_{Patterns of Inheritance}

Chapter

10

Outline

10.1 Mendel’s Laws

• Gregor Mendel discovered certain laws of heredity after doing experiments with garden peas during the mid-1800s.142–43

• When Mendel did one-trait crosses, he found that each organism contains two factors for each trait and that the factors separate during formation of gametes.144

• A testcross can be used to determine the genotype of an individual with the dominant phenotype.144

• When Mendel did two-trait crosses, he found that every possible combination of factors is present in the gametes.146

• A testcross can also be used to determine the genotype of an individual that is dominant in two traits.146

10.2 Beyond Mendel’s Laws

• The genotype must be considered an integration of all the genes as a whole, because genes often work together to control the phenotype.149

• Certain patterns of inheritance involve degrees of dominance, multiple alleles, and polygenes.149-–50

• Environmental conditions can influence gene expression.150

• When a gene has multiple effects, one mutation can affect many parts of the body, causing a syndrome.151

10.3 Sex-Linked Inheritance

• Certain traits, unrelated to gender, are controlled by genes located on the X chromosome.152

• A gene on the X chromosome has a pattern of inheritance that differs from that of genes on the autosomes.153

10.4 Inheritance of Linked Genes

• Despite linkage, crossing-over can bring about recombinant gametes, and recombinant phenotypes do occur.154

• The percentage of recombinant phenotypes when genes are linked can be used to map the chromosomes.154

Just how much influence do genes have over the develop-ment of particular traits including genetic diseases? In cases such as sickle cell disease and cystic fibrosis, the genes have complete influence over their development, and the probable occurrence of the trait is easy to predict. In other cases, the influence of the genes alone do not forecast a particular trait. Rather, environmental factors also influence whether certain specific traits develop. Determining the pattern of inheritance for traits that are not completely genetic is a difficult task.

Tests are available for some alleles associated with genetic diseases. For example, a woman can be tested to see if she has the BRCA-1 and BRCA-2 alleles, both of which are associated with breast and ovarian cancer. However, the allele alone is not sufficient to cause the development of cancer—environmental factors are also involved. Therefore, even if a woman tests positive for these alleles, she may not develop cancer. Unfortunately, it is impossible to predict for sure whether or not cancer will occur. Still, some women have resorted to extraordinary methods, such as radical mastectomy to remove all breast tissue, to prevent the possibility of cancer.

In this chapter, you will learn about the basic principles of inheritance. Stress will be placed on the rules of genetics that allow us to predict the chances of a trait being passed on from one generation to the next. However, we have to bear in mind that sometimes environmental influences affect the passage of traits.

_{10.1 Mendel’s Laws}

Today, most people know that DNA is the genetic material, and they may have heard that scientists have determined the DNA base sequence of human chromosomes. In contrast, they may not know about Gregor Mendel, an Austrian monk who developed certain laws of heredity after doing crosses between garden pea plants in 1860 (Fig. 10.1). Gregor Mendel investigated genetics at the organismal level, and this is still the level that intrigues most of us on a daily basis. We observe, for example, that facial and other features run in families, and we would like some way of explaining this observation. And so, it is appropriate to begin our study of genetics at the organismal level and to learn Mendel’s laws of heredity.

When Mendel began his work, most plant and animal breeders acknowledged that both sexes contributed equally to a new individual. However, they were unable to account for the presence of definite variations (differences) among the members of a family, generation after generation. Mendel’s model of heredity does account for such variations. Therefore, Mendel’s model is compatible with the theory of evolution, which states that various combinations of traits are tested by the environment, and those combinations that lead to reproductive success are the ones that are passed on.

Mendel’s Experimental Procedure

Mendel’s parents were farmers, so he no doubt acquired the practical experience he needed to grow pea plants during childhood. Mendel was also a mathematician; most likely, his background in mathematics prompted him to use a statistical basis for his breeding experiments. He prepared for his experiments carefully and conducted preliminary studies with various animals and plants. He then chose to work with the garden pea, Pisum sativum.

The garden pea was a good choice. The plants were easy to cultivate and had a short generation time. And although peas normally self-pollinate (pollen goes only to the same flower), they could be cross-pollinated by hand. Many varieties of peas were available, and Mendel chose 22 of them for his experiments. When these varieties self-pollinated, they were true-breeding—meaning that the offspring were like the parent plants and like each other. In contrast to his predecessors, Mendel studied the inheritance of relatively simple and easily detected traits, such as seed shape, seed color, and flower color, and he observed no intermediate characteristics among the offspring. Figure 10.2 shows Mendel’s procedure.

As Mendel followed the inheritance of individual traits, he kept careful records. He used his understanding of the mathematical laws of probability to interpret his -results and to arrive at a theory that has since been supported by innumerable experiments. This theory is called a particulate theory of inheritance because it is based on the existence of minute particles we now call genes. Inheritance involves the reshuffling of the same genes from generation to generation.

One-Trait Inheritance

After ensuring that his pea plants were true-breeding—for example, that his tall plants always had tall offspring and his short plants always had short offspring—Mendel was ready to perform a cross between these two strains. Mendel called the original parents the P generation, the first-generation offspring the F₁ (for filial) generation, and the second-generation offspring the F₂ generation. The diagram in Figure 10.3 representing Mendel’s F₁ cross is called a Punnett square. In a Punnett square, all possible types of sperm are lined up vertically, and all possible types of eggs are lined up horizontally, or vice versa, so that every possible combination of gametes occurs within the square.

As Figure 10.3 shows, when Mendel crossed tall pea plants with short pea plants, all the F₁ offspring resembled the tall parent. Did this mean that the other characteristic, shortness, had disappeared permanently? No, because when Mendel allowed the F₁ plants to self-pollinate, ³⁄4 of the F₂ generation were tall and ¹⁄4 were short, a 3:1 ratio. Therefore, the F₁ plants had been able to pass on a factor for shortness—it didn’t just disappear. Perhaps the F₁ plants were tall because tallness was dominant to shortness?

