On the Additive and Dominant Variance and Covariance of Individuals Within the Genomic Selection Scope

Genomic evaluation models can fit additive and dominant SNP effects. Under quantitative genetics theory, additive or “breeding” values of individuals are generated by substitution effects, which involve both “biological” additive and dominant effects of the markers. Dominance deviations include only a portion of the biological dominant effects of the markers. Additive variance includes variation due to the additive and dominant effects of the markers. We describe a matrix of dominant genomic relationships across individuals, D, which is similar to the G matrix used in genomic best linear unbiased prediction. This matrix can be used in a mixed-model context for genomic evaluations or to estimate dominant and additive variances in the population. From the “genotypic” value of individuals, an alternative parameterization defines additive and dominance as the parts attributable to the additive and dominant effect of the markers. This approach underestimates the additive genetic variance and overestimates the dominance variance. Transforming the variances from one model into the other is trivial if the distribution of allelic frequencies is known. We illustrate these results with mouse data (four traits, 1884 mice, and 10,946 markers) and simulated data (2100 individuals and 10,000 markers). Variance components were estimated correctly in the model, considering breeding values and dominance deviations. For the model considering genotypic values, the inclusion of dominant effects biased the estimate of additive variance. Genomic models were more accurate for the estimation of variance components than their pedigree-based counterparts.     

Simple Incorporation of Interactions into Additive Models

Often, the functional form of covariate effects in an additive model varies across groups defined by levels of a categorical variable. This structure represents a factor-by-curve interaction. This article presents penalized spline models that incorporate factor-by-curve interactions into additive models. A mixed model formulation for penalized splines allows for straightforward model fitting and smoothing parameter selection. We illustrate the proposed model by applying it to pollen ragweed data in which seasonal trends vary by year.     

The Causal Meaning of Genomic Predictors and How It Affects Construction and Comparison of Genome-Enabled Selection Models

The term “effect” in additive genetic effect suggests a causal meaning. However, inferences of such quantities for selection purposes are typically viewed and conducted as a prediction task. Predictive ability as tested by cross-validation is currently the most acceptable criterion for comparing models and evaluating new methodologies. Nevertheless, it does not directly indicate if predictors reflect causal effects. Such evaluations would require causal inference methods that are not typical in genomic prediction for selection. This suggests that the usual approach to infer genetic effects contradicts the label of the quantity inferred. Here we investigate if genomic predictors for selection should be treated as standard predictors or if they must reflect a causal effect to be useful, requiring causal inference methods. Conducting the analysis as a prediction or as a causal inference task affects, for example, how covariates of the regression model are chosen, which may heavily affect the magnitude of genomic predictors and therefore selection decisions. We demonstrate that selection requires learning causal genetic effects. However, genomic predictors from some models might capture noncausal signal, providing good predictive ability but poorly representing true genetic effects. Simulated examples are used to show that aiming for predictive ability may lead to poor modeling decisions, while causal inference approaches may guide the construction of regression models that better infer the target genetic effect even when they underperform in cross-validation tests. In conclusion, genomic selection models should be constructed to aim primarily for identifiability of causal genetic effects, not for predictive ability.     

Genetic Relationship and Genomic in situ Hybridization Analysis of the Three Genomes in Triticum aestivum

Common wheat ( Triticum　aestivum L.) is an allohexaploid, consisting of three different genomes (Au, B and D ) which are genetically closely related. Genomic DNA of the three possible genome donors, T. urartu Thum., Aegilops speltoides Tausch and Ae. tauschii Coss.,were employed as probes to hybridize with the diploid genomic DNA digested by Eco RⅠand Hin dⅢ respectively. Both the hybridization strength and band patterns among the genomes would be good indicators of genome relationships. Combining distr ibution data of some repetitive DNA sequences cloned from T. urartu in the three genomes, the authors draw a conclusion that Au and D are more closely related to each other than either one to the B genome. Genomic in situ hybridization (GISH) of T. aestivum cv. Chinese Spring with genomic DNA probes of the three diploid progenitors respectively indicated that the three genomes could be discriminated clearly via GISH. The signals on the chromosomes of Au and D genomes were even. However, when Ae. speltoides DNA was used as probe, there were very strong cross hybridization and the signals condensed on some areas of the metaphasic chromosomes. In the interphase nucleus, the chromatin of B genome dispersed on the same region and the signals on the homologous chromosomes distributed symmetrically. Rich repetitive DNA sequences in B genome, especially the tandem repetitives, perhaps take an important role for the formation of the special hybridization pattern. The main difference between B and the other two genomes probably is in the repetitive DNA sequences.     

