Biology unit 02- Section 2.5 Genetic Disease and Personalized Medicine

Number of individual tumors that can be matched to a specific drug

15-20%

How many genetic diseases cause problems in first month of life

3,500 (>20% of infant deaths due to a genetic disease, 30% babies in intensive care unit have a genetic disease) Can now sequence newborns with mystery conditions in 24 hrs (>99.5 % specificity of genotypes)

Breast Cancer

Accounts for one of every three cancer diagnoses. (most common cancer in women over 50) Four distinct genetic types of the disease were found. Tissue does not define the underlying genetic profile.

Phenomizer

Aids in reaching correct diagnosis in patients with hereditary diseases and is an expert system for clinical diagnosis. (Connects to the Phenomizer data base of 6000+ genetic variants with symptoms)

What is cancer

All cancers derive from single cells (DNA in these cells acquired mutations that conferred the ability to continually divide) Cancer cells behave abnormally because of changes in DNA of key cancer genes. Genetic disease. These changes involve unknown degree of influence from the epigenome.

Genomic tests

BRCA1 & BRCA2 genes are essential for repairing damaged DNA, mutations are usually insertions or deletions of a small number of DNA base pairs in the gene. BRCA1 and BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast and other tissue

Supreme court case

DNA's existence in an 'isolated' form alters neither this fundamental quality of DNA as it exists in the body nor the information it encodes. Therefore, the patents at issue directed to 'isolated DNA' containing sequences found in nature are unsustainable as a matter of law and are deemed unpatentable under 35

Development of cancer

Due to an accumulation of mutations associated with somatic cells which turnover frequently (90% of all cancers are of epithelial cell origin: lung, breast, colon, skin)

Epigenomics

Examines which factors act on individual genes, and how certain changes in the epigenome affect our health

The Cancer Genome Atlas Project

Impact: Realization that there is not one cancer and one type of tumor & drugs must target a specific profile for a given individual (can identify the epigenome associated with the specific cell type of a given individual's cancer)

Learned cancer genomics

Most cancers caused by 2-8 sequential alterations over 20-30 years ~140 genes are known whose mutations drive cancer Cancer genes function through dozens of signaling pathways Every individual tumor is distinct regarding genetic alterations, but pathways affected in different tumors are similar Personalized treatment is informed by assessment of patient's germline genome & genome of his/her tumor

Tumor Suppressor Genes (TSG) - Transcription factors

Normally regulate controlled cell division. Mutations in these genes can cause cancer by disrupting the amount of the transcription factors

What Is Personalized Medicine?

Preventive, diagnostic, and therapeutic interventions targeted to individuals based on their risk" Risk defined through molecular testing, genomics, proteomics, metabolomics, epigenomics, and family history & data mining. Goals: Greater effectiveness & efficiency of healthcare delivery, improved health outcomes and quality of life

Microbiome exploration

Profile an individual's microbiome to detect, prevent and diagnose infections and other diseases

EGFR - Epidermal Growth Factor Receptor (oncogene)

Protein present on the cell surface, bind to epidermal growth factor causing the cells to divide, abnormally high levels on surface of many cancer cells causing them to divide excessively in presence of epidermal growth factor

Overview of human breast tumors

Realization that there is not one cancer & one type of tumor. Drugs must target specific profile for a given individual

SNPs contributing to complex diseases

Schizophrenia, Alzheimer's, Bipolar disorder

Clinomics

The challenge is in the accurate interpretation of the vast amount of data and effectively using it to guide decisions about your health care (computer science meets biology)

Pharmacogenomics

Using a patient's genetic profile to predict a drug's efficacy, guide dosage and improve patient safety

Single Nucleotide Polymorphisms (SNPS)

Variations in the DNA sequence due to the change of a single nitrogen base.

Haplotype

a group of genes within an organism that was inherited together from a single parent, all SNPs found on a given chromosome (International effort to identify every SNP in human genome)

DNA damage

appears to be the primary underlying cause of cancer and deficiencies in

DNA repair

appears to underlie many forms of cancer

Foundation for personalized medicine

patients know risks of developing diseases from personal SNP profile •Estimated 5 million SNPs in human genome

Interactomics

protein-protein interactions

Metabolomics

study of metabolic expression in cells

Genomics

study of whole genomes, including genes and their functions

Proteomics

the study of sets of proteins and their properties

Two major classes of cancer genes

tumor suppressor genes and oncogenes

Pro patent

•Encourage investment in biotechnology •Promote innovation in genetic research by not keeping technology shrouded in secrecy

Against patent

•Stifle innovation by preventing others from conducting cancer research •Limit options for cancer patients in seeking genetic testing •Not valid because genetic information that is not inventive, but is rather produced by nature