Mendel’s mathematical approach led him to interpret his results differently than previous breeders had done. He reasoned that a 3:1 ratio among the F₂ offspring was possible only if (1) the F₁ parents contained two separate copies of each hereditary factor, one dominant and the other recessive; (2) the factors separated when the gametes were formed, and each gamete carried only one copy of each factor; and (3) random fusion of all possible gametes occurred upon fertilization. Only in this way would shortness reoccur in the F₂ generation.

One-Trait Testcross

Mendel’s experimental use of simple dominant and recessive characteristics allowed him to test his interpretation of his crosses. To see if the F₁ carries a recessive factor, Mendel crossed his F₁ generation tall plants with true-breeding, short plants. He reasoned that half the offspring would be tall and half would be short (Fig. 10.4a). And, indeed, those were the results he obtained; therefore, his hypothesis that factors segregate when gametes are formed was supported.

Today, a one-trait testcross is used to determine whether or not an individual with the dominant trait has two dominant factors for a particular trait. This is not possible to tell by observation because an individual can exhibit the dominant appearance while having only one dominant factor. Figure 10.4b shows that if the individual has two dominant factors, all the offspring will be tall.

After doing one-trait crosses, Mendel arrived at his first law of inheritance—the law of segregation, which is a cornerstone of his particulate theory of inheritance. The law of segregation states the following:

• Each individual has two factors for each trait.

• The factors segregate (separate) during the formation of the gametes.

• Each gamete contains only one factor from each pair of factors.

• Fertilization gives each new individual two factors for each trait.

The Modern Genetics View

Mendel’s law of segregation holds for all organisms, including humans. In modern terms, we say that a trait is controlled by two alleles, alternate forms of a gene. The dominant allele is so named because of its ability to mask the expression of the other allele, called the -recessive allele. The dominant -allele is identified by an uppercase (capital) letter, and the -recessive allele by the same but lowercase (small) letter. In humans, for example, alleles for finger length might be S for short fingers and s for long fingers. Alleles occur on a homologous pair of chromosomes at a particular location called the gene locus (Fig. 10.5).

As studied in the previous chapter, meiosis is the type of cell division that reduces the chromosome number. During meiosis I, the homologous chromosomes of a tetrad separate. Therefore, the process of -meiosis explains Mendel’s law of segregation and why only one allele for each trait is in a gamete, as we will see shortly.

When an organism has two identical alleles, it is termed homozygous. All the gametes from a homologous dominant parent, such as SS, contain an allele for short fingers (S), and all gametes produced by the homozygous recessive parent contain an allele for long fingers (s). Therefore, all the offspring from this couple will have one allele for short fingers and another for long fingers, as in Ss. We say that this individual is heterozygous.

Genotype Versus PhenotypeIt is obvious from our discussion that two organisms with different allelic combinations for a trait can have the same outward appearance. For instance, SS and Ss individuals both have short fingers. For this reason, it is necessary to distinguish between the -alleles present in an organism and the appearance of that -organism.

The word genotype refers to the alleles an individual receives at fertilization. Genotype may be indicated by letters or by short, descriptive phrases. Genotype SS is called -homozygous dominant; genotype ss is homozygous recessive; and genotype Ss is heterozygous.

The word phenotype refers to the physical appearance of the individual. The homozygous dominant (SS) individual and the heterozygous (Ss) individual both show the dominant phenotype and have short fingers, while the homozygous recessive individual shows the recessive phenotype and has long fingers (Table 10.1).

Two-Trait Inheritance

Mendel performed a second series of crosses in which he crossed true-breeding plants that differed in two traits. For example, he crossed tall plants having green pods with short plants having yellow pods (Fig. 10.6). The F₁ plants showed both dominant characteristics (tall with green pods). As before, Mendel then allowed the F₁ plants to self-pollinate. Two possible results could occur in the F₂ generation:

1. If the dominant factors (TG) always go into the F₁ gametes together, and the recessive factors (tg) always stay together, then two phenotypes would result among the F₂ plants—tall plants with green pods and short plants with yellow pods.

2. If the four factors segregate into the F₁ gametes independently, then four phenotypes would result among the F₂ plants—tall plants with green pods, tall plants with yellow pods, short plants with green pods, and short plants with yellow pods.

Figure 10.6 shows that Mendel observed four phenotypes among the F₂ plants, supporting the second hypothesis. Therefore, Mendel formulated his second law of heredity—the law of independent assortment—which states:

• Each pair of factors segregates (assorts) independently of the other pairs.

• All possible combinations of factors can occur in the gametes.

Two-Trait Testcross

The fruit fly Drosophila melanogaster, less than one-fifth the size of a housefly, is a favorite subject for genetic research because it has several mutant characteristics that are easily determined. The wild-type fly—the type you are most likely to find in nature—has long wings and a gray body, while some mutant flies have short (vestigial) wings and black (ebony) bodies. The key for a cross involving these traits is
L 5 long wings, l 5 short wings, G 5 gray body, and g 5 black body.

A two-trait testcross can be used to determine whether an individual is homozygous dominant or heterozygous for either of the two traits. Because it is not possible to determine the genotype of a long-winged, gray-bodied fly by inspection, the genotype may be represented as L__ G__.

In a two-trait testcross, an individual with the dominant phenotype for both traits is crossed with an individual with the recessive phenotype for both traits because this fly has a known genotype. For example, a long-winged, gray-bodied fly is crossed with a short-winged, black-bodied fly. The heterozygous parent fly (LIGg) forms four different types of gametes. The homozygous parent fly (llgg) forms only one type of gamete:

P: LlGg 3 llgg

Gametes: LG lg

Lg

lG

lg

As Figure 10.7 shows, all possible phenotypes occur among the offspring. This 1:1:1:1 phenotypic ratio shows that the L__G__ fly is heterozygous for both traits and has the genotype LlGg. Such an individual is called a dihybrid.A Punnett square can also be used to predict the chances of an offspring having a particular phenotype. What are the chances of an offspring with long wings and a gray body? The chances are ¹⁄4, or 25%. What are the chances of an offspring with short wings and gray body? The chances are ¹⁄4, or 25%, and so forth.

