* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Laboratory 4 Patterns of Inheritance (human)
Survey
Document related concepts
Behavioural genetics wikipedia , lookup
Heritability of IQ wikipedia , lookup
Human genetic variation wikipedia , lookup
Genome (book) wikipedia , lookup
Genetic drift wikipedia , lookup
Population genetics wikipedia , lookup
Polymorphism (biology) wikipedia , lookup
Hardy–Weinberg principle wikipedia , lookup
Zinc finger nuclease wikipedia , lookup
Polydactyly wikipedia , lookup
Designer baby wikipedia , lookup
Microevolution wikipedia , lookup
Transcript
Laboratory 4 Patterns of Inheritance (human) Before the lab Read in Freeman Chapter 13 (Mendel and the Gene) pp 273, 281-282, 282, Table 13.2 Print and read this lab material. Objectives 1. Understand the meaning and connections between the following terms: a. Dominant and recessive and incomplete dominance b. Homozygous and heterozygous c. Locus and gene and allele d. Polygenic e. Chromosome f. Phenotype and genotype g. Wild type and mutant 2. Compute the genotypic and phenotypic ratios from the class data generated for specified traits 3. Consider both the pattern of inheritance and the possible evolutionary significance of certain human traits. Evaluation (4%) Quiz at the beginning of lab on the background reading and terms Group presentation Timeline 0:10 – 0:20 Introduction, hand in assignments 0:20 – 0:40 Quiz 0:45 – 1:15 Part A 1:15 – 2:00 Prepare group presentation 2:00 – 2:45 Group presentations (15 minutes each—MAX) 2:45 – 3:00 wrap up Introduction Though Mendel and others asked the question of why offspring resemble their parents, the reverse question is also important—why do even closely related individuals vary considerably in appearance and behaviour? These differences exist because all individuals inherit unique combinations of genes from their parents. Unique combinations of genes are a direct result of meiosis acting on the shuffling of different alleles. If you consider humans, each child receives one-half of its genetic information from each parent or phrased more accurately each parent contributes one allele for each genetic locus (the specific location of a gene on a chromosome). Because both the father’s sperm and mother’s egg went through meiosis shuffling the genes around by independent assortment of the homologous pairs and crossing over of genetic information between non-sister chromatids, even children of the same parents will receive a different set of genes from each parent. Identical twins are an exception because they are the result of the fertilization of a single egg and sperm. 4-Patterns of Inheritance - 2 of 21 How are traits inherited? Each individual gets one allele for each characteristic from each parent; the two alleles must be either the same or different. When both alleles are a trait are the identical the individual is said to be homozygous for that trait; if the alleles are different the individual is said to be heterozygous. A gene for a trait may have one, two or many alleles in the population. What is the interaction between the two alleles for the same trait? If one allele masks the expression of another allele, the expressed allele is called dominant and the hidden allele is called recessive. Recessive alleles are only expressed when the dominant allele is absent ( = homozygous recessive or haploid), while the dominant allele is expressed whether it is homozygous or heterozygous. The genotype is the combination of allele(s) of a particular gene. The phenotype is the observable trait—commonly includes the physical, physiological, and behavioural traits. In some cases, two different alleles are both expressed. If the resulting phenotype is intermediate between the phenotypes of the homozygous alleles, the condition is called incomplete dominance. If the phenotype of heterozygotes is the expression of both alleles, the condition is called co-dominance. Sex determination varies from species to species. The pattern of inheritance in sex-linked traits (traits with genes on the sex chromosomes) is different in males and females. Is a trait autosomal or sex linked? If a trait appears about equally in males and females, it is likely autosomal. However, some the genes for traits are not on the sex chromosomes, but their expression is sex-limited, meaning their expression is limited to one sex or another. Other traits are not determined by a single gene, but by many genes with various alleles for each gene; these traits are called polygenic. Some genes influence genes at another locus; this phenomenon is called epistasis. Materials Hand lens Phenotype charts Colour charts Series of dilutions of PTC with Q-tips Preview In this lab we will look at some human traits to study Mendelian genetic patterns of inheritance. Some genes affect our shape, while others affect our physiology (including what we can taste). Many of the trait descriptions noted as (1) are from a previous course at UTM BIO203S Introductory Genetics. The other reference (2) is from V. A. McKusick, 1988, Mendelian Inheritance in Man, 8th ed. In this lab 1. Part A: You will work in pairs. 2. For each trait you and your partner will first determine your phenotypes and possible genotypes completing TABLE 1 3. Compile class data to compute the genotypic and phenotypic ratios for specified traits. 4. Examine different modes of inheritance: simple dominance and recessiveness, incomplete dominance, multiple alleles, sex-linked, sex-limited, and sex -influenced traits. 4-Patterns of Inheritance - 3 of 21 5. Part B: each bench will be assigned one topic to verbally summarize to the class—use the extra readings and class data in your summary. In your summary describe the pattern of inheritance and the plausible evolutionary significance. The three topics are PTC tasters/non-tasters; index-ring finger ratio; colour detection. PART A: Determine the phenotypes and possible genotype(s) for the following traits. Add this data to Table 1 & on the class chalk board (Work in pairs; use the phenotype charts provided). 1. Tongue rolling (1) R or r In 1940, A. H. Sturtevant reported two classes within the human population, tongue rollers and nonrollers. The roller phenotype (R) is dominant; individuals unable to roll their tongue are homozygous recessive (r) for the trait. 