Genomic mining for complex disease traits with “random chemistry”

Our rapidly growing knowledge regarding genetic variation in the human genome offers great potential for understanding the genetic etiology of disease. This, in turn, could revolutionize detection, treatment, and in some cases prevention of disease. While genes for most of the rare monogenic diseases have already been discovered, most common diseases are complex traits, resulting from multiple gene–gene and gene-environment interactions. Detecting epistatic genetic interactions that predispose for disease is an important, but computationally daunting, task currently facing bioinformaticists. Here, we propose a new evolutionary approach that attempts to hill-climb from large sets of candidate epistatic genetic features to smaller sets, inspired by Kauffman’s “random chemistry” approach to detecting small auto-catalytic sets of molecules from within large sets. Although the algorithm is conceptually straightforward, its success hinges upon the creation of a fitness function able to discriminate large sets that contain subsets of interacting genetic features from those that don’t. Here, we employ an approximate and noisy fitness function based on the ReliefF data mining algorithm. We establish proof-of-concept using synthetic data sets, where individual features have no marginal effects. We show that the resulting algorithm can successfully detect epistatic pairs from up to 1,000 candidate single nucleotide polymorphisms in time that is linear in the size of the initial set, although success rate degrades as heritability declines. Research continues into seeking a more accurate fitness approximator for large sets and other algorithmic improvements that will enable us to extend the approach to larger data sets and to lower heritabilities.     

Identification of Specific Variations in a Non-Motile Strain of Cyanobacterium Synechocystis sp. PCC 6803 Originated from ATCC 27184 by Whole Genome Resequencing

Cyanobacterium Synechocystis sp. PCC 6803 is a widely used model organism in basic research and biofuel biotechnology application. Here, we report the genomic sequence of chromosome and seven plasmids of a glucose-tolerant, non-motile strain originated from ATCC 27184, GT-G, in use at Guangzhou. Through high-throughput genome re-sequencing and verification by Sanger sequencing, eight novel variants were identified in its chromosome and plasmids. The eight novel variants, especially the five non-silent mutations might have interesting effects on the phenotype of GT-G strains, for example the truncated Sll1895 and Slr0322 protein. These resequencing data provide background information for further research and application based on the GT-G strain and also provide evidence to study the evolution and divergence of Synechocystis 6803 globally.     

Polymorphisms in Myostatin Gene and Associations with Growth Traits in the Common Carp (Cyprinus carpio L.)

Myostatin (MSTN) is a member of the transforming growth factor-β superfamily that negatively regulates skeletal muscle development and growth. In the present study, partial genomic fragments of MSTN were screened for single nucleotide polymorphisms (SNPs) in selected common carp individuals from wild populations, and two SNPs in intron 2 (c.371 + 749A > G, c.371 + 781T > C) and two synonymous SNPs in exon 3 (c.42A > G, c.72C > T) were identified. Genotyping by direct sequencing of polymerase chain reaction (PCR) products for these four SNPs were performed in 162 individuals from a commercial hatchery population. Association analysis showed that two SNPs in exon 3 were significantly associated with body weight (BW) and condition factor (K), and haplotype analyses revealed that haplotype H7H8 showed better growth performance. Our results demonstrated that some of the SNPs in MSTN may have positive effects on growth traits and suggested that MSTN could be a candidate gene for growth and marker-assisted selection in common carp.     

Characterization of a Cyclic Nucleotide‐Activated K+ Channel and its Lipid Environment by Using Solid‐State NMR Spectroscopy

Voltage‐gated ion channels are large tetrameric multidomain membrane proteins that play crucial roles in various cellular transduction pathways. Because of their large size and domain‐related mobility, structural characterization has proved challenging. We analyzed high‐resolution solid‐state NMR data on different isotope‐labeled protein constructs of a bacterial cyclic nucleotide‐activated K⁺ channel (MlCNG) in lipid bilayers. We could identify the different subdomains of the 4×355 residue protein, such as the voltage‐sensing domain and the cyclic nucleotide binding domain. Comparison to ssNMR data obtained on isotope‐labeled cell membranes suggests a tight association of negatively charged lipids to the channel. We detected spectroscopic polymorphism that extends beyond the ligand binding site, and the corresponding protein segments have been associated with mutant channel types in eukaryotic systems. These findings illustrate the potential of ssNMR for structural investigations on large membrane‐embedded proteins, even in the presence of local disorder.     

