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STUDENT DIGITAL NEWSLETTER ALAGAPPA INSTITUTIONS |
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Christopher M. Harris, DMD, MD
Youth exposure to the antismoking commercials aired under the Fairness Doctrine was captured with a series of dichotomous and interaction variables arrhythmia course discount aceon 4 mg otc. The simplest measure was a dichotomous variable that distinguished youth who were interviewed during the Fairness Doctrine period prehypertension nosebleed purchase aceon 2 mg with mastercard. Alternative measures were used to capture the possibility that youth who watch more television would be more likely to see antismoking campaign commercials arrhythmia ablation is a treatment for buy aceon 8mg low cost. The final specification of campaign exposure by Lewit and colleagues consisted of a proxy for the number of antismoking commercials that youth viewed blood pressure ranges low aceon 4mg with visa. This proxy was defined as the product of the number of antismoking commercials that aired in a given year and the number of hours per day that each youth spent watching television prehypertension thyroid discount aceon 4mg overnight delivery. The study by Lewit and colleagues also included a squared term for this variable to capture the possibility that the impact of antismoking commercials is subject to diminishing returns heart attack arm trusted aceon 8 mg. The regression analyses by Lewit and colleagues106 indicated that smoking prevalence among youth was between 3. Consistent with their hypotheses, they also found that the interaction between television watching and the Fairness Doctrine periods had a negative and statistically significant impact on the probability of smoking, suggesting that youth who watched more television during the Fairness Doctrine 518 era of antismoking commercials were less likely to smoke cigarettes. Lewit and colleagues further found that their proxy for the number of advertisements youths saw was negatively and statistically associated with a lower probability of smoking. However, the squared term for this proxy had a positive and significant effect on smoking. These results suggest that the Fairness Doctrine had a significant negative impact on smoking by youth and that this impact was subject to diminishing returns. None of the specifications estimated by the Lewit study found a significant impact of the campaign on the number of cigarettes smoked per day. This finding is not surprising, as many youth are not yet regular or addicted smokers. Lewit and colleagues106 made significant improvements in estimating the effects of Fairness Doctrine antismoking commercials. They did so by estimating youth smoking behaviors as a function of proxies for exposure to the antismoking campaign while controlling for a broad set of potentially confounding influences. This study made significant strides in using more complex measures of exposure to the campaign. As in other studies that rely on aggregate rather than self-reported individual exposure, the measures were of potential rather than actual exposure. Despite their limitations, these crosssectional studies provided fairly convincing evidence of the impact of the Fairness Doctrine and were consistent with previous time-series analyses of cigarette sales and consumption data. Thus, the Fairness Doctrine advertisements appeared to be more effective in deterring cigarette consumption than were the cigarette commercials in encouraging consumption, Monograph 19. The Fairness Doctrine and ensuing evaluations showed that antismoking advertising on television and radio, when implemented with sufficient intensity and reach, could produce behavioral changes in smoking. As such, these studies laid groundwork for further investigation and eventually for antismoking media campaigns to become one of the preeminent tools used by governments and private health organizations for curbing youth and adult smoking in the United States. Specific changes between surveys-in unprompted awareness of health effects caused by smoking, and new learning about smoking and health-were observed in relation to the main messages of the advertisements, which were time sensitive, according to the year of launch of each of the ads. White and colleagues108 used two crosssectional surveys of youth (one telephone and one school based; both postintervention only) to examine youth awareness of the "every cigarette is doing you damage" campaign and whether the campaign had any measurable impact on tobacco-related attitudes and behaviors among youth. The telephone survey assessed youth awareness of campaign messages, attitudes about smoking, intentions to smoke, and quitting behaviors. The school survey also assessed youth awareness of campaign messages and whether the students took any actions as a result of seeing the campaign advertisements. Again, the primary analytic strategy of White and colleagues108 consisted of simple descriptive analyses rather than multivariate analyses that adjusted for potential confounding factors. Analyses were conducted separately for smokers and nonsmokers and summarized youth awareness of the campaign and responses to various questions about tobacco-related attitudes and quitting behaviors. Analyses from the telephone survey indicate that a high proportion of smoking and nonsmoking youth agreed with statements about campaign-related beliefs. A high proportion of youth also indicated beliefs that the campaign was relevant to primary students, secondary students, and young smokers. Students in the Victoria school survey were asked questions about whether they took any action in response to the campaign. Students were allowed to indicate any one of a number of possible actions, such as quitting smoking, reducing their cigarette 519 12. Effectiveness of Media in Discouraging Smoking Behavior consumption, and telling someone else to quit smoking. Compared with never smokers, a significantly higher proportion of youth who had smoked at least once in their lifetime indicated taking at least one action in response to the campaign. Among current established smokers, for example, 27% said they cut down the number of cigarettes they smoked in response to the campaign, 26% indicated they thought about quitting, and 18% said the campaign made them try to quit smoking. When launched in 2000, the "truth" campaign differed from other national smoking prevention campaigns in being marketed as a popular youth brand and delivering blunt facts and messages about the tobacco industry (such as industry efforts to obscure the health effects of tobacco). The Legacy "truth" campaign strategy is generally consistent with modern theories 520 of persuasion. These theories hold that, for a message to have an effect on desired outcomes, it must not only be viewed and remembered but also must be understood and perceived as credible and relevant. The first cross-sectional studies on the effectiveness of the Legacy "truth" campaign provide fairly convincing evidence that the campaign had a significant impact on tobacco industry-related attitudes, beliefs, and other behavioral precursors, as well as a significant impact on youth smoking prevalence in the United States. Farrelly and colleagues109 used a nationally representative sample of 12- to 17-year-olds from the Legacy Media Tracking Survey. This study included self-reported measures of confirmed recall of Legacy "truth" advertisements, multiple measures of campaign-related attitudes and beliefs, and a comprehensive set of individual background