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42
Introduction to modern genetics
I. Developmental genetics
he drawing of conclusions about the developmental role of a particular wildtype gene product fromthe pattern of defects (e.g., tissue or organ changes) occurring in a mutant
II. What makes a good model system?
Requirements: easy to maintaingrow in small spaceshort generation time (life span)large number of progenysmall genome sizelow amount of repeated DNAeasy to mutagenizeability to self fertilizeability to manipulate- transformationModels:Bacteria:
 E. coli
Yeast:
Saccharomyces cerevisiae
 Nematode:
Caenorhabditis elegans
Insect:
 Drosophila melanogaster 
Vertebrates: mouse (
us musculus
, zebrafish (
 Dano rerio
)
 ,
(also
 Homo sapiens
)Plant:
 Arabidopsis thaliana
 A closer look at some models: Yeasthaploid and diploid stagesgrow and select on mediumcan transform easily 
 Arabidopsis
- “mouse-eared cress”diploid onlydozen per 5-6 cm pot5-6 weeks generation time10,000 seeds per plantself fertilization
Genome Sizes in Mb
 E. Coli
4.5Yeast 15
 Neurospora
42
. elegans
80
 Drosophila
160
hlamydomonas
100
 Arabidopsis
100omato 714Rice 970obacco 1,600Potato 1,900
Ceratopteris
5,000Corn 5,000Wheat 5,900
 
3
III. Mutation
Mutation- change in DNA sequence that can change information (protein or how and where to ex- press protein) it encodesTypes:1. chromosomal mutations2. smaller insertions/deletions3. point mutationsA->T transitionA->G transversion4. frameshift mutataionsAmino acid effects of point mutations:tyrosine TAT, TACTAT -> CAT tyr -> his misenseTAT -> TAA tyr -> stop nonsenseTAT -> TTT tyr -> phe neutral in many casesTAT -> TAC tyr -> tyr silent
TCAG
TTT Phe (F)TTC “TTA Leu (L)TTG “TCT Ser (S)TCC “TCA “TCG “TAT Tyr (Y)TACTAA
er
TAG
er
GT Cys (C)GCGA
er
GG Tr (W) 
C
CTT Leu (L)CTC “CTA “CTG “CCT Pro (P)CCC “CCA “CCG “CAT His (H)CAC “CAA Gln (Q)CAG “CGT Arg R  CGC “CGA “CGG “
A
ATT Ile (I)ATC “ATA “
ATG
Met (M) ACT Thr (T)ACC “ACA “ACG “AAT Asn (N)AAC “AAA Lys (K)AAG “GT Ser (S)GC “GA Arg (R)GG “
G
GTT Va V GTC “GTA “GTG “GCT Ala (A)GCC “GCA “GCG “GAT Asp (D)GAC “GAA Glu (E)GAG “GGT Gly (G)GGC “GGA “GGG “
Silent mutations:
Changes in base sequence that do not lead to a phenotype. Base substitution muta-tions in the third position of many codons do not change the amino-acid coding.
Lethal mutation:
a gene that leads to the death of an individual; these can be either dominant or recessive in nature
Conditional mutations
: In some instances, a null mutation is lethal to the organism. Therefore, con-ditional mutations are quite useful to the geneticist.
Temperature-sensitive (ts)
: low permissive temperature; high non-permissive (or “restrictive”) tem- perature. Temperature-dependent mutations are usually protein folding mutants affecting proteinfunction or stability.
 
44
Difference between genotype and phenotype?
Phenotype:
literally means “the form that is shown”; it is the outward, physical appearance of a particular trait
Genotype
: the specific allelic combination for a certain gene or set of genesHow does genotype lead to phenotype? What does a mutation have to do with this? (Hint: What ac-tually causes a disease — the DNA or the protein?) In classical genetics, phenotype can be observeddirectly, but genotype can has to be inferred from phenotypes of: the individual, the individual’s parents and/or progeny.Genetic variation is essential to classical genetics - genes are defined by mutations that affect genefunction. Genes can only be identified when heritable differences among individuals exist. A genemust have at least two variants (alleles) that cause marked phenotypic differences. The likelihood of identifying a “gene” (allele) depends on its degree of phenotypic influence. “Silent” variation (ge-netic change with no phenotypic manifestation) is undetectable by classical methods.Mutations that have phenotypic consequences can include:those that alter the amino acid sequence of a proteinits activityits abundance (stability)those that change the expression of a genesequences required for mRNA transcription, splicing, protein translationregulatory elements: sites of action of regulatory proteins or RNAsImportant refresher 
Mendel’s First Law
the law of segregation; during gamete formation each member of the allelic pair separates from the other member to form the genetic constitution of the gamete
Mendel’s Second Law
: the law of independent assortment; during gamete formation the segregationof the alleles of one allelic pair is independent of the segregation of the alleles of another allelic pair 
Phenotypic variation
Penetrance
- the frequency of expression of an allele when it is present in the genotype of the organ-ism (if 9/10 of individuals carrying an allele express the trait, the trait is said to be 90% pene-trant). Those individuals that do not show the mutant phenotype are sometimes called “escapers”.
Expressivity
- variation in allelic expression when the allele is penetrant. Not all phenotypes that areexpressed are manifested to the same degree. For example, for polydactyly, an extra digit mayoccur on one or more appendages, and the digit can be full size or just a stub. Therefore, whenthe “P allele” is present it expresses variable expressivity.
Catagories of genetic mutations
a. amorph (also called an null mutation)- complete absence of activity b. hypomorph (also called a partial loss of function) - loss of most of activityc. hypermorph (also called a gain of function)- new gene activityd. antipmorph (also called a dominant negative)- dominant negative activitye. neomorph- novel function or activity
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