دورية أكاديمية
Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth
| العنوان: | Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth |
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| المؤلفون: | Hamvas, Aaron, Feng, Rui, Bi, Yingtao, Wang, Fan, Bhattacharya, Soumyaroop, Mereness, Jared, Kaushal, Madhurima, Cotten, C Michael, Ballard, Philip L, Mariani, Thomas J |
| المصدر: | Journal Articles |
| بيانات النشر: | DigitalCommons@TMC |
| سنة النشر: | 2018 |
| المجموعة: | Houston Academy of Medicine-Texas Medical Center (HAM-TMC): DigitalCommons@The Texas Medical Center |
| مصطلحات موضوعية: | Bronchopulmonary Dysplasia, Case-Control Studies, DNA, Female, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Gestational Age, Humans, Infant, Newborn, Premature, Male, Exome Sequencing, Medicine and Health Sciences |
| الوصف: | BACKGROUND: Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk. RESULTS: The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for association between disease status and individual common variants, screened for rare variants exclusive to either affected or unaffected subjects, and tested the combined association of variants across gene loci. Pathway analysis was performed and disease-related expression patterns were assessed. Marginal association with BPD was observed for numerous common and rare variants. We identified 345 genes with variants unique to BPD-affected preterm subjects, and 292 genes with variants unique to our unaffected preterm subjects. Of these unique variants, 28 (19 in the affected cohort and 9 in unaffected cohort) replicate a prior WES study of BPD-associated variants. Pathway analysis of sets of variants, informed by disease-related gene expression, implicated protein kinase A, MAPK and Neuregulin/epidermal growth factor receptor signaling. CONCLUSIONS: We identified novel genes and associated pathways that may play an important role in susceptibility/resilience for the development of lung disease in preterm infants. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.library.tmc.edu/uthmed_docs/380Test; https://digitalcommons.library.tmc.edu/context/uthmed_docs/article/1379/viewcontent/12863_2018_Article_679.pdfTest |
| الإتاحة: | https://digitalcommons.library.tmc.edu/uthmed_docs/380Test https://digitalcommons.library.tmc.edu/context/uthmed_docs/article/1379/viewcontent/12863_2018_Article_679.pdfTest |
| رقم الانضمام: | edsbas.C18DA2EC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |