Alterations to Mendel

1. Alterations to Mendel • Incomplete or partial dominance • Codominance • Multiple alleles • Lethal alleles • Gene interactions & multiple genes • Sex-linked, sex-limited, & sex-influenced • Effect of environment • Extranuclear inheritance

2. Multiple genes • Sometimes a phenotype is controlled by more than one gene • Different from multiple alleles of same gene!! • Gene products don’t necessarily directly interact. • Genes may code for enzymes in a pathway • Cascade of gene during development • Epistasis: a gene (or gene pair) masks or modifies the expression of another gene (or gene pair).

3. Epistasis: gene interaction that perturbs normal Mendelian ratios • Example: interaction between two genes in the pathway for pigment production, C and P • C, P = dominant; c, p = recessive. • Because both genes are needed, if individual is homozygous recessive for either gene, no color. • CcPp, all colored in F1 • CcPp x CcPp 9:7 phenotypic ratio • Do the Punnett square and see • Independent assortment still applies • Various interactions produce different ratios.

4. Epistasis example: Bombay phenotype In the ABO blood groups, A and B are codominant. How can the person in this pedigree be type O (IO IO)?

5. Epistasis example: explanation A second gene, Ih codes for the base sugar chain to which the A and B sugars are added. A rare mutation Ih Ih prevents proper formation so that the A and B sugars cannot be added even though the enzyme for doing that is being made. (Diagram next slide) A second gene is masking the normal phenotype.

6. Molecular explanation

7. Complementation • Several different genes may contribute to phenotype. • How can you tell whether a phenotype results from one gene or from several? • Create several mutants with the same phenotype. • Perform complementation tests:Cross different mutants. If mutations are in different genes, offspring will have one good copy of each gene, restoring WT phenotype: the mutants complement.If offspring show the mutant phenotype, mutation is in same gene.

8. http://www.hort.purdue.edu/rhodcv/hort640c/proline/pr00003.htmhttp://www.hort.purdue.edu/rhodcv/hort640c/proline/pr00003.htm

9. Complementation example • Example: bacteria unable to make the amino acid proline. proB mutants: known mutations in the proB gene. proA mutants: have mutations in the proA gene, etc. In which proline gene does “pro-53” have a mutation? To find out, Create merozygotes. These are bacteria that have two copies of the genes of interest (bacteria normally have only one of each). “Cross” pro-53 with each of the known mutants.

10. Complementation crosses The unknown mutant (pro-53) is “crossed” with each of the other types of mutants. Does the cross result in a “cure” (the bacterium can now make proline) or is it still defective? In this cross, DNA from a proA- mutant is added to the pro-53 bacterium. The presence of this DNA is unable to rescue pro-53 (does not complement), because the mutation is in the SAME gene. The pro-53 must be a proA mutant.

11. The other crosses pro-53 said to be in same complementation group as other pro-A mutants. What happens when pro-53 is crossed with a proB mutant? The added DNA cures pro-53 because now it has good copies of all 3 genes: a+ b+ c+ Do a cross with a proC mutant.

12. The sex chromosomes • The rest of the chromosomes are autosomes. • Sex chromosomes determine sex of individual. • X and Y differ in size, X much bigger in humans • But still synapse during meiosis, so still a pair • In humans, fruit flies, XX = female; XY = male. • In several other organisms, other combinations of sex chromosomes determine sex. • Because there are genes on sex chromosomes, inheritance of certain traits can be sex-linked.

13. Sex linked, limited, & influenced • Sex linked inheritance is when the allele is present on a sex chromosome (usually X). • Sex limited: when other genetic factors restrict expression to one sex • Bulls don’t give milk. • Sex influenced: other genetic factors modulate expression. Example: pattern baldness • Females must be homozygous recessive for trait • Even then, hormonal factors restrict expression.

14. Environmental factors • Expression of genes is affected by genetic background (internal environment) but also by the external environment. • Penetrance vs. Expressivity • Penetrance refers to percentage of individuals in a population that show the trait to some extent. • 6 fingers is a dominant trait, but… • Expressivity: the degree to which the trait is expressed within an individual.

15. External environment • Numerous examples in other organisms, e.g. sex determination in turtles and crocodiles. • Temperature effects • Conditional mutations, especially temperature sensitive mutations. Permissive vs. restrictive. • Himalayan rabbit, Siamese cat • Lethal genes in microbes • Growth and development • Various human diseases, strike at various times of development. E.g. Huntington disease. www.tcainc.org/photos/ farpoint/saavik1.jpg

16. Mitochondrial Inheritance Endosymbiont hypothesis: mitochondria descended from endosymbiotic bacteria. Outer membrane separates organelle from cytoplasm. Inner membrane site of ATP synthesis.Inner and outer membranes analagous to Gram negative bacteria. Mitochondria have their own DNA, ribosomes, tRNA (all bacteria-like) and replicate independently of cell cycle. www.protein-ms.de/ RES/Mito/mito.htm

17. Mitochondrial Inheritance-2 • Mitochondria well integrated into cell • Some genes for structure & function of the mitochondrion are found in the nucleus. • Not a completely independent entity. • Mutations in Mt DNA cause genetic diseases which reflect function of mitochondria • Major function: ATP generation • Diseases feature breakdown of function in tissues requiring high levels of ATP • Muscle and nerve tissue disorders

18. Mitochondrial inheritance is maternal • During meiosis in females, cell division is asymmetric with most of the cytoplasm including mitochondria going into the eventual ovum. • Spermatozoa are DNA delivery devices with little cytoplasm. http://www.ucalgary.ca/UofC/eduweb/virtualembryo/PageMill_Images/image145.gifyalenewhavenhealth.org/ library/healthguide/en...