If the L__G__ fly had been homozygous for both traits, then no offspring would have short wings or a black body when it was crossed with one having the recessive phenotype. If the L__G__ fly is heterozygous for one trait but not the other, can you predict the expected phenotypic ratio assuming the other fly is doubly recessive?

Mendel’s Laws and Probability

When we use a Punnett square to calculate the results of genetic crosses, we assume that each gamete contains one allele for each trait (law of segregation) and that collectively the gametes have all possible combinations of alleles (law of independent assortment). Further, we assume that the male and female gametes combine at random—that is, all possible sperm have an equal chance to fertilize all possible eggs. Under these circumstances, it is possible to use the rules of probability to calculate the expected phenotypic ratio. The rule of multiplication says that the chance of two (or more) independent events occurring together is the product of their chances of occurring separately. For example, the chance of getting tails when you toss a coin is ¹⁄2. The chance of getting two tails when you toss two coins at once is ¹⁄2 3 ¹⁄2  ¹⁄4. The more two-coin tosses you do, the more likely you’ll see two tails in 25% of your total tosses.

Let’s use the rule of multiplication to calculate the expected results in Figure 10.7. Because each allele pair separates independently, we can treat the cross as two separate one-trait crosses:

Ll3ll: Probability of ll offspring  ¹⁄2

Gg3gg: Probability of gg offspring  ¹⁄2

The probability of the offspring’s genotype being llgg:

¹⁄2 ll3¹⁄2 gg  ¹⁄4

And the same results are obtained for the other possible genotypes among the offspring in Figure 10.7.

Mendel’s Laws and Meiosis

Today, we are aware that Mendel’s laws relate to the process of meiosis. In Figure 10.8, a human cell has two pairs of homologues, recognized by length—one pair of homologues is short and the other is long. (The color signifies that we inherit chromosomes from our parents; one homologue of each pair is the “paternal” chromosome, and the other is the “maternal” chromosome.) When the homologues separate (segregate), each gamete receives one member from each pair. The homologues separate (assort) independently; it does not matter which member of each pair goes into which gamete. In the simplest of terms, a gamete in Figure 10.8 can receive one short and one long chromosome of either color. Therefore, all possible combinations of chromosomes are in the gametes.

The alleles E for unattached earlobes and e for attached earlobes are on one pair of homologues, and the alleles W for widow’s peak and w for straight hairline are on the other pair of homologues. Because there are no restrictions as to which homologue goes into which gamete, a gamete can receive either an E or an e and either a W or a w in any combination. In the end, collectively, the gametes will have all possible combinations of alleles.

_{10.2 Beyond Mendel’s Laws}

Since Mendel’s day, variations in the dominant/recessive -relationship he described have been discovered. These variations make it clear that the concept of the genotype should be expanded to include all the genes of an individual. The idea of just two alleles per trait, one dominant and one recessive, is too restrictive because various genes work together to bring about a phenotype. In addition, the phenotype is sometimes influenced by the environment.

Incomplete Dominance

Incomplete dominance is exhibited when the heterozygote has an intermediate phenotype between that of either homozygote. In the flowering plant known as the four-o’clock, a cross between red-flowered four-o’clocks and white-flowered four-o’clocks produces offspring with pink flowers (Fig. 10.9). But this is not an example of blending inheritance, because when the pink-flowered plants self-pollinate, ¹⁄4 of the offspring have red flowers, ¹⁄4 have white flowers, and the rest have pink flowers. The reappearance of the original phenotypes makes it clear that we are still dealing with particulate inheritance of the type described by Mendel.

In humans, people with curly hair have the homozygous recessive genotype, while those with straight hair have the homozygous dominant condition. The heterozygote has wavy hair. We can explain incomplete dominance by assuming that only the dominant allele codes for a gene product and that the single dose of the product gives the intermediate result.

Multiple-Allele Traits

In ABO blood group inheritance, there are three alleles that determine the presence or absence of antigens on red blood cells and therefore blood type:

I^A 5 A antigen on red blood cells

I^B 5 B antigen on red blood cells

i 5 Neither A nor B antigen on red blood cells

Each person has only two of the three possible alleles, and both I^A and I^B are dominant over i. Therefore, there are two possible genotypes for type A blood (I^AI^A, I^Ai) and two possible genotypes for type B blood (I^BI^B, I^Bi). But, I^A and I^B are fully expressed in the presence of each other. Therefore, if a person inherits one of each of these alleles, that person will have type AB blood. Type O blood can only result from the inheritance of two i al-leles. Figure 10.10 shows that matings between certain genotypes can have surprising results in terms of blood type.

Notice that human blood type inheritance is an example of codominance, another type of inheritance that differs from Mendel’s findings because more than one allele is fully expressed. When an individual has blood type AB, both A and B antigens appear on the red blood cells. The two different capital letters signify that both alleles are coding for an antigen.

Polygenic Inheritance

Polygenic inheritance occurs when a trait is governed by two or more sets of alleles. The individual has a copy of all allelic pairs, possibly located on many different pairs of chromosomes. Each dominant allele has a quantitative effect on the phenotype, and these effects are additive. The result is a continuous variation of phenotypes, resulting in a distribution that resembles a bell-shaped curve. The more genes involved, the more continuous are the variations and distribution of the phenotypes. Also, environmental effects are involved; in the case of skin color, differences in sun exposure bring about a bell-shaped curve (Fig. 10.11).

