A mutant is different than “normal”. The mutant characteristic is passed on to the next generation.

DNA Central Dogma of Biology DNA -> RNA -> Protein mRNA Transcription Translation Protein Gene Function

Abnormal Gene Function DNA mRNA Transcription Translation Protein DNA -> RNA -> Protein Synthesis of Abnormal Proteins Mutations Often Result in the X X X

Mutation of the Fly dpp gene

Recessive versus Dominant Mutations/Alleles Recessive mutations: Both copies of the gene must be mutated to manifest defect. Dominant mutations: The defect is manifest when only copy of the gene is mutated Loss-of-function mutations are typically recessive Recessive mutations are represented by lower case letters + = wildtype, m = recessive mutation Dominant mutations can confer new activities or interfere with normal gene function Dominant mutations are represented by upper case letters + = wildtype, M = dominant mutation Allele: A particular variant of a gene (could be normal or mutant).

Genotype versus Phenotype Genotype: The genetic make-up of an individual Phenotype: The appearance of an individual Examples: +/+, +/m, m/m, +/M Example: Individuals having a +/+ or +/m genotype have a normal phenotype. Individuals having m/m genotype have mutant phenotype. Individuals with one normal (+) and one mutant (m) copy of a gene are called carriers for the mutation (+/m).

Abe Lincoln

mf/mf = 1/4 offspring = Marfan +/+ = 1/4 offspring = Normal or+/mf mf/+= 1/2 offspring = Normal ++ mf + + One quarter of the offspring from two Marfan carrier parents will have Marfan Syndrome + mf Two types of mother’s eggs + mf Two types of father’s sperm +/mf +/+ mf/+ mf/mf

Putting Mutations Into Groups A. Two Genes Function in a Common Process

Putting Mutations Into Groups B. Two non-responding mutations in the same gene Signal lacking -> No response Mutant m1Mutant m*1 Signal lacking -> No response m*1m*1 m1

Putting Mutations Into Groups C. Two non-responding mutations in different genes Signal and Receptor present -> Response Mutant m1Mutant m2 m2m2 m1 + Normal offspring Signal lacking -> No responseReceptor lacking -> No response

mf/mf = 1/4 offspring = Marfan +/+ = 1/4 offspring = Normal or+/mf mf/+= 1/2 offspring = Normal ++ mf + + One quarter of the offspring from two Marfan carrier parents will have Marfan Syndrome + mf Two types of mother’s eggs + mf Two types of father’s sperm +/mf +/+ mf/+ mf/mf

Normal red blood cells Sickle cell red blood cells

+++ sc Two types of mother’s eggs Two types of father’s sperm One half of the offspring from two Sickle Cell carrier parents will be protected from Malaria +/+ = 1/4 offspring = Normal/ Malaria Sensitive sc/sc = 1/4 offspring = Sickle Cell +/sc +/+ sc/+ sc/sc +/scor sc/+= 1/2 offspring = Normal/Malaria Resistant

Genes, Chromosomes, and Genomes Gene = Basic Unit of Inheritance Gene 1Gene 2Gene 5Gene 3Gene 4 Genome = 30,000-50,000 Genes Chromosome = 1,000-5,000 Genes ≈ 5,000 Genes Cause Disease When Mutant

Mutations Carried in Father’s Genome + Mass Scale IVF Mutations Carried in Mother’s Genome

Resistance to Malaria Low Blood Pressure Longevity Musical Ability Resistance to Flu Low Cancer Risk Reduced Risk for Alzheimer Disease Desirable Traits Can be Linked to Disease Genes Immunity to Plague