Maize (Zea mays L.) serves as model plant for heterosis research and is the crop where hybrid breeding was pioneered. We analyzed genomic and phenotypic data of 1254 hybrids of a typical maize hybrid ...breeding program based on the important Dent × Flint heterotic pattern. Our main objectives were to investigate genome properties of the parental lines (e.g., allele frequencies, linkage disequilibrium, and phases) and examine the prospects of genomic prediction of hybrid performance. We found high consistency of linkage phases and large differences in allele frequencies between the Dent and Flint heterotic groups in pericentromeric regions. These results can be explained by the Hill-Robertson effect and support the hypothesis of differential fixation of alleles due to pseudo-overdominance in these regions. In pericentromeric regions we also found indications for consistent marker-QTL linkage between heterotic groups. With prediction methods GBLUP and BayesB, the cross-validation prediction accuracy ranged from 0.75 to 0.92 for grain yield and from 0.59 to 0.95 for grain moisture. The prediction accuracy of untested hybrids was highest, if both parents were parents of other hybrids in the training set, and lowest, if none of them were involved in any training set hybrid. Optimizing the composition of the training set in terms of number of lines and hybrids per line could further increase prediction accuracy. We conclude that genomic prediction facilitates a paradigm shift in hybrid breeding by focusing on the performance of experimental hybrids rather than the performance of parental lines in test crosses.
Liver biopsy is required for staging hepatic fibrosis in patients with chronic hepatitis C, but it is an expensive procedure with occasional complications and poor patient acceptance. This cohort ...study was designed to assess the accuracy of a noninvasive method aimed to discriminate between patients with and without significant liver fibrosis (stages 2-4 versus 0-1). Clinically relevant variables were analyzed in a cohort of 476 consecutive untreated patients (estimation group, 351 patients; validation group, 125 patients) with chronic hepatitis C who underwent a liver biopsy. Multivariate analysis identified age, gamma glutamyl transpeptidase (GGT), cholesterol, platelet count, and prothrombin time as independent predictors of fibrosis. We constructed a model and a score system combining age, GGT, cholesterol, and platelet count that proved useful to identify patients without significant hepatic fibrosis. The area under the ROC curve was 0.86 for the estimation group and 0.81 for the validation group. Using the best cutoff score (less than 4.2), presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (negative predictive value of 96%) in 125 (36%) of 351 patients. Similarly, it could be excluded with the same certainty in 49 (39%) of the 125 patients of the validation group. Only 2 patients with liver fibrosis stage 2 were incorrectly classified. In conclusion, a combination of easily accessible variables accurately predicts the absence of significant fibrosis and might render liver biopsy unnecessary in more than one third of patients with chronic hepatitis C. (H
EPATOLOGY 2002;36:986-992.)
Summary
We report on a whole‐genome draft sequence of rye (Secale cereale L.). Rye is a diploid Triticeae species closely related to wheat and barley, and an important crop for food and feed in ...Central and Eastern Europe. Through whole‐genome shotgun sequencing of the 7.9‐Gbp genome of the winter rye inbred line Lo7 we obtained a de novo assembly represented by 1.29 million scaffolds covering a total length of 2.8 Gbp. Our reference sequence represents nearly the entire low‐copy portion of the rye genome. This genome assembly was used to predict 27 784 rye gene models based on homology to sequenced grass genomes. Through resequencing of 10 rye inbred lines and one accession of the wild relative S. vavilovii, we discovered more than 90 million single nucleotide variants and short insertions/deletions in the rye genome. From these variants, we developed the high‐density Rye600k genotyping array with 600 843 markers, which enabled anchoring the sequence contigs along a high‐density genetic map and establishing a synteny‐based virtual gene order. Genotyping data were used to characterize the diversity of rye breeding pools and genetic resources, and to obtain a genome‐wide map of selection signals differentiating the divergent gene pools. This rye whole‐genome sequence closes a gap in Triticeae genome research, and will be highly valuable for comparative genomics, functional studies and genome‐based breeding in rye.
