The power comparison of the haplotype-based collapsing tests and the variant-based collapsing tests for detecting rare variants in pedigrees

Background

Both common and rare genetic variants have been shown to contribute to the etiology of complex diseases. Recent genome-wide association studies (GWAS) have successfully investigated how common variants contribute to the genetic factors associated with common human diseases. However, understanding the impact of rare variants, which are abundant in the human population (one in every 17 bases), remains challenging. A number of statistical tests have been developed to analyze collapsed rare variants identified by association tests. Here, we propose a haplotype-based approach. This work inspired by an existing statistical framework of the pedigree disequilibrium test (PDT), which uses genetic data to assess the effects of variants in general pedigrees. We aim to compare the performance between the haplotype-based approach and the rare variant-based approach for detecting rare causal variants in pedigrees.

Results

Extensive simulations in the sequencing setting were carried out to evaluate and compare the haplotype-based approach with the rare variant methods that drew on a more conventional collapsing strategy. As assessed through a variety of scenarios, the haplotype-based pedigree tests had enhanced statistical power compared with the rare variants based pedigree tests when the disease of interest was mainly caused by rare haplotypes (with multiple rare alleles), and vice versa when disease was caused by rare variants acting independently. For most of other situations when disease was caused both by haplotypes with multiple rare alleles and by rare variants with similar effects, these two approaches provided similar power in testing for association.

Conclusions

The haplotype-based approach was designed to assess the role of rare and potentially causal haplotypes. The proposed rare variants-based pedigree tests were designed to assess the role of rare and potentially causal variants. This study clearly documented the situations under which either method performs better than the other. All tests have been implemented in a software, which was submitted to the Comprehensive R Archive Network (CRAN) for general use as a computer program named rvHPDT.     

Usefulness and Economic potential of the Rare Plants of the United States: A statistical Survey

The economic usefulness and potential of endangered and rare plants in the United States was surveyed to assess some of the potential impacts of plant extinction on the world’s largest economy. We analyzed relationships between an existing comprehensive database of U.S. rare plants, and a new database that synthesizes available information on worldwide plant uses and U.S. crop values. While few rare plants are directly useful, nearly 80% of the U.S. plant genera with rare taxa contain at least one useful species. Moreover, two-thirds of the 2949 U.S. rare and endangered taxa are congeneric with cultivated species. Examples of this close relationship between rare plants and their economically significant congenerics were translated into dollar values. For instance, the annual U.S. wholesale farm value of food crop congenerics of rare plants is $9 billion. Since many crops require periodic genetic infusions from close relatives to combat threats from climatic change and disease, or to supply features such as improved nutritional value, we conclude that the threats to the rare wild plants of the U.S. also constitute threats to the future of many contemporary crops.     

Finding needles in the haystack: where to look for rare species in the American tropics

Tropical America (the Neotropics) harbours more plant species than any other region on Earth. The contribution of rare species to this diversity has been recently recognised, but their spatial distribution remains poorly understood. Here, we use all collection records of angiosperms from the Global Biodiversity Information Facility to delineate Neotropical bioregions, and to identify putatively rare species within the Neotropics and the Amazonian rainforest. We analyse the spatial distribution of these species and validate the results on a largely independent dataset based on vegetation plots from the Amazon Tree Diversity Network. We find that rare species are homogeneously distributed through most parts of the lowland Neotropics and Amazonia, but more concentrated in highlands. The second collection of any rare species is most often found in the close vicinity of the first, but in 20% of cases they are more than 580 km apart. We also find cross‐taxonomic patterns of disjunct distributions within the Andes, the Atlantic forest in eastern Brazil, and between Amazonia and the Atlantic forest, but no clear disjunction patterns within lowland areas. These results suggest that a considerable proportion of rare plant species have surprisingly large distribution ranges, and that collections of rare species across most of the lowland Neotropics, and in particular in Amazonia, show no clear directionality. The second record of many rare species may be found virtually anywhere, urging the need for intensifying and broadening biological sampling.     

