Alleles and complementation and chromosomal aberrations Flashcards
Types of alleles? (gene variants)
Loss of function (most common): Amorph (genetic null) or Hypomorph (reduced) Gain of function: Hypermorph (increased gene function), or Neomorph (NEW gene function!) or Antimorph (a dominant negative, that inhibits wild type function)
Why is yeast a useful model organism for studying recessive alleles?
Because yeast can function as a haploid organism, therefore expressing phenotype of recessive alleles!
How to determine whether different mutations affecting a phenotype are allelic (versions of same gene) or non-allelic, different genes in a pathway? (in yeast)
Complementation test (cross 2 haploid yeast with different mutants to form diploid yeast), assuming the mutations are recessive, if the mutations are non-allelic (different genes) then the diploid organism should receive one wild-type (functional) copy of each gene and so should display wild-type phenotype. (if the mutations are allelic (same gene) then the diploid yeast will have 2 non-functional versions. and so display mutant phenotype)
Limitations of complementation test? (where you cross 2 mutants to determine if they are allelic mutations)
** Dominant mutants** always express their mutant phenotype. (these would be Dominant negatives, inhibiting wild-type function). [must always check if mutations are dominant before doing complementation tests]
Rarely: Intra-allelic complementation (when 2 mutations are allelic but still complement each other in heterozygous form, rescuing wild-type phenotype. Can happen in multimeric proteins where different mutant monomers can form functional multimers, whilst homomultimers are non functional. Or if multiple functional domains, each affected by different allelic mutations in same gene, in heterozygous form there is still an active version of each functional unit present)
What is epistasis?
Where the effect of one gene (determined by its alleles) is dependent on the function (determined by alleles) of other genes.
A gene (or mutation of it) is epistatic to another gene (or mutation of it) if it masks its expression. (so baldness mutation is “epistatic” to red hair mutation, which is “hypostatic” to baldness)
An epistatic relationship between 2 genes is evidence that they act in the same pathway!
Example of a dominant negative mutation in telomeres?
TRF2 acts as homodimers to bind telomeres. If one monomer is mutant and lacks binding Myb domain, it dimerises with wild-type monomers and the whole dimer cannot bind telomeres.
In a switch-regulatory genetic pathway, where is the epistatic gene?
Downstream of the hypostatic genes in a pathway.
For example in telomerase regulation, Tel1 activates telomerase [positive regulator] but is inhibited by Rap1 which is activated by Rif1 and Rif2 in an additive fashion (no epistatic interaction between ‘Rif’s).
Tel1 is epistatic to the other genes, as if double mutant form (lost function) it creates short telomere phenotypes, and the effect of Rif or Rap1 mutations (which normally cause long telomeres is hypostatic, not expressed)
In a substrate-dependent pathway, where is the epistatic gene?
Upstream of the hypostatic genes in the pathway.
Downstream enzymes depend on the product (and so the activity of) of the upstream enzymes to carry out their own reactions and so create their own phenotype.
Types of chromosomal aberrations?
Deletion (of section of chromosome)
Duplication (different types)
Reversal
And Translocation (between chromosomes)
What is haploinsufficiency?
Where for some genes the presence of only 1 functional wild-type allele of a gene is insufficient to create normal phenotype and so a mutant phenotype occurs.
What is pseudodominance?
When a recessive allele displays what appears to be a dominant inheritance pattern, (so its phenotype is expressed when only one copy is present)
This can occur on sex chromosomes in males if they have an X-linked mutation (as only 1 X). But it can also happen if the dominant allele partner is lost, perhaps by chromosomal deletion)
4 Types of chromosomal duplications?
Tandem (adjacent)
Displaced
Reversed
Displaced and reversed!
Problems caused by displaced duplications?
(and some by tandem duplications)
Displaced duplications can cause further chromosomal rearrangement/aberrations such as deletions, larger duplications and reversals (during pairing and recombination in meiosis 1)
(by a number of mechanisms such as intrachromosomal homologous recombination forming circles of DNA)
What is non-allelic homologous recombination? (NAHR)
Recombination events between homologous sequences which are NOT alleles of the same gene!
Can cause unequal crossing over, where one recombinant has some sequence deleted, and the other recombinant has duplicated sequences.
Deletions in Low Copy Number repeats can cause disease phenotypes such as in Williams syndrome
What are the 2 kinds of chromosome segment Reversals?
and why can they cause disease phenotypes despite not deleting any sequences.
Paracentric (not involving centromere)
Pericentric (around centromere)
These can disrupt or fuse genes. And cause large problems during meiotic recombination (through inversion loop formation and strange structures resulting from recombination)
