Linkage analysis and exome sequencing identify a novel mutation in KCTD7 in patients with progressive myoclonus epilepsy with ataxia

Epilepsy affects approximately 1% of the world\u27s population. Genetic factors and acquired etiologies, as well as a range of environmental triggers, together contribute to epileptogenesis.Wehave identified a family with three daughters affected with progressive myoclonus epilepsy with ataxia. Clinical details of the onset and progression of the neurologic presentation, epileptic seizures, and the natural history of progression over a 10-year period are described. Using autozygosity genetic mapping, we identified a high likelihood homozygous region on chromosome 7p12.1-7q11.22. We subsequently applied whole-exome sequencing and employed a rare variant prioritization analysis within the homozygous region. We identified p.Tyr276Cys in the potassium channel tetramerization domain-containing seven gene, KCTD7, which is expressed predominantly in the brain. Mutations in this gene have been implicated previously in epileptic phenotypes due to disturbances in potassium channel conductance. Pathogenicity of the mutation was supported by bioinformatic predictive analyses and variant cosegregation within the family. Further biologic validation is necessary to fully characterize the pathogenic mechanisms that explain the phenotypic causes of epilepsy with ataxia in these patients

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

King Alfred: A Translation Environment for Learners of Anglo-Saxon English

King Alfred is the name of both an innovative textbook and a computational environment deployed in parallel in an undergraduate course on Anglo-Saxon literature. This paper details the ways in which it brings dynamically-generated resources to the aid of the language student. We store the feature-rich grammar of Anglo-Saxon in a bi-level glossary, provide an annotation context for use during the translation task, and are currently working toward the implementation of automatic evaluation of student-generated translations

Learning Data Structures through Text Adventure Games

Pedagogical research has already established that couching lessons within the use or design of computer games can be an effective method of instruction. Text adventure games are a particularly excellent vehicle for exploring many Data Structures topics. In these games, the interface is console-based and involves a simple input-response cycle that is easy for novice programmers to master. The game\u27s player uses typed commands to move around a series of locales, each of which is described upon entering. There are physical objects in each location that can be inspected, picked up and carried, dropped, and sometimes used in some way. Meeting the requirements of a global objective causes the game to end. Beyond this, student creativity can add layers of plot complexity and puzzles, humor, and originality without requiring advanced programming expertise

AND, OR, NOT: Teaching Logic in CS0

The use of logical expressions is at the heart of much of what we do as Computer Scientists. This paper addresses the centrality of Boolean expressions as a repeating theme in an introductory Computer Science course that serves both non-majors and Information Technology majors, and is also a gateway to the Computer Science major. Booleans are the key to unlocking how to express specificity to a computer; not only are they a central component to writing computer programs, but they also play a key role in the effective use of many information systems such as databases, spreadsheets, library catalogs, and Google, all of which have high relevance to a diverse audience

Evil Robots and Helpful Droids: A Seminar for a Junior/Senior Artificial Intelligence Course

This paper addresses the creation of a discussion seminar component for an upper-level Artificial Intelligence course for junior and senior Computer Science majors. Its purpose is to contextualize ongoing work in the field within greater social, cultural, and ethical perspectives. Although our program is not ABET-accredited, we use the student outcomes as a roadmap of desirable curriculum content. Assessment of student responses to this material indicates that this is an appropriate way to address the ABET student outcomes that seek to connect Computer Science curricula with societal impact