Introduction
Recently, several studies have supported the value of clinical genome sequencing, particularly when there is diagnostic uncertainty [1]–[4]. As clinical genome sequencing becomes more widely available, it is likely to provide useful information, even when there is no family history of disease. However, interpretation of genomic data has not yet been widely incorporated into medical school curricula, and how such studies can best be employed to inform medical practice remains a subject of intense interest [5].
To address emerging implications for applying clinical genomics, students earning concurrent M.D. and Ph.D. degrees in the University of Washington Medical Scientist Training Program (MSTP) participate in a new course, also open to a limited number of M.D.-only students, in which a cadaver undergoes whole genome sequencing in association with dissection in the human anatomy lab. The cadaver selected for the inaugural exercise had been an otherwise healthy male with non-familial idiopathic pulmonary fibrosis (IPF).
Interstitial lung diseases can be difficult to clinically and pathologically characterize [6]. Many cases are diagnosed as idiopathic, highlighting a need to develop better understanding of their pathogenesis. Current evidence suggests that IPF follows a “two-hit” disease model where hereditary factors alter underlying disease susceptibility to environmental stressors such as cigarette smoke, asbestos, or silica [7], [8]. Familial IPF kindred and genome-wide association studies (GWAS) have identified several genetic variants that alter disease susceptibility [9]–[15]. Interestingly, many of the variants described in the literature are known to be involved in host defense, cell adhesion, maintenance of genomic integrity, and preservation of lung architecture. To cite one prominent example, a single nucleotide polymorphism (SNP) in the promoter of the MUC5B gene was recently reported to up-regulate expression of the gene and is both genetically linked and associated with IPF [10]–[14], [16].
As an exercise in medical education, we interpret the cadaver's genome sequence in concert with gross and microscopic anatomical examination and discuss its potential relevance for diagnosis and management of IPF.