2. Widow’s peak (1 and 2) W or w McKusick (1983) and others postulate that the inheritance of a widow’s peak, a distinct downward point of the frontal hairline, occurs as a dominant mutant in the human gene pool. Homozygous recessive individuals possess a straight hairline (p). Notice that the straight hairline is the wild type though recessive. 3. Earlobe attachment (1 and 2) EL or el The inheritance of a free (unattached) earlobe is a dominant allele; direct attachment of the earlobe to the head is a recessive trait 4. Facial dimples (1 and 2) D or d Natural indentations near the corners of the mouth are dominant to no dimples. 5. Cleft chin (2) C or c Cleft chin is dominant; no cleft chin is recessive [cc] 6. Ear pits (2) Ep or ep Pits present is dominant; no pits is recessive [ee] 7. Thumb crossing (2) Lt or lt In a relaxed interlocking of fingers, left thumb over right indicate the dominant allele is present; right thumb over left is homozygous recessive. 8. [hand] Hitchhiker’s thumb or straight thumb St or st B.l .Glass and J.C. Kistler classified distal hyperextensibility of the thumb as a recessive trait in 1953. The expression of this allele is quite variable; for class purposes, if you can not bend your thumb backward about 45º, you probably have a least one dominant allele. 9. [foot] Length of the ‘big toe’ BT or bt A. R. Koplan (1964) reported that the relative lengths of the hallux (big toe) and the 2nd toe were Mendelian traits (controlled by dominant and recessive alleles). A long hallux is recessive: the dominant allele results in a short big toe relative to the 2nd toe. If both toes are equal in length, or if the big toe is longer than the second toe, you probably carry the recessive alleles. 4-Patterns of Inheritance - 4 of 21 10. [hand] Middigital hair (1) Md or md Genetic control of midphalangeal hair was first documented by C. H. Danforth in 1921. Examine the segment between the second and terminal joints of your fingers and look for hair or hair follicles on these segments (midddigitals). Even the slightest amount of hair qualifies as the dominant condition. Notice that the same fingers on both hands have hair (or follicles if the hair is worn off). The presence of hair on specified fingers is determined by a series of multiple alleles as follows: Table 2 Class frequency of alleles for middigital hair Allele Phenotype of middigital hair #students in class H1 Hair on all four fingers (not on the thumb) H2 Hair on three fingers—not the index finger H3 Hair on two fingers—not the index or little finger H4 Hair on one finger---is it the ring or middle finger? H5 Hair on no fingers After determining both you and your partner’s phenotype, write down your possible genotypes in Table 1 at the end of the lab. When the rest of the class have added their data to the table on the chalk board write down the # students for each allele in Table 2 above. Re-write the phenotypes represented in your lab class (about 24 students) in decreasing frequency: ____ _____ _____ _____ _____ Is the phenotype determined by the recessive alleles the least frequent? _____ Why might this have happened? 4-Patterns of Inheritance - 5 of 21 PART B All members of the class will participate in the collection of the data for items 1113. One group will be assigned to summarize the class data and to present the data and background information to the class 11. Index and ring fingers (extra information in Appendix A) Some work has been done measuring the relative length of the index and ring fingers and correlating this ratio to the amount of testosterone present in the uterus during development—the ring fingers of boys and men are typically longer than their index fingers while in girls and women these fingers are usually the same or the index finger is slightly longer. More background information is in Appendix B The shorter index finger to ring finger may also be a sex-influenced trait such that the trait is dominant in the male but recessive in the female. Another example of a likely sexinfluenced trait is pattern baldness. Sex-influenced traits are different from sex-linked traits. Sex-linkage refers to the gene loci are on a chromosome associated with sex-determination. Sex-influence or sexlimited traits (expressed only in one sex such as egg production in chickens and milk production in cows) represent gene actions associated with the unique phenotypes and the internal environment related to maleness and femaleness. Place your right hand on the sheet with your fourth (ring) finger just barely touching the line below. Be sure your fingers are vertical (up and down) on the page. Make a mark across the uppermost tip of the second (index) finger. Is the mark for your index finger below or above the line? Mark second Finger here Place Fourth Finger here _________ _________ Table 3 Class results comparing the Index/ring finger length in males and females Gender # with shorter index # with longer index fingers fingers females males total 12. PTC tasting T or t (Appendix B) The inability to taste phylthiocarbamide (P.T.C.) or phenylthiourea is conditioned by a recessive allele (t). The majority of the North American Caucasian population are ‘tasters’ (T), experiencing a striking bitter or sour sensation if this substance is put on the tongue. Children of two non-tasters have non-taster children. However, expression of the allele is variable. You will be asked to test a series of numbered solutions starting with water. Enter the number of the solution you can first taste something bitter/sour. Is the class response to PTC all or nothing or can some people tasted at the different concentrations? 4-Patterns of Inheritance - 6 of 21 What is the proportion of tasters and non-tasters in the class?____ What might be the evolutionary significance (if any) for the phenomenon of being a taster (of a bitter substance) or a non-taster? 