Parental effect of DNA (Cytosine-5) methyltransferase 1 on grandparental-origin-dependent transmission ratio distortion in mouse crosses and human families

Transmission ratio distortion (TRD) is a deviation from the expected Mendelian 1:1 ratio of alleles transmitted from parents to offspring and may arise by different mechanisms. Earlier we described a grandparental-origin-dependent sex-of-offspring-specific TRD of maternal chromosome 12 alleles closely linked to an imprinted region and hypothesized that it resulted from imprint resetting errors in the maternal germline. Here, we report that the genotype of the parents for loss-of-function mutations in the Dnmt1 gene influences the transmission of grandparental chromosome 12 alleles. More specifically, maternal Dnmt1 mutations restore Mendelian transmission ratios of chromosome 12 alleles. Transmission of maternal alleles depends upon the presence of the Dnmt1 mutation in the mother rather than upon the Dnmt1 genotype of the offspring. Paternal transmission mirrors the maternal one: live-born offspring of wild-type fathers display 1:1 transmission ratios, whereas offspring of heterozygous Dnmt1 mutant fathers tend to inherit grandpaternal alleles. Analysis of allelic transmission in the homologous region of human chromosome 14q32 detected preferential transmission of alleles from the paternal grandfather to grandsons. Thus, parental Dnmt1 is a modifier of transmission of alleles at an unlinked chromosomal region and perhaps has a role in the genesis of TRD.     

群体遗传学研究中STR数据的统计方法应用

STR作为遗传多态性较高的标记, 被广泛地运用于群体遗传学的研究。对于STR分型产生的基因型频率及等位基因频率数据, 文章总结了各种参数指标的计算及分析方法。其中参数指标包括杂合度、多态信息量、连锁不平衡系数、近交系数、遗传距离以及固定指数等; 分析方法包括主成分分析、系统发生树、分子方差分析、R矩阵、地理信息系统以及空间自相关分析。通过这些参数指标及分析方法的使用, 可以既直观又科学地揭示群体遗传结构、群体间遗传分化以及人类起源与进化等群体遗传学中研究的关键问题。     

A search for transmission ratio distortions in offspring from crosses between inbred mice

Equal transmission of the two alleles at a locus from a heterozygote parent to the offspring is rarely violated. Beside the differential embryonic mortality, nondisjunction and gene conversion that are rather irregular forms of transmission-ratio distortion (TRD), there are two major forms of departure from Mendelian segregation. The first, found in females, based on the asymmetric nature of female meiosis, is usually referred to as meiotic drive, and has been well documented in a few cases. The second is segregation distortion found in males. There are several known male-related segregation distortion systems that are caused by different fertilizing capacity of sperm cells carrying alternative alleles at a particular locus. Observation of TRD effects requires a sufficient number of offspring produced by a parental pair. As individuals in a population most likely have different genotypes in TRD affecting loci, the total transmission ratio is close to the expected Mendelian ratio and masks potential TRD effects. Highly inbred strains of laboratory mice provide a very good model for studying this phenomenon, because comparing two mice strains is effectively similar as comparison of two individuals in a population. This study tests both forms of TRD in progeny of F1 hybrids from reciprocal crosses of inbred mice. Three previously unknown instances of TRD in females were observed. Therefore, this study concludes that some genes in females may carry alleles that can cause segregation distortion.     

MHC class IIB alleles contribute to both additive and nonadditive genetic effects on survival in Chinook salmon

The genes of the major histocompatibility complex (MHC) are found in all vertebrates and are an important component of individual fitness through their role in disease and pathogen resistance. These genes are among the most polymorphic in genomes and the mechanism that maintains the diversity has been actively debated with arguments for natural selection centering on either additive or nonadditive genetic effects. Here, we use a quantitative genetics breeding design to examine the genetic effects of MHC class IIB alleles on offspring survivorship in Chinook salmon (Oncorhynchus tshawytscha). We develop a novel genetic algorithm that can be used to assign values to specific alleles or genotypes. We use this genetic algorithm to show simultaneous additive and nonadditive effects of specific MHC class IIB alleles and genotypes on offspring survivorship. The additive effect supports the rare-allele hypothesis as a potential mechanism for maintaining genetic diversity at the MHC. However, contrary to the overdominance hypothesis, the nonadditive effect led to underdominance at one heterozygous genotype, which could instead reduce variability at the MHC. Our algorithm is an advancement over traditional animal models that only partition variance in fitness to additive and nonadditive genetic effects, but do not allocate these effects to specific alleles and genotypes. Additionally, we found evidence of nonrandom segregation during meiosis in females that promotes an MHC allele that is associated with higher survivorship. Such nonrandom segregation could further reduce variability at the MHC and may explain why Chinook salmon has one of the lowest levels of MHC diversity of all vertebrates.     