Multifactorial traits are ones that are controlled by polygenes subject to environmental influences. Disorders, such as cleft lip and/or palate, clubfoot, congenital dislocations of the hip, hypertension, diabetes, schizophrenia, and even allergies and cancers are likely due to the combined action of many genes plus environmental influences. In recent years, reports have surfaced that all sorts of behaviors, including alcoholism, phobias, and even suicide, can be associated with particular genes. No doubt, behavioral traits are somewhat controlled by genes, but again, it is impossible at this time to determine to what degree. And very few scientists would support the idea that these behavioral traits are predetermined by our genes.

Environment and the Phenotype

The relative importance of genetic and environmental influences on the phenotype can vary, but in some instances the environment seems to have an extreme effect. In the water buttercup, the submerged part of the plant has a different appearance from the part above water. This difference is thought to be related to a difference in water intake by the cells.

Temperature can also have a dramatic effect on the phenotypes of plants and animals. Primroses have white flowers when grown above 32°C and red flowers when grown at 24°C. The coats of Siamese cats and Himalayan rabbits are darker in color at the ears, nose, paws, and tail. Himalayan rabbits are known to be homozygous for the allele ch, which is involved in the production of melanin. Experimental evidence suggests that the enzyme encoded by this gene is active only at a low temperature and that, therefore, black fur only occurs at the extremities where body heat is lost to the environment (Fig. 10.12). When the animal is placed in a warmer environment, new fur on these body parts is light in color.

These examples lend support to the belief that human traits controlled by polygenes are also subject to environmental influences. Therefore, many investigators are trying to determine what percentage of various traits is due to nature (inheritance) and what percentage is due to nurture (the environment). Some studies use twins separated from birth, because if identical twins in different environments share the same trait, that trait is most likely inherited. Identical twins are more similar in their intellectual talents, personality traits, and levels of lifelong happiness than are fraternal twins separated from birth. Biologists conclude that all behavioral traits are partly heritable and that genes exert their effects by acting together in complex combinations susceptible to environmental influences.

Pleiotropy

Pleiotropy occurs when a single gene has more than one effect. Often, this leads to a syndrome, a group of symptoms that appear together and indicate the presence of a particular genetic mutation. For example, persons with Marfan syndrome have disproportionately long arms, legs, hands, and feet; a weakened aorta; and poor eyesight (Fig. 10.13). All of these characteristics are due to the production of abnormal connective tissue. Marfan syndrome has been linked to a mutated gene (FBN₁) on chromosome 15 that ordinarily specifies a functional protein called fibrillin. Fibrillin is essential for the formation of elastic fibers in connective tissue. Without the structural support of normal connective tissue, the aorta can burst, particularly if the person is engaged in a strenuous sport, such as volleyball or basketball. Flo Hyman may have been the best American woman volleyball player ever, but she fell to the floor and died when only 31 years old because her aorta gave way during a game. Now that coaches are aware of Marfan syndrome, they are on the lookout for it among very tall basketball players. Chris Weisheit, whose career was cut short after he was diagnosed with Marfan syndrome, said, “I don’t want to die playing basketball.”

Many other disorders, including sickle cell disease and porphyria, are examples of pleiotropic traits. Porphyria is caused by a chemical insufficiency in the production of hemoglobin, the pigment that makes red blood cells red. The symptoms of porphyria are photosensitivity, strong abdominal pain, port-wine-colored urine, and paralysis in the arms and legs. Many members of the British royal family in the late 1700s and early 1800s suffered from this disorder, which can lead to epileptic convulsions, bizarre behavior, and coma.

_{10.3 Sex-Linked Inheritance}

Geneticists of the early twentieth century were convinced that the genes are on the chromosomes because the genes and chromosomes behave similarly during gamete formation (see Fig. 10.8). They also knew that the chromosomes differ between the sexes. As you learned in Chapter 9, the sex chromosomes in females are XX, and those in males are XY (Fig. 10.14). Notice that males produce two different types of gametes-—those that contain an X and those that contain a Y. Therefore, the contribution of the male determines the sex of the new individual.

The much shorter Y chromosome contains only about 26 genes, and most of these genes are concerned with sex differences between men and women. One of the genes on the Y chromosome, SRY does not have a copy on the X chromosome. If the functional SRY gene is present, the individual becomes a male, and if it is absent, the individual becomes a female. No genes determine femaleness; it is the “default setting.”

In addition to genes that determine sex, the X chromosome carries genes for traits that have nothing to do with the gender of the individual. By tradition, the term X-linked refers to such genes carried on the X chromosome. The Y chromosome does not carry these genes, and that makes for an interesting inheritance pattern.

X-Linked Alleles

We have already mentioned that the fruit fly is a favorite subject for genetic studies. Flies can be easily and inexpensively raised in simple laboratory glassware; females mate only once and then lay hundreds of eggs during their lifetimes; and the generation time is short, taking only about ten days when conditions are favorable.

Drosophila flies have the same sex chromosome pattern as humans, which facilitates our understanding of a cross performed by early geneticists. When a mutant male with white eyes was crossed with a red-eyed female, the F₁ all had red eyes:

From these results, researchers knew that red eyes are the dominant characteristic and white eyes are the recessive characteristic. In the F₂ generation, the expected 3:1 ratio resulted, but all of the white-eyed flies were males:

Obviously, a major difference between the male flies and the female flies was their sex chromosomes. Could it be possible that an allele for eye color was on the Y chromosome but not on the X? This idea was quickly discarded because usually females have red eyes, and they have no Y chromosome. Next investigators hypothesized that perhaps an allele for eye color was on the X, but not on the Y chromosome, and this explanation turned out to match the results obtained in the experiment (Fig. 10.15). These results support the chromosome theory of inheritance by showing that the behavior of a specific allele corresponds exactly with that of a specific chromosome—the X chromosome in Drosophila.

Notice that X-linked alleles have a different pattern of inheritance than alleles on the autosomes. The Y chromosome is blank for these alleles, and so the inheritance of a Y chromosome cannot offset the inheritance of an X-linked recessive allele. For the same reason, males always receive an X-linked recessive mutant allele from their female parent; they receive the Y chromosome, which is blank for the allele, from the male parent.

