Because Stuff Happens

A. Mutation Overview  Any change or random error in the nucleotide sequence (either DNA or mRNA) is called a mutation  Can occur in any cell in body  Gamete: cell that determines sex; sperm or egg cell  Mutation passed down to offspring  Somatic cell: all other cells  Mutation stays with cell; may be copied in cell replication

Skin cancer is not inherited because it occurs in somatic or body cells

 Two types of mutations:  Point mutation: one base is mutated into another (one amino acid change)  Frameshift mutation: one base is added or deleted (all amino acids changed)  Affects may be neutral (no change in expression), positive, or negative (disease or death)

A mutation in the thumb joint changed it to an opposable thumb = positive mutation!

B.Introns & Exons  Entire DNA strand is 3 billion (3,000,000,000) base pairs  In eukaryotes, divided into two types:  Introns: no coding information (nonsense)  Exons: code for proteins

 Why would eukaryotic DNA have so many nonsense base pairs or junk?  Protection – mutation here wouldn’t harm protein (neutral mutation) INTRON EXON mutation

 Before mRNA leaves nucleus - therefore before translation (making proteins from mRNA) - introns must get cut out by process called splicing  Done by specific enzymes called spliceosomes

C.Point Mutation  Single nucleotide (base, PO4, sugar) changes  Original : The fat cat ate the wee rat.  Mutation: The fat hat ate the wee rat.  Many diseases are result of single point mutation in gene

 Sickle cell anemia  Point mutation: aa glutamine mutated into valine  Result: red blood cell changed from round shape to sickle (crescent) shape  Gets stuck on walls of blood vessels & can cause clog

 Cystic fibrosis  Point mutation: aa glutamine becomes STOP codon  Result: should be 1480 aa in protein, now only 493  Mucosal cells produce excess mucus which blocks ducts (tubes linking organs) which causes infections

D.Frameshift  Any mutation which causes shift of codon sequences or incorrect amino acid number  Caused by two scenarios:  Deletion of nucleotide (base)  Original: The fat cat ate the wee rat.  Mutation: The fat ata tet hew eer at.  Insertion of extra nucleotide(s) (base)  Original: The fat cat ate the wee rat.  Mutation: The fat caa tat eth ewe era t. Translocation: (See Illustration)  Many diseases caused by frame-shift mutations

Frameshift

 Huntington’s Disease  Mutation: additional CAG in protein  Result: early cell death in brain Huntington’s Disease Normal

 Fragile X Syndrome  Mutation: extra GGG codons inserted on X chromosome  Result: mental retardation in males normal

 Muscular dystrophy  Mutation: extra CTG or CCTG in muscle protein  Result: deteriorating (weakening) muscles

 Tay-Sachs Disease  Mutation: insertion of TACT in exon 11  Result: enzyme that breaks down fat in central nervous system (brain & spinal cord) defective  Fat accumulates on brain & spinal cord, permanently damaging cells & killing child before age 5

Acute Myeloid Leukemia  AML is a cancer that starts in cells that would normally develop into blood cells – usually white blood cells.

Translocation

Point vs. Frameshift

SUMMARY OF MUTATIONS TYPES  DELETION  INSERTION (INCLUDED DUPLICATION)  TRANSLOCATION  POINT MUTATION