Post on 19-Mar-2018
Mutations and the phenotype
• Types of mutations• Agents of mutations• Mutations:
Molecular level• Mutations: protein
level• Classes of Protein
mutations
Gene mutation
• somatic • germinal • study process of mutation • dissect a biological process
Mutagens
• Can be physical or chemical agents
• Use Ames Test for mutagens
• Mutagens are potential carcinogens
Agents of mutation
• Spontaneous• Physical agents• Chemical agents
Mutagens: UV light and X-rays Radiation
Chemical
• oxygen, ozone, superoxide
• Nitrous acid
Mutations: Molecular level
• Transitions • Transversions
DNA changes
Mutations: Protein Level• 4 groups of amino acids • silent mutation • Missense mutation &
examples • neutral • non-functional • nonsense mutation • anti-nonsense • Frameshift mutation
Inborn errors of metabolism
Classes of Protein mutations
• Enzymes• Amino Acid
metabolism• Carbohydrate
metabolism• Lipid metabolism• Nucleic acid
metabolism• Receptor proteins• Transport proteins
Amino Acid metabolism
Amino Acid metabolismPhenlyalanine
Carbohydrate metabolism
Glycogen storage
Nucleic acid metabolism
SCID/ADA deficiency Both B/T lymphocytes affected elevated dATP 50-100x inhibit synthesis of other deoxynucleotides
Lesch-Nyhan syndrome
• Lack of HGPRT • x- linked • Increase de novo
purine biosynthesis • overproduction of
urate
Problems
• Urate soluble 7 mg/dLat 37C
• cooler extremities, crstallizes
• synovial fluid • Gout
Lipid metabolism
Receptor proteins
• Heterozygote plasma levels of LDL: 320-500 mg/dL, increased residence time in blood
• Homozygous plasma levels of LDL: 600-1000 mg/dL
Transport proteins
Sickle Cell
Alpha chain
Alpha chain
Cystic Fibrosis