characteristics. Using multivariable logistic regressions, the authors also showed that awareness of specific campaign advertisements was significantly associated with greater anti tobacco-industry attitudes and with beliefs that were targeted by the campaign. The Role of the Media the same survey, examined antitobacco attitudes over time in groups of states: (1) tobacco-producing states, (2) non tobacco-producing states with low tobacco control funding, (3) non-tobacco-producing states with relatively high tobacco control funding, and (4) non-tobacco-producing states with well-funded media programs. The authors found no significant difference in how antitobacco attitudes changed over time among the state groups and concluded that response to the Legacy "truth" campaign was not influenced by residence in a tobacco-producing state. As with all cross-sectional studies, the primary limitation of this study is the potential for bias in selective attention, which precludes strong causal inferences. A subsequent cross-sectional study, published in 2005, examined effects of the Legacy "truth" campaign on smoking behavior of youth. These data captured the relative reach of and frequency of exposure to the campaign among its target audience of 12- to 17-year-olds within each of 210 media markets in the United States. This study also controlled for a wide range of individual demographic characteristics as well as preexisting levels of smoking in each of the 210 U. Findings from this study associate the Legacy "truth" campaign with a significant decline in youth smoking, resulting in approximately 300,000 fewer youth smokers in the United States. The authors showed that smoking prevalence among students in 8th, 10th, and 12th grades combined declined from 25. Although the Legacy "truth" campaign had no effect on youth smoking after only a few months of the campaign in 2000, the effects were statistically significant in 2001 and 2002. Furthermore, Thrasher and colleagues110 found that the effect on smoking was similar among high- and low-risk adolescents, when high risk was defined in multiple ways. The above studies, like all other population studies, relied on self-reported measures of youth smoking. These measures may be subject to social desirability bias; that is, youth are less likely to report smoking in media markets that received high levels of exposure to the campaign. However, in a study published in 2007,111 biochemically validated smoking status in a school-setting survey (5,511 students from 48 high schools) showed that only 1. Effectiveness of Media in Discouraging Smoking Behavior related to underreporting. These findings help rule out the possibility that the correlation between Legacy "truth" gross rating points and youth smoking was spurious. Models for the variables associated with behavior, attitude, and intention controlled for demographic and other personal data, region, the real price of cigarettes, a smoke-free air index, and exposure to state tobacco control program media. Additional models for smoking behavior also controlled for frequency of television watching, with consistent outcomes. The analyses discerned no association between smoking in the past month with 522 the youth-directed media campaigns as measured by gross rating points. In contrast, greater exposure to the rating point variable for media directed toward parents was associated with a higher likelihood of smoking in the past month for 10th and 12th graders, increased intent to smoke for all grades, and lower levels of a few antitobacco attitudes. Wakefield and colleagues112 cite theories in developmental psychology to explain these findings. As adolescents mature, they consider themselves more independent and less reliant on their parents. Thus, messages aimed at parents as authority figures invite rejection by older adolescents. The nature of the media buy for the campaign directed toward parents was unlikely to result in more rating points in areas with higher adolescent smoking rates. Sensitivity analyses explored the effect of removing some of the key control variables (cigarette price, smoke-free air index, exposure to public health-sponsored antitobacco campaigns) from the model; however, the results were basically unchanged. Cross-Sectional Results from Other Countries for Adults In addition to the studies described above, several national antismoking media campaigns in other countries have been evaluated with cross-sectional data and have shown similar results. In March through May 1977, Norway conducted a mass media campaign to inform its population about the health consequences of smoking, with no other tobacco control measures mentioned. The first showing was followed by a call-in radio program for viewers to discuss Monograph 19. An in-home population survey, conducted in June 1977 to evaluate the effect of this campaign, found that 86% of the population had seen a newspaper advertisement, 62% had seen a magazine advertisement, and 66% had seen one of the showings of the film on television. Compared with surveys conducted before the campaign, daily smoking prevalence among men dropped from 53% to 45%. Daily smoking prevalence among women had been steadily increasing from the mid-1950s through 1973, declined through 1976, but remained even between 1976 and 1977. Gredler and Kunze,114 using a pre-post design, suggested that a large-scale antismoking campaign that aired in Austria for eight weeks at the end of 1980 and the beginning of 1981 was responsible for a significant reduction in the prevalence of smoking in Austria between 1979 and 1981. Using multiple cross-sectional surveys, Doxiadis and colleagues115 found that an intensive antismoking campaign in Greece that consisted of radio and television advertisements virtually eliminated annual percentage increases in smoking between 1979 and 1980. Doxiadis and colleagues also found that when this campaign ceased, cigarette consumption again rose to precampaign rates. These findings suggest that a media campaign that reaches a high proportion of the population can influence smoking behavior, even without other tobacco control efforts in place. This study used cross-sectional data for two years (1999 and 2000) on 8th-, 10th-, and 12th-grade students from the Monitoring the Future survey to link exposure to state antismoking commercials to youth smoking outcomes. Their analysis was similar to that of Farrelly and colleagues,93 using commercial ratings data from Nielsen Media Research to calculate a measure of audience exposure to antismoking advertising across the 75 largest media markets for the years 1999 through 2000. These data enabled Emery and colleagues to measure exposure to state antismoking advertisements across the 75 media markets separately from exposure to antismoking advertisements sponsored by the tobacco industry and advertisements for smoking-cessation aids sponsored by the pharmaceutical industry. These measures were incorporated as independent variables in a series of multivariable logistic regressions that estimated outcomes related to smoking as a function of exposure to advertising. This study was the first to examine the impact of state-funded antismoking campaigns on youth smoking while controlling for other tobacco-related advertisements. These findings are particularly compelling because the models consistently yield significant associations between exposure to state antismoking campaigns and youth smoking-related outcomes. This association occurred even though state campaigns, as captured by the awareness measures used by