An X-Linked Problem

When solving autosomal genetics problems involving fruit flies, the alleles and genotypes are represented as follows:

Key: L 5 long wings Genotypes:LL, Ll, ll

l 5 short wings

As noted in Figure 10.15, however, an X-linked gene is represented by attaching the allele to an X:

Key: X^R 5 red eyes

X^r 5 white eyes

The possible genotypes in both males and females are as -follows:

Genotypes: X^RX^R 5 red-eyed female

X^RX^r 5 red-eyed female

X^rX^r 5 white-eyed female

X^RY 5 red-eyed male

X^rY 5 white-eyed male

Notice that three genotypes are possible for females, but only two are possible for males. Females can be heterozygous X^RX^r, in which case they are carriers. Carriers usually do not exhibit a recessive trait, but they are capable of passing on a -recessive allele for a trait. Males cannot be carriers; if the dominant allele is on the single X chromosome, they show the dominant phenotype, and if the recessive allele is on the single X chromosome, they show the -recessive phenotype.

Males have white eyes when they receive the mutant recessive allele from the female parent. Females can only have white eyes when they receive a recessive allele from both parents.

_{10.4 Inheritance of Linked Genes}

After completing a great number of Drosophila crosses, investigators discovered many more mutants and were able to perform various two-trait crosses. However, they did not always get the expected ratios among the offspring due to gene linkage, the existence of several alleles on the same chromosome. The alleles on the same chromosome form a linkage group because these alleles tend to be inherited together.

Drosophila has thousands of different genes controlling all aspects of its structure, biochemistry, and -behavior. Yet it has only four pairs of chromosomes (Fig. 10.16). This paradox alone allows us to reason that each chromosome must carry a large number of genes. For example, it is now known that genes controlling eye color, wing type, body color, leg length, and antennae type are all located on chromosome II, in that sequence. When investigators construct a chromosome map, it shows the relative distance between the gene loci on a chromosome.

Constructing a Chromosome Map

Crossing-over, you’ll recall, occurs between nonsister chromatids when homologous pairs of chromosomes pair up prior to separation during meiosis. During crossing-over, the nonsister chromatids exchange genetic material, and therefore genes. If crossing-over occurs between two linked alleles of a dihybrid, four types of gametes instead of two are produced (Fig. 10.17). Recombinant gametes have a new combination of alleles. The recombinant gametes occur in reduced numbers because crossing-over is infrequent.

To take an example, suppose you are crossing a gray-bodied, red-eyed heterozygous fly with a black-bodied, purple-eyed fly. Because the alleles governing these traits are both on chromosome II, you predict that the results will be 1:1 instead of 1:1:1:1, as is the case for unlinked genes. The reason, of course, is that linked alleles tend to stay together and do not separate independently, as predicted by Mendel’s laws. Under these circumstances, the heterozygote forms only two types of gametes and produces offspring with only two phenotypes (Fig. 10.18a).

When you perform the cross, however, you find that a very small number of offspring show recombinant phenotypes (i.e., those that are different from the original parents). Specifically, you find that 47% of the offspring have black bodies and purple eyes, 47% have gray bodies and red eyes, 3% have black bodies and red eyes, and 3% have gray bodies and purple eyes (Fig. 10.18b). What happened? In this instance, crossing-over led to a very small number of recombinant gametes, and when these were fertilized, recombinant phenotypes were observed in the offspring.

Linkage Data

It stands to reason that the closer together two genes are, the less likely they are to cross over. Numerous experiments have repeatedly shown that this is the case. Therefore, you can use the percentage of recombinant phenotypes to map the chromosomes, because there is a direct relationship between the frequency of crossing-over (the percentage of recombinant phenotypes) and the distance between alleles. In our example (Fig. 10.18), a total of 6% of the offspring are recombinants, and this means the rate of crossing-over is 6%. For the sake of mapping the chromosomes, it is assumed that 1% of crossing-over equals one map unit. Therefore, the allele for black body and the allele for purple eyes are six map units apart.

Suppose you want to determine the order of any three genes on the chromosomes. To do so, you can perform crosses that tell you the map distance between all three pairs of alleles. Assume, for instance, that:

1. the distance between the black-body and purple-eye alleles 5 6 map units;

2. the distance between the purple-eye and vestigial-wing alleles 5
12.5 map units; and

3. the distance between the black-body and vestigial-wing alleles 5
18.5 map units.

Therefore, the order of the alleles must be as shown in Figure 10.9. Black body must be 6 map units away from purple eyes, and purple eyes must be 12.5 map units away from vestigial wings.

Linkage data have been used to map the chromosomes of Drosophila, but the possibility of using linkage data to map human chromosomes is limited because we can work only with matings that occur by chance. This, coupled with the fact that humans tend not to have numerous offspring, means that additional methods are needed to sequence the genes on human chromosomes. Today, it is customary also to rely on biochemical methods to map the human chromosomes, as will be discussed in Chapter 13.

The Chapter in Review

Summary

10.1 Mendel’s Laws

In 1860, Gregor Mendel, an Austrian monk, developed two laws of heredity based on crosses utilizing the garden pea.

Law of Segregation

Mendel’s law of segregation states the following:

• Each individual has two factors for each trait.

•
The factors segregate (separate) during the formation of the gametes.

• Each gamete contains only one factor from each pair of factors.

• Fertilization gives each new individual two factors for each trait.

In the context of genetics today,

• Genes are on the chromosomes; each gene has two alternative forms, called alleles. Letters are used to represent the genotype of an individual. AA  homozygous dominant,
Aa  heterozygous, and aa  homozygous recessive.

• Homologues separate during meiosis and the gametes have only one allele for each trait; either an A or an a.

• Fertilization gives each new individual two alleles for each trait.

Law of Independent Assortment

Mendel’s law of independent assortment states the following:

• Each pair of factors segregates (assorts) independently of the other pairs.

• All possible combinations of factors can occur in the gametes.

