Mendel and the Gene Idea

CHAPTER 14 – MENDEL AND THE GENE IDEA 1 GREGOR MENDEL Gregor Mendel is the father of genetics. He came up with the Law of Segregation and the Law of Independent Assortment. In 1857 he began breeding garden peas to study inheritance. He was also a monk. Blending Hypothesis → proposes that the genetic material contributed by each parent mixes; similar to how blue and yellow paint mix to make green Particulate Hypothesis → proposes that parents pass on discrete heritable traits (genes) which retain their SEPARATE identities in offspring; this was Mendel’s idea 2 PEA PLANTS Mendel was actually lucky with his choice of pea plants because almost all of the characters show pure dominance. Mendel used pea plants for several reasons: -They have distinct characters (TRAITS) that are easily observable -They have male and female sex organs - He could control the mating -They produced many offspring and have a short generation time -They were easy to manage 3 GENERATIONS Mendel started off his experiments with plants that were true-breeding (homozygous) P1 = Parents F1 = Offspring of P1 x P1 F2 = Offspring of F1 x F1 F3 = Offspring of F2 x F2….etc The “F” in F1, F2, etc. stands for the word “filial” which comes from the Latin word “filius” which means son. 4 Dominant → Trait that is seen in the phenotype; represented with an uppercase letter Recessive → trait that is hidden in the phenotype; represented with a lowercase letter LAW OF SEGREGATION The Law of Segregation encompasses 4 general ideas: - Alternate versions of genes (alleles) account for variations in inherited characteristics - For each character, the offspring inherits 2 alleles (mom, dad) - If the 2 alleles are different, the dominant one is expressed - The 2 alleles separate during meiosis. 5 PUNNENT SQUARES AND VOCABULARY Genotype = the genes that an organism has; Ex. AA, Aa, or aa Phenotype = what the organism looks like; Ex. purple, white Homozygous → same alleles; AA or aa; can be homozygous dominant or homozygous recessive; also called truebreeding Heterozygous → has different alleles; one dominant and one recessive; Aa A punnent square is a tool that helps you predict the results of a genetic cross where the genotypes of the parents are known. They provide you with the probability ratios. 6 TESTCROSS A testcross is needed if you are trying to find out the genotype of a certain organism. You can cross the organism in question with a homozygous recessive organism. The offspring will tell you the genotype of the original parents. Purple plant….Aa or AA? Cross with a white (aa) to see what the results are. IF the results are all purple, you know the original plant was AA. IF half of the plants are purple and the other half are white, you know that the original plant was Aa. 7 MONOHYBRID VS. DIHYBRID   Monohybrid → ONE trait; ex. Flower color  Aa x AA Dihybrid → TWO traits; ex. Seed color AND seed shape  YyRr x yyrr When Mendel did a dihybrid cross of a homozygous dominant with a homozygous recessive, all the F1 plants were heterozygous. When he crossed two F1 plants to get an F2 generation, he observed a 9:3:3:1 ratio 8 LAW OF INDEPENDENT ASSORTMENT The Law of Independent Assortment says that each pair of alleles segregates into gametes independently. This law applies only to genes located on different, non-homologous chromosomes. Genes that are located on the SAME chromosome tend to be inherited together and are called Linked Genes. 9 RULE OF MULTIPLICATION  This rule is used to determine the probability that two or more independent events will occur together in some specific combination.  Probability that two coins tossed at the same time will both lands heads up is ¼  Chance of coin A landing heads up = ½  Chance of coin B landing heads up = ½ ½x½=¼  Probability that a heterozygous pea plant (Pp) will self-fertilize to produce a white-flowered offspring (pp) is the probability that a sperm with a white allele will fertilize an ovum with a white allele. This probability is 1/2 × 1/2 = 1/4.  Chance of parents having 3 kids that are ALL boys  Chance of kid A being a boy = ½ (same for kid B, C)  ½ x ½ x ½ = 1/8 10 RULE OF ADDITION    This rule is used to determine the probability when an event can occur in two or more mutually exclusive ways. The probability of getting Pp as offspring with both parents being heterozygous:  The probability of obtaining an F2 heterozygote by combining the dominant allele from the egg and the recessive allele from the sperm is 1⁄4.  The probability of combining the recessive allele from the egg and the dominant allele from the sperm also 1⁄4.  