Emery and colleagues, varied dramatically in the number and frequency of advertisements aired. A limitation of this study was that the authors could not control for preexisting correlations between levels of smoking in the media markets and the number and frequency of advertisements aired in each market. As Farrelly and colleagues93 noted, markets with low media exposure tend to have populations that are more rural, white, and less educated, and lower in income than do markets with high exposure. Thus, failing to control for these potential preexisting correlations could lead to a spurious negative correlation between antismoking advertising and youth smoking rates. The campaign used paid and donated spots on television and radio as well as newspaper and billboard ads, particularly in connection with sports and other events attracting large adolescent audiences. They demonstrated a 524 small but statistically significant increase in exposure to antismoking messages but no changes in attitudes or smoking behavior. This campaign, launched in the spring of 2000 and continued for three years, was phased out after state budget cuts. To evaluate the campaign, four cross-sectional surveys of approximately 1,100 12- to 17-year-olds were conducted between summer 2002 and winter 2003. The authors used several measures to test whether or not ending the campaign had a negative impact on outcomes: awareness of Target Market; smoking susceptibility ("if someone you thought was cool offered you a cigarette, would you smoke it One scale measured attitudes toward the tobacco industry (central to the campaign), one included traditional normative attitudes and beliefs, and the third reflected antitobacco empowerment. The results show that awareness of the advertising dropped from 59% to 50%, and awareness of the Target Market brand dropped from 85% to 57%. By the last survey, the two measures of smoking susceptibility increased, as did intentions to smoke in the next year. The Role of the Media comparison sample, it is difficult to know if the trends in Minnesota reflected, in part, a national trend. This assessment occurred before the implementation of most other statewide tobacco control activities and after an increase of 25 cents per pack in the state cigarette excise tax.
As outlined in Chapter 3 for independent loci arteria3d unity aceon 8mg without prescription, we can work this cross by breaking it down into two simple crosses blood pressure yahoo health aceon 2mg. At the first locus blood pressure classification chart cheap aceon 8 mg, the heterozygote Y +y is crossed with the homozygote yy; this cross produces 1 /2 Y +y and 1/2 yy progeny arrhythmia kamaliya mp3 order aceon 4 mg with amex. Similarly arrhythmia or panic attack 8mg aceon mastercard, at the second locus hypertension renal disease discount aceon 4mg with amex, the heterozygous genotype C+c is crossed with the homozygous genotype cc, producing 1/2 C+c and 1/2 cc progeny. These dogs may be black, brown, or yellow; their different coat colors are determined by interactions between genes at two loci (although a number of other loci also help to determine coat color; see pp. One locus determines the type of pigment produced by the skin cells: a dominant allele B encodes black pigment, whereas a recessive allele b encodes brown pigment. Alleles at a second locus affect the deposition of the pigment in the shaft of the hair; dominant allele E allows dark pigment (black or brown) to be deposited, whereas recessive allele e prevents the deposition of dark pigment, causing the hair to be yellow. The presence of genotype ee at the second locus therefore masks the expression of the black and brown alleles at the first locus. In this example of gene interaction, allele e is epistatic to B and b, because e masks the expression of the alleles for black and brown pigments, and alleles B and b are hypostatic to . In this case, e is a recessive epistatic allele, because two copies of e must be present to mask the expression of the black and brown pigments. The difference between the A and the B antigens is a function of chemical differences in the terminal sugar of the chain. The enzyme encoded by the i allele apparently either adds no sugar to H or no functional enzyme is specified. In most people, a dominant allele (H) at the H locus encodes an enzyme that makes H, but people with the Bombay phenotype are homozygous for a recessive mutation (h) that encodes a defective enzyme. A antigen Terminal sugar Compound H I B B antigen H Intermediate ii 6 Blood-type O can result from the absence of a terminal sugar on compound H. O (no A,B antigen) 5 People with the Bombay phenotype are homozygous for a recessive mutation (h) that fails to convert the intermediate into H. The Bombay phenotype provides us with a good opportunity for considering how epistasis often arises when genes affect a series of steps in a biochemical pathway. Note that blood-type O may arise in one of two ways: (1) from failure to add a terminal sugar to compound H (genotype H ii) or (2) from failure to produce compound H (genotype hh ). In the F2, 12/16, or 3/4, of the plants produce white squash and /16 + 1/16 = 4/16 = 1/4 of the plants produce squash having color. This outcome is the familiar 3: 1 ratio produced by a cross between two heterozygotes, which suggests that a dominant allele at one locus inhibits the production of pigment, resulting in white progeny. If we use the symbol W to represent the dominant allele that inhibits pigment production, then genotype W inhibits pigment production and produces white squash, whereas ww allows pigment and results in colored squash. Among those ww F2 plants with pigmented fruit, we observe 3/16 yellow and 1/16 green (a 3: 1 ratio). In this outcome, a second locus determines the type of pigment produced in the squash, with yellow (Y ) dominant over green (yy). This locus is expressed only in ww plants, which lack the dominant inhibitory allele W. We can assign the genotype ww Y to plants that produce yellow squash and the genotype ww yy to plants that produce green squash. The genotypes and their associated phenotypes are: 3 W Y W yy ww Y ww yy white squash white squash yellow squash green squash Dominant epistasis In recessive epistasis, which we just considered, the presence of two recessive alleles (the homozygous genotype) inhibits the expression of an allele at a different locus. In dominant epistasis, only a single copy of an allele is required to inhibit the expression of the allele at a different locus. Dominant epistasis is seen in the interaction of two loci that determine fruit color in summer squash, which is commonly found in one of three colors: yellow, white, or green. Allele W is a dominant epistatic allele because, in contrast with e in Labrador retriever coat color and with h in the Bombay phenotype, a single copy of the allele is sufficient to inhibit pigment production. Yellow pigment in the squash is most likely produced in a two-step biochemical pathway (Figure 5. The presence of W at the first locus inhibits the conversion of compound A into compound B; plants with genotype W do not make compound B and their fruit remains white, regardless of which alleles are present at the second locus. Intercross F2 /16 plants with white squash 3 /16 plants with yellow squash 1 /16 plants with green squash 12 How can gene interaction explain these results Albinism is the absence of pigment and is a common genetic trait in many plants and animals. Pigment is almost 110 Chapter 5 1 Plants with genotype ww produce enzyme I, which converts