22 Chapter 3 Chapter 3 Extensions to Mendel: Complexities in Relating Genotype to Phenotype Synopsis: This chapter builds on the principles of segregation and independent assortment that you learned in Chapter 2. An understanding of those basic principles will help you understand the more complex inheritance patterns in Chapter 3. While the basic principles for the inheritance of alleles of one or more genes hold true, the expression of the corresponding phenotypes is more complicated. Chapter 3 describes several examples of single gene inheritance in which phenotypic monohybrid ratios are different from the complete dominance examples in Chapter 2 (see Significant Elements on next page and Table 3.1). These variant phenotypic monohybrid ratios may be caused by: ♦ incomplete dominance; ♦ codominance; ♦ dominance series of multiple alleles ♦ lethal alleles; ♦ pleiotropy. Also introduced in this chapter are examples in which two or more interacting genes determine the phenotype. Remember from Chapter 2 that crosses involving two independently assorting genes have a 9 A-B- : 3 A- bb : 3 aa B- : 1 aa bb dihybrid F2 phenotypic ratio. If two genes interact then the dihybrid ratio is a modification of the 9:3:3:1 ratio. This modification involves the same genotypes for the progeny. Because of the effect of an allele of one gene on the other gene (epistasis), the four classes can be added together in different combinations. Multigene inheritance (>2 genes involved) leads to even more phenotypic classes. With more genes controlling a trait you see a continuous range of phenotypes instead of discrete traits, as in Figure 3.21. Penetrance and expressivity are terms used to describe some cases of variable phenotypic expression in different individuals. Penetrance describes the fraction of individuals with a mutant genotype who are affected while expressivity describes the extent to which individuals with a mutant genotype are affected.Chapter 3 23 Significant Elements: After reading the chapter and thinking about the concepts you should be able to: ♦ Understand that novel phenotypes arise when there is codominance or incomplete dominance. The novel phenotype will appear in the F1 generation. In the F2 generation, this same phenotype must be the largest component of the 1:2:1 monohybrid ratio. ♦ Realize that if you see a series of crosses involving different phenotypes for a certain trait, for example coat color, and each individual cross gives a monohybrid ratio, then all the phenotypes are controlled by one gene with many alleles. In other words, the problem involves an allelic series as in Figure 3.6. It is important to write a dominance hierarchy for the alleles of the gene, e.g. a = b > c. Thus, a is codominant or incompletely dominant to b and both a and b are completely dominant to c. ♦ Understand that lethal mutations are almost always recessive alleles, as shown in Figure 3.9. If there is a recessive lethal allele present in a cross you can never make that allele homozygous. Therefore the cross must have involved parents heterozygous for the lethal allele. Instead of the expected 1:2:1 ratio in the progeny, one of the 1/4 classes is lethal, so the monohybrid phenotypic ration will be 2/3 heterozygous phenotype : 1/3 other (viable) homozygous phenotype caused by homozygosity for the other allele. The recessive lethal allele may be pleiotropic and show a different, dominant phenotype, as in Figure 3.9. ♦ Remember that epistasis involves two genes. In epistasis, none of the progeny die. All are present, but instead of four phenotypic classes in a 9:3:3:1 phenotypic dihybrid ratio, you will see an epistatic variation where 2 or 3 of the phenotypes have been summed together, for example 9:3:4 or 9:7 or 12:3:1. Problem Solving Tips: ♦ Solve enough problems so you can distinguish single and two gene traits on the basis of inheritance patterns. Look for the number of classes in the F2 generation to identify single gene inheritance (3:1, 1:2:1, 1:1 or 2:1) versus 2 gene inheritance (9:3:3:1 or an epistatic variation). In the Study Guide 'monohybrid ratio' is used in a more general sense than in the text to refer to any ratio that is based on the segregation of the alleles of a single gene (3:1, 1:2:1, 1:1 or 2:1). Likewise, in the Study Guide dihybrid ratio refers to any ratio based on the segregation of the alleles of 2 genes (9:3:3:1, 1:3:4, 15:1, etc). ♦ Be able to derive the monohybrid phenotypic ratios for incomplete dominance/codominance and lethal alleles involving inheritance of a single gene.24 Chapter 3 ♦ It is critical that you understand the 9:3:3:1 phenotypic dihybrid ratio involves the 4 classes 9/16 A- B- : 3/16 A- bb : 3/16 aa B- : 1/16 aa bb, where a dashed line (-) indicates either a dominant or recessive allele. ♦ If the phenotype involves 2 genes, be able to propose ways in which two genes interact based on offspring ratios. Do not merely memorize the altered ratios (Table 3.2); instead think through what the combinations of alleles mean. ♦ Remember the product rule of probability and use it to determine proportions of genotypes or phenotypes for independently assorting genes. Problem Solving - How to Begin: THREE ESSENTIAL QUESTIONS (3EQ): #1. How many genes are involved in the cross? #2. For each gene involved in the cross: what are the phenotypes associated with the gene? Which phenotype is the dominant one and why? Which phenotype is the recessive one and why? [#3. For each gene involved in the cross: is it X-linked or autosomal?] At this point, only questions #1 and #2 may be applied. The material that is the basis of question #3 will be covered in Chapter 4. Hints: BE CONSISTENT. Always diagram the crosses and write out the genotypes. Set the problems up the same way. Note the repetitive approach to many of the problems in this chapter. Make sure you always distinguish between genotypes and phenotypes when working the problems. To answer 3EQ#1, look for the number of phenotypic classes in the F2 progeny. Two phenotypes usually means 1 gene, 4 phenotypes MUST be due to 2 genes. Three phenotypic classes is an ambiguous result - this could result from 1 gene with codominance or incomplete dominance, or from 2 genes with epistasis. Use the ratio of phenotypes to distinguish between these possibilities. One gene with codominance/incomplete dominance MUST give 1:2:1 while 2 genes with 3 phenotypes will