Dr SUZANNE MILLER suzanne.miller@nottingham.ac.uk
Senior Clinical Studies and Project Manager
Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development
Miller, Suzanne; Mel�n, Erik; Merid, S. K.; Hall, Ian P.; Sayers, Ian
Authors
Erik Mel�n
S. K. Merid
Ian P. Hall
Professor IAN SAYERS ian.sayers@nottingham.ac.uk
PROFESSOR OF RESPIRATORY MOLECULAR GENETICS
Abstract
Background
Recent meta-analyses of genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within/near 54 genes associated with lung function measures. Current understanding of the contribution of these genes to human lung development is limited. We set out to further define i) the expression profile of these genes during human lung development using a unique set of resources to examine both mRNA and protein expression and ii) the link between key polymorphisms and genes using expression quantitative trait (eQTL) approaches.
Methods
The mRNA expression profile of lung function associated genes across pseudoglandular and canalicular stages of lung development were determined using expression array data of 38 human fetal lungs. eQTLs were investigated for selected genes using blood cell and lung tissue data. Immunohistochemistry of the top 5 candidates was performed in a panel of 24 fetal lung samples.
Results
29 lung function associated genes were differentially expressed during lung development at the mRNA level. The greatest magnitude of effect was observed for 5 genes; TMEM163, FAM13A and HHIP which had increasing expression and CDC123 and PTCH1 with decreased expression across developmental stages. Focussed eQTL analyses investigating SNPs in these five loci identified several cis-eQTL’s. Protein expression of TMEM163 increased and CDC123 decreased with fetal lung age in agreement with mRNA data. Protein expression in FAM13A, HHIP and PTCH1 remained relatively constant throughout lung development.
Conclusions
We have identified that > 50 % of lung function associated genes show evidence of differential expression during lung development and we show that in particular TMEM163 and CDC123 are differentially expressed at both the mRNA and protein levels. Our data provides a systematic evaluation of lung function associated genes in this context and offers some insight into the potential role of several of these genes in contributing to human lung development.
Citation
Miller, S., Melén, E., Merid, S. K., Hall, I. P., & Sayers, I. (in press). Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development. Respiratory Research, 17(95), https://doi.org/10.1186/s12931-016-0410-z
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 19, 2016 |
Online Publication Date | Jul 29, 2016 |
Deposit Date | Aug 1, 2016 |
Publicly Available Date | Aug 1, 2016 |
Journal | Respiratory Research |
Print ISSN | 1465-9921 |
Electronic ISSN | 1465-993X |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 17 |
Issue | 95 |
DOI | https://doi.org/10.1186/s12931-016-0410-z |
Keywords | Lung function; development; expression; genetics; TMEM163; CDC123 |
Public URL | https://nottingham-repository.worktribe.com/output/798514 |
Publisher URL | https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-016-0410-z |
Contract Date | Aug 1, 2016 |
Files
art%3A10.1186%2Fs12931-016-0410-z.pdf
(1.9 Mb)
PDF
Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
You might also like
Metagenomic changes in response to antibiotic treatment in severe orthopedic trauma patients
(2024)
Journal Article
Lysyl oxidase like 2 is increased in asthma and contributes to asthmatic airway remodelling
(2022)
Journal Article
Mast Cell Tryptase Release Contributes to Disease Progression in Lymphangioleiomyomatosis
(2021)
Journal Article