Mendel on Caffeine: Human Genetics in 2012 Matthew R. Nelson, Ph.D. Chapel Hill High School March 9, 2012

A few things about me

What GSK does Our flagship products In both the medical profession and the consumer healthcare industries, we have strong portfolios of products, many of which are household names. Prescription medicines: SERETIDE/ADVAIR (respiratory), and the AVANDIA family of products (diabetes). OTC Medicines – PANADOL, TUMS, ABREVA, BREATHE RIGHT and FIBER CHOICE Oral Healthcare – AQUAFRESH, SENSODYNE and MACLEANS Nutritional Healthcare – RIBENA, LUCOZADE and HORLICKS GSK 4 products in the world’s top 60 pharmaceutical products BY SALES. These are: Avandia, Lamictal, Seretide/Advair and Valtrex. And we’re working towards the introduction of new medicines and vaccines. Next Slide: Our product pipeline The World of GSK 3

What I do How does genetics influence the way we respond to drugs? Does it work for me? How much do I need? Is it safe for me to take?

Gregor Mendel: One mutation at a time

Two!!

DNA and genetics

Revolutionizing genetic research ×20 cycles = ? = 220 > 1 Million

Measuring Genetic Variation GCTATCAGTACT DNA Gene X G Single Nucleotide Polymorphism (SNP) Exons Introns Rheumatoid Arthritis Baldness Height Asthma

Genetics tells us about our origins

Genetics tells about our origins

Taking genetics to the next level

Genome-wide association studies Liver injury due to flucloxacillin

Genome-wide association studies Body mass index (analyzed 250,000 people)

Some things we have learned Almost all traits have some genetic influence Most traits are affected by lots of genes Usually more than ten, sometimes hundreds Some genes affect lots of different traits Even when we find lots of genes involved, they usually aren’t very good for predicting what will happen to you You are not your genes Genes can influence and sometimes set bounds, but rarely determine your fate

Where can you find information about genetic effects on human diseases and conditions? What genes have been found that influence diseases or other traits you want to know more about? What are the different traits that a gene affects? Genome-wide Association Study Catalog: http://www.genome.gov/gwastudies  Online Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/omim Pubmed.org & Google Scholar: Finding scientific papers and reviews (not all are freely available) Google: Good place to find summaries, but be careful Wikipedia: Hit or miss

Partial results from the body mass index search

What else has the FTO gene been associated with?

Find out more about the FTO gene

More about the FTO gene

Your turn

Overview of Genomic Organization and Variation 23 chromosome pairs 6 billion bases ~33,000 annotated “genes” ~10,000,000 common (>5%) single nucleotide polymorphisms (SNPs) >>10,000,000 rare SNPs 1000s common insertions/ deletions (indels) 100,000s rare indels Figure from http://www.biologia.uniba.it/rmc/0-internal-images/z-ideograms/ideograms.html

Published GWA Reports, 2005 – 6/2011 951 Total Number of Publications Calendar Quarter Through 9/30/10 postings