变应性鼻炎与IRF5的单核苷酸多态性关系

目的:探讨变应性鼻炎与干扰素调节因子5(IRFS)的单核苷酸多态性(SNP)的相关性.方法:采用聚合酶链(PCR)和限制性片段长度多态性(RFL P)方法在新加坡华人中检测110例变应性鼻炎患者及101健康对照组IRF5位点上的3个单核苷酸多态性(rs4728142,rs11770589,rs2280714)计算基因型和等位基因频率.结果:IRF5基因的3个位点的基因型和等位基因频率在变应性鼻组和对照组间差异无统计学意义.结论:新加坡华人IRF5 rs4728142,rsl1770589,rs2280714多态性与变应性鼻炎无明显相关性.     

Intracellular storage and regulated secretion of von Willebrand factor in quantitative von Willebrand disease

Several missense mutations in the von Willebrand Factor (VWF) gene of von Willebrand disease (VWD) patients have been shown to cause impaired constitutive secretion and intracellular retention of VWF. However, the effects of those mutations on the intracellular storage in Weibel-Palade bodies (WPBs) of endothelial cells and regulated secretion of VWF remain unknown. We demonstrate, by expression of quantitative VWF mutants in HEK293 cells, that four missense mutations in the D3 and CK-domain of VWF diminished the storage in pseudo-WPBs, and led to retention of VWF within the endoplasmic reticulum (ER). Immunofluorescence and electron microscopy data showed that the pseudo-WPBs formed by missense mutant C1060Y are indistinguishable from those formed by normal VWF. C1149R, C2739Y, and C2754W formed relatively few pseudo-WPBs, which were often short and sometimes round rather than cigar-shaped. The regulated secretion of VWF was impaired slightly for C1060Y but severely for C1149R, C2739Y, and C2754W. Upon co-transfection with wild-type VWF, both intracellular storage and regulated secretion of all mutants were (partly) corrected. In conclusion, defects in the intracellular storage and regulated secretion of VWF following ER retention may be a common mechanism underlying VWD with a quantitative deficiency of VWF.     

Functional polymorphism in porcine CYP2E1 gene: Its association with skatole levels

Raising intact male pigs would have a significant economic impact on the pork industry. However, the presence of skatole (a major cause of boar taint) in meat from intact male pigs could be highly objectionable to consumer. The excessive accumulation of skatole in fat is a major cause of boar taint, and is associated with defective expression of cytochrome P4502E1 (CYP2E1). In pigs, it has been found that CYP2E1 is negatively correlated with accumulation of skatole. The searching for polymorphism of CYP2E1 and the relevant functional analysis would help develop a genetic marker for the selection of pigs with low skatole levels in fat. The aim of this study was to measure the expression pattern of CYP2E1 mRNA in various tissues of the pig, to identify genetic polymorphisms, and to evaluate the functional relevance of polymorphic sites with respect to the skatole level in fat. We show herein that a substitution of G → A at base 1423 of the CYP2E1 gene in the liver causes a significant decrease in the expressed CYP2E1 level. Our data suggest that the G → A substitute might be at least partially responsible for a high level of skatole in pigs. We believe that this is an important step toward the selection of genetic markers for boar taint by lowering fat levels of skatole in fat.     

The Caenorhabditis elegans FancD2 ortholog is required for survival following DNA damage

Fanconi anemia (FA) is an autosomal recessive disease characterized by bone-marrow failure, congenital abnormalities, and cancer susceptibility. There are 11 FA complementation groups in human where 8 genes have been identified. We found that FancD2 is conserved in evolution and present in the genome of the nematode Caenorhabditis elegans. The gene Y41E3.9 (CeFancD2) encodes a structural ortholog of human FANCD2 and is composed of 10 predicted exons. Our analysis showed that exons 6 and 7 were absent from a CeFancD2 EST suggesting the presence of a splice variant. In an attempt to characterize its role in DNA damage, we depleted worms of CeFANCD2 using RNAi. When the CeFANCD2(RNAi) worms were treated with a crosslinking agent, a significant drop in the progeny survival was noted. These worms were also sensitive, although to a lesser extent, to ionizing radiation (IR). Therefore, these data support an important role for CeFANCD2 in DNA damage response as for its human counterpart. The data also support the usefulness of C. elegans to study the Fanconi anemia pathway, and emphasize the biological importance of FANCD2 in DNA damage response throughout evolution.     

Natural selection on ecophysiological traits of a fern species in a temperate rainforest

Unlike other species of the genus Blechnum, the fern Blechnum chilense occurs in a wide range of habitats in Chilean temperate rainforest, from shaded forest understories to abandoned clearings and large gaps. We asked if contrasting light environments can exert differential selection on ecophysiological traits of B. chilense. We measured phenotypic selection on functional traits related to carbon gain: photosynthetic capacity (A _max), dark respiration rate (R _d), water use efficiency (WUE), leaf size and leaf thickness in populations growing in gaps and understorey environments. We assessed survival until reproductive stage and fecundity (sporangia production) as fitness components. In order to determine the potential evolutionary response of traits under selection, we estimated the genetic variation of these traits from clonally propagated individuals in common garden experiments. In gaps, survival of B. chilense was positively correlated with WUE and negatively correlated with leaf size. In contrast, survival in shaded understories was positively correlated with leaf size. We found positive directional fecundity selection on WUE in gaps population. In understories, ferns of lower R _d and greater leaf size showed greater fecundity. Thus, whereas control of water loss was optimized in gaps, light capture and net carbon balance were optimized in shaded understories. We found a significant genetic component of variation in WUE, R _d and leaf size. This study shows the potential for evolutionary responses to heterogeneous light environments in functional traits of B. chilense, a unique fern species able to occupy a broad successional niche in Chilean temperate rainforest.     

