Chapter 14 Mendel and the Gene Idea Inheritance The passing of traits from parents to offspring Humans have

known about inheritance for thousands of years Genetics The scientific study of the inheritance Genetics is a relatively new science (about 150 years). Genetic Theories 1. Blending Theory - Traits were like paints and mixed evenly from both parents. 2. Incubation Theory - Only one parent controlled the traits of the children. Ex: Spermists and Ovists 3. Particulate Model - Parents pass on traits as discrete units that retain their identities in the offspring. Gregor Mendel Father of Modern Genetics

Mendels paper published in 1866, but was not recognized by Science until the early 1900s Reasons for Mendel's Success Used an experimental approach Applied mathematics to the study of natural phenomena Kept good records Mendel was a pea picker He used peas as his study organism Why Use Peas? Short life span Bisexual Many traits known Cross- and self-pollinating (You can eat the failures) Cross-pollination Two parents Results in hybrid offspring where the offspring may be different than the parents Self-pollination

One flower as both parents Natural event in peas Results in pure-bred offspring where the offspring are identical to the parents Mendel's Work Used seven characters, each with two expressions or traits Example: Character - height Traits - tall or short Monohybrid or Mendelian Crosses Crosses that work with a single character at a time Example - Tall X short P Generation The Parental generation or the first two individuals used in a cross Example - Tall X short Mendel used reciprocal crosses, where the parents alternated for the trait Offspring F1 - first filial generation. F2 - second filial generation, bred by crossing two F1 plants together or allowing a F1 to self-pollinate.

Results - Summary In all crosses, the F1 generation showed only one of the traits regardless of which was male or female. The other trait reappeared in the F2 at ~25% (3:1 ratio). Mendel's 4 Hypothesis Genes can have alternate versions called alleles Each offspring inherits two alleles, one from each parent Mendel's Hypothesis If the two alleles differ, the dominant allele is expressed; the recessive allele remains hidden unless the dominant allele is absent Comment this does NOT mean that the dominant trait is stronger than the recessive; be careful with your use of language Mendel's Hypothesis The two alleles for each trait separate during gamete formation; this now called:

Mendel's Law of Segregation Law of Segregation Mendels Experiments Showed that the Particulate Model best fit the results Vocabulary Phenotype - the physical appearance of the organism Genotype - the genetic makeup of the organism, usually shown in a code T = tall t = short Helpful Vocabulary Homozygous - When the two alleles are the same (TT/tt). Heterozygous - When the two alleles are different (Tt). 6 Mendelian Crosses are Possible Cross TT X tt Tt X Tt TT X TT tt X tt TT X Tt Tt X tt Test Cross Ex: T_ X tt If TT - all dominant If Tt - 1 Dominant: 1 Recessive Dihybrid Cross Cross with two genetic traits Need 4 letters to code for the cross Ex: TtRr Each Gamete - Must get 1 letter for each trait Ex. TR, Tr, etc. Number of Kinds of Gametes Critical to calculating the results of higher level crosses Look for the number of heterozygous traits Equation all Tt 1TT:2Tt:1tt all TT all tt 1TT:1Tt 1Tt:1tt Genotype all Dom 3 Dom: 1 Res all Dom all Res all Dom 1 Dom: 1 Res Phenotype

Cross of a suspected heterozygote with a homozygous recessive

The formula 2n can be used, where n = the number of heterozygous traits. Ex: TtRr, n=2 22 or 4 different kinds of gametes are possible TR, tR, Tr, tr Dihybrid Cross TtRr X TtRr Each parent can produce 4 types of gametes TR, Tr, tR, tr Cross is a 4 X 4 with 16 possible offspring Results 9 Tall, Red flowered 3 Tall, white flowered 3 short, Red flowered 1 short, white flowered Or: 9:3:3:1 Law of Independent Assortment The inheritance of 1st genetic trait is NOT dependent on the inheritance of the 2nd trait Inheritance of height is independent of the inheritance of flower color Or think of it this way just because you get your eye color from your mom, does not mean that you will get your hair color from your mom too Comment Ratio of Tall to short is 3:1 Ratio of Red to white is 3:1 The cross is really a product of the ratio of each trait multiplied together. (3:1) X (3:1) Probability Genetics is a specific application of the rules of probability Probability - the chance that an event will occur out of the total number of possible events Genetic Ratios The monohybrid ratios are actually the probabilities of the results of random fertilization Ex: 3:1 75% chance of the dominant

25% chance of the recessive Rule of Multiplication or Product Rule The probability that two alleles will come together at fertilization, is equal to the product of their separate probabilities Example: TtRr X TtRr The probability of getting a tall offspring is . The probability of getting a red offspring is . The probability of getting a tall red offspring is x = 9/16 Comment Use the Product Rule to calculate the results of complex crosses rather than work out the Punnett Squares. Ex: TtrrGG X TtRrgg Solution Ts = Tt X Tt = 3:1 Rs = rr X Rr = 1:1 Gs = GG x gg = 1:0 Product is: (3:1) X (1:1) X (1:0) = 3:3:1:1 Variations on Mendel 1. Incomplete Dominance 2. Codominance 3. Multiple Alleles 4. Epistasis 5. Polygenic Inheritance Incomplete Dominance When the F1 hybrids show a phenotype somewhere between the phenotypes of the two parents. Often a dose effect Ex. Red X White snapdragons F1 = all pink F2 = 1 red: 2 pink: 1 white Result No hidden Recessive 3 phenotypes and 3 genotypes Red = CR CR Pink = CR CW (Hint! often a dose effect)

