Extension to Mendel
1. Single-gene inheritance :
a. Deviations from complete dominance and recessiveness
b.
c.
Multiple alleles
One gene determine more than one trait
2.
Multifactorial inheritance
Fig. 3.3
Incomplete dominance
Codominance
F1 hybrid display the traits of both parents
spotted
dotted
Fig. 3.5
Fig. 3.6
black/yellow
black
Monomorphic
(One wild-type allele)
agouti
Table 3.1
Pleiotropy
Sickle-cell anemia
Oxygen drops
Normal shape
Sickled Partially sickled***
Se level: A dominant
Phenylketonuria (PKU)
Phenylketonuria
Autosomal recessive disease- single gene disease Defective allele of gene coding for liver enzyme phenylalanine hydroxylase (PAH) Phe in diet converted into phenylpyruvic acid, transported to brain via bloodstream Impedes normal development, mental retardation Many mutations at different sites (allelic series): Near active site (null) or away from it with residual function (leaky)
Normally functioning wild type (P) All defective recessive mutations, null and leaky (p)
Phenylketonuria
Underlying complexity of genetic system involved: Some cases of elevated phenylalanine level and its symptoms: Not associated with PAH locus (other genes involved) Some cases: People with PKU (elevated phenylalanine) no abnormal cognitive development Hence involvement of other genes + environment (gene for tetrahydrobiopterin synthesis)
Phenylketonuria
Many steps in pathway from Phe ingestion to impaired cognitive development Amount of Phe in diet Transportation of Phe to appropriate sites in liver Liver: PAH + cofactor, tetrahydrobiopterin To affect cognitive development: Excess phenylpyruvic acid must be transported to brain via bloodstream, pass through BBB Inside brain: Developmental processes must be susceptible to action of phenylpyruvic acid
Multifactorial Inheritance
Interaction of genes
Identifying the interacting genes that contribute to a particular biological property 1. Treat cells with mutagens (UV): Set of mutants with abnormal expression of property under study 2. Test the mutants to determine how many gene loci are involved, which mutations are alleles of same gene 3. Combine mutations pairwise by means of crosses to form double mutants to see if they interact (gene product interaction). Specific ratio of progeny
Complementation
Harebell: Blue WT, three white-petaled mutants, homozygous pure-breeding strains $, , and Phenotypically alike, genetically identical ?
Are they three alleles of one gene, or of two genes, or of three genes? Check for complementation
Interaction of genes
1. Complementation: Production of a wild-type phenotype when two recessive mutant alleles are brought together in the same cell Complementation test: By intercrossing two individuals that are homozygous for different recessive mutants Observe whether progeny have wild-type phenotype
If recessive mutations are alleles of same gene: no wild-type progeny
Complementation
Two recessive mutations in different genes wild-type function provided by respective wild-type alleles Cross F1 dihybrid plants F2 9:7 (blue:white)
modification of the dihybrid 9 :3:3:1
Plant will have white petals if it is homozygous for the recessive mutant allele of either gene or both genes Blue phenotype: At least one dominant allele of both genes (both are needed to complement each other and complete sequential steps in the pathway) Three of genotypic classes will produce same phenotype, so overall only two phenotypes result. Different steps in a biochemical pathway
Three phenotypically identical white mutants$, , and are intercrossed Mutations in the same gene (such as $ and ) cannot complement, because the F1 has one gene with two mutant alleles. Pathway is blocked and flowers are white
When mutations are in different genes (such as and ), complementa tion of wildtype alleles of each gene occurs in F1 heterozygote. Pigment is synthesized and flowers are blue
Genotypes
Natural: o+/ ; b+/. Black: o/o ; b+/ Orange: o+/ ; b/b Albino: o/o ; b/b
Epistasis
Ability of a mutation at one locus to override a mutation at another in a double mutant When a mutant allele of one gene masks expression of alleles of another gene and expresses its own phenotype Overriding mutation: epistatic Overridden mutation: hypostatic Genes in same cellular pathway
WT
White (w/w)
(a) Rose
(b) pea
(c) walnut
(d) single
Comb shape: Two independently assorting genes (R and P) each with two alleles
Fig. 3.13
Epistatic: the effect of one gene hides the effect of the other gene
Addition of A or B sugars
Recessive epistasis
Suppressors
Suppressor: Mutant allele of one gene that reverses effect of a mutation of another gene, resulting in a wild-type or near wild-type phenotype Use a mutant, expose to mutagen and screen descendents for WT