Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study

Paola Carrera, Chiara Di Resta, Chiara Volonteri, Emanuela Castiglioni, Silvia Bonfiglio, Dejan Lazarevic, Davide Cittaro, Elia Stupka, Maurizio Ferrari, Marco Somaschini, Rosario Magaldi, Matteo Rinaldi, Gianfranco Maffei, Mauro Stronati, Chryssoula Tzialla, Alessandro Borghesi, Paolo Tagliabue, Tiziana Fedeli, Marco Citterio, Fabio MoscaMariarosa Colnaghi, Anna Lavizzari, Massimo Agosti, Gaia Francescato, Giulia Pomero, Cristina Dalmazzo, Antonio Boldrini, Rosa Scaramuzzo, Enrico Bertino, Silvia Borgione, Claudio Martano, Virgilio Carnielli, Stefano Nobile, Antonietta Auriemma, Cristina Bellan, Giuseppe Carrera, Chiara Zambetti, Riccardo Pucello, Sara Palatta

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. Materials and methods: We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. Results: By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (. TLR) family. All of them have been confirmed with Sanger sequencing. Conclusions: Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants.Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalClinica Chimica Acta
Volume451
DOIs
Publication statusPublished - Oct 15 2014

Fingerprint

Exome
Bronchopulmonary Dysplasia
Genes
Newborn Infant
Pulmonary diseases
Toll-Like Receptors
Low Birth Weight Infant
Lung Diseases
Chronic Disease

Keywords

  • Bronchopulmonary dysplasia
  • Exome sequencing
  • Genetics

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns : A pilot study. / Carrera, Paola; Di Resta, Chiara; Volonteri, Chiara; Castiglioni, Emanuela; Bonfiglio, Silvia; Lazarevic, Dejan; Cittaro, Davide; Stupka, Elia; Ferrari, Maurizio; Somaschini, Marco; Magaldi, Rosario; Rinaldi, Matteo; Maffei, Gianfranco; Stronati, Mauro; Tzialla, Chryssoula; Borghesi, Alessandro; Tagliabue, Paolo; Fedeli, Tiziana; Citterio, Marco; Mosca, Fabio; Colnaghi, Mariarosa; Lavizzari, Anna; Agosti, Massimo; Francescato, Gaia; Pomero, Giulia; Dalmazzo, Cristina; Boldrini, Antonio; Scaramuzzo, Rosa; Bertino, Enrico; Borgione, Silvia; Martano, Claudio; Carnielli, Virgilio; Nobile, Stefano; Auriemma, Antonietta; Bellan, Cristina; Carrera, Giuseppe; Zambetti, Chiara; Pucello, Riccardo; Palatta, Sara.

In: Clinica Chimica Acta, Vol. 451, 15.10.2014, p. 39-45.

