Cytotoxic Activity and Metabolic Profiling of Fifteen Euphorbia Species

Euphorbia is a large genus of flowering plants with a great diversity in metabolic pattern. Testing the cytotoxic potential of fifteen Euphorbia species revealed highest activity of E. officinarum L. against CACO2 cell line (IC50 7.2 µM) and of E. lactea Haw. against HepG2 and MCF-7 cell lines (IC50 5.2 and 5.1 µM, respectively). Additionally, metabolic profiling of the fifteen tested species, using LC-HRMS, for dereplication purposes, led to the annotation of 44 natural compounds. Among the annotated compounds, diterpenoids represent the major class. Dereplication approach and multivariate data analysis are adopted in order to annotate the compounds responsible for the detected cytotoxic activity. Results of PCA come in a great accordance with results of biological testing, which emphasized the cytotoxic properties of E. lactea Haw. A similarity correlation network showed that the two compounds with the molecular formula C16H18O8 and C20H30O10, are responsible for cytotoxic activity against MCF-7 and HepG2 cell lines. Similarly, the compound with molecular formula C18H35NO correlates with cytotoxic activity against CACO2

Variation in Seed Dormancy Quantitative Trait Loci in Arabidopsis thaliana Originating from One Site

A Quantitative Trait Locus (QTL) analysis was performed using two novel Recombinant Inbred Line (RIL) populations, derived from the progeny between two Arabidopsis thaliana genotypes collected at the same site in Kyoto (Japan) crossed with the reference laboratory strain Landsberg erecta (Ler). We used these two RIL populations to determine the genetic basis of seed dormancy and flowering time, which are assumed to be the main traits controlling life history variation in Arabidopsis. The analysis revealed quantitative variation for seed dormancy that is associated with allelic variation at the seed dormancy QTL DOG1 (for Delay Of Germination 1) in one population and at DOG6 in both. These DOG QTL have been previously identified using mapping populations derived from accessions collected at different sites around the world. Genetic variation within a population may enhance its ability to respond accurately to variation within and between seasons. In contrast, variation for flowering time, which also segregated within each mapping population, is mainly governed by the same QTL

Major-Effect Alleles at Relatively Few Loci Underlie Distinct Vernalization and Flowering Variation in Arabidopsis Accessions

We have explored the genetic basis of variation in vernalization requirement and response in Arabidopsis accessions, selected on the basis of their phenotypic distinctiveness. Phenotyping of F2 populations in different environments, plus fine mapping, indicated possible causative genes. Our data support the identification of FRI and FLC as candidates for the major-effect QTL underlying variation in vernalization response, and identify a weak FLC allele, caused by a Mutator-like transposon, contributing to flowering time variation in two N. American accessions. They also reveal a number of additional QTL that contribute to flowering time variation after saturating vernalization. One of these was the result of expression variation at the FT locus. Overall, our data suggest that distinct phenotypic variation in the vernalization and flowering response of Arabidopsis accessions is accounted for by variation that has arisen independently at relatively few major-effect loci

A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana

Identifying natural allelic variation that underlies quantitative trait variation remains a fundamental problem in genetics. Most studies have employed either simple synthetic populations with restricted allelic variation or performed association mapping on a sample of naturally occurring haplotypes. Both of these approaches have some limitations, therefore alternative resources for the genetic dissection of complex traits continue to be sought. Here we describe one such alternative, the Multiparent Advanced Generation Inter-Cross (MAGIC). This approach is expected to improve the precision with which QTL can be mapped, improving the outlook for QTL cloning. Here, we present the first panel of MAGIC lines developed: a set of 527 recombinant inbred lines (RILs) descended from a heterogeneous stock of 19 intermated accessions of the plant Arabidopsis thaliana. These lines and the 19 founders were genotyped with 1,260 single nucleotide polymorphisms and phenotyped for development-related traits. Analytical methods were developed to fine-map quantitative trait loci (QTL) in the MAGIC lines by reconstructing the genome of each line as a mosaic of the founders. We show by simulation that QTL explaining 10% of the phenotypic variance will be detected in most situations with an average mapping error of about 300 kb, and that if the number of lines were doubled the mapping error would be under 200 kb. We also show how the power to detect a QTL and the mapping accuracy vary, depending on QTL location. We demonstrate the utility of this new mapping population by mapping several known QTL with high precision and by finding novel QTL for germination data and bolting time. Our results provide strong support for similar ongoing efforts to produce MAGIC lines in other organisms

Joint QTL Linkage Mapping for Multiple-Cross Mating Design Sharing One Common Parent