The burden of rare cancer in Japan: Application of the RARECARE definition

BackgroundDespite the fact that rare cancer is a new target of cancer control in Japan, the incidence of rare cancers is unknown and there is no generally accepted definition of rare cancers in this country. With the aim of calculating incidences of rare cancers in Japan, we therefore adopted a definition and classification of rare cancers that had been published in the European Union (EU) in 2011.MethodsUsing incidence data between 1998 and 2007 submitted by 12 of population based cancer registries in Japan that met our quality criteria and drawing on the EU definition (incidence <6 per 100,000 per year), we estimated the incidences of 845 combinations of tumor sites and histological groups and thus identified the cancers that are rare in Japan.ResultsAfter identifying 193 combinations of tumor sites and histological groups that fit our criteria for rare cancers, we estimated their incidence to be about 75 per 100,000, which corresponds to about 94,800 new diagnoses in 2012 or approximately 15% of all cancer diagnoses. The categorization of rare and common cancers was almost the same in Japan as in EU.ConclusionsThe present study provides an indication of the size of the rare cancer burden in Japan and epidemiological information to explore this. We are expecting further discussion based on our results with stakeholders in order to construct a Japanese definition of rare cancers.     

Phylogenetic diversity and ecological features in the Egyptian flora

Until fairly recently, regional-scale ecological and evolutionarypatterns have tended to be ignored as conservation efforts have been concernedwith species and their habitats. Here we compare frequencies in the Egyptianflora of particular rank sizes (order, family and genus) with patterns ofspecies abundance (classified as very rare, rare, common, or very common) and anarray of life-history attributes. The angiosperm flora of Egypt is representedby 2446 taxa (2088 species), including taxa in 10 subclasses, 51 orders, 120families, and 742 genera. A high degree of monotypism was observed: four ordersare monotypic (each existing as single species), and have very rare overallabundances; 30 families are monotypic (17 of which are very rare or rare); and 354genera are monotypic (over 70% of which are very rare or rare). Fourteenfamilies (in particular the Resedaceae and Zygophyllaceae) have at leastone-fifth of their global species represented in the Egyptian flora. Introducedspecies in general, and tree, aquatic herb and liana life forms all are especially well represented among monotypic genera. Native taxa are highlyrepresented among rare and very rare abundance classes, while introduced taxadid not differ significantly in their abundance patterns, compared to overallflora values. Few large genera (>20 spp.) occur in the flora, with mostspecies concentrated in genera containing 8–19 species per genus.Similarly, few families were highly speciose. Annual and herbaceous species weresignificantly over-represented, mainly among large, speciose genera andfamilies. However, perennials, trees, shrubs, aquatic herbs, lianas and parasiticspecies were found mainly in families and genera having very few taxa.Life-history attributes may have important implications to speciation rates.Taxonomically based results, involving abundances and life-history attributes,are discussed in the context of biodiversity and conservation.     

Scraping the bottom of the barrel: are rare high throughput sequences artifacts?

Metabarcoding data generated using next-generation sequencing (NGS) technologies are overwhelmed with rare taxa and skewed in Operational Taxonomic Unit (OTU) frequencies comprised of few dominant taxa. Low frequency OTUs comprise a rare biosphere of singleton and doubleton OTUs, which may include many artifacts. We present an in-depth analysis of global singletons across sixteen NGS libraries representing different ribosomal RNA gene regions, NGS technologies and chemistries. Our data indicate that many singletons (average of 38 % across gene regions) are likely artifacts or potential artifacts, but a large fraction can be assigned to lower taxonomic levels with very high bootstrap support (∼32 % of sequences to genus with ≥90 % bootstrap cutoff). Further, many singletons clustered into rare OTUs from other datasets highlighting their overlap across datasets or the poor performance of clustering algorithms. These data emphasize a need for caution when discarding rare sequence data en masse: such practices may result in throwing the baby out with the bathwater, and underestimating the biodiversity. Yet, the rare sequences are unlikely to greatly affect ecological metrics. As a result, it may be prudent to err on the side of caution and omit rare OTUs prior to downstream analyses.     