Using the rule of addition, we can calculate the probability of an F2 heterozygote as 1⁄4 + 1⁄4 = 1⁄2. The chance of having 3 kids with 2 boys and 1 girl:  B, B, G = ½ x ½ x ½ = 1/8  B, G, B = ½ x ½ x ½ = 1/8  G, B, B = ½ x ½ x ½ = 1/8  SO, the chance of having a family with two boys and one girl at 3/8 11 GENETICS PROBLEMS – SAMPLE PROBLEM!    Determine the probability of an offspring having recessive phenotypes for at least two of three traits resulting from a trihybrid cross between pea plants that are PpYyRr and Ppyyrr.  The probability of producing a ppyyRr offspring:  The probability of producing pp = 1/4.  The probability of producing yy = 1/2.  The probability of producing Rr = 1/2. So, the probability of all three being present (ppyyRr) in one offspring is 1/4 × 1/2 × 1/2 = 1/16.  For ppYyrr: 1/4 × 1/2 × 1/2 = 1/16.  For Ppyyrr: 1/2 × 1/2 × 1/2 = 1/8 or 2/16. (must keep denominators the same!)  For PPyyrr: 1/4 × 1/2 × 1/2 = 1/16.  For ppyyrr: 1/4 × 1/2 × 1/2 = 1/16. Therefore, the chance that a given offspring will have at least two recessive traits is 1/16 + 1/16 + 2/16 + 1/16 + 1/16 = 6/16 or 3/8. 12 PRACTICE GENETICS PROBLEMS:  Parents → PpyyRr x PpYyrr  1. Chance of having all 3 dominant phenotypes  2. Chance of having at least 2 heterozygous genotypes  3. Chance of having at least 2 dominant phenotypes 13 Parents → PpyyRr x PpYyrr 1. Chance of having all 3 dominant phenotypes PPYyRr – ¼ x ½ x ½ = 1/16  PpYyRr – ½ x ½ x ½ = 1/8 = 2/16 ------------3/16  14 Parents → PpyyRr x PpYyrr 2. Chance of having at least 2 heterozygous genotypes PpYyrr – ½ x ½ x ½ = 1/8 = 2/16  PpYyRr – ½ x ½ x ½ = 1/8 = 2/16  PpyyRr – ½ x ½ x ½ = 1/8 = 2/16  ppYyRr – ¼ x ½ x ½ = 1/16  PPYyRr – ¼ x ½ x ½ = 1/16 -------------8/16 or 1/2  15 Parents → PpyyRr x PpYyrr 3. Chance of having at least 2 dominant phenotypes        PpYyrr – PpYyRr – PPYyrr – PPYyRr – PpyyRr PPyyRr ppYyRr - ½ x ½ x ½ = 1/8 = 2/16 ½ x ½ x ½ = 1/8 = 2/16 ¼ x ½ x ½ = 1/16 ¼ x ½ x ½ = 1/16 ½ x ½ x ½ = 1/8 = 2/16 ¼ x ½ x ½ = 1/16 ¼ x ½ x ½ = 1/16 ------------------10/16 or 5/8 16       In the 20th century, geneticists extended Mendelian principles both to diverse organisms and to patterns of inheritance more complex than Mendel described. Mendel had the good fortune to choose a system that was relatively simple genetically. Each character that Mendel studied is controlled by a single gene. (There is one exception: Mendel’s pod shape character is determined by two genes.) Each gene has only two alleles, one of which is completely dominant to the other. The heterozygous F1 offspring of Mendel’s crosses always looked like one of the parental varieties because one allele was dominant to the other. The relationship between genotype and phenotype is rarely so simple. 17 DOMINANCE Codominant – When both alleles are dominant; Red + White = a flower with BOTH red and white; the heterozygote shows a phenotype representative of both alleles. Incomplete Dominance – when the dominant allele is not COMPLETELY dominant; the heterozygote is a mix between the dominant and recessive phenotype; EX. red + white = pink 18    It is important to recognize that an allele is called dominant because it is seen in the phenotype, not because it somehow subdues a recessive allele. Alleles are simply variations in a gene’s nucleotide sequence. A dominant allele is not necessarily more common in a population than the recessive allele. For example, one baby in 400 is born with polydactyly, a condition in which individuals are born with extra fingers or toes. Polydactyly is due to a dominant allele. Clearly, however, the recessive allele is far more prevalent than the dominant allele. DOMINANT ALLELES 19 MULTIPLE ALLELES Most genes have more than 2 allelic forms (more than just dominant and recessive). The best example is the ABO blood groups. Both the IA and IB alleles are dominant to the i allele. The IA and IB alleles are codominant to each other. 20   Because each individual carries two alleles, there are six possible genotypes and four possible blood types.  Individuals who are IAIA or IAi are type A and have type A carbohydrates on the surface of their red blood cells.  Individuals who are IBIB or IBi are type B and have type B carbohydrates on the surface of their red blood cells.  Individuals who are IAIB are type AB and have both type A and type B carbohydrates on the surface of their red blood cells.  