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Allelic Differences (allelic + difference)
Selected AbstractsSERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibilityCANCER, Issue 18 2010Hyoungseok Ju PhD Abstract BACKGROUND: A primary inhibitor of plasminogen activators, SERPINE1 (serpin peptidase inhibitor 1, clade E, member 1, also known as plasminogen activator inhibitor type 1), is an important regulator in tumorigenesis and is highly expressed in many cancers. METHODS: Five tag single nucleotide polymorphisms (SNPs) and 1 insertion polymorphism within SERPINE1 were genotyped in 1101 unrelated Korean individuals (a case group of 612 patients with gastric cancer and a control group of 489 healthy individuals). Associations with susceptibility to diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer were assessed using multivariate logistic regression analyses adjusted for age and sex. Allelic differences in the contribution to gene expression were measured using luciferase assays. RESULTS: SNP c.1162+162C>T (rs2227692) in intron 7 was associated with susceptibility to DGC but not with susceptibility to intestinal-type gastric cancer. The minor allele-carrying genotypes C/T and T/T had 1.6-fold greater odds of DGC than the C/C genotype (P = .00084). This SNP was linked to a repeat-number variation c.1162+604AAAG(11_17), a deletion (del) variation c.1162+664_1162+673del, and another SNP c.1162+859T>A (rs2070683) in intron 7 based on the sequencing of 5 patients and 5 controls. The risk haplotype of the 4 variations exhibited a 30% greater gene expression level than the nonrisk haplotype in luciferase reporter assays (P = .025). In contrast, DGC susceptibility was not associated with the c.,1969_,1968insG polymorphism (rs1799768) in the promoter, commonly known as 4G/5G, in which the minor 5G allele is less active in transcription than the major 4G allele. CONCLUSIONS: An association between SERPINE1 and DGC susceptibility was observed with 4 correlated polymorphisms in intron 7 rather than the 4G/5G polymorphism in the promoter, although all polymorphisms affected gene expression. Cancer 2010. © 2010 American Cancer Society. [source] Effect of TGF- ,1 polymorphism on the susceptibility to schizophrenia and treatment response to atypical antipsychotic agentACTA NEUROPSYCHIATRICA, Issue 4 2010Hwa-Young Lee Lee H-Y, Kim Y-K. Effect of TGF- ,1 polymorphism on the susceptibility to schizophrenia and treatment response to atypical antipsychotic agent. Objective: Several studies have suggested that cytokine alterations could be related to the pathophysiology of schizophrenia. Transforming growth factor-beta1 (TGF- ,1) is believed to be an important factor in regulation of inflammatory responses and to have anti-inflammatory effects. TGF- ,1 also has trophic effects on dopaminergic neurons. We tested the hypothesis TGF- ,1 is associated with the pathophysiology of schizophrenia. Methods: The polymorphisms at codon 10 (T869C) and codon 25 (G915C) of TGF- ,1 were analysed in 99 schizophrenia patients and 130 normal controls. At baseline and after 8 weeks of treatment, clinical symptoms were evaluated on Positive and Negative Syndrome Scale (PANSS). Results: None of the subjects were polymorphic at codon 25. However, the C allele at codon 10 was more frequent in schizophrenia (p = 0.05). Although schizophrenia group showed a higher tendency of allele frequency in the subjects with C allele (p = 0.05), the allelic difference did not reach statistical significance after correction for multiple comparisons (p = 0.1). PANSS scores showed no significant correlation with genotypes. The genotype distribution was not significantly different between responders and non-responders. However, the C allele was more frequent among responders (p = 0.03). Conclusion: These results suggest that the TGF- ,1 polymorphism is associated with therapeutic response to antipsychotics. However, further studies with larger numbers of subjects are needed to confirm the effect of TGF- ,1 in schizophrenia. [source] EVOLUTION OF CHARACTER DISPLACEMENT IN SPADEFOOT TOADS: DIFFERENT PROXIMATE MECHANISMS IN DIFFERENT SPECIESEVOLUTION, Issue 8 2010David W. Pfennig Character displacement occurs when two species compete, and those individuals most dissimilar from the average resource-use phenotypes of the other species are selectively favored. Few studies have explored the sequence of events by which such divergence comes about. We addressed this issue by studying two species of spadefoot toads that have undergone ecological character displacement with each other. Previous research revealed that phenotypic shifts between sympatric and allopatric