Complex genetic nature of sex-independent transmission ratio distortion in Asian rice species: the involvement of unlinked modifiers and sex-specific mechanisms

Transmission ratio distortion (TRD), in which one allele is transmitted more frequently than the opposite allele, is presumed to act as a driving force in the emergence of a reproductive barrier. TRD acting in a sex-specific manner has been frequently observed in interspecific and intraspecific hybrids across a broad range of organisms. In contrast, sex-independent TRD (siTRD), which results from preferential transmission of one of the two alleles in the heterozygote through both sexes, has been detected in only a few plant species. We previously reported an S(6) locus-mediated siTRD, in which the S(6) allele from an Asian wild rice strain (Oryza rufipogon) was transmitted more frequently than the S(6)(a) allele from an Asian cultivated rice strain (O. sativa) through both male and female gametes in heterozygous plants. Here, we report on the effect of a difference in genetic background on S(6) locus-mediated siTRD, based on the analysis using near-isogenic lines and the original wild strain as a parental strain for crossing. We found that the degree of TRD through the male gametes varied depending on the genetic background of the female (pistil) plants. Despite the occurrence of TRD through both male and female gametes, abnormality was detected in ovules, but not in pollen grains, in the heterozygote. These results suggest the involvement of unlinked modifiers and developmentally distinct, sex-specific genetic mechanisms in S(6) locus-mediated siTRD, raising the possibility that siTRD driven by a single locus may be affected by multiple genetic factors harbored in natural populations.     

Opposites attract: MHC‐associated mate choice in a polygynous primate

We investigated reproduction in a semi‐free‐ranging population of a polygynous primate, the mandrill, in relation to genetic relatedness and male genetic characteristics, using neutral microsatellite and major histocompatibility complex (MHC) genotyping. We compared genetic dissimilarity to the mother and genetic characteristics of the sire with all other potential sires present at the conception of each offspring (193 offspring for microsatellite genetics, 180 for MHC). The probability that a given male sired increased as pedigree relatedness with the mother decreased, and overall genetic dissimilarity and MHC dissimilarity with the mother increased. Reproductive success also increased with male microsatellite heterozygosity and MHC diversity. These effects were apparent despite the strong influence of dominance rank on male reproductive success. The closed nature of our study population is comparable to human populations for which MHC‐associated mate choice has been reported, suggesting that such mate choice may be especially important in relatively isolated populations with little migration to introduce genetic variation.     

波尔山羊及其杂交改良后代群体遗传结构与亲缘关系研究

利用RAPD标记和POPGENE、PHYLIP及SPSS等统计分析软件,研究了波尔山羊及其杂交改良后代群体的遗传结构及遗传亲缘关系。结果表明,波尔山羊与其杂交改良后代间特别是高代杂种间具有相似的多态基因座百分率、等位基因数和基因多样性。随着级进杂交改良代数的递增,高代杂种之间以及与改良亲本之间的群体遗传结构的差异逐渐缩小,群体间的基因分化降低,基因流动和遗传相似度增加,遗传距离缩小,高代杂种与波尔山羊间具有更近的遗传亲缘关系。 Abstract:The genetic structure and relationship of Boer goat and its upgrading offspring to Tangshan Diary goat were studied using the RAPD marker and some statistical program,such as POPGENE,PHYLIP and SPSS.The results indicated that there were the similar percentage of polymorphic loci,observed and effective number of alleles,gene diversity between Boer goat and its upgrading offspring,especially higher upgrading offspring.With the increasing of upgrading,the difference of population structure decreased as well as the genetic distance and differentiation among higher upgrading offspring and their improving parental,but gene flow and genetic identity increased.There was a close genetic relationship between higher upgrading offspring and Boer goat.     