Individuals who are ii are type O and have neither carbohydrate on the surface of their red blood cells. Matching compatible blood groups is critical for blood transfusions because a person produces antibodies against foreign blood factors. BLOOD GROUPS 21 PLEIOTROPY Pleiotropy is when one gene affects more than one phenotype. In sickle cell anemia, even though it is only a change in one amino acid, it affects many things in the body. 22 EPISTASIS Epistatic genes are genes that affect the expression of another gene at a different locus. Example 1 – Mice: B (black) is dominant to b (brown). However, the gene for color in the fun is epistatic to it. SO, if the mice have cc as their genotype, then regardless of whether they should be brown or black, they will be white because they will have no color deposited into their fur. Example 2 – Hair: Curly hair (H) is dominant to straight hair (h). If someone has a gene for baldness, it won’t matter if they have straight or curly, because they won’t have hair to begin with. 23 POLYGENIC INHERITANCE Polygenic traits is when several genes all affect the same phenotype. It is the opposite idea of pleiotropy. It has an additive effect and usually spans a continuum. Quantitative characters → traits that vary along a continuum; ex. Skin color, eye color, height AABbcc = AaBbCc….both have 3 dominant alleles; it is an additive effect. 24       Phenotype depends on both environment and genes. Hydrangea plants may be pink or blue depending on the acidity of the soil. For humans, nutrition influences height, exercise alters build, suntanning darkens skin, and experience improves performance on intelligence tests. Even identical twins, who are genetically identical, accumulate phenotypic differences as a result of their unique experiences. The product of a genotype is generally not a rigidly defined phenotype, but a range of phenotypic possibilities, the norm of reaction, determined by the environment. Norms of reaction are broadest for polygenic characters. NORM OF REACTION 25 PEDIGREES Pedigrees are family trees that can follow genetically inherited traits through several generations. Based on this information, you can tell how a trait is inherited (autosomal dominant, autosomal recessive, sex-linked, etc). Pedigrees are used to study heredity…instead of manipulating mating patterns of humans, doctors analyze the matings that have already occurred. This can help understand the past and predict the future. 26 MENDELIAN INHERITED TRAITS IN HUMANS DOMINANT Some traits in humans follow Mendelian Inheritance. Some of the traits that show dominance and follow this type of inheritance are: - Dimples - Freckles - Mid-digital hair - Polydactly - Tongue rolling - Widow’s peak 27 MENDELIAN INHERITED TRAITS IN HUMANS RECESSIVE Some of the traits that are recessive and follow this type of inheritance are: - Hitchhickers Thumb - Attached Earlobes 28 GENETIC DISORDERS Genetic Disorders can be caused by several different things. They can be carried on the autosomal chromosomes or on the sex chromosomes. They can be caused by a dominant allele, or a recessive allele. Further, they can be the result of an incorrect number of chromosomes (due to nondisjunction – more on that in Ch. 15). Refer to the Genetic Disorders Chart for notes on each of the following diseases/disorders: We are going to look at disorders that follow autosomal recessive inheritance: - Cystic Fibrosis Heterozygotes are carriers and do - Tay Sachs Disease NOT have the disorder, but have a - Sickle Cell Disease 50% chance of passing the allele - Phenylketonuria (PKU) onto their offspring. We are also going to look at disorders that follow autosomal dominant inheritance: - Achondroplasia (dwarfism) - Huntington’s Disease Lethal dominant alleles are much LESS common than lethal recessives because a lethal dominant most likely kills the person before they can reproduce (although there ARE exceptions) but a lethal recesivce can hide in a heterozygote and that person would be phenotypically normal! NOTE: Consanguineous matings (matings between close relatives) can increase the risk of producing offspring with a genetic disorder. 29 - Autosomal Recessive - Most common lethal genetic disease in the US - Problem with the Cl- ion transport channels which leads to a high concentration of Cl- outside the cells - This higher concentration leads to mucus production which can build up in the pancreas, LUNGS, and digestive tract…which leads to infections - When the white blood cells come to the site of infection, their remains stay there and add to the mucus…this is a bad cycle - Many respiratory problems CYSTIC FIBROSIS 30 TAY-SACHS DISEASE - Autosomal Recessive (incomplete dominance at molecular level) -- Brain cells have a defective enzyme that cannot break down lipids; this leads to a build up on the brain -- The buildup causes the brain not