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Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq
Published on: March 12, 2021
Global survey of genomic imprinting by transcriptome sequencing
Tomas Babak1, Brian Deveale, Christopher Armour
1Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck & Co., 401 Terry Avenue North, Seattle, WA 98109, USA.
Current Biology : CB
|November 26, 2008
Summary
Researchers mapped genome-wide imprinted transcription using transcriptome sequencing, identifying six new imprinted genes. This method reveals novel noncoding RNAs and offers a comprehensive approach to studying genomic imprinting in normal animals.
Area of Science:
- Genomics
- Developmental Biology
- Epigenetics
Background:
- Genomic imprinting is an epigenetic phenomenon that restricts gene expression to either the paternal or maternal allele.
- Previous identification of imprinted transcripts (~90 in mouse) relied heavily on phenotype-driven assays and analysis of uniparental disomies.
- Existing methods often focus on specific loci or transcripts, limiting comprehensive genome-wide discovery.
Purpose of the Study:
- To develop and apply a transcriptome sequencing approach for genome-wide mapping of imprinted transcription in physiologically normal mouse embryos.
- To distinguish parent-of-origin allelic bias from strain-specific bias to accurately identify imprinted loci.
- To discover novel imprinted genes and noncoding RNAs within known imprinted loci.
Main Methods:
- Utilized selective priming and parallel sequencing to analyze allelic bias across whole transcriptomes.
- Employed a reciprocal cross strategy in mice to differentiate parent-of-origin effects from genetic background variations.
- Analyzed data from embryonic day 9.5 (E9.5) developmental stage.
Main Results:
- Constructed a comprehensive genome-wide map of imprinted transcription, locating over 80% of known imprinted loci.
- Identified and confirmed six novel imprinted genes.
- Discovered that over half of imprinted single-nucleotide polymorphisms (SNPs) at E9.5 did not overlap previously known imprinted transcripts, including novel noncoding RNAs within known imprinted regions (e.g., a maternally expressed antisense transcript at the Grb10 locus).
Conclusions:
- Transcriptome sequencing is a feasible and powerful method for mapping imprinted gene expression genome-wide in normal animals.
- This approach significantly expands the discovery of imprinted transcripts, including noncoding RNAs, and provides a more objective and comprehensive way to study genomic imprinting.
- Future studies can leverage this methodology to investigate imprinting without locus or transcript restrictions.
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