Leslie Waller Genomic Medicine

Genomic Medicine:

Genomic Medicine DNA Sequencing Saves the Live of a Six-Year-Old Boy b y Leslie Waller

Meet Nicolas Volker: aka “Batman”:

Meet Nicolas Volker: aka “Batman”

Disease Timeline:

Disease Timeline 2004: Nicolas is born 2006: Fistulas appear, eight months of medication, no diagnosis (IBS? Crohns ?) Late 2006: Colostomy, infection, blood transfusions, sepsis 2008: After brief remission, more inflammation and fistulas, doctors run nine individual gene tests, 35 immune system tests, all without diagnosis 2009: After 300 days in the hospital, doctors remove his colon

Decision to Sequence:

Decision to Sequence Howard Jacob A genomics expert and head of the Medical College of Wisconsin's genetics center who will decide whether to sequence Nicholas' DNA . He envisions routine sequencing at the hospital by 2014. Alan Mayer Pediatrician A pediatric gastroenterologist with a genetics background at Children's Hospital of Wisconsin and the Medical College of Wisconsin who first raises the idea of sequencing Nicholas' DNA. Unlock the exons!

Sequencing DNA:

Sequencing DNA Note: to sequence the entire genome would have cost up to $2 million.

Sequencing DNA:

Sequencing DNA Carpe Novo!

XIAP Mutation:

XIAP Mutation TGT = Cysteine (normal) TAT = Tyrosine(mutation) Nic cannot make the XIAP protein without cysteine

XIAP Mutation:

XIAP: X-linked inhibitor of apoptosis protein, a gene found on the X chromosome that provides instructions for making a protein found in many types of cells, including immune cells. It helps protect these cells from self-destructing by blocking the action of certain enzymes . More Information XLP: X-linked lymphoproliferative disorder is an inherited immune system disorder that affects fewer than 1 in a million children. The disorder is found on the X chromosome, only strikes boys and is usually fatal, rendering them unable to survive one of the most common human viruses, Epstein-Barr . More Information XIAP Mutation For the techies: DNA has 3.2 chemical base pairs! They broke up Nic’s DNA with pressurized N2 into segments of 500-800 bases . They read each segment an average of 34 times to ensure that a mutation would not be missed. XLP Disorder

Reboot Immune System:

Reboot Immune System It takes six months to one year for an immune system to reboot. The new immune system must be “retrained” with vaccinations.

Prognosis:

Prognosis Six months – one year to reboot immune system “Retrain” with vaccinations Nicolas is healthy and happy, attending kindergarten Genomic sequencing will be common in 2014, and will cost about $1000 One of the first documented successes of genomic medicine: diagnosis, treatment, and cure of a genetic disorder!

For More Information…:

For More Information… The Complete Story of Nicolas Volker: One in a Billion: A Boy’s Life, A Medical Mystery http://www.jsonline.com/features/health/111224104. html Video : How to Sequence a Genome: Introduction http://www.youtube.com/watch?v=N4i6lYfYQzY Video : Peter Robinson, M.D. - Exome Sequencing ( technical) http://www.youtube.com/watch?v=ZY_vPbpPnrc Video: DNA Test Methods - DNA Sanger Sequencing http://www.youtube.com/watch?v=oYpllbI0qF8&feature=related Video: The impact of mapping the human genome on cancer therapies with Kevin Davies, author of “The 1000 Dollar Genome” http://vodpod.com/watch/4883572-the-impact-of-mapping-the-human-genome-on-cancer-therapies National Human Genome Research Institute www.genome.gov Conference: World DNA and Genome Day in China: April 25-30, 2011 http://www.dnaday.com/ Peer reviewed article: X-linked Inhibitor of Apoptosis Regulates T Cell Effector Function http://www.jimmunol.org/content/179/11/7553.full U.S. National Library of Medicine, Information on XIAP gene http://ghr.nlm.nih.gov/gene/XIAP Three Children Cured Of Defective Immune Systems Through Unrelated Umbilical-Cord Blood Transplants At UCLA ScienceDaily (Apr. 13, 2001) http://www.sciencedaily.com/releases/2001/04/010411082559.htm Information on XLP disorder from St. Jude’s Children’s Research Hospital http://www.stjude.org/stjude/v/ index.jsp?vgnextoid =c3ac061585f70110VgnVCM1000001e0215acRCRD&vgnextchannel=9d5fbfe82e118010VgnVCM1000000e2015acRCRD Additional Sources: “A Dictionary of Biology," Oxford University Press " Oxford Dictionary of Science,” Oxford University Press