13. Red-green colour vision (Appendix C) Red-green ‘colour blindness’ is inherited as an X-linked recessive trait. During lab you will be screened for this trait. Please RECORD your phenotype on the CLASS master chart on the board and in Table 1 in your lab notes. Table 1 Personal inventory and class percentages of phenotypes and possible genotypes Class size = ______ Trait Your Your possible # in class with % of class phenotype Genotype(s) trait with trait Tongue roller RWidow’s peak WEarlobe free El- Dimples DCleft chin CEar pits EpThumb crossing Lt Straight thumb StBig toe Bt Middigital hair H1,2,3,4 or 5 Index/ring finger index PTC taster T and # Red-green vision 4-Patterns of Inheritance - 7 of 21 Discussion Questions (for general discussion at the end of lab) Based on the class data, are the dominant phenotypes the most common? Are dominant phenotypes usually the most common in a population? Explain your answer. What affects how often a phenotype occurs in a population? How could you determine the genotype of a person showing a dominant phenotype? Appendix A Ring-index finger ratio http://www.futurepundit.com/archives/002647.html March 04, 2005 Index And Ring Finger Lengths Partially Predict Violent Tendencies Higher prenatal testosterone has already been found to be correlated with a higher ratio of ring finger length to index finger length. Now University of Alberta researchers Peter Hurd and Allison Bailey have shown that the higher ring finger to index finger ratio is correlated with physically aggressive behavior in men. Dr. Peter Hurd initially thought the idea was "a pile of hooey", but he changed his mind when he saw the data. Hurd and his graduate student Allison Bailey have shown that a man's index finger length relative to ring finger length can predict how inclined that man is to be physically aggressive. Women do not show a similar effect. A psychologist at the University of Alberta, Hurd said that it has been known for more than a century that the length of the index finger relative to the ring finger differs between men and women. More recently, researchers have found a direct correlation between finger lengths and the amount of testosterone that a fetus is exposed to in the womb. The shorter the index finger relative to the ring finger, the higher the amount of prenatal testosterone, and--as Hurd and Bailey have now shown--the more likely he will be physically aggressive throughout his life. "More than anything, I think the findings reinforce and underline that a large part of our personalities and our traits are determined while we're still in the womb," said Hurd. Hurd and Bailey's research, published this March in Biological Psychology, was determined from surveys and hand measurements of 300 U of A undergraduates. In their study, they found there were no correlations between finger lengths and people who are prone to exhibit verbally aggressive, angry, or hostile behaviors, but there was to physically aggressive behavior. Hurd is conducting ongoing research in this area, including a study that involves measuring hockey players' finger lengths and cross referencing the results with each player's penalty minutes. He also has a similar study showing that men with more feminine finger ratios are more prone to depression; a paper on this will be published later this year in Personality and Individual Differences. 4-Patterns of Inheritance - 8 of 21 "Finger lengths explain about five per cent of the variation in these personality measures, so research like this won't allow you to draw conclusions about specific people. For example, you wouldn't want to screen people for certain jobs based on their finger lengths," Hurd said. "But finger length can you tell you a little bit about where personality comes from, and that's what we are continuing to explore." 2. Academics find that the finger of destiny points their way Male scientists are good at research because they have the hormone levels of women and long index fingers, a new study says. A survey of academics at the University of Bath has found that male scientists typically have a level of the hormone oestrogen as high as their testosterone level. [abridged] http://www.bath.ac.uk/pr/releases/fingerlength.htm accessed June, 2005 “The study drew on work in the last few years which established that the levels of oestrogen and testosterone a person has can be seen in the relative length of their index (second) and ring (fourth) fingers. The ratio of the lengths is set before birth and remains the same throughout life. The length of fingers is genetically linked to the sex hormones, and a person with an index finger shorter than the ring finger will have had more testosterone while in the womb, and a person with an index finger longer than the ring finger will have had more oestrogen. The difference in the lengths can be small – as little as two or three per cent – but important. A survey of the finger lengths of over 100 male and female academics at the University by senior Psychology lecturer Dr Mark Brosnan has found that those men teaching hard science like mathematics and physics tend to have index fingers as long as their ring fingers, a marker for unusually high oestrogen levels for males. It also found the reverse: those male academics with longer ring fingers than index fingers – the usual male pattern – tended not to be in science but in social science subjects such as psychology and education. A further study also suggests that prenatal hormone exposure, and hence index finger length, can also influence actual achievement levels. In a survey of male and female students on a JAVA programming course at the University, the researchers found a link between finger length ratio and test score. The smaller the difference between index and ring finger - the higher the test score at the end of the year.” From http://www.laputanlogic.com/articles/2004/11/004-0001-2474.html 4-Patterns of Inheritance - 9 of 21 3. Book Review Digit Ratio: A Pointer to Fertility, Behavior and Health by John T. Manning NJ: Rutgers University Press. 