M1 L2: Non-Mendelian Genetics

• Extending Mendelian Genetics for a Single Gene:

  The inheritance of characters determined by a single gene deviates from simple Mendelian patterns when alleles are not completely dominant or recessive, when a particular gene has more than two alleles or when a single gene produces multiple phenotypes.
• Degrees of Dominance:

  Alleles can show different degrees of dominance and recessiveness in relation to each other. In Mendel's classic pea crosses, F1 offspring always looked like one of the parental varieties because one allele in a pair showed complete dominance over the other. In such situations, the phenotypes of the heterozygote and the dominant homozygote are indistinguishable 

  
• Degrees of Dominance:

  For some genes, however, neither allele is completely dominant, and the F1 hybrids have a phenotype somewhere between the two parental varieties. This phenomenon, called incomplete dominance, is seen when red snapdragons are crossed with white snapdragons: All the F1 hybrids have pink flowers. This third, intermediate phenotype results from flowers of the heterozygotes having less red Pigment than the red homozygotes.

  
• Degrees of Dominance:

  At first glance, incomplete dominance of either allele seems to provide evidence for the blending hypothesis of inheritance = red or white trait could never reappear among offspring of the pink hybrids. But interbreeding F1 hybrids produce F2 offspring with a phenotypic ratio of 1 red: 2 pink: 1 white. The segregation of the red and white alleles in the gametes produced by the pink-flowered plants confirms that the alleles for flower color are heritable factors that maintain their identity in the hybrids = discrete rather than "blendable."

  
• Degrees of Dominance:

  Codominance: two alleles each affect the phenotype in separate, distinguishable ways. For example, the human MN blood group is determined by codominant alleles located on the surface of red blood cells, the M and N molecules. A single gene (L^M), for which two allelic variations are possible (L^M or L^N), determines the phenotype of this blood group. L^M allele (L^M L^M) = only M molecules; L^N allele(L^N L^N) = only N molecules. But both M and N molecules are present in the red blood cells of individuals heterozygous for the M and N alleles (L^M L^N).
• The Relationship Between Dominance and Phenotype:

  We've now seen that the relative effects of two alleles range from complete dominance of one allele to incomplete dominance of either allele to codominance of both alleles. An allele is called dominant because it is seen in the phenotype, not because it somehow subdues a recessive allele. Alleles are simply variations in a gene's nucleotide sequence. When a dominant allele coexists with a recessive allele in a heterozygote, they do not actually interact at all.

  
• The Relationship Between Dominance and Phenotype:

  Round vs wrinkled pea seed shape: The dominant allele (round) codes for an enzyme that helps convert an unbranched form of starch to a branched form in the seed. The recessive allele (wrinkled) codes for a defective form of this enzyme, leading to an accumulation of unbranched starch, which causes excess water to enter the seed by osmosis. = wrinkles. One dominant allele results in the enzyme synthesizing adequate amounts of branched starch, which means that dominant homozygotes and heterozygotes have the same phenotype: round seeds
• The Relationship Between Dominance and Phenotype:

  For any character, the observed dominant/recessive relationship of alleles depends on the level at which we examine phenotype. Tay-Sachs disease, an inherited disorder in humans, is an example. Brain cells of a child with Tay-Sachs disease cannot metabolize certain lipids because a crucial enzyme does not work properly. As these lipids accumulate in brain cells, the child begins to suffer seizures, blindness, and degeneration of motor and mental performance and dies within a few years
• The Relationship Between Dominance and Phenotype:

  Only children who inherit two copies of the Tay-Sachsallele (homozygotes) have the disease. Thus, at the organismal level = Tay-Sachs allele qualifies as recessive. However, the activity level of the lipid-metabolizing enzyme in heterozygotes is intermediate between the activity level in individuals homozygous for the normal allele and the activity level in individuals with Tay-Sachs disease. The intermediate phenotype observed at the biochemical level is characteristic of incomplete dominance of either allele.
• The Relationship Between Dominance and Phenotype:

  The heterozygote condition does not lead to disease symptoms apparently because half the normal enzyme activity is sufficient to prevent lipid accumulation in the brain. Extending our analysis to yet another level, we find that heterozygous individuals produce equal numbers of normal and dysfunctional enzyme molecules. Thus, at the molecular level, the normal allele and the Tay-Sachs allele are codominant. 
• Frequency of Dominant Alleles:

  Dominant allele = not the most common. For an example of a rare dominant allele, about one baby out of 400 in the United States is born with extra fingers or toes, a condition known as polydactyly. Some cases are caused by the presence of a dominant allele. The low-frequency of these types of polydactyly indicate that the recessive allele which results in five digits per appendage is far more prevalent than the dominant allele in the population
• Multiple Alleles:

  more than two alleles. The ABO blood groups in humans, for instance, are determined by the two alleles a person has of the blood group gene; the three possible alleles are I^A, I^B, i. A person's blood group may be one of four, types: A, B, AB, and O. two carbohydrates-A and B that may be found attached to specific cell-surface molecules on red blood cells. An individual's blood cells may have carbohydrate A (type A blood), carbohydrate B (type B), both (type AB), or neither (type O).

  
• Pleiotropy

  Most genes, however, have multiple phenotypic effects, a property calledpleiotropy (from the Greek pleion, more). In humans, for example, pleiotropic alleles are responsible for the multiple symptoms associated with certain hereditary diseases, such as cystic fibrosis and sickle-cell disease,. In the garden pea, the gene that determines flower color also affects the color of the coating on the outer surface of the seed, which can be gray or white.
• Extending Mendelian Genetics for Two or More Genes:

  Dominance relationships, multiple alleles, and pleiotropy all have to do with the effects of the alleles of a single gene. We now consider two situations in which two or more genes are involved in determining a particular phenotype. In the first case, called epistasis, one gene affects the phenotype of another because the two gene products interact; in the second case, called polygenic inheritance, multiple genes independently affect a single trait.
• Epistasis:

  In epistasis (from the Greek for "standing upon"), the phenotypic expression of a gene at one locus alters that of a gene at a second locus. An example will help clarify this concept Labrador retrievers (commonly called "Labs"), black coat color is dominant to brown. browned fur lab = bb. A second gene determines whether or not pigment will be deposited in the hair. The dominant allele (E), results in the deposition of either black or brown pigment, depending on the genotype at the first locus.

  
• Epistasis:

  But if the Lab is homozygous recessive for the second locus (ee), then the coat is yellow regardless of the genotype at the black/brown locus (yellow Labs). The gene for pigment deposition (E/e) is said to be epistatic to the gene that codes for black or brown pigment (B/b). Although the two genes affect the same phenotypic character (coat color), they follow the law of independent assortment. Thus, our breeding experiment represents an F, dihybrid cross, like those that produced a 9:3:3:1 ratio in Mendel's experiments.

  
• Polygenic Inheritance:

  Human skin color and height, are not one of two discrete characters, but instead vary in the population in gradations along a continuum. These are called quantitative characters. Quantitative variation usually indicates polygenic inheritance, an additive effect of two or more genes on a single phenotypic character. (In a way, this is the converse of pleiotropy) Many variations were in or near genes involved in biochemical pathways affecting the growth of the skeleton. Another study identified 124 genes that affect hair color.
• Polygenic Inheritance:

  Skin pigmentation in humans is also controlled by many separately inherited genes- 378 at latest count, many ofwhich are involved in the production of melanin skin pigments. Let's consider three genes, with a dark-skin allele for each gene (A, B, or C) contributing one "unit" of darkness (also a simplification) to the phenotype and being incompletely dominant to the other, light-skin allele (a, b, or 0). In our model, an AABBCC person would be very dark, whereas an AABBCC individual would be very light

  
• An AaBbCc person would have the skin of an intermediate shade. Because the alleles have a cumulative effect, the genotypesAaBbCc and AABbcc would make the same genetic contribution (three units) to skin darkness. There are seven skin color phenotypes that could result from a mating between AaBbCc. In a large number of such matings, the majority of offspring would be expected to have intermediate phenotypes (skin color in the middle range).