Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development
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 furthe...
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| Format: | Article |
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BioMed Central
2016
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| Online Access: | https://eprints.nottingham.ac.uk/35521/ |
| _version_ | 1848795097693421568 |
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| author | Miller, Suzanne Melén, Erik Merid, S. K. Hall, Ian P. Sayers, Ian |
| author_facet | Miller, Suzanne Melén, Erik Merid, S. K. Hall, Ian P. Sayers, Ian |
| author_sort | Miller, Suzanne |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
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| format | Article |
| id | nottingham-35521 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:26:40Z |
| publishDate | 2016 |
| publisher | BioMed Central |
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| spelling | nottingham-355212020-05-04T17:59:05Z https://eprints.nottingham.ac.uk/35521/ Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development Miller, Suzanne Melén, Erik Merid, S. K. Hall, Ian P. Sayers, Ian 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. BioMed Central 2016-07-29 Article PeerReviewed Miller, Suzanne, Melén, Erik, Merid, S. K., Hall, Ian P. and Sayers, Ian (2016) Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development. Respiratory Research, 17 (95). ISSN 1465-993X Lung function; development; expression; genetics; TMEM163; CDC123 https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-016-0410-z doi:10.1186/s12931-016-0410-z doi:10.1186/s12931-016-0410-z |
| spellingShingle | Lung function; development; expression; genetics; TMEM163; CDC123 Miller, Suzanne Melén, Erik Merid, S. K. Hall, Ian P. Sayers, Ian Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development |
| title | Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development |
| title_full | Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development |
| title_fullStr | Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development |
| title_full_unstemmed | Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development |
| title_short | Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development |
| title_sort | genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development |
| topic | Lung function; development; expression; genetics; TMEM163; CDC123 |
| url | https://eprints.nottingham.ac.uk/35521/ https://eprints.nottingham.ac.uk/35521/ https://eprints.nottingham.ac.uk/35521/ |