White = CW CW Another example Codominance Both alleles are expressed equally in the phenotype. Ex. MN blood group MM MN NN Result No hidden Recessive 3 phenotypes and 3 genotypes (but not a dose effect) Ex. You cross a black bunny (BB) with a white bunny (bb) and you get 4 black and white spotted bunnies (Bb) Multiple Alleles When there are more than 2 alleles for a trait Ex. ABO blood group IA - A type antigen IB - B type antigen i - no antigen Result Multiple genotypes and phenotypes Very common event in many traits Alleles and Blood Types Type A B AB O Genotypes IA IA or IA i IB IB or IB i IA IB ii

Comment Rh blood factor is a separate factor from the ABO blood group Rh+ = dominant Rh- = recessive A+ blood = dihybrid trait

Epistasis When 1 gene locus alters the expression of a second locus Ex: 1st gene: C = color, c = albino 2nd gene: B = Brown, b = black Gerbils In Gerbils CcBb X CcBb Brown X Brown F1 = 9 brown (C_B_) 3 black (C_bb) 4 albino (cc__) Result Ratios often altered from the expected One trait may act as a recessive because it is hidden by the second trait Epistasis in Mice Problem Wife is type A Husband is type AB Child is type O Question - Is this possible? Comment - Wifes boss is type O Bombay Effect Epistatic Gene on ABO group Alters the expected ABO outcome H = dominant, normal ABO h = recessive, no A,B, reads as type O blood Genotypes Wife: type A (IA IA , Hh) Husband: type AB (IA IB , Hh) Child: type O (IA IA , hh) Therefore, the child is the offspring of the wife and her husband (and not the boss). Bombay - Detection When ABO blood type inheritance patterns are altered from expected Polygenic Inheritance

Factors that are expressed as continuous variation Lack clear boundaries between the phenotype classes Ex: skin color, height Genetic Basis Several genes govern the inheritance of the trait Ex: Skin color is likely controlled by at least 4 genes Each dominant gives a darker skin Result Mendelian ratios fail Traits tend to "run" in families Offspring often intermediate between the parental types Trait shows a bell-curve or continuous variation Genetic Studies in Humans Often done by Pedigree charts Why? Cant do controlled breeding studies in humans Small number of offspring Long life span Pedigree Chart Symbols Male

Female

Person with trait Sample Pedigree Human Recessive Disorders Several thousand known: Albinism Sickle Cell Anemia Tay-Sachs Disease Cystic Fibrosis PKU Galactosemia

Sickle-cell Disease Most common inherited disease among African-Americans Single amino acid substitution results in malformed hemoglobin (as discussed previously) Reduced O2 carrying capacity Co-dominant inheritance Tay-Sachs Eastern European Jews Brain cells unable to metabolize type of lipid, accumulation of causes brain damage Death in infancy or early childhood Cystic Fibrosis Most common lethal genetic disease in the U.S Most frequent in Caucasian populations (1/20 a carrier) Produces defective chloride channels in membranes Recessive Pattern Usually rare Skips generations Occurrence increases with consanguineous matings Often an enzyme defect Human Dominant Disorders Less common then recessives Ex: Huntingtons disease Achondroplasia Familial Hypercholsterolemia Inheritance Pattern Each affected individual had one affected parent Doesnt skip generations Homozygous cases show worse phenotype symptoms May have post-maturity onset of symptoms Genetic Screening Risk assessment for an individual inheriting a trait Uses probability to calculate the risk General Formal

R=FXMXD R = risk F = probability that the female carries the gene. M = probability that the male carries the gene. D = Disease risk under best conditions. Example Wife has an albino parent Husband has no albinism in his pedigree Risk for an albino child? Risk Calculation Wife = probability is 1.0 that she has the allele. Husband = with no family record, probability is near 0. Disease = this is a recessive trait, so risk is Aa X Aa = .25 R = 1 X 0 X .25 R=0 Risk Calculation Assume husband is a carrier, then the risk is: R = 1 X 1 X .25 R = .25 There is a .25 chance that any child will be albino Common Mistake If risk is .25, then as long as we dont have 4 kids , we wont get any with the trait. Risk is .25 for each child. It is not dependent on what happens to other children Think of it as flipping a coin if I obtain a tails on a coin flip 20x, I still have a 50/50 chance at receiving a tails on the next flip Carrier Recognition Fetal Testing Amniocentesis Chorionic villi sampling Newborn Screening Fetal Testing Biochemical Tests Chromosome Analysis Amniocentesis Administered between 11 - 14 weeks

Extract amnionic fluid = cells and fluid Biochemical tests and karyotype Requires culture time for cells Chorionic Villi Sampling Administered between 8 - 10 weeks Extract tissue from chorion (placenta) Slightly greater risk but no culture time required Newborn Screening Blood tests for recessive conditions that can have the phenotypes treated to avoid damage Genotypes are NOT changed Ex. PKU Newborn Screening Required by law in all states Tests 1- 6 conditions Required of home births too Multifactorial Diseases Where Genetic and Environment Factors interact to cause the Disease Becoming more widely recognized in medicine Ex. Heart Disease Genetic Diet Exercise Bacterial Infection Genes & Environment Summary Know the Mendelian crosses and their patterns Be able to work simple genetic problems (practice) Watch genetic vocabulary Be able to read pedigree charts Be able to recognize and work with some of the common human trait examples