Knowledge about the origins and evolution of crop species represents an important prerequisite for efficient conservation and use of existing plant materials. This study was designed to solve the ...ongoing debate on the origins of the common bean by investigating the nucleotide diversity at five gene loci of a large sample that represents the entire geographical distribution of the wild forms of this species. Our data clearly indicate a Mesoamerican origin of the common bean. They also strongly support the occurrence of a bottleneck during the formation of the Andean gene pool that predates the domestication, which was suggested by recent studies based on multilocus molecular markers. Furthermore, a remarkable result was the genetic structure that was seen for the Mesoamerican accessions, with the identification of four different genetic groups that have different relationships with the sets of wild accessions from the Andes and northern Peru–Ecuador. This finding implies that both of the gene pools from South America originated through different migration events from the Mesoamerican populations that were characteristic of central Mexico.
We have studied the nucleotide diversity of common bean, Phaseolus vulgaris, which is characterized by two independent domestications in two geographically distinct areas: Mesoamerica and the Andes. ...This provides an important model, as domestication can be studied as a replicate experiment.
We used nucleotide data from five gene fragments characterized by large introns to analyse 214 accessions (102 wild and 112 domesticated). The wild accessions represent a cross-section of the entire geographical distribution of P. vulgaris.
A reduction in genetic diversity in both of these gene pools was found, which was three-fold greater in Mesoamerica compared with the Andes. This appears to be a result of a bottleneck that occurred before domestication in the Andes, which strongly impoverished this wild germplasm, leading to the minor effect of the subsequent domestication bottleneck (i.e. sequential bottleneck).
These findings show the importance of considering the evolutionary history of crop species as a major factor that influences their current level and structure of genetic diversity. Furthermore, these data highlight a single domestication event within each gene pool. Although the findings should be interpreted with caution, this evidence indicates the Oaxaca valley in Mesoamerica, and southern Bolivia and northern Argentina in South America, as the origins of common bean domestication.
The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. ...This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were recruited through ten sites, 2010-2014. Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%). Across CHD types, there were significant differences (p<0.05) in the distribution of all four case characteristics (e.g., sex), four parental characteristics (e.g., maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g., learning disabilities). Several characteristics (e.g., sex) were also significantly different across CHD subtypes. The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes. The majority of cases do not have a genetic diagnosis. This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND—Pulmonary valve replacement (PVR) after repair of tetralogy of Fallot is commonly required and is burdensome. Detailed anatomic and physiologic characteristics of survivors free from late ...PVR and with good exercise capacity are not well described in a literature focusing on the indications for PVR.
METHODS AND RESULTS—Survival and freedom from PVR were tracked in 1085 consecutive patients receiving standard tetralogy of Fallot repair in a single institution from 1964 to 2009. Of 152 total deaths, 100 occurred within the first postoperative year. Surviving patients between 10 and 50 years of age had an annual risk of death of 4 (confidence limit, 2.8–5.4) times that of normal contemporaries. To date, 189 patients have undergone secondary PVR at mean age of 20±13 years (36% of those alive at 40 years of age). A random sample of 50 survivors (age, 4–57 years) free from PVR underwent cardiovascular magnetic resonance, echocardiography, and exercise testing. These patients had mildly dilated right ventricles (right ventricular end-diastolic volume=101±26 mL/m) with good systolic function (right ventricular ejection fraction=59±7%). Most had exercise capacity within normal range (z peak (Equation is included in full-text article.)O2=−0.91±1.3; z (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2=0.20±1.5). In patients >35 years of age with normal exercise capacity, there was mild residual right ventricular outflow tract obstruction (mean gradient, 24±13 mm Hg), pulmonary annulus diameters <0.5z, and unobstructed branch pulmonary arteries.
CONCLUSIONS—An important proportion of patients require PVR late after tetralogy of Fallot repair. Patients surviving to 35 years of age without PVR and with a normal exercise capacity may have had a definitive primary repair; their right ventricular outflow tracts are characterized by mild residual obstruction and pulmonary annulus diameter <0.5z.
Abstract Objective Patients with repaired tetralogy of Fallot (ToF) have an increased long-term risk of cardiovascular morbidity and mortality. Risk stratification in this population is difficult. ...Initial evidence suggests that cardiopulmonary exercise testing (CPET) may be helpful to risk-stratify patients with repaired ToF. Methods and results We studied 875 patients after surgical repair for ToF (358 females, age 25.5 ± 11.7 year, range 7–75 years) who underwent CPET between 1999 and 2009. During a mean follow-up of 4.1 ± 2.6 years after CPET, 30 patients (3.4%) died or had sustained ventricular tachycardia (VT). 225 patients (25.7%) had other cardiac related events (emergency admission, surgery, or catheter interventions). On multivariable Cox regression-analysis, %predicted peak oxygen uptake ( V ˙ O 2 %) (p = 0.001), resting QRS duration (p = 0.030) and age (p < 0.001) emerged as independent predictors of mortality or sustained VT. Patients with a peak V ˙ O 2 ≤ 65% of predicted and a resting QRS duration ≥ 170 ms had a 11.4-fold risk of death or sustained VT. Ventilatory efficiency expressed as V ˙ E / V ˙ C O 2 slope (p < 0.001), peak V ˙ O 2 % (p = .001), QRS duration (p = .001) and age (p = 0.046) independently predicted event free survival. V ˙ E / V ˙ C O 2 slope ≥ 31.0, peak V ˙ O 2 % ≤ 65% and QRS duration ≥ 170 ms were the cut-off points with best sensitivity and specificity to detect an unfavorable outcome. Conclusions CPET is an important predictive tool that may assist in the risk stratification of patients with ToF. Subjects with a poor exercise capacity in addition to a prolonged QRS duration have a substantially increased risk for death or sustained ventricular tachycardia, as well as for cardiac-related hospitalizations.