2002 Reviewed by Michael Mills, Psychology Department, Loyola Marymount University, Los Angeles, CA 90045. USA. http://human-nature.com/nibbs/02/manning.html Take a look at your right-hand. Which of your fingers is longer: your ring finger, or your index finger? Surprisingly, a passing stranger who noticed a difference in length between these two fingers (and who had handy a copy of John Manning's book Digit Ratio: A Pointer to Fertility, Behavior and Health) might infer some very personal characteristics about you. With no more data than that gleaned from a passing glance at your hands, a stranger might infer whether you are likely to have homosexual inclinations, are highly fertile, may eventually suffer from a heart attack or breast cancer, have musical aptitude or sporting prowess, and a surprisingly long list of other characteristics. Why do the fingers reveal such a wide spectrum of information (albeit very probabilistic)? Manning reviews evidence to suggest that the ratio of the length between the ring and index finger is somewhat sexually dimorphic, that this ratio is determined during early fetal development, and that it is influenced by sex hormones, particularly testosterone. If this is true, the fingers may provide a permanent, and easily visible, historic marker of important hormonal events that occurred during a critical time of fetal development, the latter part of the first trimester. This is a critical time of sexual differentiation of both the brain and body. Specifically, it is the ratio of the length of the index finger (digit 2, or "2D") and the ring finger (digit 4, or "4D") that is sexually dimorphic. Generally, males have a ring finger that is longer than their index finger. Females typically have index and ring fingers of about the same length. The ratio of index finger length to ring finger length is called the “2D:4D digit ratio,” or more simply, the “digit ratio.” Manning reports that, for males, the index finger is generally about 96 percent of the length of the ring finger, which gives an average digit ratio for males of .96. The digit ratio would be 1.00 if the ring and index fingers were the same length, and greater than 1.00 if the index finger was longer than the ring finger. Males generally have a digit ratio below 1.00 -- they have what is termed a "low digit ratio." Women generally have a digit ratio of about 1.00 (the index and ring fingers are of about equal length), or a "high digit ratio." Manning links the proximate causes of digit ratio sexual dimorphism to the effects of sex hormones during early fetal development. He believes the evidence is persuasive, but not yet definitive, that higher levels of testosterone during this critical developmental stage facilitates the growth of the ring finger, while higher levels of estrogen facilitates the growth of the index finger. He states: “In general, it seems that 2D:4D is the most reliable of the predictors of hypermasculinization…” (p. 139). One of the consequences of hypermasculinization, as reflected by the digit ratio, may be higher levels of fertility in men and lower levels of fertility in women. He also suggests that hypermasculinization increases the likelihood of homosexuality or bisexuality, in both males and females. 4-Patterns of Inheritance - 10 of 21 Manning devotes separate chapters to explore the relationship between digit ratio and a variety of characteristics, including assertiveness and attractiveness (chapter 3), reproductive success (chapter 4), hand preference, verbal fluency, autism, and depression (chapter 5), health and disease (chapter 6), homosexuality (chapter 7), musical aptitude (chapter 8) and sports aptitude (chapter 9). A brief summary Manning’s findings (some of which he notes are quite preliminary) is presented below. Table 2 Some Characteristics That May Be Associated with Digit Ratio (from Manning, 2002) High 2D:4D ratio Low 2D:4D ratio Presumably due to relatively Presumably due to relatively greater fetal exposure to greater fetal exposure to estrogen in the 1st trimester. testosterone in the 1st trimester Higher risk of early heart More fertile Males disease Higher lifetime reproductive success More aggressive and assertive Greater proclivity toward homosexuality/bisexuality Higher musical and sports aptitude Lower SES (?) Females Greater proclivity toward homosexuality/bisexuality More aggressive and assertive More fertile Higher lifetime reproductive success Higher risk of breast cancer There is, however, substantial overlap between the sexes with respect to digit ratio. It is not uncommon for a man or woman to have a digit ratio that is typical of the opposite sex. Across various populations, the offset of the distributions of male and female digit ratio is a little less than ½ of a standard deviation – e.g., the digit ratio, collapsed across various populations, has an effect size of about 0.3 – 0.4 (Manning, personal communication, 10/4/02). This is a small to moderate effect size. The sexual dimorphism of height has an effect size of about 1.4. A web-based program is available at my website (at this address: http://bellarmine.lmu.edu/faculty/mmills_fp/software.htm) that will graph the distributions and calculate the effect size for a trait. Using this program, we can see that there is far more overlap between the sexes in digit ratio than there is in the overlap between the sexes in height, as noted in the following diagrams. 4-Patterns of Inheritance - 11 of 21 Figure 1 – The Sex Difference in Height in inches (American data) Figure 2 – The Sex Difference in Digit Ratio, Liverpool, UK Data (data from Manning, 2002) One of the especially interesting theoretical discussions in Manning’s book is his speculation (starting on page 54) regarding why there is any overlap between the sexes in sexually dimorphic traits in the first place, including digit ratio. If being taller than women is adaptive for men in general, why aren’t all men taller than all women? And why don’t all men have a lower digit ratio than all women? Why the overlap? Manning interprets this as an evolutionary stable equilibrium point in a conflict between sexually antagonistic genes. Genes that tend to masculinize the fetus will increase when there is an advantage to having male offspring (e.g., 4-Patterns of Inheritance - 12 of 21 when the operational sex ratio favors men, or there is a polygynous mating system). The benefits of more masculinized male fetuses (increased adult sperm count, higher libido, inclination toward sexual promiscuity, etc.) will compensate for the reduced fertility of female offspring due to their relatively higher than normal fetal exposure to male hormones. When the mating system pendulum swings to the other side, and a monogamous mating system is in place, or operational sex ratio favors females, genes that tend to feminize the fetus will be favored. The result is an overlap in male/female distributions for many sexually dimorphic traits – a somewhat middle ground as parents hedge their bets regarding the relative reproductive potential of male or female offspring. Somewhat surprisingly, the effect size for