compound A (colorless) into compound B (green). Wethington found that albinism in the common freshwater snail Physa heterostroha can result from the presence of either of two recessive alleles at two different loci. Inseminated snails were collected from a natural population and placed in cups of water, where they laid eggs. When the F1 were intercrossed, the F2 consisted of 9/16 pigmented snails and 7/16 albino snails. The 9: 7 ratio seen in the F2 snails can be understood as a modification of the 9: 3: 3: 1 ratio obtained when two individuals heterozygous for two loci are crossed. Albinism arises from the absence of compound C, which may happen in one of three ways. First, two recessive alleles at the first locus (genotype aa B ) may prevent the production of enzyme I, and so compound B is never produced. In this example of gene interaction, a is epistatic to B, and b is epistatic to A; both are recessive epistatic alleles because the presence of two copies of either allele a or allele b is necessary to suppress pigment production. This example differs from the suppression of coat color in Labrador retrievers in that recessive alleles at either of two loci are capable of suppressing pigment production in the snails, whereas recessive alleles at a single locus suppress pigment expression in Labs. A bb the 9: 7 ratio in these snails is probably produced by a two-step pathway of pigment production (Figure 5. Pigment (compound C) is produced only after compound Extensions and Modifications of Basic Principles 111 1 A dominant allele at the A locus is required to produce enzyme I, which converts compound A into compound B. Each of these examples represents a modification of the basic 9: 3: 3: 1 dihybrid ratio. In interpreting the genetic basis of modified ratios, we should keep several points in mind. First, the inheritance of the genes producing these characteristics is no different from the inheritance of genes encoding simple genetic characters. The only difference is in how the products of the genotypes interact to produce the phenotype. Thus, we cannot consider the expression of genes at each locus separately; instead, we must take into consideration how the genes at different loci interact. A second point is that, in the examples that we have considered, the phenotypic proportions were always in sixteenths because, in all the crosses, pairs of alleles segregated at two independently assorting loci. Because there are two loci, each with two alleles, the probability of inheriting any particular combination of genes is (1/2)4 = 1/16. For a trihybrid cross, the progeny proportions should be in sixty-fourths, because (1/2)6 = 1/64. In general, the progeny proportions should be in fractions of (1/2)2n, where n equals the number of loci with two alleles segregating in the cross. Crosses rarely produce exactly 16 progeny; therefore, modifications of a dihybrid ratio are not always obvious. Modified dihybrid ratios are more easily seen if the number of individuals of each phenotype is expressed in sixteenths: x number of progeny with a phenotype = 16 total number of progeny Table 5. A final point to consider is how to assign genotypes to the phenotypes in modified ratios that result from gene interaction. Instead, practice relating modified ratios to known ratios, such as the 9: 3: 3: 1 dihybrid ratio. Suppose that we obtain 15/16 green progeny and 1/16 white progeny in a cross between two plants. If we compare this 15: 1 ratio with the standard 9: 3: 3: 1 dihybrid ratio, we see that 9/16 + 3/16 + 3/16 equals 15/16. All the genotypes associated with these proportions in the dihybrid cross (A B, A bb, and aa B ) must give the same phenotype, the green progeny. In assigning genotypes to phenotypes in modified ratios, students sometimes become confused about which letters to assign to which phenotype. Suppose that we obtain the following phenotypic ratio: 9/16 black: 3/16 brown: 4/16 white. Either answer is correct because the letters are just arbitrary symbols for the genetic information. The important thing to realize about this ratio is that the brown phenotype arises when two recessive alleles are present at one locus. Therefore, we can reject the hypothesis that these results were produced by a monohybrid cross. Furthermore, a chi-square test comparing the observed numbers with an expected 1: 1 ratio yields a calculated chi-square value of 4. The F1 are intercrossed, producing an ear of corn with 119 purple kernels and 89 yellow kernels (the progeny). We now need to determine how a dihybrid cross can produce a 9: 7 ratio and what genotypes correspond to the We see that the expected numbers do not closely fit the observed numbers. If we performed a chi-square test (see Extensions and Modifications of Basic Principles 113 two phenotypes. The proportions of all the other genotypes (A bb, aa B, and aa bb) sum to 7/16, which is the proportion of the progeny in the corn cross that are yellow, and so any individual kernel that does not have a dominant allele at both the first and the second locus is yellow. Now test your understanding of epistasis by working Problem 26 at the end of the chapter. If, on the other hand, the mutations occur at different loci, each of the homozygous parents possesses wild-type genes at the other locus (aa b+b+ and a+a+ bb); so the heterozygous offspring inherit a mutant allele and a wild-type allele at each locus. In this case, the mutations complement each other and the heterozygous offspring have the wildtype phenotype: a a b+ b+ a+ a+ b b a a+ b+ b Wild-type phenotype Complementation: Determining Whether Mutations Are at the Same Locus or at Different Loci How do we know whether different mutations that affect a characteristic occur at the same locus (are allelic) or at different loci In fruit flies, for example, white is an X-linked recessive mutation that produces white eyes instead of the red eyes found in wild-type flies; apricot is an X-linked recessive mutation that produces light-orange-colored eyes. To carry out a complementation test on recessive mutations, parents that are homozygous for different mutations are crossed, producing offspring that are heterozygous. If the mutations are allelic (occur at the same locus), then the heterozygous offspring have only mutant alleles (a b) and exhibit a mutant phenotype: a a b b Complementation has occurred if an individual organism possessing two recessive mutations has a wild-type phenotype, indicating that the mutations are nonallelic genes. A lack of complementation occurs when two recessive mutations occur at the same locus, producing a mutant phenotype. When the complementation test is applied to white and apricot mutations, all of the heterozygous offspring have light-colored eyes, demonstrating that white eyes and apricot eyes are produced by mutations that occur at the same locus and are allelic. What types of crosses would you carry out to determine whether the brindle genes in bulldogs and in Chihuahuas are at the same locus The Complex Genetics of Coat Color in Dogs the genetics of coat color in dogs is an excellent example of how complex interactions between genes may take part in the determination of a phenotype. For thousands of years, people have been breeding dogs for particular traits, producing the large number of types that we see today. Each breed of dog carries a selection of genes from the ancestral dog gene pool; these genes define the features of a particular breed. The genome of the domestic dog was completely sequenced in 2004, greatly facilitating the study of canine genetics. The genetics of coat