Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map

Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers

High Diversity at PRDM9 in Chimpanzees and Bonobos

BACKGROUND: The PRDM9 locus in mammals has increasingly attracted research attention due to its role in mediating chromosomal recombination and possible involvement in hybrid sterility and hence speciation processes. The aim of this study was to characterize sequence variation at the PRDM9 locus in a sample of our closest living relatives, the chimpanzees and bonobos. METHODOLOGY/PRINCIPAL FINDINGS: PRDM9 contains a highly variable and repetitive zinc finger array. We amplified this domain using long-range PCR and determined the DNA sequences using conventional Sanger sequencing. From 17 chimpanzees representing three subspecies and five bonobos we obtained a total of 12 alleles differing at the nucleotide level. Based on a data set consisting of our data and recently published Pan PRDM9 sequences, we found that at the subspecies level, diversity levels did not differ among chimpanzee subspecies or between chimpanzee subspecies and bonobos. In contrast, the sample of chimpanzees harbors significantly more diversity at PRDM9 than samples of humans. Pan PRDM9 shows signs of rapid evolution including no alleles or ZnFs in common with humans as well as signals of positive selection in the residues responsible for DNA binding. CONCLUSIONS AND SIGNIFICANCE: The high number of alleles specific to the genus Pan, signs of positive selection in the DNA binding residues, and reported lack of conservation of recombination hotspots between chimpanzees and humans suggest that PRDM9 could be active in hotspot recruitment in the genus Pan. Chimpanzees and bonobos are considered separate species and do not have overlapping ranges in the wild, making the presence of shared alleles at the amino acid level between the chimpanzee and bonobo species interesting in view of the hypothesis that PRDM9 plays a universal role in interspecific hybrid sterility

Broadband Spectral Modeling of the Extreme Gigahertz-Peaked Spectrum Radio Source PKS B0008-421

J. R. Callingham, et al., “Broadband Spectral Modeling of the Extreme Gigahertz-Peaked Spectrum Radio Source PKS B0008-421”, Astrophysical Journal, Vol. 809(2), August 2015. © 2015. The American Astronomical Society. All rights reserved.We present broadband observations and spectral modeling of PKS B0008-421, and identify it as an extreme gigahertz-peaked spectrum (GPS) source. PKS B0008-421 is characterized by the steepest known spectral slope below the turnover, close to the theoretical limit of synchrotron self-absorption, and the smallest known spectral width of any GPS source. Spectral coverage of the source spans from 0.118 to 22 GHz, which includes data from the Murchison Widefield Array and the wide bandpass receivers on the Australia Telescope Compact Array. We have implemented a Bayesian inference model fitting routine to fit the data with various absorption models. We find that without the inclusion of a high-frequency exponential break the absorption models can not accurately fit the data, with significant deviations above and below the peak in the radio spectrum. The addition of a high-frequency break provides acceptable spectral fits for the inhomogeneous free-free absorption and double-component synchrotron self-absorption models, with the inhomogeneous free-free absorption model statistically favored. The requirement of a high-frequency spectral break implies that the source has ceased injecting fresh particles. Additional support for the inhomogeneous free-free absorption model as being responsible for the turnover in the spectrum is given by the consistency between the physical parameters derived from the model fit and the implications of the exponential spectral break, such as the necessity of the source being surrounded by a dense ambient medium to maintain the peak frequency near the gigahertz region. The discovery of PKS B0008-421 suggests that the next generation of low radio frequency surveys could reveal a large population of GPS sources that have ceased activity, and that a portion of the ultra-steep spectrum source population could be composed of these GPS sources in a relic phase.Peer reviewedFinal Published versio

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Mammalian recombination hot spots: properties, control and evolution.

Recombination, together with mutation, generates the raw material of evolution, is essential for reproduction and lies at the heart of all genetic analysis. Recent advances in our ability to construct genome-scale, high-resolution recombination maps and new molecular techniques for analysing recombination products have substantially furthered our understanding of this important biological phenomenon in humans and mice: from describing the properties of recombination hot spots in male and female meiosis to the recombination landscape along chromosomes. This progress has been accompanied by the identification of trans-acting systems that regulate the location and relative activity of individual hot spots