptors to analyze their data.

Toward high-resolution population genomics using archaeological samples.

The term ‘ancient DNA’ (aDNA) is coming of age, with over 1,200 hits in the PubMed database, beginning in the early 1980s with the studies of ‘molecular paleontology’. Rooted in cloning and limited sequencing of DNA from ancient remains during the pre-PCR era, the field has made incredible progress since the introduction of PCR and next-generation sequencing. Over the last decade, aDNA analysis ushered in a new era in genomics and became the method of choice for reconstructing the history of organisms, their biogeography, and migration routes, with applications in evolutionary biology, population genetics, archaeogenetics, paleo-epidemiology, and many other areas. This change was brought by development of new strategies for coping with the challenges in studying aDNA due to damage and fragmentation, scarce samples, significant historical gaps, and limited applicability of population genetics methods. In this review, we describe the state-of-the-art achievements in aDNA studies, with particular focus on human evolution and demographic history. We present the current experimental and theoretical procedures for handling and analysing highly degraded aDNA. We also review the challenges in the rapidly growing field of ancient epigenomics. Advancement of aDNA tools and methods signifies a new era in population genetics and evolutionary medicine research.

Microsatellite Length Scoring by Single Molecule Real Time Sequencing - Effects of Sequence Structure and PCR Regime.

Microsatellites are DNA sequences consisting of repeated, short (1–6 bp) sequence motifs that are highly mutable by enzymatic slippage during replication. Due to their high intrinsic variability, microsatellites have important applications in population genetics, forensics, genome mapping, as well as cancer diagnostics and prognosis. The current analytical standard for microsatellites is based on length scoring by high precision electrophoresis, but due to increasing efficiency next-generation sequencing techniques may provide a viable alternative. Here, we evaluated single molecule real time (SMRT) sequencing, implemented in the PacBio series of sequencing apparatuses, as a means of microsatellite length scoring. To this end we carried out multiplexed SMRT sequencing of plasmid-carried artificial microsatellites of varying structure under different pre-sequencing PCR regimes. For each repeat structure, reads corresponding to the target length dominated. We found that pre-sequencing amplification had large effects on scoring accuracy and error distribution relative to controls, but that the effects of the number of amplification cycles were generally weak. In line with expectations enzymatic slippage decreased proportionally with microsatellite repeat unit length and increased with repetition number. Finally, we determined directional mutation trends, showing that PCR and SMRT sequencing introduced consistent but opposing error patterns in contraction and expansion of the microsatellites on the repeat motif and single nucleotide level.

Rapidly Registering Identity-by-Descent Across Ancestral Recombination Graphs.

The genomes of remotely related individuals occasionally contain long segments that are identical by descent (IBD). Sharing of IBD segments has many applications in population and medical genetics, and it is thus desirable to study their properties in simulations. However, no current method provides a direct, efficient means to extract IBD segments from simulated genealogies. Here, we introduce computationally efficient approaches to extract ground-truth IBD segments from a sequence of genealogies, or equivalently, an ancestral recombination graph. Specifically, we use a two-step scheme, where we first identify putative shared segments by comparing the common ancestors of all pairs of individuals at some distance apart. This reduces the search space considerably, and we then proceed by determining the true IBD status of the candidate segments. Under some assumptions and when allowing a limited resolution of segment lengths, our run-time complexity is reduced from O(n(3) log n) for the naïve algorithm to O(n log n), where n is the number of individuals in the sample.

Will Benchtop Sequencers Resolve the Sequencing Trade-off in Plant Genetics?

Will Benchtop Sequencers Resolve the Sequencing Trade-off in Plant Genetics?

Finding the right coverage: the impact of coverage and sequence quality on single nucleotide polymorphism genotyping error rates.

Restriction-enzyme-based sequencing methods enable the genotyping of thousands of single nucleotide polymorphism (SNP) loci in nonmodel organisms. However, in contrast to traditional genetic markers, genotyping error rates in SNPs derived from restriction-enzyme-based methods remain largely unknown. Here, we estimated genotyping error rates in SNPs genotyped with double digest RAD sequencing from Mendelian incompatibilities in known mother-offspring dyads of Hoffman's two-toed sloth (Choloepus hoffmanni) across a range of coverage and sequence quality criteria, for both reference-aligned and de novo-assembled data sets. Genotyping error rates were more sensitive to coverage than sequence quality and low coverage yielded high error rates, particularly in de novo-assembled data sets. For example, coverage ≥5 yielded median genotyping error rates of ≥0.03 and ≥0.11 in reference-aligned and de novo-assembled data sets, respectively. Genotyping error rates declined to ≤0.01 in reference-aligned data sets with a coverage ≥30, but remained ≥0.04 in the de novo-assembled data sets. We observed approximately 10- and 13-fold declines in the number of loci sampled in the reference-aligned and de novo-assembled data sets when coverage was increased from ≥5 to ≥30 at quality score ≥30, respectively. Finally, we assessed the effects of genotyping coverage on a common population genetic application, parentage assignments, and showed that the proportion of incorrectly assigned maternities was relatively high at low coverage. Overall, our results suggest that the trade-off between sample size and genotyping error rates be considered prior to building sequencing libraries, reporting genotyping error rates become standard practice, and that effects of genotyping errors on inference be evaluated in restriction-enzyme-based SNP studies.