普通小麦三个基因组之间的遗传关系及原位杂交分析

以普通小麦（Ｔｒｉｔｉｃｕｍ ａｅｓｔｉｖｕｍＬ．）的３个可能的二倍体供体种（乌拉尔图小麦（Ｔ．ｕｒａｒｔｕＴｈｕｍ．）拟斯卑尔脱山羊草（ＡｅｇｉｌｏｐｓｓｐｅｌｔｏｉｄｅｓＴａｕｓｃｈ）和粗山羊草（Ａｅ．ｔａｕｓｃｈｉｉＣｏｓｓ．）的基因组ＤＮＡ为研究对象,通过它们之间的相互杂交,比较杂交强度以及泳道中带纹的不同,并结合部分ＤＮＡ重复序列在基因组间含量差异的数据,得出结论：Ａ＾ｕ和Ｄ基因组的关系     

昼夜节律钟调控代谢的研究进展

生理和行为的昼夜节律性调控对健康生活是必需的。越来越多的流行病学和遗传学证据显示昼夜节律的破坏与代谢紊乱性疾病相关联。在分子水平上,昼夜节律受到时钟蛋白组成的转录一翻译负反馈环的调控。时钟蛋白通过以下两种途径调节代谢：首先,时钟蛋白作为转录因子直接调节一些代谢关键步骤的限速酶和代谢相关核受体的表达,其次作为代谢相关核受体的辅调节因子来激活或抑制其转录活性。虽然时钟蛋白对代谢途径的调节导致代谢物水平呈昼夜节律振荡,但是产生的代谢物反过来又可以影响昼夜节律钟基因的表达,进而影响昼夜节律钟。深入研究昼夜节律钟与代谢的交互调节可能为治疗某些代谢紊乱性疾病提供新的治疗方案。     

3属3种毛茛科植物幼苗形态结构及其系统演化分析

以毛茛科升麻属植物升麻(Cimicifuga foetida)、金莲花属植物短瓣金莲花(Trollius ledebouri)和飞燕草属植物飞燕草(Consolida ajacis)为材料,应用整体透明和石蜡连续切片方法,对3种植物幼苗形态特征及初生维管系统结构进行了观察。结果表明:升麻子叶脉序为较简单的离基不完全顶聚脉,短瓣金莲花为环结曲行羽状脉,飞燕草为较复杂的基出完全顶聚脉。升麻属幼苗子叶节区下部的维管柱为中始式二原型长方形单中柱,金莲花属为外始式二原型半弧形单中柱,飞燕草属为外始式二原型双扇形单中柱。分析上述子叶脉序特征和维管柱类型,认为3属中升麻属最原始,金莲花属次之,飞燕草属进化程度最高。     

Genomic BLUP Decoded: A Look into the Black Box of Genomic Prediction

Genomic best linear unbiased prediction (BLUP) is a statistical method that uses relationships between individuals calculated from single-nucleotide polymorphisms (SNPs) to capture relationships at quantitative trait loci (QTL). We show that genomic BLUP exploits not only linkage disequilibrium (LD) and additive-genetic relationships, but also cosegregation to capture relationships at QTL. Simulations were used to study the contributions of those types of information to accuracy of genomic estimated breeding values (GEBVs), their persistence over generations without retraining, and their effect on the correlation of GEBVs within families. We show that accuracy of GEBVs based on additive-genetic relationships can decline with increasing training data size and speculate that modeling polygenic effects via pedigree relationships jointly with genomic breeding values using Bayesian methods may prevent that decline. Cosegregation information from half sibs contributes little to accuracy of GEBVs in current dairy cattle breeding schemes but from full sibs it contributes considerably to accuracy within family in corn breeding. Cosegregation information also declines with increasing training data size, and its persistence over generations is lower than that of LD, suggesting the need to model LD and cosegregation explicitly. The correlation between GEBVs within families depends largely on additive-genetic relationship information, which is determined by the effective number of SNPs and training data size. As genomic BLUP cannot capture short-range LD information well, we recommend Bayesian methods with t-distributed priors.     