color in dogs is quite complex; many genes participate, and there are numerous interactions between genes at different loci. We will consider four loci (in the list that follows) that are important in producing many of the noticeable differences in color and pattern among breeds of dogs. In interpreting the genetic basis of differences in the coat color of dogs, consider how the expression of a particular gene is modified by the effects of other genes. Keep in mind that additional loci not listed here can modify the colors produced by these four loci and that not all geneticists agree on the genetics of color variation in some breeds. Hairs encoded by this allele have a "salt and pepper" appearance, produced by a band of yellow pigment on a black hair. Saddle markings (dark color on the back, with extensive tan markings on the head and legs). Bicolor (dark color over most of the body, with tan markings on the feet and eyebrows). Areas where the A locus is not expressed may appear as yellow, red, or tan, depending on the presence of particular genes at other loci. When As is present at the A locus, the four alleles at the E locus have the following effects: Em E ebr e Black mask with a tan coat. Brindle, in which black and yellow are in layers to give a tiger-striped appearance.
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Class A mutants had carpels instead of sepals in the first whorl and stamens instead of petals in the second whorl (Figure 22 heart attack 51 buy aceon 4 mg mastercard. The third whorl consisted of stamens arrhythmia etiology aceon 2mg generic, and the fourth whorl consisted of carpels blood pressure up cheap aceon 4mg on line, the normal pattern blood pressure medication and ed aceon 8 mg online. Class B mutants had sepals in the first and second whorls and carpels in the third and fourth whorls (Figure 22 blood pressure cuff generic 8mg aceon otc. The final group blood pressure low pulse high generic 2mg aceon overnight delivery, class C mutants, had sepals and petals in the first and second whorls, respectively, as is 22. The development of the flower itself also is under genetic control, and homeotic genes play a crucial role in the determination of the floral structures. Flower Anatomy A flower is made up of four concentric rings of modified leaves, called whorls. The outermost whorl (whorl 1) Experiment Question: How do genes control the development of flower structures Methods Results (a) Wild-type flower Stamen Carpel Sepal Petal (b) Class A mutants Isolate and analyze homeotic mutants that affect flower development. Developmental Genetics and Immunogenetics 623 normal, but had petals in the third whorl and sepals in the fourth whorl (Figure 22. Meyerowitz and his colleagues concluded that each class of mutants was missing the product of a gene or the products of a set of genes that are critical to proper flower development: class A mutants were missing gene A activity, class B mutants were missing gene B activity, and class C mutants were missing gene C activity. They hypothesized that the class A genes are active in the first and second whorls. Class A gene products together with Class B gene products cause the second whorl to develop into petals. Class C gene products together with Class B gene products induce the third whorl to develop into stamens. The products of the different gene classes and their effects are summarized in the conclusion of Figure 22. To explain the results, they also proposed that the genes of some classes affect the activities of others. Where class A is active, class C is repressed, and where class C is active, class A is repressed. Class A genes are normally expressed in whorls 1 and 2, class B genes are expressed in whorls 2 and 3, and class C genes are expressed in whorls 3 and 4 (Figure 22. The interaction of these three classes of genes explains the different classes of mutants in Figure 22. For example, class A mutants are lacking class A gene products, and therefore class C genes are active in all tissues because, when A is inactivated, C becomes active. Therefore whorl 1, with only class C gene products, will consist of carpels; whorl 2, with class C and class B gene products, will produce stamens; whorl 3, with class B and class C gene products, will produce stamens; and whorl 4, with only class C gene activity, will produce carpels (see Figure 22. Findings from studies of other species have demonstrated that this system of flower development exists not only in Arabidopsis but also in other flowering plants. It is important to note that these genes are necessary but not sufficient for proper flower development; other genes also take part in the identity of the different parts of flowers. The products of four classes of homeotic genes interact to determine the formation of the four whorls that constitute a complete flower. Carpels, carpels, carpels carpels carpels (1st whorl) stamens (2nd whorl) stamens (3rd whorl) carpels (4th whorl) 22. Cells in many tissues have a limited life span, and they die and are replaced continually by new cells. As discussed in the introduction to this chapter, the death of lens cells causes the absence of eyes in blind cavefish. Cell death is also used to eliminate dangerous cells that have escaped normal controls (see section on mutations in cell-cycle control and cancer in Chapter 23). To confirm this explanation, Meyerowitz and his colleagues bred double and triple mutants and predicted the outcome. When one caspase is activated, it cleaves other procaspases that trigger even more caspase activity. The resulting cascade of caspase activity eventually cleaves proteins essential to cell function, such as those supporting the nuclear membrane and cytoskeleton. Procaspases and other proteins required for cell death are continuously produced by healthy cells, and so the potential for cell suicide is always present. A number of different signals can trigger apoptosis; for instance, infection by a virus can activate immune cells to secrete substances onto an infected cell, causing that cell to undergo apoptosis. This process is believed to be a defense mechanism designed to prevent the reproduction and spread of viruses. Damage to mitochondria and the accumulation of a misfolded protein in the endoplasmic reticulum also stimulate programmed cell death. Apoptosis in development Apoptosis plays a critical 4 Macrophage phagocytizes apoptotic cell. Cells that are injured, on the other hand, die in a relatively uncontrolled manner called necrosis. In this process, a cell swells and bursts, spilling its contents over neighboring cells and eliciting an inflammatory response (Figure 22. Apoptosis is essential to embryogenesis; most multicellular animals cannot complete development if the process is inhibited. Regulation of apoptosis Surprisingly, most cells are programmed to undergo apoptosis and will survive only if the internal death program is continually held in check. The process of apoptosis is highly regulated and depends on numerous signals inside and outside the cell. Geneticists have identified a number of genes having roles in various stages of the regulation of apoptosis. Some of these genes encode enzymes called caspases, which cleave other proteins at specific sites (after aspartic acid). As animals develop, excess cells are often produced and then later culled by apoptosis to produce the proper number of cells required for an organ or a tissue. For example, early mammalian embryos develop both male and female reproductive ducts, but the Wolffian ducts degenerate in females and the Mullerian