gene interaction
DESCRIPTION
Gene Interaction. Mutations of haplosufficient genes are recessive. Two models for dominance of a mutation. Figure 6-3. Incomplete dominance. Figure 6-4. Tailless, a recessive lethal allele in cats. Figure 6-9. Sickled and normal red blood cells. Figure 6-5. - PowerPoint PPT PresentationTRANSCRIPT
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Gene InteractionGene Interaction
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Mutations of haplosufficient genes are recessive
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Two models for dominance of a mutation
Figure 6-3
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Incomplete dominance
Figure 6-4
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Tailless, a recessive lethal allele in cats
Figure 6-9
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Sickled and normal red blood cells
Figure 6-5
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Heterozygotes can have the protein of both alleles
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The molecular basis of genetic complementation
Figure 6-15
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Hawley & Gilliland (2006) Fig. 1
Complementation= mutations in 2 different
genes
“Standard” interpretation of
complementation test
Non-complementation= mutations in same gene
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•ald is Drosophila mps1 homolog; isolated four mutations (all rescued by ald+ transgene)
•two ald alleles cause meiotic and mitotic defects (ald sequence changes)
•two ald “mutations” cause only meiotic defects (normal ald sequence)•both contain Doc element insertion into neighboring gene (silences transcription of neighboring genes in germline cells)
“Mutation” of a gene might be due to changes elsewhere!
Hawley & Gilliland (2006) Fig. 2
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updYM55 os1 upd3d232a Df(1)os1a
updYM55 Lethal OS WT Lethal
upd3d232a OS OS OS
Df(1)os1a Lethal
Shared regions between genes
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Transformation “rescue” is a variation of complementation test
m1/m1 without transgene mutant phenotype
m1/m1 with transgene mutant phenotype non-complement(transgene does not contain m+ gene)
m1/m1 with transgene wild-type phenotype complement(transgene contains the m+ gene)
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•Ku and Dmblm genes both involved in DNA repair and closely linked on the chromosome
•Old mutations of mus309 map to the region genetically
•DNA lesions of mus309 lie in Dmblm, but can be rescued with extra copies of Ku (provided on a transgene)
“False positive” of transgenic rescue
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Exceptions to “Non-Complementation = Allelism”
Intragenic complementation (usually allele-specific)
•Multi-domain proteins (e.g., rudimentary)
•Transvection – pairing-dependent allelic complementation (stay tuned!)
Second-Site Non-Complementation (“SSNC”)
•“Poisonous interactions” – products interact to form a toxic product (usually allele-specific)
•“Sequestration interactions” – product of one mutation sequesters the other to a suboptimal concentration in the cell (usually one allele-specific)
•Combined haplo-insufficiency (allele non-specific)
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Intragenic complementation in multi-domain proteins
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Transvection: synapsis-dependent allele complementation
E. Lewis (1954) among BX-C mutations in Drosophila
Numerous other genes in Drosophila and similar phenomena observed in Neurospora, higher plants, mammals
Most due to enhancer elements functioning in trans (allele-specific)
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Examples of body and wing yellow allele interactions
Transvection (allele complementation)
Fig. 2 Morris, et al. (1999) Genetics 151: 633–651.
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Cis-preference enhancer model (Geyer, et al., 1990)
W wing enhancerB body enhancerBr bristle enhancerT tarsal claw enhancer
Y2 is gypsy retrotransposon insertion at the yellow gene
Y1#8 780bp promoter deletion
Y1 ATG start codon → CTG
y2 complements y1#8 (wing & body pigmented)
y2 fails to complement y1 (wing & body pale)
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Exceptions to “Non-Complementation = Allelism”
Intragenic complementation (usually allele-specific)
•Multi-domain proteins (e.g., rudimentary)
•Transvection – pairing-dependent allelic complementation
Second-Site Non-Complementation (“SSNC”)
•“Poisonous interactions” – products interact to form a toxic product (usually allele-specific)
•“Sequestration interactions” – product of one mutation sequesters the other to a suboptimal concentration in the cell (usually one allele-specific)
•Combined haplo-insufficiency (allele non-specific)
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Example of a “Poisonous interaction” SSNC
Non-complementation of non-allelic mutations
Hawley & Gilliland (2006) Fig. 4(after Stearns & Botstein (1988) Genetics 119: 249–260)
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A model for synthetic lethality
Figure 6-23