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