Selfish DNA in protein-coding genes of Rickettsia

Rickettsia conorii, the aetiological agent of Mediterranean spotted fever, is an intracellular bacterium transmitted by ticks. Preliminary analyses of the nearly complete genome sequence of R. conorii have revealed 44 occurrences of a previously undescribed palindromic repeat (150 base pairs long) throughout the genome. Unexpectedly, this repeat was found inserted in-frame within 19 different R. conorii open reading frames likely to encode functional proteins. We found the same repeat in proteins of other Rickettsia species. The finding of a mobile element inserted in many unrelated genes suggests the potential role of selfish DNA in the creation of new protein sequences.     

Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia

Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. We hypothesize that individually rare structural variants contribute to the illness. Microdeletions and microduplications >100 kilobases were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia and 268 ancestry-matched controls. All variants were validated by high-resolution platforms. Novel deletions and duplications of genes were present in 5% of controls versus 15% of cases and 20% of young-onset cases, both highly significant differences. The association was independently replicated in patients with childhood-onset schizophrenia as compared with their parents. Mutations in cases disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways. These results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia.     

An overlapping protein-coding region in influenza A virus segment 3 modulates the host response

Influenza A virus (IAV) infection leads to variable and imperfectly understood pathogenicity. We report that segment 3 of the virus contains a second open reading frame ("X-ORF"), accessed via ribosomal frameshifting. The frameshift product, termed PA-X, comprises the endonuclease domain of the viral PA protein with a C-terminal domain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model, acting to decrease pathogenicity. Loss of PA-X expression leads to changes in the kinetics of the global host response, which notably includes increases in inflammatory, apoptotic, and T lymphocyte-signaling pathways. Thus, we have identified a previously unknown IAV protein that modulates the host response to infection, a finding with important implications for understanding IAV pathogenesis.     

An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people

Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (1 every 17 bases) and geographically localized, so that even with large sample sizes, rare variant catalogs will be largely incomplete. We used the observed patterns of variation to estimate population growth parameters, the proportion of variants in a given frequency class that are putatively deleterious, and mutation rates for each gene. We conclude that because of rapid population growth and weak purifying selection, human populations harbor an abundance of rare variants, many of which are deleterious and have relevance to understanding disease risk.     

Isoantigenic variants: isolation from human diploid cells in culture

Variant human fibroblast substrains, resistant to a cytotoxic human isoantiserum, were isolated from sensitive strains by repeated exposure to isoantiserum and rabbit complement. The resistant phenotype was stable, apparently occurred at low frequency, and was associated with loss of surface isoantigens.     

猪BMP15和BMPR-IB基因的遗传变异及其与产仔性能的关系

采用PCR-SSCP方法对莱芜猪、鲁莱黑猪、里岔黑猪、鲁烟白猪、新沂蒙黑猪5个山东地方/培育猪种和大约克夏、长白、杜洛克3个引进猪种共8个猪种481头繁殖母猪进行BMP15和BMPR-IB基因的多态性分析,并采用最小二乘法分析其对产仔数的遗传效应.结果表明:2个基因的3个位点在8个猪种的测定群体中均存在多态性,但山东地方/培育猪种与引进猪种间在基因型频率上存在较大差异;BMP15和BMPR-IB基因对产仔数性状有显著影响(P0.05).对于BMP15基因,AA基因型母猪中,引进猪种比山东地方/培育猪种母猪的总产仔数和活产仔数平均多产1.20头和1.64头(P0.05);CC基因型母猪中,引进猪种比山东地方/培育猪种母猪的总产仔数和活产仔数平均多产1.20头和0.82头(P0.05).对于BMPR-IB基因,山东地方/培育猪种内AA基因型母猪的总产仔数和活产仔数比BB基因型母猪平均多产0.49头和0.51头(P0.05);引进猪种中BB基因型母猪比AA基因型母猪总产仔数和活产仔数平均多产1.05头和0.90头(P0.05).     