BACKGROUND: Nested association mapping (NAM) is a novel genetic mating design that combines the advantages of linkage analysis and association mapping. This design provides opportunities to study the inheritance of complex traits, but also requires more advanced statistical methods. In this paper, we present the detailed algorithm of a QTL linkage mapping method suitable for genetic populations derived from NAM designs. This method is called joint inclusive composite interval mapping (JICIM). Simulations were designed on the detected QTL in a maize NAM population and an Arabidopsis NAM population so as to evaluate the efficiency of the NAM design and the JICIM method. PRINCIPAL FINDINGS: Fifty-two QTL were identified in the maize population, explaining 89% of the phenotypic variance of days to silking, and nine QTL were identified in the Arabidopsis population, explaining 83% of the phenotypic variance of flowering time. Simulations indicated that the detection power of these identified QTL was consistently high, especially for large-effect QTL. For rare QTL having significant effects in only one family, the power of correct detection within the 5 cM support interval was around 80% for 1-day effect QTL in the maize population, and for 3-day effect QTL in the Arabidopsis population. For smaller-effect QTL, the power diminished, e.g., it was around 50% for maize QTL with an effect of 0.5 day. When QTL were linked at a distance of 5 cM, the likelihood of mapping them as two distinct QTL was about 70% in the maize population. When the linkage distance was 1 cM, they were more likely mapped as one single QTL at an intermediary position. CONCLUSIONS: Because it takes advantage of the large genetic variation among parental lines and the large population size, NAM is a powerful multiple-cross design for complex trait dissection. JICIM is an efficient and specialty method for the joint QTL linkage mapping of genetic populations derived from the NAM design

A strong effect of growth medium and organ type on the identification of QTLs for phytate and mineral concentrations in three Arabidopsis thaliana RIL populations

The regulation of mineral accumulation in plants is genetically complex, with several genetic loci involved in the control of one mineral and loci affecting the accumulation of different minerals. To investigate the role of growth medium and organ type on the genetics of mineral accumulation, two existing (LerxKond, LerxAn-1) and one new (LerxEri-1) Arabidopsis thaliana Recombinant Inbred Line populations were raised on soil and hydroponics as substrates. Seeds, roots, and/or rosettes were sampled for the determination of their Ca, Fe, K, Mg, Mn, P or Zn concentrations. For seeds only, the concentration of phytate (IP6), a strong chelator of seed minerals, was determined. Correlations between minerals/IP6, populations, growth conditions, and organs were determined and mineral/IP6 concentration data were used to identify quantitative trait loci (QTLs) for these traits. A striking difference was found between QTLs identified for soil-grown versus hydroponics-grown populations and between QTLs identified for different plant organs. Three common QTLs were identified for several populations, growth conditions, and organs, one of which corresponded to the ERECTA locus, variation of which has a strong effect on plant morpholog

Structured patterns in geographic variability of metabolic phenotypes in Arabidopsis thaliana

Understanding molecular factors determining local adaptation is a key challenge, particularly relevant for plants, which are sessile organisms coping with a continuously fluctuating environment. Here we introduce a rigorous network-based approach for investigating the relation between geographic location of accessions and heterogeneous molecular phenotypes. We demonstrate for Arabidopsis accessions that not only genotypic variability but also flowering and metabolic phenotypes show a robust pattern of isolation-by-distance. Our approach opens new avenues to investigate relations between geographic origin and heterogeneous molecular phenotypes, like metabolite profiles, which can easily be obtained in species where genome data is not yet available

Low vitamin D and risk for small for gestation age babies in gestational diabetes

This study aims to find the possible correlation of vitamin D with the onset of gestational diabetes mellitus (GDM) and its effect on fetal growth. A case-control study was conducted recruiting pregnant women in their second trimester. All subjects were classified as per the guidelines of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criterion. Fetal growth scans were recorded at 28th week of gestation. Venous blood was collected and serum levels of 25-(OH) D, Calcium, TNF alpha were measured. Vitamin D concentration in cases was lower (2.40 ± 1.10 ng/ml) as compared to controls (5.50 ± 1.74 ng/ml), while serum calcium levels of both groups were under normal range. TNF alpha level in cases was higher as compared to controls (p \u3c 0.001). On ultrasound scan, 47% of the babies of GDM mothers were small for gestational age. No difference was observed in terms of femur length and fetal weight in both groups (p \u3e 0.05). Weak negative correlation of vitamin D with insulin resistance (r = −0.304; p = 0.004), positive correlation with fetal growth (r = 0.303; p = 0.043) and a strong negative correlation with TNF alpha levels (r = −0.703; p = 0.023) were observed. Low vitamin D levels may be associated with the onset of gestational diabetes and affect fetal growth and development. Hence, antenatal screening and timely intervention is recommended