Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Exposure to sublethal concentrations of methoxyfenozide disrupts honey bee colony activity and thermoregulation.

Methoxyfenozide is an insect growth regulator (IGR) commonly used in agriculture to simultaneously control pests and preserve beneficial insect populations; however, its impact on honey bees in not fully understood. We conducted field and laboratory experiments to investigate bee health in response to field-relevant concentrations of this pesticide. Significant effects were observed in honey bee colony flight activity and thermoregulation after being exposed over 9 weeks to supplemental protein patty containing methoxyfenozide. Compared to bee colonies in the control group, colonies fed pollen patty with 200 ppb methoxyfenozide (as measured by residue analysis) had: 1) a significantly reduced rate of weight loss due to forager departure in the morning; and 2) higher temperature variability during the winter. Colonies in the 100 ppb (as measured by residue analysis) treatment group had values between the 200 ppb group and control for both response variables. The dusk break point, which is the time associated with the end of forager return, differed among all treatment groups but may have been confounded with direction the hives were facing. Bee colony metrics of adult bee mass and brood surface area, and measurements of bee head weight, newly-emerged bee weight, and hypopharyngeal gland size were not significantly affected by methoxyfenozide exposure, suggesting that there may be significant effects on honey bee colony behavior and health in the field that are difficult to detect using standard methods for assessing bee colonies and individuals. The second experiment was continued into the following spring, using the same treatment groups as in the fall. Fewer differences were observed among groups in the spring than the fall, possibly because of abundant spring forage and consequent reduced treatment patty consumption. Residue analyses showed that: 1) observed methoxyfenozide concentrations in treatment patty were about 18-60% lower than the calculated concentrations; 2) no residues were observed in wax in any treatment; and 3) methoxyfenozide was detected in bee bread only in the 200 ppb treatment group, at about 1-2.5% of the observed patty concentration

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes

Identifying genetic risk factors for highly heterogeneous disorders such as epilepsy remains challenging. Here we present, to our knowledge, the largest whole-exome sequencing study of epilepsy to date, with more than 54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies and generalized and focal epilepsies, whereas most other gene discoveries are subtype specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single-nucleotide/short insertion and deletion variants, copy number variants and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies