Biology subjects

Hermann, P.

Publications and source records attributed to Hermann, P..

4 recordsLinked to original sources

bioRxiv2018

Length asymmetry and heterozygosity strongly influences the evolution of poly-A microsatellites at meiotic recombination hotspots

Meiotic recombination has strong, but poorly understood, effects on short tandem repeat (STR) instability. Here, we screened thousands of single recombinant products to characterize the transmission and evolution of polymorphic poly-A repeats at a human recombination hotspot. We show that length asymmetry between heterozygous poly-As plays a key role in the recombination outcome and their transmission. A difference of 10 As (9A/19A) elevates the frequency of non-crossovers, complex recombination products, and long conversion tracts. Moreover, asymmetry also influences STR transmission: the shorter allele is transmitted more frequently (deletion bias) at the asymmetric STR (9A/19A), while the longer allele is favored (insertion bias) at the site with a small STR length difference (6A/7A). Finally, potentially due to this opposing insertion/deletion driven evolution, we find that poly-As are enriched at human recombination hotspots predominantly with short poly-As, possibly influencing open chromatin regions that in turn can activate hotspots.

evolutionary biology↗

bioRxiv2018

Age of onset in genetic prion disease and the design of preventive clinical trials

Regulatory agencies worldwide have adopted programs to facilitate drug development for diseases where the traditional approach of a randomized trial with a clinical endpoint is expected to be prohibitively lengthy or difficult. Here we provide quantitative evidence that this criterion is met for the prevention of genetic prion disease. We assemble age of onset or death data from N=1,094 individuals with high penetrance mutations in the prion protein gene (PRNP), generate survival and hazard curves, and estimate statistical power for clinical trials. We show that, due to dramatic and unexplained variability in age of onset, randomized preventive trials would require hundreds or thousands of at-risk individuals in order to be statistically powered for an endpoint of clinical onset, posing prohibitive cost and delay and likely exceeding the number of individuals available for such trials. Instead, the characterization of biomarkers suitable to serve as surrogate endpoints will be essential for the prevention of genetic prion disease. Biomarker-based trials may require post-marketing studies to confirm clinical benefit. Parameters such as longer trial duration, increased enrollment, and the use of historical controls in a post-marketing study could provide opportunities for subsequent determination of clinical benefit.

neuroscience↗

bioRxiv2017

LDJump: Estimating Variable Recombination Rates from Population Genetic Data

As recombination plays an important role in evolution, its estimation, as well as, the identification of hotspot positions is of considerable interest. We propose a novel approach for estimating historical recombination along a chromosome that involves a sequential multiscale change point estimator. Our method also permits to take demography into account. It uses a composite likelihood estimate and other summary statistics within a regression model fitted on suitable scenarios. Our proposed method is accurate, computationally fast, and provides a parsimonious solution by ensuring a type I error control against too many changes in the recombination rate. An application to human genome data suggests a good congruence between our estimated and experimentally identified hotspots. Our method is implemented in the R-package LDJump, which is freely available from https://github.com/PhHermann/LDJump.

bioinformatics↗

bioRxiv2017

Face inversion reveals holistic processing of peripheral faces

Face perception is accomplished by face-selective neural processes, involving holistic processing that enables highly efficient integration of facial features into a whole face representation. It has been shown that in face-selective regions of the ventral temporal cortex, neural resources involved in holistic processing are primarily dedicated to the central portion of the visual field. These findings raise the intriguing possibility that holistic processing might be the privilege of centrally presented faces and could be strongly diminished in the case of peripheral faces. We addressed this question using the face inversion effect, a well established marker of holistic face processing. The behavioral results revealed impaired identity discrimination performance for inverted peripheral faces scaled according to the V1 magnification factor, compared to upright presented faces. The size of peripheral face inversion effect (FIE) was comparable to that found for centrally displayed faces. Face inversion affected the early ERP responses to faces in two time intervals. The earliest FIE was most pronounced in the time window between 130-140 ms following stimulus presentation, for both centrally and peripherally displayed faces and in the latter case, it was present only over the contralateral hemisphere. The timing of the next component FIE corresponded closely with the temporal interval of the N170 ERP component and showed strong right hemisphere lateralization, both when faces were displayed in the left or right visual field. Furthermore, we also showed that centrally presented face masks impaired peripheral face identity discrimination performance, but did not reduce the magnitude of the FIE. These findings revealed robust behavioral and neural inversion effects for peripheral faces and thus suggest that faces are processed holistically throughout the visual field.\n\nHighlightsRobust behavioral and neural inversion effect was found for peripheral faces.\n\nP1 ERP component is modulated by inverted central and contralateral faces.\n\nN170 ERP component is modulated by centrally and peripherally presented faces.\n\nNeural face inversion effect shows strong right hemisphere lateralization.\n\nFaces are processed holistically throughout the visual field.

neuroscience↗