Open AccessHuman perforin gene variation is geographically distributed
Author(s) -
Willenbring Robin C.,
Ikeda Yasuhiro,
Pease Larry R.,
Johnson Aaron J.
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.344
Subject(s) - biology , genetics , exome , context (archaeology) , perforin , mutation , population , gene , exome sequencing , medicine , cytotoxic t cell , environmental health , paleontology , in vitro
Background Deleterious mutations in PRF 1 result in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 ( FHL 2). However, not all mutations in PRF 1 are deleterious and result in FHL 2. Currently, these nondeleterious mutations are being investigated in the onset of numerous disorders, such as lymphomas and diabetes. Yet, there is still an overwhelmingly large amount of PRF 1 mutations that are not associated with disease. Methods We conducted a post hoc analysis of the PRF 1 mutations in the coding region using the recently published Exome Aggregation Consortium genomes, Leiden Open Variation Database, NCBI SNP database, and primary literature to better understand PRF 1 variation in the human population. Results This study catalogs 460 PRF 1 mutations in the coding region, and demonstrates PRF 1 is more variant then previously predicted. We identify key PRF 1 mutations with high allelic frequency and are only found in certain populations. Additionally, we define PRF 1 SNV s are geographically distributed. Conclusions This study concludes with a novel hypothesis that nondeleterious mutation in PRF 1 , which decreases perforin expression and/or activity, may be an example of selective advantage in the context of environmental stressors prevalent near the equator. Our studies illustrate how perforin deficiency can be protective from injuries resulting in blood–brain barrier ( BBB ) disruption.