Genetic Disease WHEN MUTATIONS CAUSE PROBLEMS Genetics can contribute to disease process п‚— Environment can enhance or suppress genetic expression Mutations п‚— Mutations are natural, random mistakes п‚— Mutations can be produced unnaturally by exposure to mutagens like radiation and carcinogenic chemicals п‚— Many mutations go unnoticed because the change is small and does not affect protein function. п‚— Some mutations have positive effects on protein functions, these can be naturally selected by the environment an increase in frequency in future generations Types of mutations п‚— Deletion: a piece of a chromosome is lost п‚— Duplication: A piece remains attached after meiosis, leaving the gamete with 2 alleles for a gene п‚— Inversion: a piece reattaches to a chromososme in reverse п‚— Translocation: a piece of a chromosome ends up on a completely different (wrong) chromosome п‚— Gene rearrangement: an entire gene moves to a different chromosome Other types of genetic change п‚— Non disjunction: During meiosis chromosomes fail to separate properly, leaving some gametes with too many chromosomes, and some with too few. п‚— Polyploidy: Non disjunction of all chromosomes, resulting in a doubling of the chromosome number. п‚— 30-80% of plant species are polyploid Pedigree charts- tracking a disease through time Genetic Diseases found on autosomes вЂ”Some well known examples п‚— Recessive alleles: п‚Ў Albinism п‚Ў Cystic fibrosis п‚Ў Galactosemia п‚Ў Phenylketonuria (PKU) п‚Ў Tay Sachs Disease п‚— Dominant Alleles: п‚Ў Achondroplasia п‚Ў HuntingtonвЂ™s disease п‚Ў Hypercholesterolemia п‚— Codominant Alleles: п‚Ў Sickle Cell Disease п‚— An example of Repetition mutation (autosomal): п‚Ў Myotonic Muscular Dystrophy вЂ“a repeated section of DNA on either chromosome 19 or 3 Genetic disease found on sex chromosomes п‚— Duchennes Muscular dystrophy- x linked recessive п‚— Colorblindness- x linked recessive п‚— Hemophilia-x linked recessive п‚— Fragile X syndrome x linked recessive п‚— Hyphophophatic rickets- x linked dominant п‚— RettвЂ™s syndrome-x linked dominant Genetic Disease caused by nondisjunction п‚— DownвЂ™s syndrome Triosomy 21-extra chromosome # 21 п‚— TurnerвЂ™s Syndrome- XO infertility, undeveloped sex organs п‚— Klinefelters syndrome XXY, XXXY, XXXXY infertility, underdeveloped testes п‚— XYY syndrome weak muscle tone, behavioral and learning disabilities A few moreвЂ¦ п‚— MarfanвЂ™s syndrome п‚— Hemochromatosis п‚— Breast Cancer п‚— Alzheimers Mitochondrial genetic disorders: п‚— myoclonus epilepsy with Ragged Red Fibers п‚— mitochondrial encephalopathy, lactic acidosis п‚— Leber's hereditary optic atrophy Human Genome Project An ongoing global effort to analyze the human gene sequence So far they know: п‚— About 25,000 gene locations п‚— The base pair sequences п‚— The location of DNA repeats between genes п‚— The location of the genetic вЂњculpritвЂќ involved in many genetic diseases Human Genome Project is ongoing п‚— NCBI п‚— Scientists use open databases to further research п‚— Adrenoleukodystrophy ALD X Alzheimer disease, type 3 AD3 14 Alzheimer disease, type 4 AD4 1 Amyotrophic lateral sclerosis SOD1 21 Apolipoprotein E APOE 19 Ataxia telangiectasia ATM 11 Breast cancer, type 1 BRCA1 17 Breast cancer, type 2 BRCA2 13 Burkitt lymphoma MYC 8 Colon cancer, nonpolyposis, type 1 MSH2 2 Colon cancer, nonpolyposis, type 2 MLH1 3 Cystic fibrosis CFTR 7 DiGeorge syndrome DGS 22 Diastrophic dysplasia DTD 5 Duchenne muscular dystrophy DMD X Ellis-van Creveld syndrome EVC 4 Gaucher disease GBA 1 Gyrate atrophy of the choroid and retina OAT 10 Harvey ras oncogene HRAS 11 Huntington disease HD 4 Juvenile onset diabetes IDDM1 6 Long QT syndrome LQT1 11 Malignant melanoma CDKN2 9 Marfan syndrome FBN1 15 Menkes syndrome ATP7A X Multiple endocrine neoplasia MEN2A 10 Myotonic dystrophy DM 19 Neurofibromatosis, type 2 NF2 22 Obesity OBS 7 Phenylketonuria PAH 12 Polycystic kidney disease PKD1 16 Retinoblastoma, type 1 RB1 13 Severe combined immunodeficiency ADA 20 Small cell lung carcinoma SCLC1 3 Spinocerebellar atrophy SCA1 6 Steroid 5-alpha-reductase-1 SRD5A1 5 Suppressor of pancreatic carcinoma DPC4 18 Testis-determining factor TDF Y Tuberous sclerosis TSC1 9 Tumor suppressor protein p53 TP53 17 Von Hippel-Lindau syndrome VHL 3 Waardenberg syndrome PAX3 2 Werner syndrome WRN 8 Wilson disease ATP7B 13 X-linked mental retardation FMR1 X Zellweger syndrome PXR1 12 Got Ethics? п‚—What ethical questions need to be considered as genetic research progresses?