Transcript File
Nutrigenomics Chapter 11 © 2007 Thomson - Wadsworth Human Genome • Human Genome Sequencing Consortium Finished human genome – 2003 • Entire set of genes Blueprint 30,000 different proteins © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth Nutrigenomics • Interaction between nutrients and genotype Variants can determine individual response to dietary factors…propensity to develop disease • Pharmacogenomics © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth Overview of Genetics • DNA – how to build an organism Code varies from person to person • Genome lies within nucleus of cell Comprised of 22 pairs of chromosomes During mitosis all pairs are copied During meiosis only one member of each pair are copied Karyotype © 2007 Thomson - Wadsworth Karyotype for Down syndrome © 2007 Thomson - Wadsworth Overview of Genetics • Chromosomes 22 pairs are autosomes 1 pair determines sex Alleles • Nucleotides Purine or pyrimidine base • Adenine (A), guanine (G), thymine (T), cytosine (C) Ribose Phosphate group © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth Overview of Genetics • Complementary strands As always with Ts Gs always with Cs Doublestranded helical formation © 2007 Thomson - Wadsworth DNA to protein • Genetic Code Codons - encode specific amino acid chain Promoter regions – noncoding regulatory sequences Intervening sequences © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth DNA to protein • Transcription DNA unwinds encoding gene of interest • Translation Copied by means of base pairing into messenger RNA (mRNA) Partly dependent on dietary factors • Posttranscriptional processing • Protein assembly in ribosomes of RER © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth DNA to protein • Transfer RNA (tRNA) serve as anticodons • Amino acids positioned in sequence until stop codon is reached • Posttranslational modification © 2007 Thomson - Wadsworth Genetic Variation • Polymorphisms – variations within genes May have profound effects © 2007 Thomson - Wadsworth Genetic Variation • Inheritance Autosomal dominant • Familial hypercholesterolemia Autosomal recessive • PKU • Cystic fibrosis X-linked recessive • Hemophilia Y-linked • Very rare – only in males © 2007 Thomson - Wadsworth Genetic Variation • Inheritance Phenotype – physical properties Heterozygous – 2 different alleles Homozygous – 2 identical alleles © 2007 Thomson - Wadsworth Genetic Variation • Polygenic diseases Obesity Diabetes Cancer CVD Single nucleotide polymorphisms • SNPs © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth Genetic Variation • SNPs Single nucleotide exchanged for another Range from no alteration of function to deleterious effects Identification now focus of research • Haplotypes – group of variants that occur together © 2007 Thomson - Wadsworth Genetic Variation • Other polymorphisms Insertion or deletion • Down syndrome • Angelman syndrome © 2007 Thomson - Wadsworth Epigenetic Regulation • Pattern of gene expression DNA methylation • See Fig. 11.8 • B12, folate, choline, methionine • Impaired fetal development and cancer Histone methylation Acctylation Phosphorylation © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth Diet and Gene Expression • PUFAs as ligands for PPARs • Soy isoflavones • Sulforaphane (broccoli) • Measured using microarray © 2007 Thomson - Wadsworth © 2007 Thomson - Wadsworth Nutrigenomics and Disease • Cancer Use of omega-3 & EPA for rare types Predicting benefit difficult in other types • Responders and non-responders Colon cancer • Folate intake and alcohol • Fruits and vegetables Breast cancer • Antioxidants © 2007 Thomson - Wadsworth Nutrigenomics and Disease • Obesity Susceptibility with conducive environment Polygenic trait Promising research • Perilipin • Serotonin receptor gene promoter © 2007 Thomson - Wadsworth Nutrigenomics and Disease • Thrifty Gene hypothesis Metabolic status and fetal adaptation predict disease in adulthood Proneness to metabolic syndrome, obesity, diabetes, CVD © 2007 Thomson - Wadsworth Nutrigenomics and Disease • Diabetes Focus on type 2 Metabolic syndrome, insulin resistance GLUT 2 PPARy APOE © 2007 Thomson - Wadsworth Nutrigenomics and Disease • Cardiovascular Disease Dyslipidemias Familial hypercholesterolemia PUFAs on HDL Omega-3s and TG Omega-6s and inflammation © 2007 Thomson - Wadsworth Dietetics and Genetics • Understanding nutrient interactions and genes • Future of diet counseling • Beware of home testing kits “DNA diet” Sciona Costly • EGAPP Project To establish a coordinated process © 2007 Thomson - Wadsworth