Significance statement
Rye is a diploid Triticeae species closely related to wheat and barley. Here we present a draft genome and a high‐density genotyping array that will facilitate genome‐based research in rye and comparative genomics in Triticeae.
Key message
A comparative genetics approach allowed to precisely
determine the map position of the restorer gene
Rfp3
in rye and revealed that
Rfp3
and the restorer gene
Rfm1
in barley reside at ...different positions in a syntenic 4RL/6HS segment
.
Cytoplasmic male sterility (CMS) is a reliable and striking genetic mechanism for hybrid seed production. Breeding of CMS-based hybrids in cereals requires the use of effective restorer genes as an indispensable pre-requisite. We report on the fine mapping of a restorer gene for the Pampa cytoplasm in winter rye that has been tapped from the Iranian primitive rye population Altevogt 14160. For this purpose, we have mapped 41 gene-derived markers to a 38.8 cM segment in the distal part of the long arm of chromosome 4R, which carries the restorer gene. Male fertility restoration was comprehensively analyzed in progenies of crosses between a male-sterile tester genotype and 21 recombinant as well as six non-recombinant BC
4
S
2
lines. This approach allowed us to validate the position of this restorer gene, which we have designated
Rfp3
, on chromosome 4RL.
Rfp3
was mapped within a 2.5 cM interval and cosegregated with the EST-derived marker c28385. The gene-derived conserved ortholog set (COS) markers enabled us to investigate the orthology of restorer genes originating from different genetic resources of rye as well as barley. The observed localization of
Rfp3
and
Rfm1
in a syntenic 4RL/6HS segment asks for further efforts towards cloning of both restorer genes as an option to study the mechanisms of male sterility and fertility restoration in cereals.
The diversity of maize (Zea mays) is the backbone of modern heterotic patterns and hybrid breeding. Historically, US farmers exploited this variability to establish today's highly productive Corn ...Belt inbred lines from blends of dent and flint germplasm pools. Here, we report de novo genome sequences of four European flint lines assembled to pseudomolecules with scaffold N50 ranging from 6.1 to 10.4 Mb. Comparative analyses with two US Corn Belt lines explains the pronounced differences between both germplasms. While overall syntenic order and consolidated gene annotations reveal only moderate pangenomic differences, whole-genome alignments delineating the core and dispensable genome, and the analysis of heterochromatic knobs and orthologous long terminal repeat retrotransposons unveil the dynamics of the maize genome. The high-quality genome sequences of the flint pool complement the maize pangenome and provide an important tool to study maize improvement at a genome scale and to enhance modern hybrid breeding.
Background and Aims
There is controversy about the length of low‐residue diet (LRD) for colonoscopy preparation. The aim of the study was to compare one‐day vs. three‐day LRD associated to standard ...laxative treatment for achieving an adequate colonoscopy preparation in average risk subjects with positive fecal immunochemical test undergoing screening colonoscopy.
Methods
A non‐inferiority, randomized, controlled, parallel‐group clinical trial was performed in the setting of average risk colorectal cancer screening program. Participants were randomized to receive 1‐day vs. 3‐day LRD in addition to standard polyethilenglicol treatment. Adequacy of preparation was evaluated using the Boston Bowel Preparation Scale (BBPS). Primary outcome was achieving a BBPS ≥ 2 in all colon segments. Analysis was performed for a non‐inferiority margin of 5%, a 95% statistical power and one‐sided 0.05 significance level.
Results
A total of 855 patients were randomized. Adequate bowel preparation was similar between groups: 97.9% of patients in the 1‐day LRD group vs 96.9% in the 3‐day LRD group achieved the primary outcome (P‐value for non‐inferiority < 0.001). The percentage of patients with BBPS scores ≥ 8 was superior in the 1‐day LRD group (254 vs 221 in the 3‐day LRD group, P = 0.032). The 1‐day regimen was better tolerated than the 3‐day diet. 47.7% (vs 28.7%, P < 0.05) of patients rated the 1‐day LRD as very easy to follow.