Review of the Dual-Clock Control of Tidal Rhythms and the Hypothesis that the Same Clock Governs Both Circatidal and Circadian Rhythms

Discoveries first published in 1986 did not fit the de rigueur working hypothesis that the clocks governing tide-associated rhythms had a fundamental period of 12.4 h, a value equal to the average interval between successive tides on most coastlines of the world. To explain the results a dual-clock schema was fashioned that envisioned two clocks, strongly coupled together 180° antiphase, each running at a basic rate of 24.8 h (the interval of a lunar day), as the driving agents of tide-associated rhythms (details are given in the text). This elaboration has been named the circalunidian-clock hypothesis, a hypocorism used in some armchair ruminations back in 1973. In the decade since 1986, a goodly amount of evidence has been garnered that is consistent with this hypothesis—suggesting that first-call divination appears to have been visionary. Acceptance of this hypothesis leads to further cerebration that a 24.8-h clock, its circa periods in constant conditions, and other properties—which fully overlap with our perception of the circadian clock that drives daily rhythms—may indicate that circadian and circalunidan timepieces are not different entities. The known properties of both daily and lunar clock-types are compared and contrasted, and, with the exception of one feature (for which there is at least a philosophical explanation), it is concluded that the same clock that drives tidal rhythms could also motor daily rhythms, i.e., there may be no such thing as a 12.4-h horologue.     

A Foundation for Provitamin A Biofortification of Maize: Genome-Wide Association and Genomic Prediction Models of Carotenoid Levels

Efforts are underway for development of crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency. As a global staple crop with considerable variation in kernel carotenoid composition, maize (Zea mays L.) could have a widespread impact. We performed a genome-wide association study (GWAS) of quantified seed carotenoids across a panel of maize inbreds ranging from light yellow to dark orange in grain color to identify some of the key genes controlling maize grain carotenoid composition. Significant associations at the genome-wide level were detected within the coding regions of zep1 and lut1, carotenoid biosynthetic genes not previously shown to impact grain carotenoid composition in association studies, as well as within previously associated lcyE and crtRB1 genes. We leveraged existing biochemical and genomic information to identify 58 a priori candidate genes relevant to the biosynthesis and retention of carotenoids in maize to test in a pathway-level analysis. This revealed dxs2 and lut5, genes not previously associated with kernel carotenoids. In genomic prediction models, use of markers that targeted a small set of quantitative trait loci associated with carotenoid levels in prior linkage studies were as effective as genome-wide markers for predicting carotenoid traits. Based on GWAS, pathway-level analysis, and genomic prediction studies, we outline a flexible strategy involving use of a small number of genes that can be selected for rapid conversion of elite white grain germplasm, with minimal amounts of carotenoids, to orange grain versions containing high levels of provitamin A.     

Genomic control for association studies under various genetic models

Case-control studies are commonly used to study whether a candidate allele and a disease are associated. However, spurious association can arise due to population substructure or cryptic relatedness, which cause the variance of the trend test to increase. Devlin and Roeder derived the appropriate variance inflation factor (VIF) for the trend test and proposed a novel genomic control (GC) approach to estimate VIF and adjust the test statistic. Their results were derived assuming an additive genetic model and the corresponding VIF is independent of the candidate allele frequency. We determine the appropriate VIFs for recessive and dominant models. Unlike the additive test, the VIFs for the optimal tests for these two models depend on the candidate allele frequency. Simulation results show that, when the null loci used to estimate the VIF have allele frequencies similar to that of the candidate gene, the GC tests derived for recessive and dominant models remain optimal. When the underlying genetic model is unknown or the null loci and candidate gene have quite different allele frequencies, the GC tests derived for the recessive or dominant models cannot be used while the GC test derived for the additive model can be.     

