Chapter 4: Extensions of Mendelian Genetics

Normal Dominant/Recessive Patterns

Keep table 4.1 on page 72 handy. It has all the Mendelian inheritance patterns involving a single gene.  Recessive Alleles & Loss of Function: Wild-type alleles are prevalent alleles in a natural population (72). In larger populations, more than 1 wild-type allele may occur. This is called genetic polymorphism.  Wild-types typically encode a protein that is made in the proper amount and funcitons normally. Mutant alleles are random mutations that occur in a population and alter the preexisting alleles (72) These alleles are often defective in ability to express a functional protein.  Recessive alleles usually cause a substantial decrease in the expression of a functional protein. This is supported by analysis of many human genetic diseases, as genetic diseases are usually caused by a recessive allele (73).  In simple dominant/recessive patterns, the recessive allele does not affect phenotype. A single copy of the dominant allele can mask it (73).  The theory is that 50% of the functional protein is all that's needed to provide the wild-type phenotype. A homozygous individual has more than enough protein to produce the gene (73-74) This phenomenon is fairly common among many genes (74)  

Incomplete Patterns

Incomplete dominance Incomplete dominance is when a heterozygote displays an intermediate phenotype between the corresponding homozygous individuals  (74).  Incomplete dominant traits do not follow the "50% is enough" rule for proteins. The heterozygotes do not produce the same amount as a homozygous individual, and will therefore display a different phenotype (74).  Sometimes traits that phenotypically look controlled by a normal dominant/recessive pattern will actually have an incomplete dominance pattern at a molecular level (74).  Incomplete penetrance This occurs when the dominant allele does not always "penetrate" into the individuals' phenotype (75). An example is polydactyly. The measure of penetrance is described at a populational level (75). Expressivity is the degree to which the trait is expressed. How much the allele is penetrating in an individual is displayed in the individual's phenotype (73). The range in phenotypes for these traits is often due to environmental influences and/or a modifier gene (75). 

Other Inheritance Patterns

Environment and Outcome In addition to genetics, the environmental conditions have a great impact on phenotype (76) A human example of the environment changing the outcome of a disease is the use of diet in phenylketonuria (76).  The norm of reaction refers to the effects of environmental variation on a phenotype. Specifically, it is the phenotypic range seen in individuals with a particular genotype (76-77). Overdominance The phenomenon in which a heterozygote has a greater reproductive success compared to either of the corresponding homozygotes is called overdominance, or heterozygote advantage (77). A well documented example is sickle-cell disease (77).  Overdominance is usually due to 2 alleles that produce proteins with slightly different amino acid sequences. It can, however, also be explained by the subunit composition of proteins and the functional ability of the proteins encoded by each allele (78). Heterosis, or hybrid vigor, is when the hybrids of 2 highly inbred strains display traits that are superior to both corresponding parental strains (78).     It differs from overdominance because the hybrid may be heterozygous for many genes, not just single gene. Genes existing as 3+ Alleles Most genes exist in multiple alleles. The book's example consists of the fur of rabbits (79) Temperature-sensitive alleles are alleles that only work at certain temperatures. In animals this explains the himilayan pattern of coat color (79).  Blood The phenomenon in which 2 alleles are both expressed in the heterozygous individual is called codominance (80).

Let's Talk About Sex

X-Linked Traits (Again) X-linked recessive traits are recessive traits that have the allele on the X chromosome (81).  A reciprocal cross is a 2nd cross in which the sexes and phenotypes are reverses (81). The male will transmit the gene only to female offspring, while the female transmits an X chromosome to both genders. Therefore the male will not be contribute to X-linked phenotypes in his male sons (82).  Sex-linked gene A sex linked gene refers to a gene that is found on 1 of the 2 types of sex chromosomes, but not on both (82). Hemizygous is used to describe the single copy of an X linked gene in the male (82). As a result, males are more likely to be affected by rare, recessive X disorders.  Holandric genes are the few genes located only on the Y chromosome (82). Pseudoautosomal inheritance is a pattern in which a gene located on a sex chromosome transmits like an autosome would (83).  This can occur in the few regions where the X and the Y chromosomes display homology.  Sex-influenced gene Sex-influenced gene refers to the phenomenon in which an allele is dominant in one sex but recessive in the opposite (83).  The genes that influence this are usually autosomal.  A major example of this is baldness. It's a common misconception that it's X linked, but it's actually inherited as an autosomal trait (83).  Sex-limited inheritance is when the trait occurs in only 1 of the 2 sexes (84). 