Conclusion
The 1‐day LRD is non‐inferior to 3‐day LRD for achieving an adequate colon cleansing before average risk screening colonoscopy and it is better tolerated.
Endostatin, the C-terminal fragment of type XVIII collagen, was shown to be one of the most potent endothelial cell-specific inhibitors of angiogenesis. As altered circulating endostatin ...concentration is associated with impaired kidney function, new tools for measuring endostatin in rodents may be helpful to further investigate and understand its role within kidney disease progression. A novel and commercially available ELISA for the quantification of mouse and rat endostatin was developed and validated according to international quality guidelines including the parameters specificity, robustness, accuracy, dilution linearity, precision, limit of detection (LOD) and lower limit of quantification (LLOQ). Endostatin and blood urea nitrogen (BUN) concentration were measured in mice with a glomerulonephritis phenotype. The validation revealed that within the range of 0.5-32 nmol/L the immunoassay is robust and highly specific for the measurement of rodent endostatin with high sensitivity (LOD 0.24 nmol/L, LLOQ 0.5 nmol/L) and good reproducibility (intra- and inter-assay CV <10%). Also accuracy and dilution linearity were within the range of acceptance. BCL2 transgenic and ETV6/RUNX1;BCL2 double transgenic mice develop a glomerulonephritis phenotype over time, which was displayed by staining of kidney sections. Even before full manifestation of disease serum endostatin concentration rises significantly, whereas BUN levels just slightly increase. This newly developed and commercially available ELISA provides a reliable and accurate tool for the quantification of mouse and rat endostatin and may give new perspectives in the investigation of the role of endostatin as an important and early biomarker for reduced kidney function. Measurement of endostatin concentration is recommended to be used as a superior biomarker for chronic kidney disease compared to BUN.
Background & Aims:
Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response (SVR) when treated for 48 weeks. This study ...investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment.
Methods:
A total of 510 treatment-naive patients were treated with peginterferon-alfa2a (180 μg/wk) plus ribavirin (800 mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were randomized to complete 48 (group A, n = 165) or 72 weeks (group B, n = 161) of treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were allocated into group C (n = 148) or group D (n = 36), according to HCV genotype and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients were followed-up for 24 weeks after the end of treatment.
Results:
The end-of-treatment response rate (61%) was similar in groups A and B, but the SVR rate was higher in group B (45% vs 32% in A;
P = .01). In genotype 1–infected patients randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%, respectively (
P = .003). The incidence of adverse events was similar in all groups. Treatment discontinuation was more frequent in group B (36%) than in group A (18%) (
P = .0004). SVR rates in groups C and D were 79% and 64%, respectively.
Conclusions:
Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment.
The transition from liquid to solid feed during weaning results in morphological, histological and microbial changes in the young animal's intestinal tract and often is associated with diarrhoea. The ...ban of in-feed antibiotics in pig production in the European Union has led to increasing interest in alternatives to overcome weaning-associated problems. Among others, nucleotides may have the potential to alleviate health impairments due to weaning. Nucleotides are natural components of the non-protein fraction of milk and have important effects on the maintenance of health in young animals. Nucleotides and their related metabolic products play key roles in many biological processes and become essential dietary components when endogenous supply is insufficient for normal function. The present review summarises nucleotide composition of milk from different species, the biology of nucleotides and possible effects of dietary nucleotides on intestinal morphology and function, intestinal microbiota, immune function, nutrient metabolism, hepatic morphology and function as well as growth performance. Special attention is given to data available for pigs, and suggestions are made for inclusion of nucleotides in the diet to benefit piglets' health and reduce the consequences accompanying early weaning.
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