Review of the Dual-Clock Control of Tidal Rhythms and the Hypothesis that the Same Clock Governs Both Circatidal and Circadian Rhythms

Discoveries first published in 1986 did not fit the de rigueur working hypothesis that the clocks governing tide-associated rhythms had a fundamental period of 12.4 h, a value equal to the average interval between successive tides on most coastlines of the world. To explain the results a dual-clock schema was fashioned that envisioned two clocks, strongly coupled together 180° antiphase, each running at a basic rate of 24.8 h (the interval of a lunar day), as the driving agents of tide-associated rhythms (details are given in the text). This elaboration has been named the circalunidian-clock hypothesis, a hypocorism used in some armchair ruminations back in 1973. In the decade since 1986, a goodly amount of evidence has been garnered that is consistent with this hypothesis—suggesting that first-call divination appears to have been visionary. Acceptance of this hypothesis leads to further cerebration that a 24.8-h clock, its circa periods in constant conditions, and other properties—which fully overlap with our perception of the circadian clock that drives daily rhythms—may indicate that circadian and circalunidan timepieces are not different entities. The known properties of both daily and lunar clock-types are compared and contrasted, and, with the exception of one feature (for which there is at least a philosophical explanation), it is concluded that the same clock that drives tidal rhythms could also motor daily rhythms, i.e., there may be no such thing as a 12.4-h horologue.     

灰树花总DNA的制备及基因组文库的构建A

灰树花是一种珍贵的药用真菌,因为多糖含量较高,较难获得高质量的总DNA,本文提出了一种制备高质量灰树花总DNA及构建灰树花基因组文库的方法。该方法制备的灰树花总DNA,经Sau3AI酶切后,用于构建基因组文库,可得到2×105个转化子/50mg,平均插入片段为14kb。本研究为下一步克隆灰树花中的基因以及进行其他分子生物学研究奠定了基础。Abstract： Grifola frondosa, is a valuable medicinal fungus. High quality total genomic DNA is difficult to prepare due to its high polysaccharide content. A method for the preparation of Grifola frondosa total genomic DNA and construction of Grifola frondosa, genomic library is described. Genomic DNA prepared by this method is digested by Sau3A I restriction enzyme. Constructed genomic library give a titer of 2×105 transformants/50mg , with a average insert size of 14kb. This has paved way for the cloning of other Grifola frondosa genes and molecular biology studies.     

一种蜘蛛基因组DNA的简易提取方法

本文介绍了1种改进的蜘蛛基因组DNA的提取方法.通过与传统DNA提取方法的比较,本方法具有可在常温条件下进行、DNA得率高、简便、经济等优势.     

A story from the Miocene: Clock‐dated phylogeny of Sisymbrium L. (Sisymbrieae,Brassicaceae)

Morphological variability and imprecise generic boundaries have hindered systematic, taxonomical, and nomenclatural studies of Sisymbrium L. (Brassicaceae, Sisymbrieae DC.). The members of this almost exclusively Old‐World genus grow mostly on highly porous substrates across open steppe, semidesert, or ruderal habitats in the temperate zone of the Northern Hemisphere and African subtropics. The present study placed the biological history of Sisymbrium L. into time and space and rendered the tribus Sisymbrieae as monotypic. Five nuclear‐encoded and three chloroplast‐encoded loci of approximately 85% of all currently accepted species were investigated. Several accessions per species covering their whole distribution range allowed for a more representative assessment of intraspecific genetic diversity. In the light of fossil absence, the impact of different secondary calibration methods and taxon sets on time spans was tested, and we showed that such a combinatorial nested dating approach is beneficial. Multigene phylogeny accompanied with a time divergence estimation analysis placed the onset and development of this tribus into the western Irano‐Turanian floristic region during the Miocene. Continuous increase in continentality and decrease in temperatures promoted the diversity of the Sisymbrieae, which invaded the open grasslands habitats in Eurasia, Mediterranean, and South Africa throughout the Pliocene and Pleistocene. Our results support the assumption of the Irano‐Turanian region as a biodiversity reservoir for adjacent regions.     

