trfermikit: a tool to discover VNTR-associated deletions.

Summary: We present trfermikit, a software tool designed to detect deletions larger than 50 bp occurring in Variable Number Tandem Repeats using Illumina DNA sequencing reads. In such regions, it achieves a better tradeoff between sensitivity and false discovery than a state-of-the-art structural variation caller, Manta and complements it by recovering a significant number of deletions that Manta missed. trfermikit is based upon the fermikit pipeline, which performs read assembly, maps the assembly to the reference genome and calls variants from the alignment.

Survival of the Curviest: Noise-Driven Selection for Synergistic Epistasis.

A major goal of human genetics is to elucidate the genetic architecture of human disease, with the goal of fueling improvements in diagnosis and the understanding of disease pathogenesis. The degree to which epistasis, or non-additive effects of risk alleles at different loci, accounts for common disease traits is hotly debated, in part because the conditions under which epistasis evolves are not well understood. Using both theory and evolutionary simulation, we show that the occurrence of common diseases (i.

The protective role of symmetric stem cell division on the accumulation of heritable damage.

Stem cell divisions are either asymmetric-in which one daughter cell remains a stem cell and one does not-or symmetric, in which both daughter cells adopt the same fate, either stem or non-stem. Recent studies show that in many tissues operating under homeostatic conditions stem cell division patterns are strongly biased toward the symmetric outcome, raising the question of whether symmetry confers some benefit. Here, we show that symmetry, via extinction of damaged stem-cell clones, reduces the lifetime risk of accumulating phenotypically silent heritable damage (mutations or aberrant epigenetic changes) in individual stem cells.

Gene length may contribute to graded transcriptional responses in the Drosophila embryo.

An important question in developmental biology is how relatively shallow gradients of morphogens can reliably establish a series of distinct transcriptional readouts. Current models emphasize interactions between transcription factors binding in distinct modes to cis-acting sequences of target genes. Another recent idea is that the cis-acting interactions may amplify preexisting biases or prepatterns to establish robust transcriptional responses.

Small regulatory RNAs may sharpen spatial expression patterns.

The precise establishment of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low spatial expression domains requires a genetic mechanism that exhibits sensitivity, yet is robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently, it has been demonstrated that small RNAs (and, in particular, microRNAs) play many roles in embryonic development.

Embryonic pattern scaling achieved by oppositely directed morphogen gradients.

Morphogens are proteins, often produced in a localized region, whose concentrations spatially demarcate regions of differing gene expression in developing embryos. The boundaries of gene expression are typically sharp and the genes can be viewed as abruptly switching from on to off or vice versa upon crossing the boundary. To ensure the viability of the organism these boundaries must be set at certain fractional positions within the corresponding developing field.