The establishment and test run of a computerized endodontic record keeping system

Thesis (M.Sc.D.)--Boston University, School of Graduate Dentistry, 1972. Endodontics.Bibliography included

Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk

Coding variants represent many of the strongest associations between genotype and phenotype; however, they exhibit interindividual differences in effect, termed 'variable penetrance'. Here, we study how cis-regulatory variation modifies the penetrance of coding variants. Using functional genomic and genetic data from the Genotype-Tissue Expression Project (GTEx), we observed that in the general population, purifying selection has depleted haplotype combinations predicted to increase pathogenic coding variant penetrance. Conversely, in cancer and autism patients, we observed an enrichment of penetrance increasing haplotype configurations for pathogenic variants in disease-implicated genes, providing evidence that regulatory haplotype configuration of coding variants affects disease risk. Finally, we experimentally validated this model by editing a Mendelian single-nucleotide polymorphism (SNP) using CRISPR/Cas9 on distinct expression haplotypes with the transcriptome as a phenotypic readout. Our results demonstrate that joint regulatory and coding variant effects are an important part of the genetic architecture of human traits and contribute to modified penetrance of disease-causing variants.Peer reviewe

Preoperative Localization of a Gastrin-Secreting Tumour by Total Body Imaging with 111Indium-Labelled Pentatreotide

A 41-year-old female presented with persistent diarrhea, and was diagnosed with Zollinger-Ellison syndrome when her gastrin level was greater than 3000 ng/L. All modalities for preoperative localization of her gastrinoma were unsuccessful, including transabdominal and endoscopic ultrasound, computed tomography, pancreatic angiogram, selective transhepatic portal venous sampling and magnetic resonance imaging. The gastrin-secreting tumour was visualized using the somatostatin analogue pentatreotide labelled with 111Indium, combined with gamma camera imaging. A successful resection of the tumour resulted in the normalization of serum gastrin levels 3.5 years after presentation. A discussion of the merits and sensitivities of these tests for preoperative localization of gastrin-secreting tumours will be presented