Research output: Contribution to journalArticle

Carrera, P, Di Resta, C, Volonteri, C, Castiglioni, E, Bonfiglio, S, Lazarevic, D, Cittaro, D, Stupka, E, Ferrari, M, Somaschini, M, Magaldi, R, Rinaldi, M, Maffei, G, Stronati, M, Tzialla, C, Borghesi, A, Tagliabue, P, Fedeli, T, Citterio, M, Mosca, F, Colnaghi, M, Lavizzari, A, Agosti, M, Francescato, G, Pomero, G, Dalmazzo, C, Boldrini, A, Scaramuzzo, R, Bertino, E, Borgione, S, Martano, C, Carnielli, V, Nobile, S, Auriemma, A, Bellan, C, Carrera, G, Zambetti, C, Pucello, R & Palatta, S 2014, 'Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study', Clinica Chimica Acta, vol. 451, pp. 39-45. https://doi.org/10.1016/j.cca.2015.01.001
Carrera, Paola ; Di Resta, Chiara ; Volonteri, Chiara ; Castiglioni, Emanuela ; Bonfiglio, Silvia ; Lazarevic, Dejan ; Cittaro, Davide ; Stupka, Elia ; Ferrari, Maurizio ; Somaschini, Marco ; Magaldi, Rosario ; Rinaldi, Matteo ; Maffei, Gianfranco ; Stronati, Mauro ; Tzialla, Chryssoula ; Borghesi, Alessandro ; Tagliabue, Paolo ; Fedeli, Tiziana ; Citterio, Marco ; Mosca, Fabio ; Colnaghi, Mariarosa ; Lavizzari, Anna ; Agosti, Massimo ; Francescato, Gaia ; Pomero, Giulia ; Dalmazzo, Cristina ; Boldrini, Antonio ; Scaramuzzo, Rosa ; Bertino, Enrico ; Borgione, Silvia ; Martano, Claudio ; Carnielli, Virgilio ; Nobile, Stefano ; Auriemma, Antonietta ; Bellan, Cristina ; Carrera, Giuseppe ; Zambetti, Chiara ; Pucello, Riccardo ; Palatta, Sara. / Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns : A pilot study. In: Clinica Chimica Acta. 2014 ; Vol. 451. pp. 39-45.
@article{849d125f2bdf4d1fa91d12c1dcaf082f,
title = "Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study",
abstract = "Background: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. Materials and methods: We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. Results: By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (. TLR) family. All of them have been confirmed with Sanger sequencing. Conclusions: Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants.Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.",
keywords = "Bronchopulmonary dysplasia, Exome sequencing, Genetics",
author = "Paola Carrera and {Di Resta}, Chiara and Chiara Volonteri and Emanuela Castiglioni and Silvia Bonfiglio and Dejan Lazarevic and Davide Cittaro and Elia Stupka and Maurizio Ferrari and Marco Somaschini and Rosario Magaldi and Matteo Rinaldi and Gianfranco Maffei and Mauro Stronati and Chryssoula Tzialla and Alessandro Borghesi and Paolo Tagliabue and Tiziana Fedeli and Marco Citterio and Fabio Mosca and Mariarosa Colnaghi and Anna Lavizzari and Massimo Agosti and Gaia Francescato and Giulia Pomero and Cristina Dalmazzo and Antonio Boldrini and Rosa Scaramuzzo and Enrico Bertino and Silvia Borgione and Claudio Martano and Virgilio Carnielli and Stefano Nobile and Antonietta Auriemma and Cristina Bellan and Giuseppe Carrera and Chiara Zambetti and Riccardo Pucello and Sara Palatta",
year = "2014",
month = "10",
day = "15",
doi = "10.1016/j.cca.2015.01.001",
language = "English",
volume = "451",
pages = "39--45",
journal = "Clinica Chimica Acta",
issn = "0009-8981",
publisher = "Elsevier",

}

TY - JOUR

T1 - Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns

T2 - A pilot study

AU - Carrera, Paola

AU - Di Resta, Chiara

AU - Volonteri, Chiara

AU - Castiglioni, Emanuela

AU - Bonfiglio, Silvia

AU - Lazarevic, Dejan

AU - Cittaro, Davide

AU - Stupka, Elia

AU - Ferrari, Maurizio

AU - Somaschini, Marco

AU - Magaldi, Rosario

AU - Rinaldi, Matteo

AU - Maffei, Gianfranco

AU - Stronati, Mauro

AU - Tzialla, Chryssoula

AU - Borghesi, Alessandro

AU - Tagliabue, Paolo

AU - Fedeli, Tiziana

AU - Citterio, Marco

AU - Mosca, Fabio

AU - Colnaghi, Mariarosa

AU - Lavizzari, Anna

AU - Agosti, Massimo

AU - Francescato, Gaia

AU - Pomero, Giulia

AU - Dalmazzo, Cristina

AU - Boldrini, Antonio

AU - Scaramuzzo, Rosa

AU - Bertino, Enrico

AU - Borgione, Silvia

AU - Martano, Claudio

AU - Carnielli, Virgilio

AU - Nobile, Stefano

AU - Auriemma, Antonietta

AU - Bellan, Cristina

AU - Carrera, Giuseppe

AU - Zambetti, Chiara

AU - Pucello, Riccardo

AU - Palatta, Sara

PY - 2014/10/15

Y1 - 2014/10/15

N2 - Background: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. Materials and methods: We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. Results: By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (. TLR) family. All of them have been confirmed with Sanger sequencing. Conclusions: Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants.Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.

AB - Background: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. Materials and methods: We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. Results: By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (. TLR) family. All of them have been confirmed with Sanger sequencing. Conclusions: Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants.Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.

KW - Bronchopulmonary dysplasia

KW - Exome sequencing

KW - Genetics

UR - http://www.scopus.com/inward/record.url?scp=84945473845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945473845&partnerID=8YFLogxK

U2 - 10.1016/j.cca.2015.01.001

DO - 10.1016/j.cca.2015.01.001

M3 - Article

AN - SCOPUS:84945473845

VL - 451

SP - 39

EP - 45

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

SN - 0009-8981

ER -