ducts degenerate in males. Three genes in Drosophila activate caspases that are essential for apoptosis: reaper (rpg), grim, and head involution defective (hid). Embryos possessing a deletion that removes all three genes exhibit no apoptosis and die in the course of embryogenesis with an excess of cells. Apoptosis is also crucial in metamorphosis, the process by which larval structures are transformed into adult structures. For example, the large salivary glands of larval fruit flies regress during metamorphosis. Ecdysone induces the expression of rpg and hid and inhibits the expression of other genes, which then leads to apoptosis of salivary gland cells. Apoptosis in disease the symptoms of many diseases and disorders are caused by apoptosis or, in some cases, its absence. In neurodegenerative diseases such as Parkinson disease and Alzheimer disease, symptoms are caused by a loss of neurons through apoptosis. In heart attacks and stroke, some cells die through necrosis, but many others Developmental Genetics and Immunogenetics 625 undergo apoptosis. Cancer is often stimulated by mutations in genes that regulate apoptosis, leading to a failure of apoptosis that would normally eliminate cancer cells. Apoptosis plays an important role in animal development and is implicated in a number of diseases. Scientists have long recognized that organisms do not pass through the adult stages of their ancestors during their development, but the embryos of these related organisms often display similarities. Sometimes called "evo-devo," the study of evolution through the analysis of development is revealing that the same genes often shape developmental pathways in distantly related organisms. Biologists once thought that segmentation in vertebrates and invertebrates was only superficially similar, but we now know that, in both Drosophila and the primative chordate Branchiostoma, the engrailed gene divides the embryo into specific segments. A gene called distalless, which creates the legs of a fruit fly, plays a role in the development of crustacean branched appendages. This same gene also stimulates body outgrowths of many other organisms, from polycheate worms to starfish. An amazing example of how the same genes in distantly related organisms can shape similar developmental pathways is seen in the development of eyes in fruit flies, mice, and humans. Walter Gehring and his collaborators examined the effect of the eyeless gene in Drosophila, which is required for proper development of the fruit-fly eye. Gehring and his coworkers genetically engineered cells that expressed eyeless in parts of the fly where the gene is not normally expressed. When these flies hatched, they had eyes on their wings, antennae, and legs (Figure 22. These structures were not just tissue that resembled eyes, but complete eyes with a cornea, cone cells, and photoreceptors that responded to light, although the flies could not use these eyes to see, because they lacked a connection to the nervous system. The eyeless gene has counterparts in mice and humans that affect the development of mammalian eyes. There is a striking similarity between the eyeless gene of Drosophila and the Small eye gene that exists in mice. In mice, a mutation in one copy of Small eye causes small eyes; a mouse that is homozygous for the Small eye mutation has no eyes. There is also a similarity between the eyeless gene in Drosophila and the Aniridia gene in humans; a mutation in Aniridia produces a severely malformed human eye. Similarities in the sequences of eyeless, Small eye, and Aniridia suggest that all three genes evolved from a common ancestral sequence. This possibility is surprising, because the eyes of insects and mammals were thought to have evolved independently. Similarities among eyeless, Small eye, and Aniridia suggest that a common pathway underlies eye development in flies, mice, and humans. Similar genes may be part of a developmental pathway common to two different species but have quite different effects. For example, a Hox gene called AbdB helps define the posterior end of a Drosophila embryo; a similar group of genes in birds divides the wing into three segments. In another example, the sog gene in fruit flies stimulates cells to assume a ventral orientation in the embryo, but the expression of a similar gene called chordin in vertebrates causes 626 Chapter 22 cells to assume dorsal orientation, exactly the opposite of the situation in fruit flies. Similar genes in vertebrates encode proteins called Toll-like receptors that bind to molecules on pathogens and stimulate the immune system. The theme emerging from these studies is that a small, common set of genes may underlie many basic developmental processes in many different organisms. Although this assumption holds for most cells, there are some important exceptions, one of which concerns genes that encode immune function in vertebrates. In the development of immunity, individual segments of certain genes are rearranged into different combinations, producing immune cells that contain different genetic information and that are each adapted to attack one particular foreign substance. This rearrangement and loss of genetic material is key to the power of our immune systems to protect us against almost any conceivable foreign substance. The immune system provides protection against infection by bacteria, viruses, fungi, and parasites. The focus of an immune response is an antigen, defined as any molecule (usually a protein) that elicits an immune reaction. The immune system is remarkable in its ability to recognize an almost unlimited number of potential antigens. The body is full of proteins, and so it is essential that the immune system be able to distinguish between self-antigens and foreign antigens. Occasionally, the ability to make this distinction breaks down, and the body produces an immune reaction to its own antigens, resulting in an autoimmune disease (Table 22. Evolution through change in gene expression Another concept revealed by studies in evo-devo is that many major evolutionary adaptations are not through changes in the types of proteins produced but through changes in the expression of genes that encode proteins that regulate development. This concept is seen in the evolution of blind cavefish discussed in the introduction to the chapter, where a small difference in the expression of two transcription-factor-encoding genes, sonic hedgehog and tiggy-winkle hedgehog, cause the development of the lens to abort and result in eyelessness. The birds differ primarily in the size and shape of their beaks: ground finches have deep and wide beaks, cactus finches have long and pointed beaks, and warbler finches have sharp and thin beaks. These differences are associated with diet, and evolutionary changes in beak shape and size have taken place in the past when climate changes brought about shifts in the abundance of food items. They found differences in the expression of a gene that encodes a protein called calmodulin (CaM); the gene that encodes CaM was more highly expressed in the long and pointed beak of cactus-finch embryos than in the beaks of the other species. CaM takes part in a process called calcium signaling, which is known to affect many aspects of development. When Abzhanov and his coworkers activated calcium signaling in developing chicken embryos, the chickens had longer beaks, like those of the cactus finch. Thus, these researchers were able to reproduce, at least in part, the evolutionary difference that distinguishes cactus finches. The importance of this experiment is that it shows that changes in the expression of a single gene in the course of development can produce significant anatomical differences in adults. In these studies and others, the combined efforts of developmental biologists, geneticists, and evolutionary biologists are sources of important insights into how evolution takes place. Lymphocyte stem cell B cell Plasma cell Antibodies 3 When B cells encounter antigens, they mature into plasma cells, which secrete antibodies that bind to the antigen (humoral immunity). Although it is convenient to think of these classes as separate systems, they interact and influence each other significantly. Humoral immunity Immune function is carried out by specialized blood cells called lymphocytes, which are a type of white blood cell. Humoral immunity centers on the production of antibodies by specialized lymphocytes called B cells (Figure 22.