Deadly Genetics

Loss of function in essential genes: A lethal allele is an allele that has the potential to cause death of an organism (84). These are usually recessive. Many of these prevent cell division, and thereby kill an organism at a very early stage (85).  An essential gene is one that encodes for a protein that, if missing, will cause death (84). Nonessential genes are not absolutely required for survival, although they are likely to be beneficial (85). A loss-of-function mutation in one of these will generally not cause death, but it still may cause death.  In the rare instances where a lethal allele does not kill the organism immediately, the age of onset is when the symptoms of the disease will appear (85). Conditional lethal alleles only kill the organism when certian environmental conditions occur (85).  A subset of this are temperature-sensitive lethal alleles. These ones only kill the organism in a particular temperature range.  Semilethal alleles are alleles that act only in some individuals. Inside of a population, these alleles will kill some individuals, but not all of them (85). Lethal alleles may produce ratios that deviate from Mendelian ratios (85). 

Pleiotropy and Epistasis

Single genes with multiple effects: Most genes actually have multiple effects throughout a cell and/or throughout a multicellular organism.  The multiple effects of a single gene on the phenotype of an organism is called pleiotropy It can occur due to the following (86) Expression of a single gene that can affect cell function in more than 1 way.  A gene may be expressed in different cell types in a multicellular organism. A gene may be expressed at different stages of development.  Gene interactions (section 4.2): Essentially all traits are affected by the contributions of many genes (86).  The phenomenon of how the allelic variants of 2 different genes affect a single trait is called gene interaction (86). A Cross Can Produce 4 Distinct Phenotypes Epistasis  is when the alleles of one gene mask the phenotypic effects of the alleles of another gene (87).  Recessive epistasis is when the individual must be homozygous for either recessive allele to mask the phenotypic effects of the dominant allele.  2 Gene Interaction and Epistasis In the case of flowers, homozygosity for the while allele of one gene masks the expression of the purple-producing allele of another gene (88) Epistasis often occurs because 2 or more different proteins participate in a common function (88).  Complementation is when 2 parents displaying a recessive phenotype produce an offspring with a wild-type phenotype (88). This will usually occur because the recessive phenotype in the parents is due to homozygosity at 2 different genes.  Epistasis can produce 3 distinct phenotypes: Hair color in rats is the example used in the book (88-89). A gene modifier effect is when the alleles of one gene modify the phenotypic effect of the alleles of a different gene (89).

Gene redundancy and suppressor mutations

Gene redundancy and loss-of-function alleles A gene knockout is when a geneticist abolishes a gene function by creating an organism that is homozygous for a loss-of-function allele (91). The reason for this is to understand how a gene affects the structure and function of cells or the phenotypes of organisms.  Geneticists have discovered that many knockouts have no obvious effect on phenotype at any level. Gene redundancy is the phenomenon that one gene can compensate for the loss of function of another gene. This can explain why a single gene knockout may not have any phenotypic effect (91). When one gene is missing, a paralog may be able to carry out the missing function (91). Alternatively, gene redundancy may involve proteins that are involved in a common cellular function. Suppressor Mutations A suppressor mutation is a second mutation that reverses the phenotypic effects of a first mutation (92). Sometimes these can occur in a gene different from the one the first mutation occured in. Then it's called an intergenic suppressor or extragenic suppressor. The reason for identifying an intergenic suppressor is to identify proteins that participate in a common cellular process that ultimately affects the traits of an organism (92).  The analysis of a mutant and its suppressor often provides key info that 2 proteins participate in a common function (92).  Alternatively, 2 distinct proteins encoded by different genes may participate in a common function, but do not directly interact with each other (92-93).  Some suppressors exert their effects by altering amount of protein encoded by a mutant gene (93).