Rare plants at the extremes of distribution: broadly and narrowly distributed rare species

The flora of North America north of Mexico was used to study rare species at the two extremes of geographic distribution: endemic species, those with large local populations but small geographic ranges, and suffusively rare species, those with small local populations but large geographic ranges. The taxonomic distribution, geographic distribution, and life history characteristics of the two groups were compared. Only 2% of North American species are suffusively rare, while 22.6% of species are endemic to one state or province. Suffusively rare species are significantly more likely to be seedless vascular plants and monocots than expected, and are less likely to be eudicots. Conversely, endemic species are more likely to be eudicots, and less likely to be monocots. Suffusively rare species are most abundant in Canada and the northeastern United States, whereas there are few endemic species in those areas. The highest proportions of endemic species are found in California, Florida, and Texas. Wetland habitats support many suffusively rare species, but few endemic species. Neither are common in alpine habitats. Suffusively rare and endemic species also differ in the dominant growth form. Suffusively rare species are most likely to be herbaceous eudicots, and less likely to be shrubs or shrub-herbs. Endemic species are also likely to be herbaceous, but are also frequently shrubs. A high proportion of endemic species exhibit plasticity in growth form, whereas few suffusively rare species have plastic growth forms. While both groups contain rare species, they differ considerably in geographic distribution and life history traits.     

Salt marsh sediment diversity: a test of the variability of the rare biosphere among environmental replicates

Much of the phylogenetic diversity in microbial systems arises from rare taxa that comprise the long tail of taxon rank distribution curves. This vast diversity presents a challenge to testing hypotheses about the effects of perturbations on microbial community composition because variability of rare taxa among environmental replicates may be sufficiently large that it would require a prohibitive degree of sequencing to discern differences between samples. In this study we used pyrosequencing of 16S rRNA tags to examine the diversity and within-site variability of salt marsh sediment bacteria. Our goal was to determine whether pyrosequencing could produce similar patterns in community composition among replicate environmental samples from the same location. We hypothesized that repeated sampling from the same location would produce different snapshots of the rare community due to incomplete sequencing of the taxonomically rich rare biosphere. We demonstrate that the salt marsh sediments we sampled contain a remarkably diverse array of bacterial taxa and, in contrast to our hypothesis, repeated sampling from within the same site produces reliably similar patterns in bacterial community composition, even among rare organisms. These results demonstrate that deep sequencing of 16s tags is well suited to distinguish site-specific similarities and differences among rare taxa and is a valuable tool for hypothesis testing in microbial ecology.     

Nutrients Changed the Assembly Processes of Profuse and Rare Microbial Communities in Coals

Nutrient stimulation is considered effective for improving biogenic coalbed methane production potential. However, our knowledge of the microbial assembly process for profuse and rare microbial communities in coals under nutrient stimulation is still limited. This study collected 16S rRNA gene data from 59 microbial communities in coals for a meta-analysis. Among these communities, 116 genera were identified as profuse taxa, and the remaining 1,637 genera were identified as rare taxa. Nutrient stimulation increased the Chao1 richness of profuse and rare genera and changed the compositions of profuse and rare genera based on nonmetric multidimensional scaling with Bray-Curtis dissimilarities. In addition, many profuse and rare genera belonging to Proteobacteria and Acidobacteria were reduced, whereas those belonging to Euryarchaeota and Firmicutes were increased under nutrient stimulation. Concomitantly, the microbial co-occurrence relationship network was also altered by nutrient addition, and many rare genera mainly belonging to Firmicutes, Bacteroides, and Euryarchaeota also comprised the key microorganisms. In addition, the compositions of most of the profuse and rare genera in communities were driven by stochastic processes, and nutrient stimulation increased the relative contribution of dispersal limitation for both profuse and rare microbial community assemblages and that of variable selection for rare microbial community assemblages. In summary, this study strengthened our knowledge regarding the mechanistic responses of coal microbial diversity and community composition to nutrient stimulation, which are of great importance for understanding the microbial ecology of coals and the sustainability of methane production stimulated by nutrients.     