Background Previous studies have shown that older Fontan patients and those with an underlying morphologically right ventricle have lower exercise capacity. We sought to assess the natural history of ...exercise capacity after the Fontan operation in individual patients, and to identify the factors influencing the rate of decrease of exercise capacity over time. Methods We studied, longitudinally, 53 Fontan patients with cardiopulmonary exercise tests (average 3.2 ± 1.1 tests for each patient). Age at the first test was 14 ± 6 years. Time intervals between tests ranged from 1 to 16 years (average, 7.7 ± 4.0 years). The morphology of the functionally single ventricle was left in 29 patients (55%) and right in 24 patients (45%). Twenty-two patients had undergone a total cavopulmonary connection (TCPC) at a mean age of 5.9 ± 2.8 years. Thirty-one patients had undergone an atriopulmonary or an atrioventricular connection at an age of 6.9 ± 4.4 years. Exercise capacity was expressed as percentage of predicted peak oxygen uptake (V o2 ). Results Overall, peak V o2 decreased at a rate of −2.6 ± 2.7%/year. Ventricular morphology (r = 0.525, p = 0.0001) and type of Fontan operation (r = 0.381, p = 0.0057) appeared as the only predictors of the rate of decrease of peak V o2 at multivariate analysis. Patients with an underlying left ventricular morphology (−1.7 ± 2.0 vs −3.7 ± 3.2%/year, p = 0.005), and those who underwent a TCPC (−1.9 ± 1.8 vs −3.3 ± 3.2%/year, p = 0.042), had the lowest rate of decrease in peak V o2. Conclusions Exercise capacity progressively declines in Fontan subjects. The decline of exercise capacity seems to be slower in patients with an underlying left ventricular morphology and in those who received a TCPC.
Although DNA methylation is the best characterized epigenetic mark, the mechanism by which it is targeted to specific regions in the genome remains unclear. Recent studies have revealed that local ...DNA methylation profiles might be dictated by cis-regulatory DNA sequences that mainly operate via DNA-binding factors. Consistent with this finding, we have recently shown that disruption of CTCF-binding sites by rare single nucleotide variants (SNVs) can underlie cis-linked DNA methylation changes in patients with congenital anomalies. These data raise the hypothesis that rare genetic variation at transcription factor binding sites (TFBSs) might contribute to local DNA methylation patterning. In this work, by combining blood genome-wide DNA methylation profiles, whole genome sequencing-derived SNVs from 247 unrelated individuals along with 133 predicted TFBS motifs derived from ENCODE ChIP-Seq data, we observed an association between the disruption of binding sites for multiple TFs by rare SNVs and extreme DNA methylation values at both local and, to a lesser extent, distant CpGs. While the majority of these changes affected only single CpGs, 24% were associated with multiple outlier CpGs within ±1kb of the disrupted TFBS. Interestingly, disruption of functionally constrained sites within TF motifs lead to larger DNA methylation changes at nearby CpG sites. Altogether, these findings suggest that rare SNVs at TFBS negatively influence TF-DNA binding, which can lead to an altered local DNA methylation profile. Furthermore, subsequent integration of DNA methylation and RNA-Seq profiles from cardiac tissues enabled us to observe an association between rare SNV-directed DNA methylation and outlier expression of nearby genes. In conclusion, our findings not only provide insights into the effect of rare genetic variation at TFBS on shaping local DNA methylation and its consequences on genome regulation, but also provide a rationale to incorporate DNA methylation data to interpret the functional role of rare variants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Landraces are heterogeneous plant varieties that are reproduced by farmers as populations that are subject to both artificial and natural selection. Landraces are distinguished by farmers due to ...their specific traits, and different farmers often grow different populations of the same landrace. We used simple sequence repeats (SSRs) to analyse 12 barley landrace populations from Sardinia from two collections spanning 10 years. We analysed the population structure, and compared the population diversity of the landraces that were collected at field level (population). We used a representative pool of barley varieties for diversity comparisons and to analyse the effects of gene flow from modern varieties. We found that the Sardinian landraces are a distinct gene pool from those of both two-row and six-row barley varieties. There is also a low, but significant, mean level and population-dependent level of introgression from the modern varieties into the Sardinian landraces. Moreover, we show that the Sardinian landraces have the same level of gene diversity as the representative sample of modern commercial varieties grown in Italy in the last decades, even within population level. Thus, these populations represent crucial sources of germplasm that will be useful for crop improvement and for population genomics studies and association mapping, to identify genes, loci and genome regions responsible for adaptive variations. Our data also suggest that landraces are a source of valuable germplasm for sustainable agriculture in the context of future climate change, and that in-situ conservation strategies based on farmer use can preserve the genetic identity of landraces while allowing adaptation to local environments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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