to function properly and progressively destroys the central nervous system. This can lead to seizures, blindness, and degeneration of motor and mental capabilities -A baby with TSD appears to develop normally for the first few months, then there is a relentless deterioration of mental and physical abilities. The child gradually becomes blind, is unable to swallow, and has inefficient pulmonary function. Muscles begin to atrophy, paralysis sets in, and response to the environment diminishes. There is no cure or treatment 31 and average life expectancy is 3-5 years of age. SICKLE CELL DISEASE -Autosomal recessive, demonstrates pleiotropy; codominant at molecular level -Caused by a substitution of one amino acid in the hemoglobin protein of RBC’s -When there is a low level of oxygen, the RBC’s change their shape to a sickle shape - Symptoms range over a wide spectrum: low # of RBC’s, fatigue, sharp pains, and infections - Being a carrier is beneficial because they are immune to malaria (common in Africa) 32 PHENYLKETONURIA (PKU) -Autosomal recessive -Screened for at birth -Body cannot properly break down the amino acid phenylalanine, which, if accumulated, can reach toxic levels and cause mental deficiencies - If its confirmed that a baby is afflicted, they are put on a 33 special diet and are usually OK -Autosomal dominant -Homozygous recessive = normal height -Heterozygous = dwarf - Homozygous dominant = lethal ACHONDROPLASIA 34 HUNTINGTON’S DISEASE -Autosomal Dominant -This is a deterioration of the nervous system -It does not show up until the person’s late 30’s or early 40’s, so by this point the gene has probably already been passed on if they have already procreated -This leads to death 35 MULTIFACTORIAL DISORDERS Some disorders are multifactorial, and have a genetic component plus significant environmental influence.  Multifactorial disorders include heart disease, diabetes, cancer, alcoholism, and certain mental illnesses, such as schizophrenia and manic-depressive disorder.  36 GENETIC COUNSELING Genetic counseling is based on Mendelian genetics and the laws of probability.  Many hospitals have genetic counselors to provide information to prospective parents who are concerned about a family history of a specific disease.   See the example on the next slide 37          A hypothetical couple, John and Carol, are planning to have their first child. Both John and Carol had brothers who died of the same recessive disease. John, Carol, and their parents do not have the disease. Their parents must have been carriers (Aa × Aa). John and Carol each have a 2/3 chance of being carriers and a 1/3 chance of being homozygous dominant. The probability that their first child will have the disease is 2/3 (chance that John is a carrier) × 2/3 (chance that Carol is a carrier) × 1/4 (chance that the offspring of two carriers is homozygous recessive) = 1/9. If their first child is born with the disease, we know that John and Carol’s genotype must be Aa and they are both carriers. In that case, the chance that their next child will also have the disease is 1/4. Mendel’s laws are simply the rules of probability applied to heredity. The chance that John and Carol’s first three children will have the disorder is 1/4 × 1/4 × 1/4 = 1/64. Should that outcome happen, the likelihood that a fourth child will also have the disorder is still 1/4. 38 FETAL TESTING 39 AMNIOCENTESIS Amniocentesis is a process that is done if a woman is having a high risk pregnancy. A needle is inserted into the amniotic sac and some of the fetal cells are extracted. Those cells are then cultured in a petri dish until enough cells form. Then the cells are used to make a karyotype, which will show genetic disorders. 40 CHORIONIC VILLI SAMPLING (CVS) This is a fetal testing procedure that suctions out some of the fetal cells through the cervix. Because the cells are mature enough and enough are in the sample, a karyotype can be done immediately and the results of the test are returned usually within 24 hours. This test can be done between 8-10 weeks.41 ULTRASOUND An ultrasound is a non-invasive procedure that allows doctors to see anatomical features of the baby. Typically this is used to determine the sex of the child. 42 FETOSCOPY Fetoscopy is a process when a thin viewing scope is inserted into the uterus to view the fetus. 43 GENETIC TESTS  Newer techniques can isolate fetal cells or DNA from the mothers blood – HARMONY test  This  test is performed around 10-12 weeks Some genetic traits can be detected at birth by simple tests that are now routinely performed in the hospitals as soon as the baby is born. 44