Genome Sequencing of Idiopathic Pulmonary Fibrosis in Conjunction with a Medical School Human Anatomy Course

Abstract

Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF). Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP), as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP), rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD) adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

Genomics Education in the Era of Personal Genomics: Academic, Professional, and Public Considerations

“…Numerous studies support the finding that genomic education facilitates student interest and develops student confidence [52,103]. Genomic education can also foster research ideas that increase our understanding about genomics and recruit more students to study science and prepare for scientific careers [37,77]. Studies have also shown that genomics can be scaled to teach many students and still provide meaningful learning experiences [49].…”

“…This ATG program allowed students to draw conclusions about the cadaver's traits and disease phenotype regarding its genomic profile. Another group performed a similar study on a cadaver who had been diagnosed with idiopathic pulmonary fibrosis [77]. Interestingly, the genomic characterization of the cadaver revealed that the individual could have died from nonspecific interstitial pneumonia rather than idiopathic pulmonary fibrosis as had been suspected by the attending physician.…”

“…Many of these strategies and suggestions can easily be applied across multiple platforms; for example, many academic platforms can incorporate personal learning experiences by having students acquire and analyze their own genomic data [46,47]. Hands-on learning experiences that utilize genomic research are also a useful tool that can be utilized for many platforms [41,68,77]. Backward education design is also a helpful education strategy to fill in existing gaps in genomic knowledge and enhance retention and learning [96].…”

Genome sequencing in a case of Niemann–Pick type C

“…With the ever-growing promise of precision medicine and increasing use of genomic technologies in the clinic, WGS and interpretation allows students to explore both its utility and challenges. We hope this class may serve as a model for the possibilities created by integrating this type of patient analysis into medical education (Kumar et al 2014). In this course, students took responsibility for every aspect of the study, including the clinical history, gross anatomical dissection, and microscopic analysis of the brain, analysis of sequencing data, and preparation of the manuscript.…”

Nonspecific Interstitial Pneumonia: What Is the Optimal Approach to Management?

“…2 NSIP has been recently recognized also as one of the histologic features in the complex spectrum of familial pulmonary fibrosis. [16][17][18][19][20][21] The most important distinction to decipher in understanding the clinical relevance of NSIP is whether it is idiopathic or secondary (identifiable cause or underlying disease). Therefore, it has been suggested that the identification of NSIP should prompt the physician to redouble efforts to find potential etiologies.…”