intergenic long noncoding RNAs Project for Solving Biological Problems that require Math Jennifer Tan Intergenic long noncoding RNAs Pervasive transcription of eukaryotic genomes not just in proteincoding regions ID: 1047304
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1. Identification of obesity-associated intergenic long noncoding RNAsProject for “Solving Biological Problems that require Math”Jennifer Tan
2. Intergenic long noncoding RNAsPervasive transcription of eukaryotic genomes (not just in protein-coding regions)Large proportion of functional information is embedded within noncoding regions
3. Intergenic long noncoding RNAsPervasive transcription of eukaryotic genomes (not just in protein-coding regions)Large proportion of functional information is embedded within noncoding regions Rinn and Chang, 2012
4. Intergenic long noncoding RNAs> 200 bpNo apparent open reading frame (ORF)Pol II transcribed, capped and polyadenylated, and frequently splicedTend to be expressed at lower levels and with temporal/tissue-specific profilesCurrently > 10,000 lincRNAs annotated in human genome
5. Intergenic long noncoding RNAslincRNAs have been implicated in all levels of gene regulation< 0.5% of lincRNAs have an established biological functionUlitsky and Bartel, 2013
6. Project aimIdentify lincRNAs likely associated with genetic variants (SNPs) linked to OBESITY Obesity is a growing global health problemOver 13% of adults were considered to be obese in 2014 (WHO)Body Mass Index (BMI) is commonly used to assess obesityGenetic factors found to contribute to variability in BMI between individuals
7. Project aimIdentify lincRNAs likely associated with genetic variants (SNPs) linked to OBESITY
8. Project aimIdentify lincRNAs likely associated with genetic variants (SNPs) linked to OBESITY97 genomic loci linked to BMI
9. Project aimIdentify lincRNAs likely associated with genetic variants (SNPs) linked to OBESITY97 genomic loci linked to BMIRNAseq data for 373 individuals
10. Project aimIdentify lincRNAs likely associated with genetic variants (SNPs) linked to OBESITYcis-eQTL analysis: Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinity
11. eQTL analysisexpression Quantitative Trait Loci (eQTL)Goal : identify genomic locations where genotype significantly affects gene expression
12. eQTL analysisexpression Quantitative Trait Loci (eQTL)Goal : identify genomic locations where genotype significantly affects gene expressionDNA
13. eQTL analysisexpression Quantitative Trait Loci (eQTL)Goal : identify genomic locations where genotype significantly affects gene expressionGenotype dataDNASNPs
14. eQTL analysisexpression Quantitative Trait Loci (eQTL)Goal : identify genomic locations where genotype significantly affects gene expressionGenotype dataGene expression dataDNARNASNPs
15. eQTL analysisexpression Quantitative Trait Loci (eQTL)Goal : identify genomic locations where genotype significantly affects gene expressionGenotype dataGene expression dataDNARNASNPsC/CC/TT/TGene expression levelGenotype of risk factor
16. eQTL analysisGoal : Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinity
17. eQTL analysisGoal : Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinityGenotype dataGene expression dataDNARNASNPs
18. eQTL analysisGoal : Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinityGenotype dataGene expression dataDNARNABMI/obesity associated SNPs
19. eQTL analysisGoal : Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinityGenotype dataGene expression dataDNAlincRNABMI/obesity associated SNPs
20. eQTL analysisGoal : Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinityGenotype dataGene expression dataDNAlincRNABMI/obesity associated SNPsC/CC/TT/TGene expression levelGenotype of risk factor
21. Project aimeQTL analysis: Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinityData: RNAseq: gene expression levels from lymphoblastoid cell lines (LCLs) from 373 individuals of European descent (Lappalainen et al. 2013)Genotype: BMI/obesity associated genetic markers (Locke et al. 2015)
22. Project aimeQTL analysis: Test correlations between BMI/obesity associated variants and expression levels of lincRNAs in their genomic vicinityData: RNAseq: gene expression levels from lymphoblastoid cell lines (LCLs) from 373 individuals of European descent (Lappalainen et al. 2013)Genotype: BMI/obesity associated genetic markers (Locke et al. 2015)What does it involve?Gene expression data normalizationEstimation of correlation between lincRNA expression and genotype genetic variantsMultiple hypothesis testing correction
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