Week 2 Summary:
Structural Molecular Differences between alleles:
- Alleles usually differ at one or several nucleotides out of thousands
- Alleles are replicated during the S-phase
- Alleles: different versions of the same gene
- Mutations: nucleotide sequence of an allele changes as a result of a rare chemical accident.
Chromosome Segregation at eh Molecular Level:
1. Restriction Fragment Length Polymorphism:
Restriction enzymes: bacterial enzymes that cut DNA at specific base sequences (by
Southern Hybridization is used to reveal RFLP. If for example, albinism allele has an extra
restriction site, the probe detects one extra fragment
2. Direct Sequencing: most comprehensive picture but is time consuming and expensive
3. Polymerase Chain Reaction (PCR): used when alleles differ in number of times a sequence is
Alleles at the Molecular Level:
- Allelic series: multiple alleles with the wild type and a known mutant.
- Full/Complete Dominance: expressed when at least one copy is present
- Alternate Allele: fully recessive
- Null Mutations: produces non-functional proteins.
o Do not produce a functional protein
o Many genes are haplosufficient so null mutations have no effect on phenotype
o Happloinsufficiency makes null alleles dominant and affects phenotype
- Dominant negative: interference between alleles. The mutant allele interferes with the
wildtype, blocking it.
- Incomplete Dominance: occurrence of intermediate phenotype (Black + white = gray)
- Codominance: expression of BOTH alleles of the heterozygote (black + white = spotted)
- Recessive Lethal Alleles: capable of causing the death of an organism
- Pleiotropic: allele that affects several properties in an organism. If lethal, only so when
- Temperature Sensitive Mutations (ts): heat-sensitive alleles can be maintained as heterozygous:
o Permissive temperature: wild-type phenotype
o Restrictive temperature (higher): mutant phenotype
- Knock-out technique: To test if a gne is essential. A null allele is tested for lethality
- Phenylketonuria: defective live phenylalanine hydroxylase (PAH).
- PAH normally helps convert phenylalanine into tyrosine.
- Phenylalanine buildup leads to phenyl pyruvic acid which leads to mental retardation
- Plethora of mutations : o Null alleles: mutant, completely lacking PAH functions
o Leaky Mutations: reduced PAH function
- Haplosufficient: one functional gene is enough for wild-type phenotype. The mutations are
- Complementation test: crossing two individuals homozygous for recessive traits
If the wildtype phenotype is produced when 2 haploid genomes bearing different
recessive mutations are united in the same cell. Then it’s a multiple gene phenotype wth
Interfering Gene Interactions:
1. Obtain single-gene mutants and test for dominance
2. Test the mutants for allelism (one or several loci)
3. Combine mutants in pairs (double mutant) – see if they interact
If they interact phenotype will differ from the single allele phenotype complementation test
Epistasis: overriding mutation which masks the allele of other gene
Double Mutant for Random Mutations
9:3:3:1 – no interaction
9:7 – absence of gene function leads to absence