title: 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.
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Akash
authors.initials: A
authors.lastname: Kumar
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Max
authors.initials: M
authors.lastname: Dougherty
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Findlay
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Geisheker
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Klein
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Lazar
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Heather
authors.initials: H
authors.lastname: Machkovech
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: Jesse
authors.initials: J
authors.lastname: Resnick
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Resnick
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Salter
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Talebi-Liasi
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Arakawa
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: Jacob
authors.initials: J
authors.lastname: Baudin
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America; Medical Scientist Training Program (MSTP), University of Washington, Seattle, Washington, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bogaard
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Salesky
authors.affiliation: University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Smith
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, United States of America.
authors.forename: John I
authors.initials: JI
authors.lastname: Clark
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Marshall S
authors.initials: MS
authors.lastname: Horwitz
mesh_terms: D000715:Anatomy / Q000193:education*; D002102:Cadaver; D004501:Education, Medical / Q000379:methods*; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055257:Mucin-5B / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D044465:White People / Q000235:genetics
chemical_list: C524578:MUC5B protein, human; D055257:Mucin-5B