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2 results on '"IAP-retrotransposon"'

1. Nonlinear gene expression‐phenotype relationships contribute to variation and clefting in the A/WySn mouse

Author

Green, Rebecca M, Leach, Courtney L, Diewert, Virginia M, Aponte, Jose David, Schmidt, Eric J, Cheverud, James M, Roseman, Charles C, Young, Nathan M, Marcucio, Ralph S, and Hallgrimsson, Benedikt

Subjects
Biological Sciences, Genetics, Dental/Oral and Craniofacial Disease, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Animals, Biological Variation, Individual, Cleft Lip, Cleft Palate, DNA Methylation, Disease Models, Animal, Embryo, Mammalian, Face, Gene Expression Regulation, Developmental, Genetic Association Studies, Genetic Heterogeneity, Humans, Mice, Mice, Transgenic, Palate, Phenotype, Retroelements, Wnt Proteins, CL, P, facial development, IAP-retrotransposon, methylation, Wnt9b, CL/P, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology, Bioinformatics and computational biology, Evolutionary biology
Abstract

BackgroundCleft lip and palate is one of the most common human birth defects, but the underlying etiology is poorly understood. The A/WySn mouse is a spontaneously occurring model of multigenic clefting in which 20% to 30% of individuals develop an orofacial cleft. Recent work has shown altered methylation at a specific retrotransposon insertion downstream of the Wnt9b locus in clefting animals, which results in decreased Wnt9b expression.ResultsUsing a newly developed protocol that allows us to measure morphology, gene expression, and DNA methylation in the same embryo, we relate gene expression in an individual embryo directly to its three-dimensional morphology for the first time. We find that methylation at the retrotransposon relates to Wnt9b expression and morphology. IAP methylation relates to shape of the nasal process in a manner consistent with clefting. Embryos with low IAP methylation exhibit increased among-individual variance in facial shape.ConclusionsMethylation and gene expression relate nonlinearly to nasal process morphology. Individuals at one end of a continuum of phenotypic states display a clinical phenotype and increased phenotypic variation. Variable penetrance and expressivity in this model is likely determined both by among-individual variation in methylation and changes in phenotypic robustness along the underlying liability distribution for orofacial clefting.

Published
2019

2. Nonlinear gene expression-phenotype relationships contribute to variation and clefting in the A/WySn mouse

Author

Rebecca M. Green, Virginia M. Diewert, Courtney L. Leach, Nathan M. Young, Eric J. Schmidt, Ralph S. Marcucio, Jose D Aponte, Charles C. Roseman, Benedikt Hallgrímsson, and James M. Cheverud

Subjects
0301 basic medicine, CL/P, Retrotransposon, Medical and Health Sciences, Transgenic, Mice, 0302 clinical medicine, Gene expression, 2.1 Biological and endogenous factors, Developmental, Aetiology, 10. No inequality, Genetics, Biological Variation, Individual, Gene Expression Regulation, Developmental, Biological Variation, Embryo, Methylation, Biological Sciences, Phenotype, Penetrance, Cleft Palate, DNA methylation, CL, Biotechnology, Retroelements, IAP-retrotransposon, Cleft Lip, Locus (genetics), Mice, Transgenic, Individual, Biology, facial development, Article, 03 medical and health sciences, Genetic Heterogeneity, Wnt9b, Animals, Humans, Dental/Oral and Craniofacial Disease, Genetic Association Studies, Palate, Animal, Mammalian, Human Genome, DNA Methylation, Embryo, Mammalian, Wnt Proteins, Disease Models, Animal, 030104 developmental biology, Gene Expression Regulation, Face, Disease Models, methylation, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Background Cleft lip and palate is one of the most common human birth defects, but the underlying etiology is poorly understood. The A/WySn mouse is a spontaneously occurring model of multigenic clefting in which 20% to 30% of individuals develop an orofacial cleft. Recent work has shown altered methylation at a specific retrotransposon insertion downstream of the Wnt9b locus in clefting animals, which results in decreased Wnt9b expression. Results Using a newly developed protocol that allows us to measure morphology, gene expression, and DNA methylation in the same embryo, we relate gene expression in an individual embryo directly to its three-dimensional morphology for the first time. We find that methylation at the retrotransposon relates to Wnt9b expression and morphology. IAP methylation relates to shape of the nasal process in a manner consistent with clefting. Embryos with low IAP methylation exhibit increased among-individual variance in facial shape. Conclusions Methylation and gene expression relate nonlinearly to nasal process morphology. Individuals at one end of a continuum of phenotypic states display a clinical phenotype and increased phenotypic variation. Variable penetrance and expressivity in this model is likely determined both by among-individual variation in methylation and changes in phenotypic robustness along the underlying liability distribution for orofacial clefting.

Published
2019

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