digit ratio between the sexes varies substantially as a function of geography and race. For example, among the Zulu the effect size was found to be as low as about .2, while the effect size for a German sample was .56. Surprisingly, the females in some cultures may have a lower digit ratio than males of other cultures, although men have a lower digit ratio than women within populations in all cultures for which there is data. It is unclear why the effect size of the digit ratio of the sexes varies between different populations. This is a curious fact, one for which Manning provides little in the way of definitive conclusions -- and the reader may be left to wonder whether some of Manning's interpretations are threatened by this between population variability in effect sizes. However, the fact that the average height of men of some populations is lower than women of other populations doesn't negate the sex difference in height, nor does the fact that the gender effect size of height varies in different populations. Height, like digit ratio, is still sexually dimorphic. But the causes of between population variation in sexually dimorphic traits, such as digit ratio, is certainly puzzling, and it is a fertile area for future research. One might be tempted to speculate that racial variation in digit ratio may correspond to Ruston’s (1997) theory that populations closer to the equator are more r-selected, and thus are relatively more masculinized in utero and have higher adult testosterone levels. By this reckoning, one might expect to find low digit ratios near the equator, and progressively higher digit ratios in populations farther away from the equator. Indeed, Caucasians tend to have higher digit ratios than do Blacks. Data for Asian populations has not yet been published, however, some preliminary data suggests that Asians tend to have low digit ratios (Manning, personal communication, 10/5/02). Manning suggests that populations in middle latitudes may have higher digit ratios compared to populations nearer to the equator or nearer to the poles. This is inconsistent with Rushton’s theory, and Manning, so far, has not speculated about a possible theoretical explanation for this curvilinear pattern. The curious relationship between digit ratio and geographic latitude may require much additional research to disentangle what may be some complex determinants of these population variations. It is clear why men and women have sexually dimorphic reproductive organs. But why did they evolve a sexually dimorphic digit ratio? Manning notes that it has been suggested that the male digit ratio pattern may be functional -- a longer ring finger may help to stabilize the third digit (the middle finger) when throwing objects, thus increasing throwing accuracy. This implies that the throwing accuracy required for successful hunting and/or tribal warfare was of sufficient importance to drive the evolution of this sexually dimorphic trait. While gathering, ancestral women presumably did not need this extra stability for the third finger. Today, this sex difference may be seen in male superiority in throwing darts. And, it would be interesting to know if men with lower digit ratios were better dart throwers and men with higher digit ratios. Another hypothesis for the origin of this sexually dimorphic trait was that it was driven by direct sexual selection -- female choice. If so, it is surprising that women today are not conscious of 4-Patterns of Inheritance - 13 of 21 being particularly attracted to men with low digit ratios. However, it is interesting that women sometimes comment that they were attracted to a man's "masculine looking" hands, albeit without commenting directly on digit ratio. One wonders if the appearance of "masculine looking hands" includes an (unconscious?) assessment by females of male digit ratio? If so, this would lead more credence to the direct sexual selection hypothesis. Manning's book summarizes a cutting-edge area of research. He provides an outstanding (and currently the only) review and synthesis of the literature on digit ratio. This is a book that will serve as a valuable resource for researchers conducting studies in this area. He provides a wealth of statistical data (right down to the number of subjects and F test values) from a variety of studies. Many of these studies he has conducted himself. However, to a casual reader, lay or professional, trudging through statistical information will likely be an obstacle. Manning may have been able to capture a far wider readership if much of the detailed statistical data from specific studies had been relegated to footnotes or end notes. Indeed, this is a fascinating topic – what other easily visible physical trait (other than sex itself) is likely to be associated with such a variety of behavioral, reproductive, and health characteristics? In the final chapter, Manning provides an interesting discussion about possibilities for further research that may help to further disentangle the consequences of early fetal hormonalization. Given the results from such future research, a brief glance at the hands may be even more revealing. Don't wish others to glean too much personal information about you from a brief glance? Manning might suggest that you may wish to keep your hands in your pockets… References Manning, J. T. (2002). Digit ratio: A pointer to fertility, behavior and health. NJ: Rutgers University Press. Rushton, J. P. (1997). Race, evolution and behavior, 2nd Ed. New Brunswick, NJ: Transaction Publishers Appendix B Additional background on PTC tasters/non-tasters 1. Natural selection at work in genetic variation 28 Jun 2004 Medical News Today accessed June 8, 2005 to taste A genetic variation seen worldwide in which people either taste or do not taste a bitter, synthetic compound called PTC has been preserved by natural selection, University of Utah and National Institutes of Health researchers have reported. Phenylthiocarbamide (PTC) is not found in nature, but the ability to taste it correlates strongly with the ability to taste other bitter substances that occur naturally, especially toxins. Eons ago, the ability to discern bitter tastes developed as an evolutionary mechanism to protect early humans from eating poisonous plants. "We found evidence at the molecular level that natural selection has maintained the variation in the gene that allows us to taste or not taste PTC," said geneticist Stephen Wooding, Ph.D., corresponding author on the study and a post-doctoral fellow at the Eccles Institute of Human Genetics at the University of Utah School of Medicine. 