In the context of genetics today,

• Each pair of homologues separate independently of the other pairs.

• All possible combinations of chromosomes and their alleles occur in the gametes.

• Mendel’s laws are consistent with the manner in which homologues and their alleles separate during meiosis.

Common Autosomal Genetic Crosses

A Punnett square allows all types of sperm to fertilize all types of eggs and gives these results

Aa  Aa 3:1 phenotypic ratio

Aa  aa 1:1 phenotypic ratio

AaBb  AaBb 9:3:3:1 phenotypic ratio

AaBb  aabb 1:1:1:1 phenotypic ratio

10.2 Beyond Mendel’s Laws

In some patterns of inheritance, the alleles are not just dominant or recessive.

Incomplete DominanceIn incomplete dominance, the heterozygote is intermediate between the two homozygotes. For example, the offspring of red 3 white four-o’clocks produce pink flowers. The red and white phenotypes reappear when pink four o’clocks are crossed.

Multiple AllelesThe multiple-allele inheritance pattern is exemplified in humans by blood type inheritance. Every individual has two out of three possible alleles: I^A, I^B, i. Both I^A and I^B are expressed; therefore, this is also a case of codominance.

Polygenic InheritanceIn polygenic inheritance a trait is controlled by more than one set of alleles. The dominant alleles have an additive effect on the phenotype.

PleiotropyIn pleiotropy, one gene (consisting of two alleles) has multiple effects on the body. For example, all the disorders common to Marfan syndrome are due to a mutation that leads to a defect in the composition of connective tissue.

10.3 Sex-Linked Inheritance

Males produce two different types of gametes—those that contain an X and those that contain a Y. The contribution of the male determines the gender of the new individual. XX  female XY  male

Certain alleles are carried on the X chromosome, but the Y is blank. Therefore, a male only needs to inherit one recessive allele on the X chromosome to have a recessive genetic disorder.

Common X-Linked Genetic Crosses

X^BX^b 3 X^BYAll daughters will be normal, even though they have 50% chance of being carriers, but sons have a 50% chance of being color blind.

X^BX^B 3 X^bYAll children are normal (daughters will be carriers).

10.4 Inheritance of Linked Genes

All the alleles on a particular chromosome form a linkage group. Crossing-over data can be used to construct a chromosome map, which shows the sequence of alleles along the chromosome.

Thinking Scientifically

1. In peas, genes C and P are required for pigment production in flowers. Gene C codes for an enzyme that converts a compound into a colorless intermediate product. Gene P codes for an enzyme that converts the colorless intermediate product into anthocyanin, a purple pigment. A flower, therefore, will be purple only if it contains at least one dominant allele for each of the two genes (C__ P__). Flowers are white if they do not produce anthocyanin (ccpp). a. What phenotypic ratio would you expect in the F₂ generation following a cross between two double heterozygotes (CcPp)? b. What phenotypic ratio would you expect if a double heterozygote was crossed with a plant that is homozygous recessive (ccpp) for both genes?

2. Geneticists often look for unusual events to provide insight into genetic mechanisms. In one such instance, researchers studied XX men and XY women. They found that the XX men contained a chromosomal segment normally found in men but not in women, while XY women were missing that region. What gene do you suppose is on that chromosome piece? How did XX men gain that piece and XY women lose it?

Testing Yourself

Choose the best answer for each question.

1. In Mendel’s particulate theory of inheritance, the “particles” are

a. chromosomes. c. plants.

b. genes. d. pollen grains.

2. The offspring ratio from a testcross (F₁  homozygous recessive) should be

a. all dominant.

b. ³⁄4 dominant: ¹⁄4 recessive.

c. ¹⁄2 dominant: ¹⁄2 recessive.

d. all recessive.

3. Which of the following is not a component of the law of segregation?

a.
Each gamete contains one factor from each pair of factors in the parent.

b. Factors segregate during gamete formation.

c.
Following fertilization, the new individual carries two factors for each trait.

d. Each individual has one factor for each trait.

4. When using a Punnett square to predict offspring ratios, we assume that

a. each gamete contains one allele of each gene.

b. the gametes have all possible combinations of alleles.

c. male and female gametes combine at random.

d. All of these are correct.

5. If you cross a black spaniel with a red spaniel and get a litter of 8 black and 1 red, what is the genotype of the black parent?

a. BB c. bb

b. Bb d. impossible to determine

6. Short hair is dominant over long hair in dogs. If a short-haired dog whose mother was long-haired is crossed with a long-haired dog, what proportion of the offspring will be short-haired?

a. 25% d. 100%

b. 50% e. impossible to determine

c. 75%

7. When one physical trait is affected by two or more pairs of alleles, the condition is called

a. incomplete dominance. d. multiple allele.

b. codominance. e. polygenic inheritance.

c. homozygous dominant.

8. Fill in the blank spaces in the following Punnett square.

For questions 9–11, consider that coat color and spotting pattern in cocker spaniels depend on two genes. Black (B) is dominant to red, and solid color (S) is dominant to spotted.

9. What phenotypic ratio do you expect in the F₂ generation?

a. 1 black solid : 1 red solid : 1 black spotted : 1 red spotted

b. 9 black solid : 3 red solid : 3 black spotted : 1 red spotted

c. 1 black solid : 3 red solid : 3 black spotted : 9 red spotted

d. all black solid

10. If you cross a black spotted dog with a black solid dog and get a ratio of 3 black solid : 3 black spotted : 1 red solid : 1 red spotted, what is the genotype of black spotted parent?

a. BBss d. bbSs

b. BbSs e. bbss

c. Bbss

11. What is the genotype of black solid parent in question 10?

a. BBSS d. Bbss

b. BbSS e. bbSs

c. BbSs

For questions 12–15, match the cross with the results in the key.

