05_GeneticInteractions_ST

Chapter 5: Genetic Interactions BIL250 with Dr. Laffitte-Peslak [email protected].

[Audio] Key Questions 1. How do the alleles of a single gene interact? (Variations on dominance) 2. What are penetrance and expressivity? 3. What are multigene pathways? 4. How do separate genes interact in these pathways?.

[Audio] Introduction The broad objective in this chapter is to catalog the inheritance patterns that reveal various types of gene interaction, focusing on deducing how the genes in a set interact to influence phenotype. 1. Interactions between alleles of a single gene (a single locus) may display variations on dominance. 2. Interactions between two or more loci can reveal the number and types of genes in the overall program that underlies a biological function..

[Audio] Haplosufficient genes require just a single copy for function Haplosufficient genes require just a single copy for function.

[Audio] Haploinsufficient genes require both gene copies for function Haploinsufficient genes require both gene copies for function One copy is not enough to provide normal function. Ex: heterozygous deletion mutations in Tbx1 (encoding a transcription factor) genes are dominant and cause loss of pharyngeal aortic arches in humans with DiGeorge syndrome..

[Audio] Dominant-negative mutations can dominantly interfere with wild-type function, causing loss-of-function phenotype Dominant-negative mutations can dominantly interfere with wild-type function, causing loss-of-function phenotype Dominant-negative proteins are still expressed, and might even retain some function including their interactions with other proteins, RNA, or DNA. These interactions can interfere with the endogenous WT protein function, causing a loss-of-function phenotype. Mutations in genes that encode subunits in a protein complex can also behave as dominant negatives, acting through other subunits..

[Audio] Incomplete dominance also reflects phenotypically relevant dosage effects Incomplete dominance refers to the phenotype of a heterozygote that is intermediate between those of the two homozygotes, on some quantitative scale of measurement. Ex: protein encodes an enzyme that makes a pigmented molecule. Heterozygous mutants make half as much enzyme, meaning there may be half as much pigment, leading to an intermediate phenotype..

[Audio] Some genes, including the A or S Sickle-cell hemoglobin alleles, can show co-dominance Co-dominance: expression of both alleles in a heterozygote Why would the HbS allele persist in the human population? Cellular level: incomplete dominance (Het still shows SOME sickle- cell trait).

[Audio] ome genes can show co-dominance where individual alleles can have distinct features Some genes can show co-dominance where individual alleles can have distinct features Ex: the ABO blood groups https://en.wikipedi a.org/wiki/ Blood_type Genotype: IA/IA, IA/I IB/IB, IB/I IA/IB i/i.

[Audio] Multiple alleles present in a population can interact and cause unique phenotypes Seven alleles determine the chevron pattern on the leaves of white clover. There is a variety of dominance interactions. Different combinations of alleles produce different phenotypes..

[Audio] Some genes show homozygous recessive lethality, suggesting they are present in the population despite affecting essential genes Some genes show homozygous recessive lethality, suggesting they are present in the population despite affecting essential genes Notes: A dominant allele causing taillessness in cats is lethal in the homozygous state. Lethality may range from 0-100%, depending on the gene itself, the rest of the genome, and the environment..

[Audio] Changes in phenotypic expression can arise through interactions with other genes and/or the environment Penetrance: the percentage of individuals with a given allele who exhibit the phenotype associated with that allele. Expressivity: the range of phenotypic expression, measures the intensity of the phenotype. Why do penetrance and expressivity occur? The influence of the environment. The range of phenotypes for mutant and WT individuals may overlap. The influence of other interacting genes. The subtlety of the mutant phenotype..

[Audio] Changes in phenotype penetrance and expressivity can arise through interactions with other genes and/or the environment Yes/No How much Yes/No + How much Note: Penetrance and expressivity quantify the modification of a gene's effect by varying environment and genetic background; they measure the percentage of cases in which the phenotype is observed and its severity..

[Audio] dentifying the extent to which a phenotype is controlled by one or more genes Identifying the extent to which a phenotype is controlled by one or more genes Growth of identified Neurospora auxotrophic mutants (Beadle & Tatum,1940) Auxotrophic: requiring a specific growth substance beyond the minimum required for normal metabolism and reproduction of the parental or wild-type strain..

[Audio] ification of arg arginine auxotrophic mutants Identification of arg arginine auxotrophic mutants.

[Audio] Characterization of arg auxotrophic mutants Characterization of arg auxotrophic mutants Growth of identified Neurospora arg mutants which require arginine for growth in response to other molecules (Beadleand Tatum, 1940) Supplement: Mutant Supplement: Arginine Ornithine Citrulline Arg-1 + + + Arg-2 − + + Arg-3 − − + Note:A plus sign means growth; a minus sign means no growth. What do you think the ability of Ornithine or Citrulline to rescue some mutants but not others indicates about Arginine biosynthesis?.