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Notable Histologie Findings in a \Normal\ Cohort The National Institutes of Health Genotype-Tissue Expression (GTEx) Project
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Notable Histologie Findings in a \Normal\ Cohort The National Institutes of Health Genotype-Tissue Expression (GTEx) Project
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Journal Article
Notable Histologie Findings in a \Normal\ Cohort The National Institutes of Health Genotype-Tissue Expression (GTEx) Project
2025
Overview
(Arch Pathol Lab Med. 2025;149:233-241; doi: 10.5858/ arpa.2023-0468-OA) The Genotype-Tissue Expression (GTEx) project, a National Institutes of Health (NIH) Common Fund study, was designed to evaluate how genetic variation and epigenetic effects influence gene expression in normal tissue and to gain insight into tissue-specific gene expression and regulation.1'2 GTEx tissue collection was coordinated by the National Cancer Institute (NCI) Biorepositories and Biospecimen Research Branch using a specialized infra-structure developed in accordance with the NCI Best Practices for Biospecimen Resources.3,4 Tissue collection, when completed, resulted in more than 25 000 tissue samples from up to 40 grossly nondiseased tissues from nearly 1000 postmortem or organ donors. The GTEx project has (1) established a molecular resource database with aggregated genotypic and gene expression data (www.gtexportal.org), (2) shared the full data set, including raw DNA/RNA sequences and the available clinical data for each donor, to the database of genotypes and phenotypes (dbGaP; dbGaP accession No. phs000424; https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/ study.cgi?study_id=phs000424), (3) created a view-only tissue image library of micrographs (biospecimens.cancer.gov/gtex-biobank/histology_viewer.asp) as well as micrographs compatible with image analysis that are available upon request (email: ncibbrb@nih.gov), and (4) established an associated tissue bank (biospecimens.cancer.gov/gtexbiobank and gtex-portal.org/home/biobank) for the scientific community to pur-sue additional studies. Uninten-tional inclusion of missampled or diseased tissue could increase variability and potentially confound genetic analysis. [...]a multiphase approach was applied: tissue that appeared grossly normal upon collection was preferentially sampled; each tissue sample collected underwent histologie review by a project pathologist to confirm the sample was rep-resentative of the target tissue, was of suitable quality and was absent of disease; and sequencing data were used to ver-ify recorded donor sex and the absence of chromosomal anomalies and genetic conditions. Briefly, research authorization was obtained from a member of each donor's family.3'6'7 In the present study, any of the following resulted in donor exclusion: an antemortem transfusion within 48 hours of death, a history of metastatic malignancy, expo-sure to HrV/AIDS or the hepatitis C virus within the 5 years pre-ceding death, repeated positive reactive screening tests for HIV-1 or HIV-2 antibodies, active sepsis, or multiple documented or con-firmed pathologie conditions.
