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Targeted Sequencing and Meta-Analysis of Preterm Birth.

Uzun A, Schuster J, McGonnigal B, Schorl C, Dewan A, Padbury J - PLoS ONE (2016)

Bottom Line: We compared variants identified by targeted sequencing of women with 2-3 generations of preterm birth with term controls without history of preterm birth.Additionally, SERPINB8, AZU1 and WASF3 showed significant differences in abundance of variants in the univariate comparison of cases and controls.The biological processes impacted by these gene sets included: cell motility, migration and locomotion; response to glucocorticoid stimulus; signal transduction; metabolic regulation and control of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, United States of America.

ABSTRACT
Understanding the genetic contribution(s) to the risk of preterm birth may lead to the development of interventions for treatment, prediction and prevention. Twin studies suggest heritability of preterm birth is 36-40%. Large epidemiological analyses support a primary maternal origin for recurrence of preterm birth, with little effect of paternal or fetal genetic factors. We exploited an "extreme phenotype" of preterm birth to leverage the likelihood of genetic discovery. We compared variants identified by targeted sequencing of women with 2-3 generations of preterm birth with term controls without history of preterm birth. We used a meta-genomic, bi-clustering algorithm to identify gene sets coordinately associated with preterm birth. We identified 33 genes including 217 variants from 5 modules that were significantly different between cases and controls. The most frequently identified and connected genes in the exome library were IGF1, ATM and IQGAP2. Likewise, SOS1, RAF1 and AKT3 were most frequent in the haplotype library. Additionally, SERPINB8, AZU1 and WASF3 showed significant differences in abundance of variants in the univariate comparison of cases and controls. The biological processes impacted by these gene sets included: cell motility, migration and locomotion; response to glucocorticoid stimulus; signal transduction; metabolic regulation and control of apoptosis.

No MeSH data available.


Related in: MedlinePlus

Ontology groups.Diagram showing the clusters of terms from the Gene Ontology analysis for biological processes related to preterm birth. Gene Ontology Database terms for biological processes shown in clusters A thru I are detailed in S3 Table.
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pone.0155021.g005: Ontology groups.Diagram showing the clusters of terms from the Gene Ontology analysis for biological processes related to preterm birth. Gene Ontology Database terms for biological processes shown in clusters A thru I are detailed in S3 Table.

Mentions: We performed gene ontology analysis to identify the biological processes for the genes belonging to the significant modules [44]. A total of 80 groups of biological processes were identified which segregated into 9 individual and overlapping clusters, S3 Table. Fig 5 shows these individual and shared ontology groups. The most abundant association was with mechanisms regulating programmed cell death. Likewise, control of cell motility, migration and cell cycle regulation were associated with several of the most highly connected genes in Module 4 of the exome library. Metabolic processes, phosphate and lipid metabolism, protein phosphorylation and various forms of signal transduction were common biological functions attributed to the other most highly connected genes from the exome library. Similarly, the results from the gene ontology analysis of the haplotype library showed a high degree of association with cellular metabolism, signal transduction and nucleic acid metabolism. Regulation of immune cell system development, responses to glucocorticoid signaling, signal transduction pathways in immune regulatory cells and regulation of smooth muscle cell proliferation were associated with the genes identified in the haplotype library.


Targeted Sequencing and Meta-Analysis of Preterm Birth.

Uzun A, Schuster J, McGonnigal B, Schorl C, Dewan A, Padbury J - PLoS ONE (2016)

Ontology groups.Diagram showing the clusters of terms from the Gene Ontology analysis for biological processes related to preterm birth. Gene Ontology Database terms for biological processes shown in clusters A thru I are detailed in S3 Table.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4862658&req=5

pone.0155021.g005: Ontology groups.Diagram showing the clusters of terms from the Gene Ontology analysis for biological processes related to preterm birth. Gene Ontology Database terms for biological processes shown in clusters A thru I are detailed in S3 Table.
Mentions: We performed gene ontology analysis to identify the biological processes for the genes belonging to the significant modules [44]. A total of 80 groups of biological processes were identified which segregated into 9 individual and overlapping clusters, S3 Table. Fig 5 shows these individual and shared ontology groups. The most abundant association was with mechanisms regulating programmed cell death. Likewise, control of cell motility, migration and cell cycle regulation were associated with several of the most highly connected genes in Module 4 of the exome library. Metabolic processes, phosphate and lipid metabolism, protein phosphorylation and various forms of signal transduction were common biological functions attributed to the other most highly connected genes from the exome library. Similarly, the results from the gene ontology analysis of the haplotype library showed a high degree of association with cellular metabolism, signal transduction and nucleic acid metabolism. Regulation of immune cell system development, responses to glucocorticoid signaling, signal transduction pathways in immune regulatory cells and regulation of smooth muscle cell proliferation were associated with the genes identified in the haplotype library.

Bottom Line: We compared variants identified by targeted sequencing of women with 2-3 generations of preterm birth with term controls without history of preterm birth.Additionally, SERPINB8, AZU1 and WASF3 showed significant differences in abundance of variants in the univariate comparison of cases and controls.The biological processes impacted by these gene sets included: cell motility, migration and locomotion; response to glucocorticoid stimulus; signal transduction; metabolic regulation and control of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, United States of America.

ABSTRACT
Understanding the genetic contribution(s) to the risk of preterm birth may lead to the development of interventions for treatment, prediction and prevention. Twin studies suggest heritability of preterm birth is 36-40%. Large epidemiological analyses support a primary maternal origin for recurrence of preterm birth, with little effect of paternal or fetal genetic factors. We exploited an "extreme phenotype" of preterm birth to leverage the likelihood of genetic discovery. We compared variants identified by targeted sequencing of women with 2-3 generations of preterm birth with term controls without history of preterm birth. We used a meta-genomic, bi-clustering algorithm to identify gene sets coordinately associated with preterm birth. We identified 33 genes including 217 variants from 5 modules that were significantly different between cases and controls. The most frequently identified and connected genes in the exome library were IGF1, ATM and IQGAP2. Likewise, SOS1, RAF1 and AKT3 were most frequent in the haplotype library. Additionally, SERPINB8, AZU1 and WASF3 showed significant differences in abundance of variants in the univariate comparison of cases and controls. The biological processes impacted by these gene sets included: cell motility, migration and locomotion; response to glucocorticoid stimulus; signal transduction; metabolic regulation and control of apoptosis.

No MeSH data available.


Related in: MedlinePlus