九宫山自然保护区珍稀濒危植物调查研究

据估计 ,在我国约 3 0 0 0 0种高等植物中至少有3 0 0 0种处于受威胁或濒临灭绝的境地[1] 。保护植物的多样性 ,特别是保护珍稀濒危植物等工作已被世界上许多国家的政府、学术组织和有关机构以及科学家们所普遍重视。湖北九宫山自然保护区分布有许多珍稀濒危植物 ,不仅是宝贵的种质资源 ,具有十分重要的经济意义 ,而且在植物分类学与地理学研究中具有重要价值。杨春锋等[2 ] 曾对九宫山自然保护区的植被进行了调查研究 ,目前对九宫山自然保护区的珍稀濒危植物尚未见报道。九宫山自然保护区的珍稀濒危植物由于多种原因日趋枯竭。因此 ,有必要…     

The biogeography of abundant and rare bacterioplankton in the lakes and reservoirs of China

Bacteria play key roles in the ecology of both aquatic and terrestrial ecosystems; however, little is known about their diversity and biogeography, especially in the rare microbial biosphere of inland freshwater ecosystems. Here we investigated aspects of the community ecology and geographical distribution of abundant and rare bacterioplankton using high-throughput sequencing and examined the relative influence of local environmental variables and regional (spatial) factors on their geographical distribution patterns in 42 lakes and reservoirs across China. Our results showed that the geographical patterns of abundant and rare bacterial subcommunities were generally similar, and both of them showed a significant distance–decay relationship. This suggests that the rare bacterial biosphere is not a random assembly, as some authors have assumed, and that its distribution is most likely subject to the same ecological processes that control abundant taxa. However, we identified some differences between the abundant and rare groups as both groups of bacteria showed a significant positive relationship between sites occupancy and abundance, but the abundant bacteria exhibited a weaker distance–decay relationship than the rare bacteria. Our results implied that rare subcommunities were mostly governed by local environmental variables, whereas the abundant subcommunities were mainly affected by regional factors. In addition, both local and regional variables that were significantly related to the spatial variation of abundant bacterial community composition were different to those of rare ones, suggesting that abundant and rare bacteria may have discrepant ecological niches and may play different roles in natural ecosystems.     

鄂西南后河一个典型稀有濒危植物群落的结构特征研究

研究了鄂西南后河一个典型的稀有濒危植物群落的结构特征。结果表明：在1400m^2的样地中自然分布有15种稀有濒危植物;群落优势种为水青树（Tetracentron sinensis)、金钱戚（Dipteronia sinensis);主要种群的空间分布格局除银鹊树为随机分布外,都为集群分布的格局;水青树银鹊树（Tapiscia sinsis)和珙桐（Davidia involucrata）种群结构呈衰老型,金钱椒、天师栗（Aesculus wilsonii)和光叶珙桐（Davidia involucrata var.vilkmorniana)种群表现为旺盛增长型结构,水青冈（Fagus longipetiolata)则表现为成熟的种群结构;群落垂直分层明显,可分为乔木层、灌木层和草本层;整个群落结构稳定,稀有濒危植物在群落中无论是在乔木层还是在其他层次中均占有很大的优势;但如果人为大量采挖稀有濒危植物小苗,群落将会演替成以水青冈等稀有濒危植物为主的群落。     

Simulating the maintenance of a rare fish morph experiencing negative frequency dependent selection

