Chapter 9: Part 2. Breeding plants identical for 5 traits, but differing in 2

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1 Chapter 9: Part 2 Dihybrid crosses Human Traits and diseases controlled by a single gene Pedigrees Beyond Mendel Incomplete dominance Multiple alleles Pleiotropy and Polygenic inheritance Linked genes Sex linked genes and sex-linked disorders The next question Mendel asked, was What happens when I study the inheritance of TWO different traits at the same time? To answer this question, he used Dihybrid Crosses Cross two true-breeding plants differing in two characters Flower color Breeding plants identical for 5 traits, but differing in 2 Dominant Recessive Dominant Recessive Purple White Pod shape Inflated Constricted There are two different hypotheses for gene assortment in a dihybrid cross 1. Dependent assortment 2. Independent assortment Pod Color Green Yellow Flower position xial Terminal Seed color Yellow Green Seed shape Round Wrinkled Stem length Tall Dwarf 2. Seed color Yellow Green 1. Seed shape Round Wrinkled One plant has the genotype RRYY, one plant has the genotype rryy. What is the phenotype of each plant? Dihybrid Cross P generation: RRYY x rryy (true breeding) F1 generation: all offspring are heterozygous for both characters Rr Yy Question: re Y and R sorted into gametes together as a package (the same way they were received), or separately? The question, then, is directed at the gametes of the F1 generation. What type of gametes will the F1 generation have? Will the gametes have a combination of parental traits, or will the gametes produced look like the gamete it received from parents? Will Y and R stay together generation after generation (is their assortment dependent) OR are they inherited independently of one another? 1

2 What happens in a dihybrid cross -If it is dependent assortment? If it is dependent assortment? P generation F1 generation First, if it is dependent assortment, what are the possible gametes of the F 1 generation? What would the outcome look like if it is dependent assortment? RY In this scenario, the genes (R and Y) were passed on as a package exactly as they were inherited. r y NOTE that these gametes are identical to those received. If it is independent assortment? What are the possible gametes that the F1 generation can make? (meiosis) If it is independent assortment? What are the possible gametes that the F1 generation can make? (meiosis) R r Y y R r OR R r RY yr Ry ry Y y y Y RY ry Ry ry 2

3 Dependent ssortment Independent ssortment RY r y RY yr r y RY RY r y Ry ry Which of the two predicted outcomes did Mendel see? Which hypothesis, or prediction did his data resemble? Mendel s 2 nd Law The law of independent assortment States that each PIR of alleles segregates independently of the other pairs during gamete formation Supported by the 9:3:3:1 phenotypic ratio he observed during the dihybrid cross His data (the seeds of the pea plants) looked like this. Mendel s 2 nd Law Different alleles can line up on either side of the metaphse plate, independent of other gene pairs OR Need a reminder of Mendel s first law? The 2 alleles separate (segregate) during gamete formation Meaning, egg or sperm get only one of 2 alleles Baby ****Mendel s law of segregation**** 3

4 Mendel s Contributions 1. Segregation (the two alleles of each gene an organism has are separated during gamete formation) 2. Independent ssortment: as far as Mendel found, which gamete (sperm or egg) an allele for one gene ends up distributed to is independent of other genes Figuring out the possible gametes for a dihybrid cross, knowing that genes sort independently YyRr (Yy) (Rr) Distribute!! FOIL =YR, Yr, yr, yr Practice problem In a dihybrid cross, BbCc x BbCc, what fraction of the offspring will be homozygous for both recessive traits? Some human traits (not many) exhibit simple Mendelian Inheritance What does that title mean??. 1/16 B. 1/8 C. 3/16 D. 1/4 E. 3/4 Some human traits exhibit simple Mendelian Inheritance Dominant Recessive Simple Mendelian Genetics refers to ONE TRIT being controlled by ONE GENE, and that the GENE has only two possible alleles, and that one allele is completely dominant over the other, recessive allele. Some Human Traits Exhibit Mendelian Inheritance How did geneticists arrive at this conclusion? Do you think they used test crosses on humans?? NO! Geneticists study the results of matings that have already occurred. 4

5 Family Pedigrees What is a carrier? What is the genotype of a carrier? Do carriers display the disorder? The earliest generation studied is at the top of the pedigree. Notice that deafness did not appear in this generation. How could you explain to someone that this form of deafness is controlled by a recessive allele?? Why do none of the 7 children have the genotype DD? Who in this pedigree is a carrier for this deafness gene? Some human disorders are controlled by a single gene Recessively Inherited Disorders that exhibit simple Mendelian Inheritance Some genetic disorders are known to be inherited as simple recessive traits. (For the recessive phenotype to be seen, the organism needs TWO copies of the recessive allele). lbinism, Tay-Sachs, cystic fibrosis Remember that genes C code for proteins! Carriers = genotype is heterozygous but c phenotype is normal C CC Cc carrier c Cc carrier cc Cystic fibrosis Recessively Inherited Disorders Cystic Fibrosis (CFTR) How do heterozygotes fair? With some diseases the heterozygotes are perfectly healthy, while with other diseases the heterozygotes have an intermediate phenotype Why don t these recessive alleles become weeded out of the gene pool? Is it obvious, or outwardly apparent, if someone is a carrier for a recessively inherited disorder? Why/why not? Dominantly Inherited Disorders that exhibit simple Mendelian Inheritance These diseases require only ONE copy of allele to produce disease How do carriers or heterozygotes fair? (think about the Pp flowers) Dominant alleles that cause a lethal disease are much less common than recessive alleles that do so Often arise from spontaneous mutations in sperm or egg YEOWCH! 5