Potential Germline Competition in Animals and Its Evolutionary Implications

Mutation, mitotic crossing over and mitotic gene conversion can create genetic diversity in otherwise uniform diploid cell lineages. In the germline this diversification may result in competition between diploid germline phenotypes, with subsequent biases in the frequency of alleles transmitted to the offspring. Sperm competition is a well documented feature of many higher organisms and a model is developed to quantify this process. Competition, and hence selection, can also occur by differential survival of diploid lineages before meiosis. It is concluded that under certain circumstances germline selection is an efficient means of eliminating unfavorable alleles from the population. This does not require differences in adult fertility or viability which is the usual mechanism cited as causing changes in gene frequency in a population. It is proposed that such competition may play a role in maintaining the efficiency of basic metabolic pathways.     

Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division

We have observed maternal transmission ratio distortion (TRD) in favor of DDK alleles at the Ovum mutant (Om) locus on mouse chromosome 11 among the offspring of (C57BL/6 x DDK) F(1) females and C57BL/6 males. Although significant lethality occurs in this backcross ( approximately 50%), differences in the level of TRD found in recombinant vs. nonrecombinant chromosomes among offspring argue that TRD is due to nonrandom segregation of chromatids at the second meiotic division, i.e., true meiotic drive. We tested this hypothesis directly, by determining the centromere and Om genotypes of individual chromatids in zygote stage embryos. We found similar levels of TRD in favor of DDK alleles at Om in the female pronucleus and TRD in favor of C57BL/6 alleles at Om in the second polar body. In those embryos for which complete dyads have been reconstructed, TRD was present only in those inheriting heteromorphic dyads. These results demonstrate that meiotic drive occurs at MII and that preferential death of one genotypic class of embryo does not play a large role in the TRD.     

Reciprocal translocation of small numbers of inbred individuals rescues immunogenetic diversity

Genetic rescue can reduce inbreeding depression and increase fitness of small populations, even when the donor populations are highly inbred. In a recent experiment involving two inbred island populations of the New Zealand South Island robin, Petroica australis, reciprocal translocations improved microsatellite diversity and individual fitness. While microsatellite loci may reflect patterns of genome‐wide diversity, they generally do not indicate the specific genetic regions responsible for increased fitness. We tested the effectiveness of this reciprocal translocation for rescuing diversity of two immunogenetic regions: Toll‐like receptor (TLR) and major histocompatibility complex (MHC) genes. We found that the relatively small number of migrants (seven and ten per island) effectively brought the characteristic TLR gene diversity of each source population into the recipient population. However, when migrants transmitted TLR alleles that were already present at high frequency in the recipient population, it was possible for offspring of mixed heritage to have decreased gene diversity compared to recipient population diversity prior to translocation. In contrast to TLRs, we did not observe substantial changes in MHC allelic diversity following translocation, with limited evidence of a decrease in differentiation, perhaps because most MHC alleles were observed at both sites prior to the translocation. Overall, we conclude that small numbers of migrants may successfully restore the diversity of immunogenetic loci with few alleles, but that translocating larger numbers of animals would provide additional opportunity for the genetic rescue of highly polymorphic immunity regions, such as the MHC, even when the source population is inbred.     

Reduction in post-invasion genetic diversity in <Emphasis Type="Italic">Crangonyx pseudogracilis</Emphasis> (Amphipoda: Crustacea): a genetic bottleneck or the work of hitchhiking vertically transmitted microparasites?

Parasites can strongly influence the success of biological invasions. However, as invading hosts and parasites may be derived from a small subset of genotypes in the native range, it is important to examine the distribution and invasion of parasites in the context of host population genetics. We demonstrate that invasive European populations of the North American Crangonyx pseudogracilis have experienced a reduction in post-invasion genetic diversity. We predict that vertically transmitted parasites may evade the stochastic processes and selective pressures leading to enemy release. As microsporidia may be vertically or horizontally transmitted, we compared the diversity of these microparasites in the native and invasive ranges of the host. In contrast to the reduction in host genetic diversity, we find no evidence for enemy release from microsporidian parasites in the invasive populations. Indeed, a single, vertically transmitted, microsporidian sex ratio distorter dominates the microsporidian parasite assemblage in the invasive range and appears to have invaded with the host. We propose that overproduction of female offspring as a result of parasitic sex ratio distortion may facilitate host invasion success. We also propose that a selective sweep resulting from the increase in infected individuals during the establishment may have contributed to the reduction in genetic diversity in invasive Crangonyx pseudogracilis populations.     

