An arrayed human genomic library constructed in the PAC shuttle vector pJCPAC-Mam2 for genome-wide association studies and gene therapy

The various iterations of the HapMap Project and many genome-wide association studies (GWAS) have identified hundreds of potential genes involved in monogenic and multifactorial traits. We constructed an arrayed 115,000-member human genomic library in the PAC shuttle vector pJCPAC-Mam2 that can be propagated in both bacterial and human cells. The library appears to represent a two-fold coverage of the human genome. Transient transfection of a p53-containing PAC clone into p53-null Saos-2 human osteosarcoma cells demonstrated that both p53 mRNA and protein were produced. Additionally, expression of the p53 protein triggered apoptosis in a subset of the Saos-2 cells. This library should serve as a valuable resource to validate potential disease genes identified by GWAS in human cell lines and in animal models. Also, individual library members could potentially be used for gene therapy trials for a variety of recessive disorders.     

Mapping QTLs and candidate genes for iron and zinc concentrations in unpolished rice of Madhukar×Swarna RILs

Identifying QTLs/genes for iron and zinc in rice grains can help in biofortification programs. 168 F(7) RILs derived from Madhukar×Swarna were used to map QTLs for iron and zinc concentrations in unpolished rice grains. Iron ranged from 0.2 to 224ppm and zinc ranged from 0.4 to 104ppm. Genome wide mapping using 101 SSRs and 9 gene specific markers showed 5 QTLs on chromosomes 1, 3, 5, 7 and 12 significantly linked to iron, zinc or both. In all, 14 QTLs were identified for these two traits. QTLs for iron were co-located with QTLs for zinc on chromosomes 7 and 12. In all, ten candidate genes known for iron and zinc homeostasis underlie 12 of the 14 QTLs. Another 6 candidate genes were close to QTLs on chromosomes 3, 5 and 7. Thus the high priority candidate genes for high Fe and Zn in seeds are OsYSL1 and OsMTP1 for iron, OsARD2, OsIRT1, OsNAS1, OsNAS2 for zinc and OsNAS3, OsNRAMP1, Heavy metal ion transport and APRT for both iron and zinc together based on our genetic mapping studies as these genes strictly underlie QTLs. Several elite lines with high Fe, high Zn and both were identified.     

Informative Dorfman screening

Since the early 1940s, group testing (pooled testing) has been used to reduce costs in a variety of applications, including infectious disease screening, drug discovery, and genetics. In such applications, the goal is often to classify individuals as positive or negative using initial group testing results and the subsequent process of decoding of positive pools. Many decoding algorithms have been proposed, but most fail to acknowledge, and to further exploit, the heterogeneous nature of the individuals being screened. In this article, we use individuals' risk probabilities to formulate new informative decoding algorithms that implement Dorfman retesting in a heterogeneous population. We introduce the concept of "thresholding" to classify individuals as "high" or "low risk," so that separate, risk-specific algorithms may be used, while simultaneously identifying pool sizes that minimize the expected number of tests. When compared to competing algorithms which treat the population as homogeneous, we show that significant gains in testing efficiency can be realized with virtually no loss in screening accuracy. An important additional benefit is that our new procedures are easy to implement. We apply our methods to chlamydia and gonorrhea data collected recently in Nebraska as part of the Infertility Prevention Project.     

MHC-dependent mate choice in humans: why genomic patterns from the HapMap European American dataset support the hypothesis

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC-dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC-dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC-dependent mate choice in some human populations.     

HUPO 2011: The new Cardiovascular Initiative - integrating proteomics and cardiovascular biology in health and disease

A newly reorganized HUPO Cardiovascular Initiative was announced at the HUPO 2011 Cardiovascular Initiative Workshop at Geneva. The new initiative is now part of the biology- and disease-driven component of the HUPO Human Proteome Project (B/D-HPP). Here we report the recent achievements and future directions of the initiative, and offer a perspective on the present challenges of cardiovascular proteomics and its integration with the cardiovascular biology community at large.     