Key:

a. 3:1 c. 1:1

b. 9:3:3:1 d. 1:1:1:1

12. TtYy  TtYy

13. Tt  Tt

14. Tt  tt

15. TtYy  ttyy

16. When two monohybrid round squashes are crossed, the offspring ratio is ¹⁄4 flat : ¹⁄2 oblong : ¹⁄4 round. Squash shape, therefore, is controlled by incomplete dominance. What offspring ratio would you expect from a cross between a plant with oblong fruit and one with round fruit?

a. all oblong

b. all round

c. ³⁄4 oblong : ¹⁄4 round

d. ³⁄4 round : ¹⁄4 oblong

e. ¹⁄2 oblong : ¹⁄2 round

17. If a man of blood group AB marries a woman of blood group A whose father was type O, what phenotypes could their children be?

a. A only d. A, AB, and B

b. A, AB, B, and O e. O only

c. AB only

18. Anemia sometimes results from a mutation in a single gene, causing the blood’s oxygen supply to be inadequate. A homozygous recessive person has a number of problems, including lack of energy, fatigue, rapid pulse, pounding heart, and swollen ankles. This is an example of

a. pleiotropy.

b. sex-linked inheritance.

c. incomplete dominance.

d. polygenic inheritance.

e. codominance.

For questions 19–22, list the progeny phenotypes from the following key that would result from each of the crosses in Drosophila. Red eye color is dominant over white. The gene for eye color is on the X chromosome. Answers can be used more than once.

Key:

a. red-eyed female

b. red-eyed male

c. white-eyed female

d. white-eyed male

19. Homozygous red-eyed female  white-eyed male.

20. Heterozygous female  white-eyed male.

21. White-eyed female  white-eyed male.

22. Heterozygous female  red-eyed male.

23. Alice and Henry are at the opposite extremes for a polygenic trait. Their children will

a. be bell-shaped.

b. be a phenotype typical of a 9:3:3:1 ratio.

c. have the middle phenotype between their two parents.

d. look like one parent or the other.

Go to www.mhhe.com/maderessentials for more quiz questions.

Bioethical Issue

You may feel it is ethically wrong to choose which particular embryo can continue development following in vitro fertilization (see page 521). But, what about choosing whether an X-bearing or Y-bearing sperm should fertilize the egg? As you know, the sex of a child depends upon whether an X-bearing sperm or a Y-bearing sperm enters the egg. A new technique has been developed that can separate X-bearing sperm from Y-bearing sperm. First, the sperm are dosed with a DNA-staining chemical. Because the X chromosome has slightly more DNA than the Y chromosome, it takes up more dye. When a laser beam shines on the sperm, the X-bearing sperm shine more brightly than the Y-bearing sperm. A machine sorts the sperm into two groups on this basis. The results are not perfect. Following artificial insemination, there’s about an 85% success rate for a girl and about a 65% success rate for a boy.

Some might believe that this is the simplest way to make sure they have a healthy child if the mother is a carrier of an X-linked genetic disorder, such as hemophilia or Duchenne muscular dystrophy. Previously, a pregnant woman with these concerns had to wait for the results of an amniocentesis test and then decide whether to abort the pregnancy if it were a boy. Is it better to increase the chances of a girl to begin with?

Or, do you believe that gender selection is not acceptable for any reason. Even if it doesn’t lead to a society with far more members of one sex than another, there could be problems. Once you separate reproduction from the sex act, it might open the door to genetically designing children. On the other hand, is it acceptable to bring a child into the world with a genetic disorder that may cause an early death or lifelong disability? Would it be better to select sperm for a girl, who at worst would be a carrier like her mother?

Understanding the Terms

allele145

carrier153

chromosome map154

codominance149

dihybrid147

dominant allele145

gene linkage154

gene locus145

genotype145

heterozygous145

homozygous145

incomplete dominance149

law of independent
assortment146

law of segregation145

linkage group154

multifactorial trait150

phenotype145

pleiotropy151

polygenic inheritance150

Punnett square144

recessive allele145

recombinant gamete154

rule of multiplication147

testcross144

wild-type146

X-linked152

Match the terms to these definitions:

a. _______________ Alternate forms of a gene.

b. _______________ Organism that contains two identical alleles.

c. _______________ Physical appearance of an individual.

d. _______________ Phenotype that is most common in nature.

e. _______________ Probability that two or more independent events will happen together is the product of the probabilities that they will occur separately.

f. _______________ Genetic system in which the heterozygote is intermediate in phenotype compared to the homozygotes.

g. _______________ Genes on the same chromosome.

Having six fingers is dominant; having five fingers is recessive.

Sex chromosomes contain genes for traits unrelated to gender.

Environmental factors can influence how your genes are expressed.

Figure 10.17Crossing-over.

When homologous chromosomes are in synapsis, the nonsister chromatids exchange genetic material. Following crossing-over, recombinant chromosomes occur. Recombinant chromosomes are found in recombinant gametes.

Figure 10.16Chromosomes of Drosophila.

The DNA of the Drosophila chromosomes contains about 165 million base pairs and an estimated 14,000 genes. However, Drosophila has only four pairs of chromosomes: Three pairs are autosomes (II-IV) and one pair of sex chromosomes (I). Therefore, many alleles must be on each chromosome.

Figure 10.14Inheritance of gender in human
beings.

Sperm determine the gender of an offspring because sperm can carry an X or a Y chromosome. Males inherit a Y chromosome.

Figure 10.11Skin color.

In this model, skin color is controlled by three pairs of alleles. When two F₁ individuals with genotypes AaBbCc are crossed, seven phenotypes are seen among the F₂ generation. If environmental effects are considered, a bell-shaped curve results because of many intervening phenotypes.

Figure 10.8Mendel’s laws and meiosis.

A human cell has 23 pairs of homologous chromosomes (homologues), of which two pairs are represented here. The homologues, and the alleles they carry, segregate independently during gamete formation. Therefore, all possible combinations of chromosomes and alleles occur in the gametes.

Figure 10.6Two-trait cross done by Mendel.