Beyond race: towards a whole-genome perspective on human populations and genetic variation

The renewed emphasis on population-specific genetic variation, exemplified most prominently by the International HapMap Project, is complicated by a longstanding, uncritical reliance on existing population categories in genetic research. Race and other pre-existing population definitions (ethnicity, religion, language, nationality, culture and so on) tend to be contentious concepts that have polarized discussions about the ethics and science of research into population-specific human genetic variation. By contrast, a broader consideration of the multiple historical sources of genetic variation provides a whole-genome perspective on the ways i n which existing population definitions do, and do not, account for how genetic variation is distributed among individuals. Although genetics will continue to rely on analytical tools that make use of particular population histories, it is important to interpret findings in a broader genomic context.     

Genetic diversity of Andean Polylepis (Rosaceae) woodlands and inferences regarding their fragmentation history

There is a long‐standing debate on whether the occurrence of the iconic high‐Andes Polylepis woodlands as small and isolated fragments is of natural or anthropogenic origin. We make inferences regarding the fragmentation history based on both a new population genetic study on P. besseri and a synthesis of available studies on the population genetics of Polylepis woodlands. We infer the timing of the main woodland fragmentation event by analysing: (1) the remaining levels of population genetic diversity and the relation to population size; (2) among‐population genetic differentiation; and (3) the difference in genetic diversity between the offspring and adult generation. We retrieved seven publications on the population genetics of five Polylepis spp. We did not find a relationship between population size and genetic diversity, and genetic differentiation was low compared with that reported for similar plant species. These findings do not support a history of long‐term fragmentation. The offspring showed a loss of genetic diversity and increasing differentiation compared with adults, suggesting that the main habitat fragmentation event is of relatively recent origin. For P. besseri, no significant differences were found between the adult and offspring genetic variation. We discuss the conservation and restoration consequences for this important high‐Andean genus. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 172 , 544–554.     

遗传多样性与濒危植物保护生物学研究进展

尽管对于濒危物种的遗传学人们已经进行了大量研究,但是种群遗传学在植物保护中的实际地位尚存在很大争议。濒危物种的遗传多样性可能会由于遗传漂变、近交的作用而丧失;但这种丧失更可能是濒危的结果而不是濒危的起因。遗传多样性水平与物种生存力之间没有任何必然的联系。但植物种群遗传结构如果由于自交不亲和等位基因的丧失和与亲缘种杂交造成的遗传同化而发生改变,那么它对物种生存力会产生明显负作用。     

Discriminating between allele- and genotype-specific transmission ratio distortion

Transmission ratio distortion (TRD) is defined as the observed deviation from the expected Mendelian inheritance of alleles from heterozygous parents. This phenomenon is attributed to various biological mechanisms acting on germ cells, embryos or fetuses, or even in early postnatal life. Current statistical approaches typically use two independent parametrizations assuming that TRD relies on allele- or genotype-related mechanisms, although they have never been tested and compared. This study compared allele- and genotype-related TRD models on simulated datasets with 1000 genotyped offspring and real data from 168 sire–dam–offspring beef cattle trios. The analysis of simulated datasets favored the true model of analysis in most cases (>93%), and a low percentage of missidentification occurred under (almost) null dominance (genotype-related model) or similar and moderate-to-low sire- and dam-specific TRD parameters (allele-related model). Moreover, the correlation between simulated and predicted distortion parameters was high (>0.97) under the true model. The comparison of allele- and genotype-related TRD models is an appealing tool to infer the biological source of TRD (i.e. haploid vs. diploid cells) when screening the whole genome. The analysis of beef cattle data corroborated a TRD region previously reported in chromosome 4, although discarding allele-related mechanisms and favoring the genotype-related model as the more reliable one. The results of this study highlight the relevance of implementing and comparing different parametrizations to capture all kinds of TRD, and to compare them using appropriate statistical methods.     