4-Patterns of Inheritance - 14 of 21 Today, the ability to taste, or not taste, the compound influences what people eat and even whether they smoke cigarettes. People who can taste PTC are less likely to eat cruciferous vegetables such as broccoli, according to Wooding, which could be a problem because these vegetables contain important nutrients. If the ability to discern bitter tastes discourages PTC tasters from eating broccoli, it also may have the advantage of dissuading them from inhaling the acrid smoke of cigarettes. "Among smokers, there seems to be an excess of PTC non-tasters," Wooding said. "So it seems that PTC tasters are less likely to smoke." The researchers recently published their findings in the American Journal of Human Genetics. Typically, over hundreds of thousands years, genetic drift takes place, a process in which gene frequencies and genetic traits change randomly within a population. Under that expectation, everybody either would be a PTC taster or non-taster by now. But worldwide the ratio has remained at roughly 75/25 between PTC tasters and non-tasters. The Utah researchers found that two versions of the PTC allele (genes) are present worldwide, from America to Africa. After comparing thousands of genes, the researchers found that the presence of such divergent alleles is highly unusual. But the existence of two PTC alleles can be explained by evolutionary pressure to avoid the toxins that plants produce to defend themselves against herbivores. Everybody carries two copies of the PTC taster gene, meaning any individual could carry two copies of the PTC taster allele, two of the non-taster allele, or one of each. "We hypothesize that people carrying one copy of each allele are able to taste a broader range of toxic, bitter compounds, and have an evolutionary advantage," Wooding said. Last year, researchers at the National Institutes of Health and the University of Utah discovered the PTC gene and found that it comes in two major alleles. One allele encodes the receptor to bind PTC, and the other, which differs by three amino acids from the first, encodes a receptor that probably binds with different bitter compounds. Those researchers included the U of U medical school's Mark F. Leppert, Ph.D., professor and co-chair of the Department of Human Genetics, and Hilary Coon, Ph.D., associate professor of psychiatry. The ability to taste or not taste PTC was discovered in 1930. An American chemist named Arthur Fox accidentally let loose a quantity of PTC in a laboratory and noticed that while some people could taste it, others could not. After that, it was long hypothesized that alleles were responsible for the ability to taste PTC, according to Wooding. The PTC gene is only one of 24 bitter taste genes. Wooding and the others would like to research the remaining genes to make a stronger correlation to smoking and diet. "I would like to know which genes contribute most to smoking tendencies," Wooding said. Other authors of the latest study include: Lynn B. Jorde, Ph.D., professor of human genetics at the U of U School of Medicine; Michael J. Bamshad, M.D., associate professor of pediatrics, U of U School of Medicine; Un-kyung Kim and Jennifer Larsen, both of the National Institute of Deafness and Other Communication Disorders, National Institutes of Health. Contact: Stephen Wooding 4-Patterns of Inheritance - 15 of 21 801-585-7423 University of Utah Health Sciences Center 2. [abridged] THIOUREA TASTING OMIM 171200 Online Mendelian Inheritance in Man http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=171200 accessed June, 2005 PHENYLTHIOCARBAMIDE TASTING, INCLUDED PTC TASTING, INCLUDED PROPYLTHIOURACIL TASTING, INCLUDED PROP TASTING, INCLUDED Gene map locus 7q35-q36 DESCRIPTION Humans worldwide display a bimodality in sensitivity to the bitter taste of PTC, with approximately 75% of individuals perceiving it as intensely bitter, whereas the rest perceive it as tasteless. This difference has been the basis of study of taste perception in humans for over 70 years. Kim and Drayna (2004) provided an historical review of the subject. Propylthiouracil (PROP) and PTC are members of a class of compounds known as thioureas. The compounds carry the chemical group N-C=S, which is responsible for their characteristic bitter taste (Bartoshuk et al., 1994; Drewnowski and Rock, 1995). CLINICAL FEATURES Variation in the ability to taste PTC was discovered by Fox (1931). Supplementation of the standard test using quinine in the intermediate cases was suggested by Kalmus (1958). There has been a suggestion that PTC tasting in man is related to a component of saliva: Cohen and Ogdon (1949) claimed that PTC tasters can taste PTC only if it is dissolved in their own saliva. If the tongue is dried and then presented with PTC dissolved in someone else's saliva, it is tasteless. Jones and McLachlan (1991) described a technique for fitting mixture distributions to data on PTC sensitivity. It has long been proposed that there is a relationship between athyreotic hypothyroidism (218700; formerly called athyreotic cretinism) and PTC nontasting (e.g., Shepard, 1961). Both PTC and PROP are structurally similar to the naturally occurring antithyroid substance l-goitrin; all members of this class of chemicals have antithyroidal activity and are not tasted by PTC nontasters (Shepard, 1961). Nearly all individuals with athyreotic hypothyroidism are nontasters. Tepper (1998) reviewed the literature for the ability to taste PTC and PROP and the implications for food preference and dietary habits [her article is linked for extra reading-not required, but interesting]. Tepper (1998) discussed the classic explanation for the persistence of the PROP polymorphism, i.e., a selective advantage for avoidance of harmful compounds in the environment that are often bitter tasting (Drewnowski and Rock, 1995). This taste aversion may have special relevance for the avoidance of certain bitter-tasting vegetables. PROP and PTC are chemically related to the isothiocyanates and goitrin, bitter-tasting compounds that are present