Genomics at the Forefront of Health and Medicine ECONOMIC OPPORTUNITIES IN GENOMICS WORKSHOP November 12, 2016 National Institute of Molecular Biology and Biotechnology Building University of the Philippines Diliman Quezon City, Philippines Zenaida V. Magbanua, PhD Deputy Executive Director Philippine Genome Center

Science says a poo transplant through the nose works better than antibiotics. It treated 85 percent of cases of a life-threatening infection. From Science Alert, 25 Oct 2015 http://www.sciencealert.com/science-says-a-poo-transplant-through-the-nose-works-better-than-antibiotics

A 2-week diet swap between Westerners and Africans showed a significant improvement in the digestive system of Westerners fed with African diet while Africans fed with Western diet showed changes in their digestive systems that may lead to colon cancer. From nbcnews.com

Diseases of civilization Diabetes Cardiovascular diseases Obesity These diseases showed up along with industrialization and have been shown to be strongly influenced by a person’s diet.

Gluten-free? Low carb? High protein? Low fat? High fiber? Mediterranean diet?

Phenotype Genome Food Other environmental factors Water Air

Phenotype = Genotype + food + air + water + others + interactions There are genes and/or genetic loci that are linked or associated with certain diseases or disorders, such that, in some cases, are influenced by the food intake

Nutrigenomics branch of genomics that deals with the effect/interaction of food with the genome aims to develop Personalized Nutrition to optimize benefit from food intake utilize food to prevent certain types of diseases

Personalized Medicine (Aka Precision, Individualized or Genomic Medicine) Tailoring health care to each person’s unique genetic makeup

Genomics is the study of the genome is the totality of all heritable sequences in an organism, DNA in most cases.

Genome

Variability (polymorphism) in the genome of individuals of the same organism Variability occurs in coding and non-coding regions Single nucleotide polymorphisms (SNPs) Insertions/deletions (Indel) Inversions Copy number variation (CNV)

Variability (polymorphism) in the genome of individuals of the same organism Variability occurs in coding and non-coding regions Single nucleotide polymorphisms (SNPs)

Genome Wide Association Studies (GWAS) utilize this variability by associating the polymorphism to specific conditions like a disease or disorder* and use them as markers In most cases, this variation occurs in the coding regions of the genomes or the genic regions. *Heart disease, diabetes, obesity, cancer, malnutrition

Genome Wide Association Studies (GWAS) Identify polymorphisms between the genomes of individuals with the disorder (test population) and normal (control) Use statistics to determine which polymorphisms are associated with the condition  markers

Applications of Nutrigenomics Question: Is coffee good or bad? It depends whether a person is a slow or fast caffeine metabolizer

Applications of Nutrigenomics CYP1A2 gene Slow caffeine metabolizer (AC & CC) Fast caffeine metabolizer (AA) Coffee metabolism: Gene CYP1A2, belongs to the cytochrome P450 superfamily. It metabolizes caffeine. Carriers of the at least 1 copy of the C allele accumulate caffeine in the blood stream and should not consume more than 1 cup a day. Those who are homozygous for AA metabolizes caffeine efficiently and actually benefit from caffeine consumption. Another example: vitamin intake. It depends on the genome whether a person will benefit or not. Caffeine accumulation may lead to high blood pressure and heart disease Significantly reduced risk of heart disease

The genomic link to eating disorder Applications of Nutrigenomics The genomic link to eating disorder Some genomes have propensities towards eating disorders Heritable

7% frequency APO E 79% frequency 14% frequency Apolipoprotein E E2 carriers clear dietary fats fast and need a high healthy fat diet and aerobic exercise. May be associated with either increased and decreased risk for atherosclerosis, depending on the lifestyle. E4 allele has been implicated in atherosclerosis, Alzheimer's disease, impaired cognitive function, reduced hippocampal volume, HIV, faster disease progression in multiple sclerosis, unfavorable outcome after traumatic brain injury, ischemic cerebrovascular disease, sleep apnea, accelerated telomere shortening and reduced neurite outgrowth. It responds well to low fat diet, higher vitamin D intake and aerobic exercise. 7% frequency APO E Apolipoprotein E 79% frequency APO E is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. It is involved in the production, delivery, and utilization of cholesterol in the body. Although the alleles differ by 1 or 2 amino acids at positions 112 and 158, it has been shown that this function is dependent on the type of allele. E3 is the neutral allele and the normal metabolizer. Carriers need a normal amount of healthy fat and both aerobic and non-aerobic exercise. 14% frequency

Personalized Medicine

Knowledge of one’s genomic information may lead to more effective medication and better management, intervention and prevention of certain disorders and diseases.

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