populations of one species, Spea multiplicata, reflect a condition-dependent maternal effect. Here, we show that analogous shifts in the other species, S. bombifrons, cannot similarly be explained by such a maternal effect, and that these shifts instead appear to be underlain by allelic differences. We hypothesize that these two species have evolved different mechanisms of character displacement because they differ in duration in sympatry. Specifically, because they occur at the edge of a range expansion, populations of S. bombifrons have been exposed to S. multiplicata for a longer period. Consequently, S. bombifrons have likely had more time to accumulate genetic changes that promote character displacement. Generally, character displacement may often progress through an initial phase in which trait differences are environmentally induced to one in which they are constitutively expressed. [source] Genetic differences among the LPS biosynthetic loci of serovars of Leptospira interrogans and Leptospira borgpeterseniiFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2001Alejandro de la Peña-Moctezuma Abstract The gene organization in the lipopolysaccharide biosynthetic (rfb) locus was analyzed in seven Leptospira interrogans serovars within serogroup Icterohemorrhagiae, seven non-Icterohemorrhagiae serovars and one Leptospira borgpetersenii serovar. Two groups of loci were delineated based on DNA hybridization and sequence analysis. Group 1 contained the two Hardjo subtypes, Hardjoprajitno and Hardjobovis. Group 2 (containing Copenhageni, Pomona, Naam, Mwogolo, Smithi, Lai, Canicola, Autumnalis, Pyrogenes, Australis and Icterohemorrhagiae) differed from Group 1 in its organization upstream of orf11, where five ORFs (32, 33, 34, 35, 37) were identified that were not contained in the Group 1 loci. These ORFs encoded a putative epimerase (orf32), a glycosyltransferase (orf33), two integral membrane proteins (orfs 34 and 35), and a galactosyltransferase (orf37). Serovars Australis, Pomona and Autumnalis did not contain orf37. Serovar Bataviae was excluded from the grouping because of its unique genetic organization upstream of orf13. In the Group 2 loci, comparison of the genetic layout at the 5, end revealed differences which included mutations disrupting reading frames in either or both orf34 and orf35 and apparent allelic differences between orf33 homologs that may be sufficient to account for the genetic basis of serovar identity. [source] Asymmetric allele-specific expression in relation to developmental variation and drought stress in barley hybridsTHE PLANT JOURNAL, Issue 1 2009Maria Von Korff Summary In the present study, we analysed allele-specific expression (ASE) in the selfing species barley to assess the frequency of cis -acting regulatory variation and the effects of genetic background, developmental differences and drought stress on allelic expression levels. We measured ASE ratios in 30 genes putatively involved in stress responses in five hybrids and their reciprocals, namely Hordeum spontaneum 41-1/Alexis (HAl), Hordeum spontaneum 41-1/Arta (HAr), Sloop/WI3408 (SW), Tadmor/Sloop (TS) and Tadmor/WI3408 (TW). In order to detect cis -acting variation related to drought and developmental changes, the barley hybrids were grown under control and water-limited conditions, and leaf tissue was harvested at two developmental stages. The analysis demonstrated that more than half of the genes measured (63%) showed allelic differences in expression of up to 19-fold due to cis -regulatory variation in at least one cross by treatment/stage combination. Drought stress induced changes in allelic expression ratios, indicating differences between drought responsive cis -elements. In addition, ASE differences between developmental stages suggested the presence of cis -acting elements interacting with developmental cues. We were also able to demonstrate that the levels and frequency of allelic imbalance and hence differences in cis -regulatory elements are correlated with the genetic divergence between the parental lines, but may also arise as an adaptation to diverse habitats. Our findings suggest that cis -regulatory variation is a common phenomenon in barley, and may provide a molecular basis of transgression. Differential expression of near-isogenic members of the same gene family could potentially result in hybrid lines out performing their parents in terms of expression level, timing and response to developmental and environmental cues. Identification and targeted manipulation of cis -regulatory elements will assist in breeding improved crops with a better adaptation to changing environments. [source] | |||||||||||||