in cruciferous vegetables such as cabbage, broccoli, brussels sprouts, turnips, and kale. When eaten in large quantities, these compounds interfere with iodine metabolism, producing thyroid enlargement and goiterlike symptoms. Tepper (1998) noted that the incidence of thyroid deficiency disease is relatively rare among PTC tasters. In modern society, however, avoidance 4-Patterns of Inheritance - 16 of 21 of bitter-tasting foods may have health disadvantages, since epidemiologic studies indicate that diets low in fruits and vegetables and high in fat may be associated with increased risk of heart disease and cancer. INHERITANCE Reddy and Rao (1989) examined the genetics of PTC taste thresholds by studying 100 nuclear families. They concluded that variability in thresholds is controlled by a major locus with incomplete dominance, as well as by a multifactorial component. Olson et al. (1989) studied 120 families and concluded that the data fitted best a 2-locus model in which one locus controls PTC tasting and the other locus controls a more general taste ability. Appendix C Colour detection The series of plates you will be tested with provides a quick and accurate assessment of colour vision deficiency of congenital origin which is the most common form of colour disturbance. Colour Blindness The following information is based on http://www.tiresias.org/guidelines/colour_blindness.htm developed with the help of Prof Lindsay Sharpe, Professor of Vision Science, University of Newcastle. What is it? Colour blindness is the reduced ability to distinguish between certain colours or wavelengths of light. To see colours properly, light detecting photoreceptor cells, called cones, are needed in the retina of the eye. Three different types of cones exist, each containing a different photopigment: the short-wave (S, sometimes called 'blue'), middle-wave (M, sometimes called 'green')- and long-wave (L, sometimes called 'red') sensitive cones. These have distinct, spectral sensitivities, which define the probability curve of photon capture as a function of wavelength. The absorbance spectra of the S-, M- and L-cone photopigments overlap considerably, but have their wavelengths of maximum absorbance in different parts of the visible spectrum. If one or more of these types of cells is faulty then colour blindness results. To help you understand the differences consider the normal visible spectrum of light: Figure 3 Electomagnetic spectrum of ‘light’ (http://www.arpansa.gov.au/images/nir/spectrum.gif) 4-Patterns of Inheritance - 17 of 21 The following section is from www.city.ac.uk/ colourgroup/colourblind.html : Every colour can be defined by 3 properties: • Hue - type of colour, ie red, green etc • Saturation - depth of colour from grey • Luminance - brightness 1. HUE (type of colour) People with normal colour vision are able to differentiate colour through 3 colour sensitive light receptors in the eye. The receptors are sensitive respectively to red, green and blue incident light. The spectral response of the 3 receptors is shown below: Figure 4 Normal colour perception Colour blind persons may have one or more receptors missing or more frequently the receptor responses are less separated so that colour differences cannot be perceived or can only be seen with great difficulty. In the most common form - 'red-green' colour blindness this means that sufferers at best will have difficulty distinguishing colour differences in the red-green part of the spectrum so that separating reds, greens and yellows is extremely difficult. At worst, sufferers will only perceive blues, yellows and shades of grey in between. Figure 5 Colour perception with the red receptor missing 4-Patterns of Inheritance - 18 of 21 Figure 6 Poor red-green separation 2. Saturation –density of colour (see figure below) Figure 7 Comparison of hue and saturation 3. Brightness Our perception of brightness depends mainly on the eyes combined response to the red and green receptors. This means that if a red green colour blind person perceives two colours to have the same brightness they will not be able to distinguish between them, unless the blue receptor is stimulated differently, eg 'yellow and bright green' have a similar 'blue' content so will appear as the same tone of grey. A yellow and a darker green with a high blue content will appear as a pale and dark grey and will be able to be distinguished as separate parts of the image. Detecting colour deficiencies Colour blindness is normally diagnosed through clinical testing and a number of tests have been devised. The most common test is the use of special test plates called "pseudo-isochromatic" plates or colour confusion plates. The plates are made up of a series of spots of varying hues and lightnesses so that a central number or letter stands out from the background. Those with defective vision are unable to distinguish these figures or will see a different figure due to the different appreciation of the hues. By changing the figure and background colours, the basic types of defective colour vision can be identified. Other more specific tests, such as the anomaloscope, can pinpoint the more subtle defects in colour vision and provide a more accurate classification. 4-Patterns of Inheritance - 19 of 21 There is no cure for colour blindness, however there are techniques that can be used to help discriminate between colours, for example: hand held filters, tinted spectacles and monocular contact lenses. However, such devices must be used with caution. For instance, wearing a coloured filter over one eye reduces luminance, and can actually diminish colour discrimination and visual acuity, induce visual distortions, alter stereopsis (binocular vision) and impair depth perception. And, indeed, a review of research on whether tinted lenses or filters improve visual performance in low vision concluded they actually worsen colour vision. It should be emphasised that improving test scores on specialized colour vision tests is not the same thing as curing colour blindness. Types Phenotypically, there are 3 main types of inherited colour blindness, resulting from alterations in the cone photopigments: (i) One of the three cone pigments is altered in its spectral sensitivity, but normal threedimensional colour vision is not fully impaired. (ii) One of the cone pigments is