The National Organization for Rare Diseases (NORD) estimates at least 6000 rare diseases, affect fewer than 200,000 people in USA, 25 million affected, many caused by genes approach to understanding of how life works has been profoundly affected by access to complete DNA sequence scientists go beyond emperical or superficial explanations of disease, instead into molecular basis. Pinpoint specific glitches in DNA sequence All DNA of organism = genome, size of genome
we have 3.1 billion base pairs, rungs of genetic ladder
Genetic mutations: missense, nonsense, frameshift
exons and introns of protein-coding genes add up to ~30% of genome 1.5% coding exons, 28.5% removable introns
rest are spacer segments of DNA, don’t code for protein, can form long stretches of “gene deserts” humans descended from common set of 10,000 founders in East Africa 100,000 years ago 0.4% of genome differs between individuals
family health history = strongest of all measurable risk factors for many common conditions, incorporating both heredity and shared environment first degree relatives with heart disease before age 55: risk 5x first degree relatives with colon, prostate, breast cancer: 2-3x new paradigm radically different: know each individual is unique, endowed with certain genetic variants that may provide advantages, others cause vulnerabilities “long QT syndrome” associated with fainting spells and sudden death, predisposed victims to a potentially fatal heart rhythm called ventricular fibrillation CF, sickle-cell anemia, Huntington’s: predictable result of mutations in specific genes, referred to as “single-gene” or Mendelian diseases easiest to understand on DNA level, discovering causes represented first wave of genomic revolution Principle 1: humans are diploid, genes are carried on chromosomes, can be seen under microscopes when cell’s about to divide 23 pairs of chromosomes...