AUG 21, 2013 4:00 PM PDT

Lighting up the dark matter of the genome: Unravelling the roles of noncoding DNA in disease and development

C.E. Credits: CE
Speaker

Abstract

Approximately 98% of the human genome comprises noncoding DNA, the function of which is largely unknown. Intriguingly, more than 85% of single nucleotide polymorphisms identified to be associated with disease in genome-wide studies (GWAS) occur within noncoding regions, suggesting that examining the role of these regions of the genome will be important for understanding and potentially treating disease. The relatively recent discovery of widespread transcription of potentially functional long noncoding RNAs (lncRNAs) from the mammalian genome led us to investigate whether or not GWAS hits in noncoding regions could be reconciled by the transcription of regulatory RNAs from these loci. LncRNAs typically show highly developmental-stage- and tissue-specific expression, and therefore cannot be easily detected by conventional RNA-Seq, which requires exponentially greater depth to detect increasingly rare transcripts. To overcome this problem, we developed a technique termed RNA-Capture-Seq, which combines custom capture tiling arrays with RNA sequencing to target transcription arising from specific areas of the genome. We have used this approach to target 300 chromosomal regions identified by GWAS. Using RNA from diverse human tissues, we identify thousands of novel transcripts associated with the majority of the targeted regions. To further realise the potential of the method to understand specific diseases, we have designed further capture arrays to target GWAS regions linked to specific diseases. For these experiments, RNA from biologically relevant normal and disease tissues were used to look for novel transcripts. As a result, we have identified numerous new lncRNAs whose expression appears to be specifically associated with disease and arise from disease-associated regions. Although functional investigation of these transcripts is still underway, we propose that the results of these experiments bring an intriguing new perspective into our understanding of how information in the genome is encoded and has considerable potential to identify novel regulators, which may prove valuable as biomarkers and therapeutic targets, involved in disease and development.


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AUG 21, 2013 4:00 PM PDT

Lighting up the dark matter of the genome: Unravelling the roles of noncoding DNA in disease and development

C.E. Credits: CE

Specialty

Antibodies

Virology

Immunology

Dna Sequencing

Personalized Medicine

Clinical Diagnostics

Immunity

Cancer Diagnostics

Immunotherapy

Bioinformatics

Flow Cytometry

Immuno-Oncology

Gene Expression

Dna

Big Data

Geography

Europe100%

Registration Source

Website Visitors100%

Job Title

Student100%

Organization

Academic Institution100%


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