C5 interrogating the coding and non-coding genome

Question 1

Contribution to the BP phenotype by genes and environment?

Answer 1

• 30% genes
• 70% env

Question 2

Difference between genomics and transcriptomics

Answer 2

• Genomics: Looking at variation of genes
• Transcriptomics: Looking at variation of RNA

Question 3

Genomic variations

Answer 3

• SNPs
• Copy number variation

Question 4

Genomic variation 1: SNPs

Answer 4

• (Single nucleotide polymorphism)
• Changes in DNA
• Powerful for association studies
• SNPs mapped in human genomes

Question 5

GWAS

Answer 5

• (Genomic wide association study)
• Compares SNPs b/w individuals and find locations of differences which affects BP
• Shows which SNP is responsible for what phenotype
• Strict p-values used → control for false discoveries

Question 6

Microarrays

Answer 6

• Measures the SNPs in bulk
• Have 1.8m genetic markers (the SNPs)
• Mech:
  
  • Extract DNA → amplify → label → hybridise → gives genotype
• Able to locate position on the genome associated with hypertension

Question 7

What do the green and red dots represent in a microarray analysis?

Answer 7

• Red = High expression
• Green = Low expression

Question 8

How many genes are associated with hypertension?

Answer 8

• ~20 genes found associated with hypertension
• But there is a high missing heritability

Question 9

Genetic variation 2: Copy number variation (duplications)

Answer 9

• Variations in the number of copies of larger segments of genome (Bulk changes in genome)
• In 12% of genome
• Deletion/insertion of one or multiple copies of the DNA segment

Question 10

What are non-coding genomes?

Answer 10

• DNA not coding for proteins
• Accounts for 80-90% of genes
• Able to control function & physiology of the body
• Long RNA (over 100bp)
  
  • Affects chromatin modifications
  • Transriptional interference
• i.e. miRNA

Question 11

miRNA

Answer 11

• 20-22bp
• Binds to mRNA
  
  • May degrade mRNA or could block translation
• RNA degrades quickly → samples need to be collected immediated after surgery
  
  • Not needed hanging around → may have detrimental effects

Question 12

miRNA181a

Answer 12

• Dysregulated in hypertension
• Target gene is renin
• Overexpressed in cortex → hypertension

Question 13

What is Transcriptomics

Answer 13

• Sample RNA → changed to DNA (RNA cannot be hybridised) → hybridised to microarray → screened

Question 14

RNA sequencing

Answer 14

• Need to extract tissues for RNA screening (i.e. need kidney tissues to screen kidney RNA)