6 Dominantly Inherited Disorders chondroplasia (form of dwarfism) Heterozygotes have dwarf phenotype Homozygous dominant embryos spontaneously abort 99.9% of population are NOT achondroplasic and are homozygous recessive Dominantly Inherited Disorders Huntington s Disease is a dominantly inherited disorder Why don t these dominant alleles become weeded out of the gene pool? What is the average age of onset of Huntington s disease? Beyond Mendel Mendel laid down important rules that established the foundations of genetics But, his two principles do not explain everything Next, we ll look at examples of inheritance that do not adhere to Mendel s rules. Glitch #1 (Mendel was lucky) Incomplete dominance Heterozygotes have a unique appearance between the phenotypes of the homozygous recessive or dominant parents Why is this not blended inheritance? How do we know? P Generation Red RR F 1 Generation Gametes R r Gametes 1 / 2 R 1 / 2 r Pink Rr White rr Eggs 1 / 2 R 1 / 2 R Sperm 1 / 2 r Red RR 1 / 2 r F 2 Generation Pink rr Pink Rr White rr Glitch #1 (Mendel was lucky) LDL Receptor Incomplete dominance (another example) 6

7 Glitch #2 (Mendel was lucky) nother exception: Multiple lleles BO blood groups Blood groups are determined by the type of glycoproteins that are attached to the surface of red blood cells n enzyme (protein) is responsible for attaching these glycoproteins to the surface this is the protein in question glycoprotein RBC BO Blood Groups Three alleles: I : Enzyme that attaches to RBC surface I B Enzyme that attaches B to RBC surface i Enzyme that attaches neither or B to RBC surface Mulitple lleles I and I B are dominant over i. and B are co-dominant BO Blood Types BO Blood Groups Type Type B Type B Type O For a person with type blood, the antigens (surface proteins) inform the body s defense system that is self. For a person with type blood, which antigen(s) would alert the body as non-self or foreign? 4 phenotypes, 6 genotypes Thus, O is the universal donor and B is the universal acceptor Practice Question man who has type B blood and a woman who has type blood could have children of which of the following phenotypes?, B, B, or O B only, B, or O B or O or B only 7

8 Practice Question: Who s your daddy? Suppose mother is Type, baby is Type B. Consider these three putative fathers; can any be the actual father? #1 (Type ): Yes or no? #2 (Type B): Yes or no? #3 (Type O): Yes or no? What does the PHENOTYPE of DD have to be? What are the possible genotypes of DD? nother blood type question Which of the following matings cannot produce a child with blood type O? The letters refer to blood types (phenotypes). a) x b) x B c) O x B d) O x O e) none of the above Hint: for each possible multiple choice answer, write out what the GENOTYPES of the two parents COULD be!! For instance, a phenotype of could have a genotype of: I I or I i Glitch #3: Pleiotropy Most genes have multiple phenotypic effects (not only one). Pleiotropy One gene multiple effects One gene multiple effects Glitch #4: Polygenic Inheritance Mendel studied traits that were either or Many characters vary in a population along a continuum Polygenic inheritance = 2 or more genes affect a single phenotypic character Consequence of One trait multiple genes Skin color/ Height Polygenic Inheritance of a trait results in a broad range of phenotypes 8

9 Even further departure from Mendel: Effect of the Environment on Phenotype Many factors, including genetics and environment determine the phenotype Chromosomal Basis of Inheritance In 1902 the Chromosome Theory of Inheritance was proposed. In states that Mendelian genes have specific loci on chromosomes, and these chromosomes undergo segregation and independent assortment. Effects of Nutrition on height Effects of Exercise on build Effects of elevation on RBC count (but not blood type, right?) Oh! They finally realized that those gene-things were ON the chromosomes! gene resides on a chromosome T-D!!!!! Mendel got lucky here, again, why? Correlating the results of Mendel s dihybrid crosses with the behavior of chromosomes during meiosis In Mendel s experiments, he found that the inheritance of two different characters was independent. Mendel got lucky here, again, why? Linked Genes In Mendel s experiment, although he didn t know it at the time, the genes he studied during the dihybrid cross were on DIFFERENT chromosomes! R Y r y The number of genes in a cell is much, much greater than the number of chromosomes. Human chromosome number 1 contains ~2400 genes!! Hmm, in the microscope I see that the nuclei of pea plants have 14 chromosomes, and there are two of each size. There have to be more than 14 genes in a pea plant, right? 9