Empirical work assessing the maintenance of rare genotypes in natural populations is difficult over very long time scales. Skirting this problematic issue is possible with theory and simulations. Major theoretical constructs, including mutation-selection balance and balancing selection, explain the theoretical maintenance of rare genotypes, and the occurrence of multiple, rare genotypes over time. Additionally, numerical simulations are valuable tools for assessing evolving biological systems because they allow for monitoring systems over long time scales, as well as for controlling model parameters, thus contributing to the exploration of system dynamics that cannot be assessed in nature. Here we employed numerical simulations to explore the importance of several biological factors that contribute to the maintenance of a fish color-pattern polymorphism. We present a numerical model of a two-morph fish polymorphism that allowed us to test the sensitivity of the rare morph's persistence and the population's stability to multiple parameters. Our simulations ran over 10,000 years (where one year is approximately one generation) and demonstrated the maintenance of a stable polymorphism with a rare morph which persisted at a frequency of ∼10⁻², which is in-fact the frequency of the rare, mottled black mosquitofish morph in natural populations. This pigmentation polymorphism is stable, independent of changes in population size, but can be destabilized with very high predation when coupled with very low birth rates. Employing models with empirical fitness estimates is a valuable tool for monitoring rare vertebrate morphs in nature, however few studies exist that have accomplished this task. Our approach can be adapted for modeling rare morphs (particularly in additional live-bearing fishes like sailfin mollies) that also harbor rare, pigmentation morphs within large populations.     

江苏省珍稀濒危保护植物资源及其园林应用前景

珍稀濒危保护植物是人类重要的植物资源之一,江苏地处暖温带和亚热带的过渡地带,自然条件优越,植物种类多样,蕴含着丰富的珍稀濒危保护植物。文章调查整理出78种江苏省珍稀濒危保护植物,隶属40科65属,其中本省自然分布的有21种,从其他省份引种栽培的有57种。为了能促进江苏省珍稀濒危保护植物在园林绿化中的应用,分别从江苏省珍稀濒危保护植物的概况、观赏价值、园林应用现状以及在园林中的应用前景等方面进行论述,以期为绿化工作者提供参考。     

稀有种和常见种对植物群落物种丰富度格局的相对贡献

物种丰富度格局的形成不仅依赖于群落的构建过程, 同样也依赖于群落中的物种组成(如稀有种和常见种)。本文以黄土高原子午岭林区的辽东栎(Quercus wutaishanica)林为研究对象, 根据频度大小对物种进行排序, 形成稀有-常见种和常见-稀有种两条物种序列, 通过逐一添加(去除)物种, 分析引起的总体物种丰富度及其成分(α多样性和β多样性)的变化, 确定稀有种和常见种对物种丰富度格局的相对贡献。结果表明: (1)常见-稀有种序列与群落总体物种丰富度的相关性呈先剧增后平稳的对数增长曲线, 而稀有-常见种序列与群落总体的相关性与前者刚好相反, 呈先平稳后剧增的指数增长曲线; (2) α多样性在常见-稀有种序列中呈明显的对数变化曲线, 而在稀有-常见种序列中呈指数增长曲线; (3)与α多样性变化相反, β多样性在常见-稀有种序列中随物种的进入先迅速降低后逐渐平稳, 而在稀有-常见种序列中先平稳后急剧降低。可以看出, 常见种不仅主导群落的总体物种丰富度格局, 同时也是α多样性和β多样性格局的重要贡献者。因此, 常见种是群落物种丰富度格局的指示者, 也应该是优先保护的物种。     

Osteonecrosis of the jaw

The paper concerns osteonecrosis of the jaw (ONJ). It is a rare but serious clinical condition. It can develop in patients treated in oncologic doses with bisphosphonates but also with denosumab. In osteoporosis ONJ seems to be very rare. Definition, pathogenesis, risk factors, prevention and treatment, and the frequency of ONJ are presented.     

稀土元素的生物安全性探讨

采用微核检测、单细胞凝胶电泳、同工酶等技术研究了稀土元素遗传毒理效应的有关结果。大量试验表明,稀土元素断裂DNA的能力,因而在一定浓度范围内,稀土元素确有致突变性。稀土元素在土壤中可专性吸附、不可降解,在动植物和人体皆有累积效应,因此稀土元素的生物安全性值得深入探讨。     

河南大别山区野生珍稀濒危植物资源初步研究

论述了河南大别山区野生珍稀濒危植物资源现状、地理分布和生境特点,分析了珍稀濒危植物产生的原因,提出了保护和开发利用珍稀濒危植物资源相应对策.