Genetics of idiopathic pulmonary fibrosis: repeat expansion of the leucine aminopeptidase 3 gene (LAP3)
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Date
2023-09-04
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Saudi Digital Library
Abstract
Genetics of idiopathic pulmonary fibrosis: repeat expansion of the leucine aminopeptidase 3 gene (LAP3)
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic lung disease characterised by the formation of scar tissue in the interstitium. The cause of IPF is unknown, it is a result of a combination of genetic and environmental factors. However, the genetics of IPF are not fully understood. It poses a serious and life-threatening health concern, with a prevalence of between 3 and 60 cases per 100,000 individuals. IPF is more common in individuals older than 65 years; it is associated with a substantial mortality rate and an average life expectancy of 3-5 years following diagnosis. There is no known cure for IPF; however, medications can help reduce symptoms. The association of variable number tandem repeat (VNTR) expansion in the 5’ untranslated region (UTR) of LAP3 with IPF was identified in a case-control study. The aim of this study is to determine the extent of the VNTR variations in the LAP3 gene in CEU Trios of the HapMap project and their association with the transcription levels of the gene in the H292 cell line (the human bronchial epithelial NCI-H292), and to assess the quality of genotyping tools in whole genome sequence (WGS), giving insight into the potential implication of this variation in IPF disease.
Result: The extent of the variation of VNTRs of the LAP3 gene in the H292 cell line and CEU Trios of the HapMap project was sequenced using the Sanger sequence. This verified the utility of the two genotyping tools GangSTR and Expansion Hunter (EH) for genotyping LAP3 VNTR variation. Nonetheless, both approaches have shown inaccuracies in margin error of +/- 2 that require further validation using the standard Sanger method. LAP3 was highly expressed in the H292 cell line using Quantitative qPCR.
Conclusion: Our results support the variation in VNTR of LAP 3 in the H292 cell line and CEU Trios of the HapMap project. Further investigation of the VNTR variations functions in IPF is required.
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Keywords
IPF, LAP3 gene, H292 cell line, STR, VNTRs, Sanger sequence, GangSTR, Expansion Hunter
Citation
(Hannan, 2010).