Lecture Notes for Friday, November 13; BTNY 1210, Fall 1998

Two New Handouts today - Genetics Study Sheet and the Genetics Lab Exercise for next week.

Outline

Non-Mendelian Genetics (continued) - dominant alleles, multiple alleles, polygenetic inheritance,

Interaction of phenotype and genotype

Human Genetics - family pedigrees, recessively inherited disorders, genetic counseling and testing

Mutations

Dominant alleles -- A dominant allele is not dominant because it "subdues" and "mutes" a recessive allele. Dominant and recessive alleles do not actually interact. Round (R) vs. wrinkled (r) seeds provides an example. The dominant R allele codes for the synthesis of enzyme that converts sugar to starch; the recessive r allele codes for a defective enzyme. Without the enzyme, sugar accumulates; during seed development, the seed swells with water by osmosis and then shrinks as the seed dries out during maturation. In general, a recessive allele usually codes for a bad (malfunctioning) or missing protein; a single dominant allele is enough to produce enough enzyme to provide the normal phenotype. Both proteins are there; i.e. the dominant allele has not suppressed the synthesis of the protein coded for by the recessive allele. Thus it is usually the dominant alleles that are most common in a population. But dominant alleles are not always the most common. For example, polydactyly (extra fingers or toes) is found in 1/400 people in the US and is a dominant allele. Most of us with 5 fingers and toes are homozygous recessives for this character.

Multiple alleles is a situation in which more than two alleles of a gene exist in the population (but only two of them are found in any one individual (recall that an individual only has two homologous chromosomes with a given locus). Human blood groups (A, B, AB, O) are an example. There are three alleles involved; A and B alleles each somehow specify a particular carbohydrate that resides on the surface of blood cells. The O allele is recessive and does not specify a carbohydrate. A and B alleles are said to be codominant because when each is present, both are expressed and the blood cells carry both carbohydrates.

Polygenic inheritance occurs when several genes control one character. In other words, 2 or more alleles affect a single phenotypic character in an additive effect. This is different from what we have seen so far in which one gene (with 2 alleles) affects one character (e.g. seed color in peas). Fig. 10-14 shows the range of continuous variation in ear length in Mexican corn resulting from many different combinations of alleles, all influencing this one character. Height and skin pigmentation in humans exhibit polygenic inheritance. In your pet plants, plant height and the amount of hairiness are polygenic characters.

Phenotype is the result of genotype interacting with the environment. In many cases, there is not a one-to-one relationship between genotype and phenotype, because the environment affects the expression of the phenotype. In our society, we often here about the "nature vs. nurture" debate, especially as regards intelligence and personality. Nature refers to the genes we inherit, whereas nurture refers to the environment in which are raised and our life experiences. It is clear that our genotype limits the potential (or range) of possible phenotypes. But the environment affects the expression of those possibilities to produce the actual phenotype. Figure 10-16 illustrates the very different types of leaves produced by the water buttercup, depending on whether the leave form underwater or in the air. Hydrangea flowers are pink in more acidic soil and blue in less acidic (more basic) soil.

Human Genetics. I went over a family pedigree using the human forehead hairline as an example. The "widow's peak" trait is dominant to a straight hairline. Other examples of family pedigrees are found in the Pre-Lab Genetics Assignment, in the Genetics lab itself and in the Genetics Study Sheet. Attached earlobes are recessive to free earlobes which are dominant in humans.

There are several 1000 recessively inherited human disorders. The recessive allele codes for a malfunctioning or missing protein, often an enzyme. Thus the disorder is only expressed in the homozygous recessive offspring. Heterozygotes are phenotypically normal because the normal (dominant) allele codes for enough of the protein to prevent the disorder, but heterozygotes are carriers and can pass the allele to their offspring. Cystic fibrosis, Tay-Sachs disease and Sickle-cell disease are among the most common of deadly genetic disorders (see Lecture Supplement #4 for a discussion of two of these disorders). Dominantly inherited human disorders are less common, especially if they are lethal, because the individual dies before he/she can pass it on to their offspring. Huntington's disease is an exception, because it's symptoms (always lethal degeneration of the nervous system) occur late in life (35-50 years of age) after the gene has been passed on to offspring.

There are a number of options for couples who suspect they might carry a genetic disorder and do not want children with the disorder. Genetic counseling based on family pedigrees has been used for a long time and is now supplemented with genetic tests that can identify carriers of genetic disorders. Counselors can give couples the probability that they will have a child with the disorder. If both parents are carriers, the chances having a child with the disorder is 1 in 4. The chances of having children who are carriers is 50%. The chances of having a child who is free of the recessive allele is 1 in 4. Prepare a Punnett square to convince yourself that a cross of two heterozygotes will result in the above 1:2:1 genetic ratios and a 3:1 phenotypic ratio. Again, these ratios reflect probabilities, and do not predict the actual genotype of any one child.

Fetal testing for genetic disorders is also available. Ultrasound is a very safe, non-invasive procedure that can detect several abnormalities. Amniocentesis involves sampling the amniotic fluid at 14-16 weeks of the pregnancy. The fluid itself sometimes provides evidence of the disorder or the fetal cells in the fluid can be grow in the laboratory and examined for visible chromosomal abnormalities or tested for biochemical evidence of a disorder. Fetal placental tissue can also be sampled or a small camera can be inserted into the womb to examine the fetus, the procedure is called fetoscopy. If a severe disorder is detected, the couple is faced with the difficult decision to terminate the pregnancy. If the fetus is carried to term, prior warning of the condition might help with early treatment. A number of tests are routinely performed on newborns, including PKU (phenylketonuria) which detects an inability to metabolize the amino acid phenylalanine. A modified diet prevents this amino acid from building up and causing mental retardation.

Mutations can be defined as relatively small changes in the structure of the gene itself (the DNA) as well as bigger changes in chromosomes. Mutations are thought of as bad things, and generally, they are. But mutation increases genetic diversity and is an absolute requirement for life. It is the raw material (the fuel) for evolutionary change, without which life would never have evolved beyond a few replicating chemicals. What happens following a mutation? Mutations are often lethal and the cell dies. If the mutation is not lethal, it will be passed on to the descendents of that cell. If the mutation occurs in a sex cell or a precursor to a sex cell, it will be passed on to the next generation. A non-lethal (to the cell) mutation often contributes to cancer. There are two general types of mutations. A point mutation affects one or a few bases in a gene; this is the source of alternative forms of a gene (alleles). I presented a figure from another book showing how UV light causes mutations by forming thymine dimers (i.e. a side to side bond between two adjacent thymine bases in DNA). The thymine dimer distorts the DNA molecule causing mistakes next time the chromosome is replicated. Fortunately we have DNA repair enzymes that repair most of these errors, but the few that are missed cause skin cancer. The second general type of mutation involves wholesale changes in chromsomes. In some cases there are deletions of sections of a chromosome or duplications of a section. Some genes are known to move "jump" from one chromosome to another. In plants, a common form of mutation involves the acquisition of additional chromosomes beyond the 2n number. This condition is known as polyploidy and is important in plant evolution.