missing and colour is reduced to two dimensions. (iii) Two or all three of the cone pigments are missing and colour and lightness vision is reduced to one dimension. The most common, hereditary colour blindnesses are known as red-green colour vision deficiencies, which are associated with disturbances in either the L-cone photopigment (protan defects) or M-cone photopigment (deutan defects). Tritan defects affect the S-cones. They are often referred to as yellow-blue disorders, but the term blue-green disorder is more accurate because they affect the ability to discriminate colours in the short- and middle-wave regions of the spectrum. Tritan defects arise from alterations in the gene encoding the S-cone photopigment and are autosomal dominant (linked to chromosome 7). Incidences are equivalent in males and females. In the UK, the frequency of inherited tritan defects has been estimated as being as low as 1:13,000 to 1:65,000. Like many autosomal dominant disorders, it is complicated by frequent incomplete manifestation. Although congenital tritan defects are rare, the most frequently acquired colour vision defects, whether due to ageing or to retinal or neural disorders are the acquired blue-yellow defects. These are similar, but not identical to tritan defects. Unlike tritan defects, which are assumed to be stationary, acquired defects are usually progressive and have other related signs, such as associated visual acuity deficits. Total colour blindness or monochromacy occurs when a person has only a single functioning cone class (blue or S-cone monochromacy, green or M-cone monochromacy or red or L-cone monochromacy) or has no functioning cones (complete achromatopsia or rod monochromacy). These forms of colour blindness are extremely rare. 4-Patterns of Inheritance - 20 of 21 Frequency of occurence • Because these defects are inherited as recessive traits, the incidences are much higher in males whose cells have a single X-chromosome, than in females whose cells have two. • Incidences of red-green colour deficiencies vary between human populations of different racial origin. The highest rates are found in Europeans and the Brahmins of India (c. 8% of males) and Asians (c. 4%); the lowest in Africans (c. 2.5%) and the aborigines in Australia (c. 2%), Brazil, North America (c. 2.0%) and the South Pacific Islands (c. 1.0%) (Source: Opsin genes, cone photopigments, color vision, and color blindness in Color Vision: from Genes to Perception, Cambridge University Press, New York, 1999) Problem Official term % of males per 1000 males Weak in red "protanomalous" 0.5 % 5 No red "protoanopia" 0.8 % 8 Weak in green "deuteranomalous" 3.3 % 33 No green "deuternopia" 0.6 % 6 Fruit stall http://www.tiresias.org/guidelines/colour_blindness.htm A fruit stall as seen by colour normal (A), protanopic - a form of red-green blindness (B), deuteranopic - another form of red-green blindness (C) and tritanopic - a form of blue-green blindness (D) shoppers. A. Colour Normal C. Deuteranopic B. Protanopic D. Tritanopic 4-Patterns of Inheritance - 21 of 21 What are the consequences of being ‘colour blind’? Below is a partial list of potential problems—can you think of others? “Life's minor frustrations (and occasional dangers) for the color blind:” [the following list is from http://www.toledo-bend.com/colorblind/aboutCB.html] • • • • • • • • Weather forecasts - especially the Weather Channel - where certain colors just can not be distinguished on their weather maps. Also, maps in general because of the color coding on the legends. Bi-color and tri-color LEDs (Light Emitting Diodes): Is that glowing indicator light red, yellow, or green? Traffic lights, and worst of all, Caution lights: Color blind people always know the position of the colors on the traffic light - in most states, Red on top, Yellow in the center, Green (or is that blue?) on the bottom. It isn't good when we go to a city or state where they put traffic lights horizontal - it takes a couple of days to get used to that one! But caution lights present an entirely different problem. In this situation there is only one light; no top or bottom, no right or left, just one light that is either red or yellow - but which is it? Getting in the sun with your friend: So, you're out in the boat or on the beach with your friend and soaking up the rays. But I can't tell until far too late if I'm getting red - or if she/he is. If I can tell it's red, by that time it's fire engine red and a painful sunburn is already present. Color observation by others: "Look at those lovely pink flowers on that shrub". My reply, looking at a greenish shrub "What flowers?" Purchasing clothing: I've got some really neat colors of clothes. Not everyone appreciates them like I do though; they seem to think the colors are strange. I just don't know why! Test strips for hard water, pH, swimming pools, etc.: A color blind person is generally unable to : o interpret some chemical reactions o see that litmus paper turns red by acid o identify a material by the color of its flame such as lead blue or potassium purple o interpret the chemical testing kits for swimming pool water, test strips for hard water, soil or water pH tests - all of which rely on subtle color differences and a band of similar colors to compare against. Cooking and foods: o When cooking, red deficient individuals cannot tell whether their piece of meat is raw or well done. Many can not tell the difference between green and ripe tomatoes or between ketchup and chocolate syrup. o Some food can even look definitely disgusting to color deficient individuals. For example, people with a green deficiency cannot possibly eat spinach which to them just look like cow pat. They can however distinguish some citrus fruits. Oranges seem to be of a brighter yellow than that of lemons. from http://vischeck.com/info/wade.php Dr Alex Wade, Research Fellow at Stanford University April 2000 “On the positive side, there is some evidence that colour-blind people are much better than average at certain jobs. They are very good at finding green things hidden against green backgrounds - for example grass or leaves. They tend to find things by shape and get less confused by camouflage. Because of this, colour-blind entomologists still catch lots of bugs and in wartime, armies prize their colour-blind snipers and spotters.”