不同养殖地区克氏原螯虾肌肉熟制前后滋味差异

该研究选取了2个养殖地区（以湖北仙桃和潜江为例）的克氏原螯虾为研究对象,研究生虾和熟虾肉在滋味上的差异,对虾肉中呈味核苷酸、有机酸、游离氨基酸和无机离子等含量测定,并采用味道强度值和味精当量值来评价滋味物质的呈味强度,同时用电子舌对滋味和气味进行分析。结果表明：经热处理,呈味核苷酸中腺苷酸含量最高,仙桃地区（AX-1）和潜江地区（AX-2）虾肉中的腺苷酸含量分别为2.914、2.751 mg/g,对虾肉的鲜味形成有显著贡献;甘氨酸和丙氨酸对其甜味形成有显著贡献,缬氨酸和组氨酸能产生苦味;而热处理后AX-1中甘氨酸和丙氨酸含量分别增长约50.79%和3.79%,AX-2则分别增长约67.03%和28.82%,有趣的是AX-1中的苦味氨基酸含量也显著增大,从而影响其整体滋味;味精当量值呈上升趋势,无机离子含量、电子舌滋味分析和感官评价与核苷酸、氨基酸等指标结果对应。研究表明：不同养殖地区克氏原螯虾虾肉的滋味特征存在显著差异,综合考虑,热处理后AX-2的虾肉整体滋味更佳。     

保健食品铁皮石斛及其混淆品的分子鉴别及亲缘关系分析

目的：寻找简易且重复性高的分子标记方法对保健食品铁皮石斛及其混淆品进行分子鉴别并对其亲缘关系进行分析。方法：对铁皮石斛及其混淆品的matK 基因进行扩增、测序并进行序列分析,寻找其中存在的单核苷酸多态性(SNP)位点并根据SNP 位点设计特异性鉴别引物;运用Mega 3.0 等软件进行遗传关系分析。结果：根据matK 基因序列中存在的SNP 位点及特异性鉴别引物,可将铁皮石斛与其混淆品成功分开;各样品之间存在较大的遗传差异。结论：SNP 位点及特异性鉴别引物可对保健食品铁皮石斛及其混淆品进行快速、简便的鉴别,通过matK 基因可以分析正品与混淆品之间的亲缘关系。     

5’-核苷酸喂养SD大鼠90天实验研究

目的:评价5’-核苷酸的安全性。方法:采用大鼠90d喂养实验,96只SD大鼠随机分为6组,每组16只,雌雄各半,分别喂饲添加不同剂量核苷酸(0、0.01、0.04、0.16、0.64、1.28g/kgbw)的饲料。观察大鼠体质量、进食量、食物利用率、血压、血液常规、生化指标及病理结果的变化。结果:5’-核苷酸组与对照组相比,大鼠的总体质量增大、总进食量、总食物利用率、血压均没有明显差异(P>0.05);雄性大鼠前4周的体质量明显增高(P<0.05),雄性0.04g/kgbw组第4周、雌性0.16g/kgbw组第1周和0.01g/kgbw组第2周的食物利用率显著增高(P<0.05);雄性大鼠的白细胞、红细胞、血红蛋白、血小板、总蛋白含量、白蛋白、甘油三酯与对照组比较有统计学差异,但均未超出正常范围。镜下观察各组大鼠的脏器未见有意义的病理学改变。结论:在本实验的剂量范围内添加5’-核苷酸是安全的。     

The interaction of biological molecules with clay minerals: a scanning force microscopy study

We have used the technique of scanning force microscopy (SFM) to investigate the reaction of both amino acids and activated nucleotides in the presence of the clay mineral Cu(II)-exchanged hectorite. Using simulated prebiotic heating and wetting cycles, we have shown that the clay mineral acts to adsorb, concentrate, and subsequently catalyze the polymerization of these biological monomers into short peptides and oligonucleotides. The presence of the Cu(II) cations within the clay intergallery regions, and at surface step edges and cracks, is crucial for the observed reactions to occur. Clay minerals such as hectorite may have thus played an important role in the evolution of biologically viable molecules on the prebiotic earth.