Assessing parent-of-origin transcriptional effects in Xenopus laevis

评估非洲爪蟾的亲本转录效应

基本信息

批准号：
8911356
负责人：
Alexander Gimelbrant
金额：
$ 20.84万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-15 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8911356
关键词：
Affect African Alleles Allelic Imbalance Amphibia Angelman Syndrome Angiosperms Animals Beckwith-Wiedemann Syndrome Biochemistry Biological Assay Biological Models Biology Candidate Disease Gene Cellular biology Collaborations Complement Complex Data Development Developmental Biology Diploidy Disease Embryo Employee Strikes Epigenetic Process Exhibits Gene Expression Gene Expression Profile Generations Genes Genetic Polymorphism Genomic Imprinting Genotype Goals Health Heterozygote Human Inbreeding Individual Inherited Lead Link Live Birth Mammals Molecular Biology Mothers Nucleotides Parents Phenotype Placenta Play Post-Translational Protein Processing Proteomics RNA Sequences Regulator Genes Resources Role Seeds Study models Surveys Tadpoles Technology Vertebrates Xenopus Xenopus laevis Xenopus sp.base deep sequencing design developmental disease gene function imprint in vivo infancy mouse model research study tool trait transcriptome sequencing transcriptomics treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Parent-of-origin effects are epigenetic phenomena that appear as phenotypic differences between heterozygotes depending on the allelic parent of origin. The primary epigenetic phenomenon that can lead to the parent-of-origin effects is genomic imprinting. Some imprinted loci are expressed from the maternal copy only, while others from the paternal copy. Imprinted genes play an important part in a number of complex traits, notably in early development. Though the taxonomic distribution of gene imprinting remains uncertain, a widely-accepted view holds that among animals it is limited to mammals, and most studies had been performed in mouse models. There are significant technical challenges in assessment of imprinting in a wider variety of species. A major limiting factor is lack of multiple inbred lines with significant nucleotide-level differences between them, since the most direct way to identify imprinting involves generation of reciprocal crosses between such lines. In addition, transcriptome-wide surveys of allele-specific expression have only recently become feasible, and the analytical and statistical tools for analysis of such data are still in thir infancy. We have pioneered several technologies for the analysis of allele-specific expression. In collaboration with experts in the biology of the African clawed frog, Xenopus laevis, we have performed preliminary RNA sequencing experiments on mixed crosses between inbred lines that strongly suggest that there are genes in X. laevis that exhibit parent-of-origin imprinting. The goal of this project is to carefully and thoroughly assess this striking hypothesis. In order t do that, we will execute a "zoom in sequencing" approach which consists of a "wide but shallow" round where we screen for candidate genes, complemented by a "deep but narrow" round where we focus in detail on the allelic bias of a set of candidate genes. Identification of parent of-origin imprinting in an amphibian would represent a significant conceptual advance in understanding the evolutionary origins of that epigenetic mechanism and its role in development. Moreover, Xenopus has long been an important tool for in vivo studies in molecular, cell, and developmental biology of vertebrate animals. It is the only vertebrate model system that allows for high-throughput in vivo analyses of gene function and biochemistry. Xenopus as a model for the study of imprinting would allow for the development of screens to identify new targets important for disease and for the design of new therapies involving imprinted genes.