Impact of altitude and topography on the genetic diversity of Quercus serrata populations in the Chichibu Mountains, central Japan

In order to elucidate the factors affecting the genetic diversity of Quercus serrata in secondary forests in mountainous regions, we evaluated the level and distribution of genetic variation within and between 15 populations using seven microsatellite markers. The populations were at altitudes ranging from 140 to 1200 m in and around the Chichibu Mountains, central Japan.The expected heterozygosity (H_E) ranged from 0.766 to 0.837. The two populations that exhibited the highest and the second highest values of H_E are located beside a river and a lake, respectively. The two populations exhibiting the lowest and the second lowest values of H_E are, in contrast, located on a summit and a ridge. The observed heterozygosity (H_O) varied between 0.638 and 0.844, and the value of this variable was also higher for the populations beside water than those on summits or ridges. The soils at the waterside are wet, in contrast to those on ridges and summits, which tend to be shallow and subject to rapid desiccation. These results suggest that a lack of soil moisture is likely to inhibit the development and regeneration of Q. serrata, and that genetic diversity is reduced in arid areas. The genetic differentiation was low (F_ST=0.013) among the investigated populations, although all five populations in Yamanashi prefecture clustered together in an UPGMA tree. According to a multiple regression analysis, there was no significant isolation by distance among the populations along either the horizontal or vertical axes. Therefore, genetic variation within populations is affected by topography, but variation between populations is hardly affected by geographical factors. Furthermore, the results of this study suggest two conclusions. First, that altitude is not always a useful variable when estimating the genetic diversity of plant populations in mountainous regions. Second, that genetic diversity can vary even among the undifferentiated plant populations in small areas like the Chichibu Mountains.     

Excavating ghost footprints and tangled trees from modern genomes

Due to pervasive gene flow and admixture, simple bifurcating trees often do not provide an accurate representation of relationships among diverging lineages, but limited resolution in the available genomic data and the spatial distribution of samples has hindered detailed insights regarding the evolutionary and demographic history of many species and populations. In this issue of Molecular Ecology, Foote et al. (2019) combine a powerful sampling design with novel analytical methods adopted from human genetics to describe previously unrecognized patterns of recurrent vicariance and admixture among lineages in the globally distributed killer whale (Orcinus orca). Based on sequence data from modern samples alone, they discover clear signatures of ancient admixture with a now extinct “ghost” lineage, providing one of the first accounts of archaic introgression in a nonhominid species. Coupling a cost‐effective sequencing strategy with novel analytical approaches, their paper provides a roadmap for advancing inference of evolutionary history in other nonmodel species, promising exciting times ahead for our field.     

Genotype identification and assessment of genetic relationships in pearl millet [Pennisetum glaucum (L.) R. Br] using microsatellites and RAPDs

 The potential of DNA markers such as microsatellites, minisatellites and RAPDs was investigated in pearl millet [Pennisetum glaucum (L.) R. Br] with respect to their abundance and variability. Southern analysis, using 22 different di-, tri-, tetra- and penta-oligonucleotide probes and five minisatellite probes, identified (GATA)₄ as the most useful probe for the detection of multiple polymorphic fragments among pearl millet cultivars and landraces from India. The clustering patterns of pearl millet cultivars and landraces based on (GATA)₄ and RAPD (randomly amplified polymorphic DNA) markers differed. The landraces, representing eight states in India, could not be grouped based on their geographical distribution with the DNA markers. RAPD analysis revealed a high degree of genetic diversity among the cultivars and landraces employed in this study. The probability of an identical match by chance for any two genotypes using (GATA)₄ and RAPDs was 3.02×10^-20 for cultivars and 5.2×10^-9 for landraces. The microsatellite (GATA)₄ and RAPDs provide useful tools for genotype identification and for the assessment of genetic relationships in pearl millet. Received: 19 October 1997 / Accepted: 9 December 1997     

Complexities and pitfalls in analyzing and interpreting mitochondrial DNA content in human cancer

Mutations in the human mitochondrial genome have been observed in all types of human cancer, indicating that mutations might contribute to tumorigenesis, metastasis, recurrence, or drug response. This possibility is appealing because of the known shift from oxidative metabolism to glycolysis, known as the Warburg effect, that occurs in malignancy. Mitochondrial DNA (mtDNA) mutations could either be maternally inherited and predispose to cancer (germ line mutations) or occur sporadically in the mtDNA of specific tissues (tissue- or tumor-specific somatic mutations) and contribute to the tumor initiation and progression process. High-throughput sequencing technologies now enable comprehensive detection of mtDNA variation in tissues and bodily fluids, with the potential to be used as an early detection tool that may impact the treatment of cancer. Here, we discuss insights into the roles of mtDNA mutations in carcinogenesis, highlighting the complexities involved in the analysis and interpretation of mitochondrial genomic content, technical challenges in studying their contribution to pathogenesis, and the value of mtDNA mutations in developing early detection, diagnosis, prognosis, and therapeutic strategies for cancer.