10 Linked Genes Genes located on the same chromosome that tend to be inherited together B a b Lets look at a different dihybrid cross In this cross (for some reason) Purple is still dominant, but to red. Long pollen is dominant to round pollen. P generation (grandparents) are PPLL and ppll. What is the genotype and phenotype of all of the offspring? P generation Short pollen E e F1 generation When the F1 plants self fertilize, notice the predicted and observed phenotypic ratios What Mendel had been observing Beyond Mendel a P p We might have expected to see the classic 9:3:3:1 ratio, as this is a diyhybrid cross! Linked Genes Genes located on the same chromosome that tend to be inherited together Linked Genes Genes located on the same chromosome that tend to be inherited together a P a p What does this mean, tend? Imply? P p Vs. P a p 10

11 Linked Genes Crossing Over Genes located on the same chromosome that tend to be inherited together What does this mean, tend? Imply? CROSSING OVER Get a room!! Remember that in crossing over, homologous regions of chromosome arms can swap information. The point at which the arms cross is called the chiasma. Everything beyond the crossing over spot, will be swaped B C B C How does linkage affect inheritance of two different characters? If 2 genes are physically close together, on a chromosome arm, do you think they will be more or less likely to be separated during crossing over? Recombination Frequency Crossing over is random Thus the more places/points for crossing over to physically occur, the greater the likelihood that two genes ( and B) will be separated or recombined, thus, the higher the recombination frequency. C B What about B and C?? Constructing a genetic map Recombination frequencies reflect the distances between genes on chromosomes. Thomas Morgan Hunt Utilized Drosophila melanogaster (fruit flies) to study genetics. One map unit (or centrimorgan) = 1 % recombination frequency 11

12 Drosophila melanogaster as a model system Single mating produces 100+ offspring new generation can be bred every two weeks Only four pairs of chromosomes- 3 pairs of autosomes, 1 pair sex chromosomes (XX and XY) Unlike Mendel, Morgan does not have access to truebreeding strains. He breeds flies for a year, looking for distinct varieties. He discovers a male fly with white eyes, instead of red. In Drosophila, Look, important vocab over here! red eyes = Wild type (the most common phenotype in a natural population) white eyes = a mutant Phenotype (the less common version). Look at Me, I m WILD! Those white eyes are so unusual Morgan s First Experiment: Morgan crosses a red-eyed female with a white-eyed male. LL the offspring have red eyes. I like my mates WILD- TYPE! How would Mendel explain these results?? What would Mendel do next?? Mendel might say that Red eyes are DOMINNT to WHITE eyes, and the genotype of the mom in P generation was probably (homozygous dominant or heterozygous)???? Morgan s Next Experiment: Morgan crosses two of the red-eyed F1 flies with each other. If all of F1 are heterozygous for eye color.. What should he see if Mendel is correct?? Results: He DOES find a 3:1 ratio, but LL of the white-eyed flies are male!! How ODD! 12

13 Morgan Discovers Sex-Linked Genes! (and wins Nobel Prize, 1933) He DOES find a 3:1 ratio, but LL the white-eyed flies are male!! Was Mendel wrong?? What happened?!? This is weird. Inheritance of a Sex-linked trait Sex Chromosomes and Sex determination In humans, and many other organisms, sex is determined by the presence of X and Y chromosomes. X and Y chromosomes Because the X chromosome is so much larger than the Y (carries more genes), the majority of sex-linked genes, not related to sex determination, are found on the X chromosome If a gene resides on Chromosome X, how many copies does a female get? male? Human Sex-linked Disorders Red-Green color blindness (enzymes that make pigments that absorb red or green wavelengths of light) Duchenne muscular dystrophy (dystrophin) Hemophilia (clotting factor) These are recessive traits!! It takes two copies of the recessive allele to present with the disorder (if you are female). HOW many copies does a male get? 13

14 Human Sex-linked Disorders The Transmission of SEX-LINKED RECESSIVE Traits If a male hemophiliac mates with a normal woman, who happens to be a carrier for the mutated gene X H X h X h What percent of their offspring are hemophiliacs? What percent are carriers? Y In this diagram represents a dominant allele carried on the X chromosome; a represents the recessive allele. White boxes indicate unaffected individuals, light-colored boxes are carriers, and dark-colored boxes are affected individuals. Note that both males and females are affected by sex-linked disorders! Practice Question: Sex-Linked Chromosomal Inheritance If you see the number 7, then you do not have red-green color blindness. totally color-blind person will not be able to see the number 7. Practice Question If a color blind man has children with a heterozygous, wildtype woman, what are the chances that a daughter of theirs will be colorblind? What are the chances that their son will be colorblind? Can females be colorblind? What would the genotype of the parents have to be? How can the Y chromosome measure time? How can mitochondrial DN measure time? The Y chromosome is passed from father to son, more or less unchanged There is very little space on the Y chromosome that isn t critical to male development, thus mutations are rare What about crossing over? Is Y highly homologous to the X chromosome? 14

15 When rare mutations in the Y chromosome occur, they can be traced. Scientists use DN, and changes in DN sequence to estimate when things have happened in the past by assuming a certain rate of mutations over time. Let s say that the Y chromosome gets 1 new mutation/generation (much higher than the actual rate). If this is the case, then if two people have 10 differences between them, then they are 10 generations apart. 15

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