With this technique blood pressure chart for 19 year old buy aceon 8mg lowest price, a large number of different proteins are applied to a glass slide as a series of spots arteria urethralis order 8mg aceon, with each spot containing a different protein blood pressure chart omron discount aceon 8mg. In one application blood pressure medication used for nightmares purchase aceon 4 mg online, each spot is an antibody for a different protein arrhythmia vs afib purchase 2mg aceon fast delivery, labeled with a tag that fluoresces when bound blood pressure band generic aceon 4 mg online. A spot of fluorescence appears when a Genomics and Proteomics 585 proteins are required for studies of the proteome, researchers ultimately hope to be able to predict the structure of a protein from its amino acid sequence. This method is not possible at the present time, but the hope is that, if enough high-resolution structures are solved, it may be possible in the future to model the structure from the amino acid sequence alone. As scientists work on automated methods that will speed the structural determination of proteins, bioinformaticists are developing better computer programs for predicting protein structure from sequence. Techniques of protein separation and mass spectrometry are used to identify the proteins present within a cell. Affinity capture and microarrays are used to determine sets of interacting proteins. Physical maps are based on the physical distances between genes and are measured in base pairs. The project began officially in 1990; rough drafts of the human genome sequence were completed in 2000. The individual sequences can be ordered into a whole-genome sequence with the use of a map-based approach, in which fragments are assembled in order by using previously created genetic and physical maps, or with the use of a whole-genome shotgun approach, in which overlap between fragments is used to assemble them into a whole-genome sequence. Orthologs are homologous sequences found in different organisms, whereas paralogs are homologous sequences found in the same organism. Gene function may be determined by looking for homologous sequences (both orthologs and paralogs) whose function has been previously determined. Microarrays can be used to monitor the expression of thousands of genes simultaneously. Genes affecting a particular function can also be identified through whole-genome mutagenesis screens. Compared with that of eukaryotic genomes, the density of genes in prokaryotic genomes is relatively uniform, with about one gene per 1000 bp. Horizontal gene transfer (the movement of genes between different species) has been an important evolutionary process in prokaryotes. Proteins within a cell can be separated and identified with the use of mass spectrometry. Structural proteomics attempts to determine the threedimensional shape of proteins. Species with larger genomes generally have more genes than species with smaller genomes, and so gene density is quite constant. Structure often provides important information about how a protein functions and the types of proteins with which it is likely to interact. Genomics and Proteomics 587 We have accounted for all the restriction sites, but we must still determine the order of the sites on the original 30-kb fragment. What is the difference between a map-based approach to sequencing a whole genome and a whole-genome shotgun approach Describe the different approaches to sequencing the human genome that were taken by the international collaboration and by Celera Genomics. What are some of the ethical concerns arising out of the information produced by the Human Genome Project Explain how a reporter sequence can be used to provide information about the expression pattern of a gene. Is this variation closely related to the number of genes and the complexity of the organism More than half of the genome of Arabidopsis thaliana consists of duplicated sequences. What mechanisms are thought to have been responsible for these extensive duplications What accounts for much of the differences in genome size among species of Drosophila The human genome does not encode substantially more protein domains than do invertebrate genomes, yet it encodes many more proteins. How are more proteins encoded when the number of domains does not differ substantially The fragments resulting from each of the three digestions are placed in separate wells of an agarose gel, separated by gel electrophoresis, and stained by ethidium bromide. You will be shown a picture of this chromosome and a histogram illustrating the densities of total genes (uncolored bars) and of known genes (colored bars). The total numbers of genes, along with the chromosome length in base pairs are given at the bottom of the diagram. Write down the total length of the chromosome and the number of protein-coding genes. Now go to chromosome 21 by pulling down the Jump to Chromosome menu and selecting chromosome 21. Examine the total length and total number of proteincoding genes for chromosome 21. Calculate the gene density (number of genes/length) for chromosomes 22, 21, and Y. Examine in more detail the genes at the tip of the short arm of the Y chromosome by clicking on the top bar in the histogram of genes. How does the density of genes found on chromosome 22 compare with the density of genes found on chromosome 21, two similar-sized chromosomes How does the number of genes on chromosome 22 compare with the number found on the Y chromosome First noticed by beekeepers in 2004, the disorder has been responsible for the loss of 50% to 90% of beekeeping operations in the United States. Why did they use a metagenomics approach when their objective was to sequence the genome of one species (the cave bear) What conclusions can you make about which genes might be implicated in antibiotic resistance in these bacteria How might this information be used to design new antibiotics that are less vulnerable to resistance Red indicates the overexpression of a gene and Table for Problem 39 Feature Organism Cellularity Genome size (millions of base pairs) Number of genes Average gene length (bp) Genes with introns (%) Mean number of introns Mean intron size (bp) Mean G + C (exons) *nd = not determined D. What are some of the major differences in the ways in which genetic information is organized in the genomes of prokaryotes compared with eukaryotes How do the following genomic features of prokaryotic organisms compare with those of eukaryotic organisms A group of 250 scientists sequenced and analyzed the genomes of 12 species of Drosophila (Drosophila 12 Genomes Consortium. Data on genome size and number of protein-encoding genes from this study