Recent ecosystem dynamics in nine North African lakes in the CASSARINA Project

An integrated multi-disciplinary study of nine North African lakes (CASSARINA) aims to establish ecological baselines and to explore responses to 20th century human impacts on their ecosystems. Water chemistry measurements (1997–1998) demonstrate a wide range from dilute oligotrophic to calcareous freshwaters and from mildly brackish to hypersaline lagoons. The biota are consequently highly diverse. Aquatic ecosystem responses to environmental stress over the last 100–200 years in all nine lakes are summarised by detrended correspondence analysis (DCA) of plant and animal macrofossil, zooplankton, diatom, and pollen data from short sediment cores. DCA proved to be a powerful tool for summarising multi-proxy sediment records and ecosystem dynamics. Compositional changes measured by the DCAs have been very large and rapid, often over a few decades; as great as climate-controlled late-glacial changes over 2000 years and larger than most Holocene (11000 years) changes. These results emphasise the strength of human impact on the lakes and the surprisingly great resilience and dynamism of their ecosystems. The DCA summaries for the most recent decades indicate ecosystem disequilibrium in all the lakes, implying that their future stability is uncertain and that large or damaging changes may soon occur if the stresses are maintained. Thresholds have recently been passed in 3 lakes. During the project, Merja Bokka (Morocco) was drained and cultivated. The unique acid Megene Chitane (Tunisia) is in danger of drying up permanently due to water extraction. Freshwater diversion from Garaet El Ichkeul (Tunisia) has dramatically altered its wildlife habitat, as reed-marshes were replaced by salt-marsh and bare mud within 20 years. In contrast, the ecosystems of the Delta lakes (Egypt) have responded dramatically to the year-round inflow of fresh irrigation water controlled by Nile dams and the rise in the freshwater table due to inadequate drainage in the flat delta. The Project has demonstrated remarkably rapid responses by the lakes to environmental stresses. In particular, it highlights the threats to wetland-lake ecosystems in North Africa if uncontrolled exploitation continues.     

神经信息学的原理与展望

神经信息学是研究神经系统信息的载体形式,神经信息的产生、传输、加工、编码、存储与提取机理,以及建立神经数据库系统的科学。它是脑科学,信息科学和计算机科学相互交叉的边缘学科。神经信息学可分为分子神经信息学和系统神经信息学两个层次。神经信息编码可分为神经元脉冲序列的数字编码和突触联结权重编码两种编码方式。对21世纪神经信息学可能取得的新进展进行分析和预测,并论证开展人类神经组计划（HuNP）和建立神经数据库系统的必要性与可行性。对人类神经计划与人类脑计划的异同步,进行比较和讨论。     

Updated Italian checklist of Soldier Flies (Diptera,Stratiomyidae)

An updated checklist for Stratiomyidae of Italy is presented. Previous knowledge and information are put together in a comprehensive way, integrated also with results obtained by sampling with Malaise traps in some of the test areas of the LIFE+ project ManFor C.BD.At the time of writing, with 91 known species, the Italian fauna of Stratiomyidae is the richest in Europe. Neopachygaster meromelas (Dufour, 1841) and Zabrachia minutissima (Zetterstedt, 1838) are new to the Italian fauna. A comprehensive key to the European species of Chorisops Rondani, 1856 is given.     

An evaluation of a novel estimator of linkage disequilibrium

The analysis of systems involving many loci is important in population and quantitative genetics. An important problem is the study of linkage disequilibrium (LD), a concept relevant in genome-enabled prediction of quantitative traits and in exploration of marker–phenotype associations. This article introduces a new estimator of a LD parameter (ρ²) that is much easier to compute than a maximum likelihood (or Bayesian) estimate of a tetra-choric correlation. We examined the conjecture that the sampling distribution of the estimator of ρ² could be less frequency dependent than that of the estimator of r², a widely used metric for assessing LD. This was done via an empirical evaluation of LD in 806 Holstein–Friesian cattle using 771 single-nucleotide polymorphism (SNP) markers and of HapMap III data on 21 991 SNPs (chromosome 3) observed in 88 unrelated individuals from Tuscany. Also, 1600 haplotypes over a region of 1 Mb simulated under the coalescent were used to estimate LD using the two measures. Subsequently, a simulation study compared the new estimator with that of r² using several scenarios of LD and allelic frequencies. From these studies, it is concluded that ρ² provides a useful metric for the study of LD as the distribution of its estimator is less frequency dependent than that of the standard estimator of r².