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A genome resource to address mechanisms of developmental programming: determination of the fetal sheep heart transcriptome
Author(s) -
Cox Laura A.,
Glenn Jeremy P.,
Spradling Kimberly D.,
Nijland Mark J.,
Garcia Roy,
Nathanielsz Peter W.,
Ford Stephen P.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.222398
Subject(s) - transcriptome , biology , genome , fetus , computational biology , gene , genetics , bioinformatics , pregnancy , gene expression
Key points• The sheep is a valuable model for biomedical research, including the study of developmental programming mechanisms that are critical to better understand gene–environment interactions responsible for each individual's phenotype and predisposition to chronic diseases. • The lack of genetic and genomic resources for the sheep has limited the power of this model, impeding progress in emerging areas of pregnancy biology and other fields of biomedical research. • In this study, we examined the expressed fetal sheep heart transcriptome using high‐throughput sequencing technologies. • We identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms. • The data presented in this study provide a foundation of genetic information on the repertoire of genes expressed in the fetal heart transcriptome, which will augment annotation and assembly of the sheep genome.Abstract The pregnant sheep has provided seminal insights into reproduction related to animal and human development (ovarian function, fertility, implantation, fetal growth, parturition and lactation). Fetal sheep physiology has been extensively studied since 1950, contributing significantly to the basis for our understanding of many aspects of fetal development and behaviour that remain in use in clinical practice today. Understanding mechanisms requires the combination of systems approaches uniquely available in fetal sheep with the power of genomic studies. Absence of the full range of sheep genomic resources has limited the full realization of the power of this model, impeding progress in emerging areas of pregnancy biology such as developmental programming. We have examined the expressed fetal sheep heart transcriptome using high‐throughput sequencing technologies. In so doing we identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms. Genes with the highest expression levels and with novel exons in the fetal heart transcriptome are known to play central roles in muscle development. We show that high‐throughput sequencing methods can generate extensive transcriptome information in the absence of an assembled and annotated genome for that species. The gene sequence data obtained provide a unique genomic resource for sheep specific genetic technology development and, combined with the polymorphism data, augment annotation and assembly of the sheep genome. In addition, identification and pathway analysis of novel fetal sheep heart transcriptome splice variants is a first step towards revealing mechanisms of genetic variation and gene environment interactions during fetal heart development.