Boosting predictive ability of tropical maize hybrids via genotype-by-environment interaction under multivariate GBLUP models.

Genomic selection has been implemented in several plant and animal breeding programs and it has proven to improve efficiency and maximize genetic gains. Phenotypic data of grain yield was measured in 147 maize (Zea mays L.) singlecross hybrids at 12 environments. Single-cross hybrids genotypes were inferred based on their parents (inbred lines) via single nucleotide polymorphism (SNP) markers obtained from genotyping-by-sequencing (GBS). Factor analytic multiplicative genomic best linear unbiased prediction (GBLUP) models, in the framework of multienvironment trials, were used to predict grain yield performance of unobserved tropical maize single-cross hybrids. Predictions were performed for two situations: untested hybrids (CV1), and hybrids evaluated in some environments but missing in others (CV2). Models that borrowed information across individuals through genomic relationships and within individuals across environments presented higher predictive accuracy than those models that ignored it. For these models, predictive accuracies were up to 0.4 until eight environments were considered as missing for the validation set, which represents 67% of missing data for a given hybrid. These results highlight the importance of including genotype-by-environment interactions and genomic relationship information for boosting predictions of tropical maize single-cross hybrids for grain yield

A genetic history of the pre-contact Caribbean

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1,2,3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500–1,500 and a maximum of 1,530–8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.This work was supported by a grant from the National Geographic Society to M. Pateman to facilitate analysis of skeletal material from The Bahamas and by a grant from the Italian ‘Ministry of Foreign Affairs and International Cooperation’ (Italian archaeological, anthropological and ethnological missions abroad, DGPSP Ufficio VI). D.R. was funded by NSF HOMINID grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul Allen Foundation, the John Templeton Foundation grant 61220 and the Howard Hughes Medical Institute.Peer reviewe

Stable population structure in Europe since the Iron Age, despite high mobility

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000–3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire’s mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history

A genetic linkage map for the hexaploid <i>U</i>. <i>humidicola</i> based on single-dose markers.

<p>A genetic linkage map for the hexaploid <i>U</i>. <i>humidicola</i> based on single-dose markers.</p

Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: The GOLFIG-2 multicentric open-label randomized phase III trial

The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/ label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m 2, day 1); oxaliplatin (85 mg/m2, day 2); levofolinate (100 mg/m2, days 1-2), 5-fluorouracil (5-FU) (400 mg/m2 in bolus followed by 24 h infusion at 800 mg/m2,days 1-2), sc. GM-CSF (100 μg, days 3-7); sc. aldesleukin (0 ° 5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9 ° 23 (95% confidence interval (CI), 6 ° 9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0 ° 002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37 °0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57mo (95% CI, 9.07-20.07); HR: 0 ° 79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4+ T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3+CD4 +CD25+ FoxP3+) T cells. Taken together, these findings provide proofof- principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC. Copyright © 2014 by Lippincott Williams & Wilkins

Suggested origin of <i>U</i>. <i>humidicola</i>.

<p>Illustrative scheme of the origin of the hexaploid <i>Urochloa humidicola</i>, based on cytogenetic and molecular data. The two different genomes are indicated as A and B. The figures represent the amplification profiles of two microsatellite loci (I. BhUNICAMP010 and II. BhUNICAMP037) and the corresponding amplification regions of genomes A and B.</p

Data from: Repeat variants for the SbMATE transporter protect sorghum roots from aluminum toxicity by transcriptional interplay in cis and trans

Acidic soils, where aluminum (Al) toxicity is a major agricultural constraint, are globally widespread and are prevalent in developing countries. In sorghum, the root citrate transporter SbMATE confers Al tolerance by protecting root apices from toxic Al3+, but can exhibit reduced expression when introgressed into different lines. We show that allele-specific SbMATE transactivation occurs and is caused by factors located away from SbMATE. Using expression-QTL mapping and -GWAS, we establish that SbMATE transcription is controlled in a bipartite fashion, primarily in cis but also in trans. Multi-allelic promoter transactivation and ChIP analyses demonstrated that intermolecular effects on SbMATE expression arise from a WRKY and a zinc finger-DHHC transcription factor (TF) that bind to and trans-activate the SbMATE promoter. A haplotype analysis in sorghum RILs indicate that the TFs influence SbMATE expression and Al tolerance. Variation in SbMATE expression likely results from changes in tandemly repeated cis sequences flanking a transposable element (MITE) insertion in the SbMATE promoter, which are recognized by the Al3+-responsive TFs. According to our model, repeat expansion in Al-tolerant genotypes increases TF recruitment and, hence, SbMATE expression, which is, in turn, lower in Al-sensitive genetic backgrounds due to lower TF expression and fewer binding sites. We thus show that even dominant cis regulation of an agronomically-important gene can be subjected to precise intermolecular fine-tuning. These concerted cis/trans interactions, which allow the plant to sense and respond to environmental cues, such as Al3+ toxicity, can now be used to increase yields and food security on acidic soils