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Gene Interaction

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.

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Gene Interaction

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  1. Gene Interaction

  2. Mutations of haplosufficient genes are recessive

  3. Two models for dominance of a mutation Figure 6-3

  4. Incomplete dominance Figure 6-4

  5. Tailless, a recessive lethal allele in cats Figure 6-9

  6. Sickled and normal red blood cells Figure 6-5

  7. Heterozygotes can have the protein of both alleles

  8. The molecular basis of genetic complementation Figure 6-15

  9. “Standard” interpretation of complementation test Complementation= mutations in 2 different genes Non-complementation= mutations in same gene Hawley & Gilliland (2006) Fig. 1

  10. “Mutation” of a gene might be due to changes elsewhere! • 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) Hawley & Gilliland (2006) Fig. 2

  11. Shared regions between genes

  12. 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)

  13. “False positive” of transgenic rescue • Ku and Dmblm genesboth 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)

  14. 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)

  15. Intragenic complementation in multi-domain proteins

  16. 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)

  17. Examples of body and wing yellow allele interactions Transvection (allele complementation) Fig. 2 Morris, et al. (1999) Genetics 151: 633–651.

  18. Cis-preference enhancer model (Geyer, et al., 1990) W wing enhancer B body enhancer Br bristle enhancer T tarsal claw enhancer Y2is 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)

  19. 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)

  20. Example of a “Poisonous interaction” SSNC Non-complementation of non-allelic mutations Hawley & Gilliland (2006) Fig. 4 (after Stearns & Botstein (1988) Genetics119: 249–260)

  21. A model for synthetic lethality Figure 6-23

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