The Mizon–Richard Encompassing Test for the Cox and Aalen Additive Hazards Models

Summary .   The Cox hazards model ( Cox, 1972 , Journal of the Royal Statistical Society, Series B 34, 187–220) for survival data is routinely used in many applied fields, sometimes, however, with too little emphasis on the fit of the model. A useful alternative to the Cox model is the Aalen additive hazards model ( Aalen, 1980 , in Lecture Notes in Statistics-2 , 1–25) that can easily accommodate time changing covariate effects. It is of interest to decide which of the two models that are most appropriate to apply in a given application. This is a nontrivial problem as these two classes of models are nonnested except only for special cases. In this article we explore the Mizon–Richard encompassing test for this particular problem. It turns out that it corresponds to fitting of the Aalen model to the martingale residuals obtained from the Cox regression analysis. We also consider a variant of this method, which relates to the proportional excess model ( Martinussen and Scheike, 2002 , Biometrika 89, 283–298). Large sample properties of the suggested methods under the two rival models are derived. The finite-sample properties of the proposed procedures are assessed through a simulation study. The methods are further applied to the well-known primary biliary cirrhosis data set.     

A mathematical investigation of a Clock and Wavefront model for somitogenesis

Somites are transient blocks of cells that form sequentially along the antero-posterior axis of vertebrate embryos. They give rise to the vertebrae, ribs and other associated features of the trunk. In this work we develop and analyse a mathematical formulation of a version of the Clock and Wavefront model for somite formation, where the clock controls when the boundaries of the somites form and the wavefront determines where they form. Our analysis indicates that this interaction between a segmentation clock and a wavefront can explain the periodic pattern of somites observed in normal embryos. We can also show that a simplification of the model provides a mechanism for predicting the anomalies resulting from perturbation of the wavefront.     

Genomic imprinting in the development and evolution of psychotic spectrum conditions

I review and evaluate genetic and genomic evidence salient to the hypothesis that the development and evolution of psychotic spectrum conditions have been mediated in part by alterations of imprinted genes expressed in the brain. Evidence from the genetics and genomics of schizophrenia, bipolar disorder, major depression, Prader‐Willi syndrome, Klinefelter syndrome, and other neurogenetic conditions support the hypothesis that the etiologies of psychotic spectrum conditions commonly involve genetic and epigenetic imbalances in the effects of imprinted genes, with a bias towards increased relative effects from imprinted genes with maternal expression or other genes favouring maternal interests. By contrast, autistic spectrum conditions, including Kanner autism, Asperger syndrome, Rett syndrome, Turner syndrome, Angelman syndrome, and Beckwith‐Wiedemann syndrome, commonly engender increased relative effects from paternally expressed imprinted genes, or reduced effects from genes favouring maternal interests. Imprinted‐gene effects on the etiologies of autistic and psychotic spectrum conditions parallel the diametric effects of imprinted genes in placental and foetal development, in that psychotic spectrum conditions tend to be associated with undergrowth and relatively‐slow brain development, whereas some autistic spectrum conditions involve brain and body overgrowth, especially in foetal development and early childhood. An important role for imprinted genes in the etiologies of psychotic and autistic spectrum conditions is consistent with neurodevelopmental models of these disorders, and with predictions from the conflict theory of genomic imprinting.     

Evidence for Multiple Lateral Transfers of the Circadian Clock Cluster in Filamentous Heterocystic Cyanobacteria Nostocaceae

Cyanobacteria are the first prokaryotes reported to show circadian rhythmicity, which is regulated by a cluster of three genes: kaiA, kaiB, and kaiC. Phylogenetic analysis of the kaiBC cluster in filamentous cyanobacteria of the family Nostocaceae including Nodularia spumigena and Nostoc linckia from Arubotaim Cave, Mt. Sedom, Israel, indicated that this cluster has experienced multiple lateral transfers. The transfers have occurred in different periods of the species evolution. The data obtained suggest that lateral transfers of the circadian clock cluster in filamentous cyanobacteria have been common and might have adaptive significance.