Predictive identification of exonic splicing enhancers in human genes

Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic splicing enhancers (ESEs), play important roles in constitutive and alternative splicing. A computational method, RESCUE-ESE, was developed that predicts which sequences have ESE activity by statistical analysis of exon-intron and splice site composition. When large data sets of human gene sequences were used, this method identified 10 predicted ESE motifs. Representatives of all 10 motifs were found to display enhancer activity in vivo, whereas point mutants of these sequences exhibited sharply reduced activity. The motifs identified enable prediction of the splicing phenotypes of exonic mutations in human genes.     

Three distinct genes in human DNA related to the transforming genes of mammalian sarcoma retroviruses

Southern blot hybridization was used to identify human and other vertebrate DNA sequences that were homologous to cloned DNA fragments containing the oncogenic nucleic acid sequences of three different type C mammalian retroviruses (simian sarcoma virus, the Snyder-Theilen strain of feline sarcoma virus, and the Harvey strain of murine sarcoma virus). Each onc gene counterpart has a single genetic locus, which probably contains non-onc intervening sequences. The human DNA sequences may represent genes important to cell growth or cell differentiation, or both. Their identification and isolation may allow elucidation of their role in these processes and in neoplasias.     

Transforming fusions of FGFR and TACC genes in human glioblastoma

The brain tumor glioblastoma multiforme (GBM) is among the most lethal forms of human cancer. Here, we report that a small subset of GBMs (3.1%; 3 of 97 tumors examined) harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor (FGFR) genes (FGFR1 or FGFR3) to the transforming acidic coiled-coil (TACC) coding domains of TACC1 or TACC3, respectively. The FGFR-TACC fusion protein displays oncogenic activity when introduced into astrocytes or stereotactically transduced in the mouse brain. The fusion protein, which localizes to mitotic spindle poles, has constitutive kinase activity and induces mitotic and chromosomal segregation defects and triggers aneuploidy. Inhibition of FGFR kinase corrects the aneuploidy, and oral administration of an FGFR inhibitor prolongs survival of mice harboring intracranial FGFR3-TACC3-initiated glioma. FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition.     

Recent explosive human population growth has resulted in an excess of rare genetic variants

Human populations have experienced recent explosive growth, expanding by at least three orders of magnitude over the past 400 generations. This departure from equilibrium skews patterns of genetic variation and distorts basic principles of population genetics. We characterized the empirical signatures of explosive growth on the site frequency spectrum and found that the discrepancy in rare variant abundance across demographic modeling studies is mostly due to differences in sample size. Rapid recent growth increases the load of rare variants and is likely to play a role in the individual genetic burden of complex disease risk. Hence, the extreme recent human population growth needs to be taken into consideration in studying the genetics of complex diseases and traits.     

The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene

The Xist noncoding RNA is the key initiator of the process of X chromosome inactivation in eutherian mammals, but its precise function and origin remain unknown. Although Xist is well conserved among eutherians, until now, no homolog has been identified in other mammals. We show here that Xist evolved, at least partly, from a protein-coding gene and that the loss of protein-coding function of the proto-Xist coincides with the four flanking protein genes becoming pseudogenes. This event occurred after the divergence between eutherians and marsupials, which suggests that mechanisms of dosage compensation have evolved independently in both lineages.     

A survey of separative techniques

Separative science has recently undergone numerous advances. This article discusses many developments and trends in liquid, ion, gas, and countercurrent chromatography, field-flow fractionation, and electrophoresis.     

蜜蜂发育相关基因研究

蜜蜂是一种重要的授粉昆虫,也是研究人类疾病及社会行为的模式生物之一。由其基因组测序可知,蜜蜂基因组中(A+T)及CpG含量较高,其昼夜节律、RNAi和DNA甲基化基因更类似脊椎动物。先天免疫、表皮蛋白和味觉受体基因较少,气味受体基因较多。蜜蜂早期发育途径中的一些基因与果蝇的相似,功能却显著不同。本文综述了蜜蜂卵、幼虫、蛹和成虫期发育相关基因及其研究进展。     

浙江鸟类研究

本文记录了浙江鸟类19目64科203属410种(包括亚种),其中留鸟125种,夏候鸟71种,冬候鸟126种,旅鸟88种。白鹤、白枕鹤、灰鹤、红脚鹜、栗苇鸦、栗头蜂虎等为本省新记录。本文较前人记载增加67种及亚种。