Copy number variation in bronchopulmonary dysplasia

Hoffmann, Thomas J.; Shaw, Gary M.; Stevenson, David K.; Wang, Hui; Quaintance, Cecele C.; Oehlert, John; Jelliffe‐Pawlowski, Laura L.; Gould, Jeffrey B.; Witte, John S.; O’Brodovich, Hugh

doi:10.1002/ajmg.a.36659

Cited by 15 publications

(11 citation statements)

References 13 publications

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“…not unique to this single study cohort, we would expect to observe similar findings in an independent study cohort. Because current and available genome-wide association studies (GWAS) were mostly focused on maternal genomes, and the GWAS signals themselves are hard to interpret (because of linkage disequilibrium), we examined copy number variants (CNVs) from our recent PTB study[31], where, 1,631 PTB (gestational age, 25 0 –29 6/7 weeks) infant genomes were genotyped for CNVs (a subset of the newborns were diagnosed with bronchopulmonary dysplasia, a common pulmonary morbidity in PTB). The original study defined 131 broad large CNV regions (CNVRs, 74 deletions and 57 duplications) across all the PTB infants by collapsing SNPs of comparable statistical significance within a 1MB window[31].…”

Section: Resultsmentioning

confidence: 99%

“…We obtained copy number variants (CNVs) data from our previous study, where CNVs were identified in 1,631 PTB infants (gestational age, 25 0 −29 6/7 weeks)[31]. The original study defined 131 large CNV regions (CNVRs, 74 deletions and 57 duplications) across all the PTB infants by collapsing SNPs of comparable statistical significance within a 1MB window.…”

Section: Methodsmentioning

confidence: 99%

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Fetal de novo mutations and preterm birth

Oehlert

Snyder

et al. 2017

PLoS Genet

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Preterm birth (PTB) affects ~12% of pregnancies in the US. Despite its high mortality and morbidity, the molecular etiology underlying PTB has been unclear. Numerous studies have been devoted to identifying genetic factors in maternal and fetal genomes, but so far few genomic loci have been associated with PTB. By analyzing whole-genome sequencing data from 816 trio families, for the first time, we observed the role of fetal de novo mutations in PTB. We observed a significant increase in de novo mutation burden in PTB fetal genomes. Our genomic analyses further revealed that affected genes by PTB de novo mutations were dosage sensitive, intolerant to genomic deletions, and their mouse orthologs were likely developmentally essential. These genes were significantly involved in early fetal brain development, which was further supported by our analysis of copy number variants identified from an independent PTB cohort. Our study indicates a new mechanism in PTB occurrence independently contributed from fetal genomes, and thus opens a new avenue for future PTB research.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Fetal de novo mutations and preterm birth

Oehlert

Snyder

et al. 2017

PLoS Genet

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“… 114 A number of additional studies, evaluating exome sequencing in extremes of disease, epigenomic regulation, transcriptome responses to exposures such as hyperoxia, and pathway analyses are ongoing to identify gene and gene regulatory susceptibility factors involved in pathogenesis of BPD. 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 …”

Section: Susceptibility Factors For Enhanced Inflammationmentioning

confidence: 99%

Postnatal Infections and Immunology Affecting Chronic Lung Disease of Prematurity

Pryhuber

2015

Clinics in Perinatology

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Synopsis Premature infants suffer significant respiratory morbidity during infancy with long-term negative consequences on health, quality of life, and health care costs. Enhanced susceptibility to a variety of infections and inflammation play a large role in early and prolonged lung disease following premature birth, though the mechanisms of susceptibility and immune dysregulation are active areas of research. This chapter will review aspects of host-pathogen interactions and immune responses that are altered by preterm birth and that impact chronic respiratory morbidity in these children.

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“…72,73 However, no common polymorphisms have been identified between three genome-wide association studies of BPD patients, 74–76 nor have loci been identified in a large copy number variant study. 77 However, rare variant studies performed using exome sequencing suggest that populations with BPD may have an excess of rare variants in genes associated with host defense, extracellular matrix breakdown, collagen fibril organization, morphogenesis of embryonic epithelium, and regulation of Wnt signaling pathway. 78,79…”

Section: Genetic Factors In Bpd and Copdmentioning

confidence: 99%

Bronchopulmonary dysplasia: what are its links to COPD?

McGrath‐Morrow¹,

Collaco

2019

Ther Adv Respir Dis

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Emerging evidence suggests that adverse early life events can affect long-term health trajectories throughout life. Preterm birth, in particular, is a significant early life event that affects approximately 10% of live births. Worldwide, prematurity is the number one cause of death in children less than 5 years of age and has been shown to disrupt normal lung development with lasting effects into adult life. Along with impaired lung development, interventions used to support gas exchange and other sequelae of prematurity can lead to the development of bronchopulmonary dysplasia (BPD). BPD is a chronic respiratory disease of infancy characterized by alveolar simplification, small airways disease, and pulmonary vascular changes. Although many survivors of BPD improve with age, survivors of BPD often have chronic lung disease characterized by airflow obstruction and intermittent pulmonary exacerbations. Long-term lung function trajectories as measured by FEV1 can be lower in children and adults with a history BPD. In this review, we discuss the epidemiology and manifestations of BPD and its long-term consequences throughout childhood and into adulthood. Available evidence suggests that disrupted lung development, genetic susceptibility and subsequent environment and infectious events that occur in prenatal and postnatal life likely increase the predisposition of children with BPD to develop early onset chronic obstructive pulmonary disease (COPD). The reviews of this paper are available via the supplemental material section.

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Copy number variation in bronchopulmonary dysplasia

Cited by 15 publications

References 13 publications

Fetal de novo mutations and preterm birth

Fetal de novo mutations and preterm birth

Postnatal Infections and Immunology Affecting Chronic Lung Disease of Prematurity

Bronchopulmonary dysplasia: what are its links to COPD?

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