RESUMO
A total of nine non-coding variants on 11q13.5 predispose men to prostate cancer (PrCa). rs200331695 within the EMSY intron is associated with aggressive PrCa and two high linkage disequilibrium (LD) groups of single-nucleotide polymorphisms (SNPs) in the intergenic region are associated with PrCa death. Here, the cis-effect of the SNPs on gene expression using expression quantitative trait loci analysis was investigated. The regulatory potential was screened in prostate tumors (n = 41) and in whole blood (n = 99). The results were validated in a second tumor set (n = 41), in lymphoblastoid cell lines (LCLs) (n = 38), and using the GTEx Portal. The effects of haplotypes were analyzed in the whole blood. The high LD SNPs (rs143975731, rs12277366, rs2155225, and rs2155222) were associated with DGAT2 expression in both tumors sets (screening P = 0.035-0.043; validation P = 0.005-0.018). The PrCa death-associated alleles decreased the expression by two-fold. rs200331695 decreased DGAT2 expression in LCLs (P = 0.006). The findings of SNPs regulating CAPN5 (P = 0.026-0.046) and AP001189.4 (P = 0.03-0.039) in the whole blood were not observed in LCLs, but the association with AP001189.4 expression was validated via the GTEx Portal (P = 8.7 × 10(-5) to 4.3 × 10(-4) ), which suggests that the high LD intergenic SNPs exert a tissue-dependent effect on the expression of two genes. No haplotypes including the risk SNPs at 11q13.5 were associated with gene expression and PrCa. The findings indicate the functionality of the PrCa death-predisposing SNPs rs143975731, rs12277366, rs2155225, and rs2155222 as DGAT2 regulators in prostate tumors. © 2016 Wiley Periodicals, Inc.
Assuntos
Diacilglicerol O-Aciltransferase/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 11/genética , Diacilglicerol O-Aciltransferase/biossíntese , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Locos de Características Quantitativas/genéticaRESUMO
1. In insects, the length of larval development time typically influences adult body size and individual fitness, and hence development time can be expected to respond in an adaptive manner to variation in environmental conditions. In the wild, larval growth may be influenced by individual condition, which can be affected by population-level parameters such as population density and abundance and quality of resources. 2. We sampled larvae of the Glanville fritillary butterfly (Melitaea cinxia) from 514 local populations across a large metapopulation before the winter diapause and reared the larvae in common garden conditions after diapause. Here, we report that small post-diapause larvae prolonged their development via an extra larval instar, apparently to compensate for their 'bad start' after diapause. The number of instars was additionally a plastic response to environmental conditions, as the frequency of the extra instar increased under cooler thermal conditions. 3. The benefit of the extra instar is clear, as it allows individuals to develop into larger adults, but the cost is delayed adult eclosion, which is likely to select against the extra instar especially in males, in which early eclosion is critical for mating success. In support of this, the frequency of the extra instar was significantly lower in males (7%) than in females (42%). 4. Polymorphisms in three genes, serpin-1, vitellin-degrading protease precursor and phosphoglucose isomerase, which are known to influence development in insects, were associated with the occurrence of the extra instar. 5. At the level of local populations, the frequency of the extra instar was higher in newly established populations than that in old local ones, possibly reflecting maternal effects, as new populations are often established by females with heavy investment in dispersal. The frequency of the extra instar in turn correlated with the change in population size over 1 year and the risk of local extinction in the natural metapopulation of the Glanville fritillary. 6. Our results highlight the importance of the physiological condition of individuals in shaping subsequent life-history events and even population dynamics.
Assuntos
Borboletas/fisiologia , Glucose-6-Fosfato Isomerase/genética , Proteínas de Insetos/genética , Polimorfismo Genético , Serina Endopeptidases/genética , Serpinas/genética , Animais , Borboletas/genética , Borboletas/crescimento & desenvolvimento , Diapausa de Inseto , Comportamento Alimentar , Feminino , Finlândia , Glucose-6-Fosfato Isomerase/metabolismo , Proteínas de Insetos/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Masculino , Dinâmica Populacional , Estações do Ano , Serina Endopeptidases/metabolismo , Serpinas/metabolismo , TemperaturaRESUMO
BACKGROUND: Adaptation to local habitat conditions may lead to the natural divergence of populations in life-history traits such as body size, time of reproduction, mate signaling or dispersal capacity. Given enough time and strong enough selection pressures, populations may experience local genetic differentiation. The genetic basis of many life-history traits, and their evolution according to different environmental conditions remain however poorly understood. METHODS: We conducted an association study on the Glanville fritillary butterfly, using material from five populations along a latitudinal gradient within the Baltic Sea region, which show different degrees of habitat fragmentation. We investigated variation in 10 principal components, cofounding in total 21 life-history traits, according to two environmental types, and 33 genetic SNP markers from 15 candidate genes. RESULTS: We found that nine SNPs from five genes showed strong trend for trait associations (p-values under 0.001 before correction). These associations, yet non-significant after multiple test corrections, with a total number of 1,086 tests, were consistent across the study populations. Additionally, these nine genes also showed an allele frequency difference between the populations from the northern fragmented versus the southern continuous landscape. DISCUSSION: Our study provides further support for previously described trait associations within the Glanville fritillary butterfly species across different spatial scales. Although our results alone are inconclusive, they are concordant with previous studies that identified these associations to be related to climatic changes or habitat fragmentation within the Åland population.