ACMG guidelines are limited to Mendelian disease genes and dichotomous variant classification. Study uses chronic pancreatitis as disease model with four main genes. Framework extends ACMG guidelines to include disease-causing and predisposing genes
Chromosome abnormalities involve missing, extra, or irregular DNA portions. Can occur in numerical (aneuploidy) or structural forms. Most arise during cell division errors after meiosis or mitosis. Can be inherited or occur spontaneously
Deletion is a genetic mutation where part of chromosome or DNA sequence is lost. Can occur from single base to entire chromosome pieces. Types include terminal, intercalary, and microdeletions
Shotgun sequencing was first proposed in 1979 by Staden. Method breaks DNA into fragments and reassembles them using overlapping regions. First developed by Messing in 1981 using M13 phage vector. Now often done using next-generation sequencing platforms
CASR gene provides instructions for calcium-sensing receptor (CaSR) protein. CaSR monitors and regulates blood calcium levels. Protein is abundant in parathyroid glands and kidney cells. Activated CaSR blocks processes increasing blood calcium
JAK2 gene controls blood cell production from hematopoietic stem cells. JAK2 V617F mutation occurs randomly, not inherited. Mutation affects 0.2% of general population, 96% in polycythemia vera