P generation plants differ in two regards—length of the stem and color of the pod. The F₁ generation shows only the dominant phenotypes, but all possible phenotypes appear among the F₂ generation. The 9:3:3:1 ratio allowed Mendel to deduce that factors segregate into gametes independently of other factors. (Arrow indicates yellow pods.)

Figure 10.3One-trait cross.

The P generation plants differ in one regard—length of the stem. The F₁ generation plants are all tall, but the factor for short has not disappeared because ¹⁄4 of the F₂ generation are short. The 3:1 ratio allowed Mendel to deduce that individuals have two discrete and separate genetic factors for each trait.

Figure 10.4One-trait testcross.

Crossing an individual with a dominant appearance (phenotype) with a recessive individual indicates the genotype. a. If a parent with the dominant phenotype has only one dominant factor, the results among the offspring are 1:1. b. If a parent with the dominant phenotype has two dominant factors, all offspring have the dominant phenotype.

Figure 10.15X-linked inheritance.

Once researchers deduced that the allele for red/white eye color is only on the X chromosome in Drosophila, they were able to explain their experimental results. Males with white eyes in the F₂ inherit the recessive allele only from the female parent; they receive a blank Y chromosome from the male parent.

Figure 10.13Marfan syndrome, multiple effects of a single human gene.

Individuals with Marfan syndrome exhibit defects in the connective tissue throughout the body. Important changes occur in the skeleton, heart, blood vessels, eyes, lungs, and skin. All these conditions are due to mutation of the gene FBN₁, which codes for a constituent of connective tissue. *Most life-threatening.

Figure 10.9Incomplete dominance in four-o’clocks.

In incomplete dominance, the heterozygote is intermediate between the homozygotes. In this case, the heterozygote is pink, whereas the homozygotes are red or white.

Figure 10.10Inheritance of ABO blood type.

A mating between individuals with type A blood and type B blood can result in any one of the four blood types. Why? Because the parents are I^Bi and I^Ai. The i allele is recessive; both I^A and I^B are dominant.

Figure 10.7Two-trait testcross.

If a fly heterozygous for both traits is crossed with a fly that is recessive for both traits, the expected ratio of phenotypes is 1:1:1:1.

Figure 10.5Homologous chromosomes.

a. The letters represent alleles—that is, alternate forms of a gene. Each allelic pair, such as Gg or Tt, is located on homologous chromosomes at a particular gene locus. b. Sister chromatids carry the same alleles in the same order.

Figure 10.18Complete linkage versus incomplete linkage.

a. Hypothetical cross in which genes for body and eye color on chromosome II of Drosophila are completely linked. Instead of the expected 1:1:1:1 ratio among the offspring from this cross, there would be a 1:1 ratio. b. Crossing-over occurs, and 6% of the offspring show recombinant phenotypes. The percentage of recombinant phenotypes is used to map the chromosomes (1%  1 map unit).

Figure 10.19Mapping chromosomes.

Genes are arranged linearly on the chromosome at specific gene loci. Using the crossing-over data supplied by the text, these genes are sequenced as shown.

Check Your Progress

1. Contrast homozygous with heterozygous.

2. Contrast genotype with phenotype.

Answers:1. A homozygous individual has two identical alleles of a gene.
A heterozygous individual has two different alleles of a gene.2. Genotype is the genetic makeup of an individual, while phenotype is the physical appearance of the individual.

Check Your Progress

1. A black mouse with a bent tail reproduces with a yellow mouse with a straight tail. Of 42 offspring, all are black with straight tails. Which traits are dominant?

2. A black mouse with a straight tail reproduces with a yellow mouse with a bent tail. The phenotypic ratio among the offspring is 1:1:1:1. What is the genotype of the first mouse?

3. What would the result be if the test individual in
Figure 10.7 were a. homozygous dominant for both traits? b. Homozygous dominant for one trait but heterozygous for the other?

Answers:1. Black and straight tail.2. Heterozygous for both traits.
3. a. All long winged, gray bodied flies. b. either 1 long wings, gray body : 1 long wings, black body or 1 long wings, gray body : 1 short wings, gray body.

Check Your Progress

1. Polygenic inheritance is controlled by three pairs of alleles. What are the two extreme genotypes?

2. What’s the difference in the pattern of inheritance for polygenic inheritance and pleiotropy?

3. If both parents have type AB blood, no child would have what blood type?

Answers:1. AABBCC and aabbcc.2. Several genes affect one trait in polygenic inheritance, while one gene has several phenotypic effects in pleiotropy.
3. Type O blood.

Check Your Progress

1. Why do males produce two different gametes with respect to sex chromosomes?

2. Why are sex-linked recessive conditions more likely in males than females?

Answers:1. Being XY, ¹⁄2 of the gametes carry an X and ¹⁄2 carry a Y.2. Only the X carries the alleles (Y is blank), and therefore recessive alleles are always expressed in males.

Table 10.1

Genotype Versus Phenotype

Genotype	Genotype	Phenotype
SS	Homozygous dominant	Short fingers
Ss	Heterozygous	Short fingers
ss	Homozygous recessive	Long fingers

Figure 10.2Garden pea anatomy and traits.

a. In the garden pea, pollen grains produced in the anther contain sperm, and ovules in the ovary contain eggs. b. When Mendel performed crosses, he brushed pollen from one type pea plant onto the stigma of another type pea plant. After sperm fertilized the eggs, the ovules developed into seeds (peas). For a cross involving a parent with round yellow seeds and a parent with wrinkled yellow seeds, he observed and counted a total of 7,324 peas.

Figure 10.1Mendel working in his garden.

a. Mendel grew and tended the garden peas, Pisum sativum, he used for his experiments. b. Mendel selected these seven traits for study. Before he did any crosses, he made sure the parents bred true. All the offspring either had the dominant trait or the recessive trait.

Figure 10.12Coat color in Himalayan rabbits.

Hair growing under an ice pack in these rabbits is black. The dark color on the ears, nose, and feet of these rabbits is believed to be due to a lower body temperature in these areas.