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Alternative RNA Splicing02:18

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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases. 
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Detecting Allele-Specific Alternative Splicing from Population-Scale RNA-Seq Data.

Levon Demirdjian1, Yungang Xu2, Emad Bahrami-Samani2

  • 1Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Statistics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

American Journal of Human Genetics
|August 12, 2020
PubMed
Summary
This summary is machine-generated.

PAIRADISE is a new method for detecting allele-specific alternative splicing (ASAS) from RNA sequencing data. It analyzes multiple individuals to find ASAS events linked to complex traits and diseases.

Keywords:
RNA sequencingallelealternative splicingexongenetic variationmRNA isoform

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Area of Science:

  • Genomics
  • Transcriptomics
  • Bioinformatics

Background:

  • RNA sequencing (RNA-seq) is crucial for understanding human transcriptome variation.
  • Detecting allele-specific alternative splicing (ASAS) is challenging with conventional methods.

Purpose of the Study:

  • Introduce PAIRADISE (Paired Replicate Analysis of Allelic Differential Splicing Events) for robust ASAS detection.
  • Aggregate ASAS signals across multiple individuals and paired replicates.

Main Methods:

  • Formulate ASAS detection as a statistical problem using paired replicates.
  • Utilize heterozygous SNPs to treat individuals as replicates.
  • Compare PAIRADISE against alternative statistical models in simulations.

Main Results:

  • PAIRADISE demonstrates superior performance over existing statistical models in simulations.
  • Successfully detected ASAS events associated with GWAS signals for complex traits.
  • Identified the impact of rare variants on alternative splicing.

Conclusions:

  • PAIRADISE is an effective computational tool for analyzing population-scale ASAS.
  • Facilitates the study of genetic variation and phenotypic associations of alternative splicing.