are given in Table 20. How does this result compare with the relation between genome size and number of genes across all eukaryotes A scientist determines the complete genomes and proteomes of a live cell and a muscle cell from the same person. Would you expect bigger differences in the genomes or proteomes of these two cell types What are some characteristics of ribosomal sequences that make them useful for determining what species are present Some synthetic biologists have proposed creating an entirely new, free-living organism with a minimal genome, the smallest set of genes that allows for replication of the organism in a particular environment. This genome could be used to design and create, from "scratch," novel organisms that might perform specific tasks such as the breakdown of toxic materials in the environment. What, if any, social and ethical concerns might be associated with the construction of an entirely new organism with a minimal genome In spite of its long association with human culture, the origins of domesticated donkeys have been uncertain. What little archeological evidence is available suggests that donkeys were domesticated approximately 5000 years ago-about the same time as the domestication of horses. Domesticated donkeys are clearly related to other asses, which include two subspecies of African wild asses, the Nubian wild ass (E. Which of these asses gave rise to donkeys and where domestication took place have, until recently, been unclear. To study the genetic origin of donkeys, Beja-Pereira and his colleagues obtained tissue from domestic donkeys in 52 countries throughout the Old World and from African wild asses and Asian half asses. All the domestic donkeys clustered within the African wild-ass group, indicating that donkeys evolved from the wild asses rather than from the half asses. Another interesting feature indicated by the analysis was that donkeys appear to have at least two distinct origins from African wild asses, as revealed by the fact that some donkeys cluster with the Somalian wild asses and other donkeys cluster with the Nubian wild asses. This finding suggests that at least two independent domestication events took place. There was also significantly more genetic diversity in the domestic donkeys of North Africa than in the donkeys of other regions of the world. The clear affinity between domestic donkeys and African wild asses, coupled with the finding of greater diversity among North African donkeys, suggests that donkey domestication took place at least twice in Africa. Much evidence indicates that the first farm animals-sheep and goats-were domesticated in the Middle East. Donkeys are the only ungulate known to have been domesticated solely in Africa, highlighting the important role North Africa played in early population expansion and trade throughout the Old World. We begin by briefly considering the structures of mitochondria and chloroplasts, the inheritance of traits encoded by their genes, and the evolutionary origin of these organelles. Mitochondrion and Chloroplast Structure Mitochondria are tubular structures that are from 0. In mitochondria, the inner membrane is highly folded; embedded within it are the enzymes that catalyze electron transport and oxidative phosphorylation. Chloroplasts have a third membrane, called the thylakoid membrane, which is highly folded and stacked to form aggregates called grana. New mitochondria and chloroplasts arise by the division of existing organelles-divisions that take place throughout the cell cycle and are independent of mitosis and meiosis. Paternal inheritance of organelles is common in gymnosperms (conifers) and in a few angiosperms (flowering plants). Replicative segregation Individual cells may contain from dozens to hundreds of organelles, each with numer- 21. When a heteroplasmic cell divides, the organelles segregate randomly into the two progeny cells in a process called replicative segregation (Figure 21. Although most progeny cells will inherit a mixture of mutant and normal organelles, just by chance some cells may receive organelles with only mutant or only wildtype sequences; this situation, in which all organelles are genetically identical, is known as homoplasmy. When replicative segregation takes place in somatic cells, it may create phenotypic variation within a single organism; different cells of the organism may possess different proportions of mutant and wild-type sequences, resulting in different degrees of phenotypic expression in different tissues. When replicative segregation takes place in the germ cells of a heteroplasmic cytoplasmic donor there may be different phenotypes among the offspring. The results of biochemical studies demonstrated that petite mutants were unable to carry out aerobic respiration; they obtained all of their energy from anaerobic metabolism (glycolysis and fermentation), which is much less efficient than aerobic respiration and results in the smaller colony size. Isolated by Mary Mitchell in 1952, poky mutants grow slowly, display cytoplasmic inheritance, and have abnormal amounts of cytochromes. Most organisms have three primary types of cytochromes: cytochrome a, cytochrome b, and cytochrome c. This diagram illustrates replicative segregation in mitosis; the same process also takes place in meiosis. One of the first to be examined in detail was the phenotype produced by petite mutations in yeast (Figure 21. In the late 1940s, Boris Ephrussi and his colleagues noticed that, when grown on solid medium, some colonies of yeast were much smaller than normal. Examination of these petite colonies revealed that the growth rates of the cells within the colonies were Colony of petite mutant cells 21. Des Clark-Walker, Research School of Biological Sciences, the Australian National University. All of these diseases exhibit cytoplasmic inheritance and variable expression (see Chapter 5). A trait in plants that is produced by mutations in mitochondrial genes is cytoplasmic male sterility, a mutant phenotype found in more than 140 different plant species and inherited only from the maternal parent. The degree of expression of the trait is highly variable among members of the family: some are only slightly affected, whereas others developed severe symptoms at an early age. The physician concludes that this disorder is due to a mutation in the mitochondrial genome. Random segregation of mitochondria in meiosis may produce gametes having different proportions of mutant and wild-type sequences, resulting in different degrees of phenotypic expression among the offspring. Most likely, symptoms of the disorder develop when some minimum proportion of the mitochondria are mutant. Just by chance, some of the gametes produced by an affected mother contain few mutant mitochondria and result in offspring that lack the disorder. Another possible explanation for the disorder is that it results from an autosomal dominant gene. A physician examines a young man who has a progressive muscle disorder and visual abnormalities. The variable expression could be explained by variable expressivity (see Chapter 5). For more experience with the inheritance of organelle-encoded traits, try working Problem 14 at the end of the chapter. The Endosymbiotic Theory Chloroplasts and mitochondria are in many ways similar to bacteria. This resemblance is not superficial; indeed there is compelling evidence that these organelles evolved from eubacteria (see p. With time, the endosymbiont became an integral part of the eukaryotic host cell, and its descendants evolved into present-day mitochondria.