Cell population-based framework of genetic epidemiology in the single-cell omics era

Genetic epidemiology is a rapidly advancing field due to the recent availability of large amounts of omics data. In recent years, it has become possible to obtain omics information at the single-cell level, so genetic epidemiological models need to be updated to integrate with single-cell expression data. In this perspective paper, we propose a cell population-based framework for genetic epidemiology in the single-cell era. In this framework, genetic diversity influences phenotypic diversity through the diversity of cell population profiles, which are defined as high-dimensional probability distributions of the state spaces of biomolecules of each omics layer. We discuss how biomolecular experimental measurement data can capture the different properties of this distribution. In particular, single-cell data constitute a sample from this population distribution where only some coordinate values are observable. From a data analysis standpoint, we introduce methodology for feature extraction from cell population profiles. Finally, we discuss how this framework can be applied not only to genetic epidemiology but also to systems biology.     

Molecular and cellular interactions responsible for intrasegmental patterning during Drosophila embryogenesis

The elaboration of pattern within insect segments is a well-studied example of cellular patterning during development. This process requires that each cell develop appropriately for its position. Experimental embryology suggests that intercellular communication plays a key role in imparting positional information to cells. Drosophila genetics has identified numerous genes whose activity is required for patterning within segments, and whose molecular genetic analyses suggest they constitute and control cell communication circuits. Particular genes are expressed or required by cells that will follow distinct developmental pathways, and some appear to confer or interpret intercellular signals. Other patterning genes are ubiquitously required and may provide the machinery through which the signals are transmitted.     

Challenging views on the peopling history of East Asia: the story according to HLA markers

The peopling of East Asia by the first modern humans is strongly debated from a genetic point of view. A north-south genetic differentiation observed in this geographic area suggests different hypotheses on the origin of Northern East Asian (NEA) and Southern East Asian (SEA) populations. In this study, the highly polymorphic HLA markers were used to investigate East Asian genetic diversity. Our database covers a total of about 127,000 individuals belonging to 84 distinct Asian populations tested for HLA-A, -B, -C, -DPB1, and/or -DRB1 alleles. Many Chinese populations are represented, which have been sampled in the last 30 years but rarely taken into account in international research due to their data published in Chinese. By using different statistical methods, we found a significant correlation between genetics and geography and relevant genetic clines in East Asia. Additionally, HLA alleles appear to be unevenly distributed: some alleles observed in NEA populations are widespread at the global level, while some alleles observed in SEA populations are virtually unique in Asia. The HLA genetic variation in East Asia is also characterized by a decrease of diversity from north to south, although a reverse pattern appears when one only focuses on alleles restricted to Asia. These results reflect a more complex migration history than that illustrated by the "southern-origin" hypothesis, as genetic contribution of ancient human migrations through a northern route has probably been quite substantial. We thus suggest a new overlapping model where northward and southward opposite migrations occurring at different periods overlapped.     

Assessing the Effect of Sequencing Depth and Sample Size in Population Genetics Inferences

Next-Generation Sequencing (NGS) technologies have dramatically revolutionised research in many fields of genetics. The ability to sequence many individuals from one or multiple populations at a genomic scale has greatly enhanced population genetics studies and made it a data-driven discipline. Recently, researchers have proposed statistical modelling to address genotyping uncertainty associated with NGS data. However, an ongoing debate is whether it is more beneficial to increase the number of sequenced individuals or the per-sample sequencing depth for estimating genetic variation. Through extensive simulations, I assessed the accuracy of estimating nucleotide diversity, detecting polymorphic sites, and predicting population structure under different experimental scenarios. Results show that the greatest accuracy for estimating population genetics parameters is achieved by employing a large sample size, despite single individuals being sequenced at low depth. Under some circumstances, the minimum sequencing depth for obtaining accurate estimates of allele frequencies and to identify polymorphic sites is , where both alleles are more likely to have been sequenced. On the other hand, inferences of population structure are more accurate at very large sample sizes, even with extremely low sequencing depth. This all points to the conclusion that under various experimental scenarios, in cost-limited population genetics studies, large sample sizes at low sequencing depth are desirable to achieve high accuracy. These findings will help researchers design their experimental set-ups and guide further investigation on the effect of protocol design for genetic research.