Mendelian Inheritance: Patterns, Mechanisms, and Exceptions

1. Patterns of Inheritance Chapter 12 You are not responsible for the section on epistasis Read on your own the sections on -- Environmental influences -- Pleiotrophy Chromosomes & Inheritance Chapter 13 you are not responsible for: Section 13.4 (genetic mapping) Genomic imprinting (in section 13.5) Genetic test – we’ll cover this later Gregor Mendel, 1862 Mendelian Inheritance

2. Genetics: the study of heredity What is the mechanism of inheritance? There have been earlier theories… Homunculus – 1695 “little man in a sperm” Blending of traits But how could traits “skip a generation” ?? Gregor Mendel solved the riddle Mendelian Inheritance

3. What was Mendel’s contribution to Biology? Mendel uncovered ‘rules’ of heredity Augustinian Monk (Czech republic) 1856-1865 Why pea plants? Variation in traits Can control pollination Peas normally self- pollinating Gregor Mendel, 1862 Mendelian Inheritance Convent Garden, 1920s

4. P P F1 F1 x F1 F2 What were some typical results of Mendel’s experiments? Worked with “true breeding” varieties cross-pollinated true breeding: P, F1 & F2 generations some traits “skip” a generation Why? 3 : 1 ratio Mendelian Inheritance

5. P P F1 Why do traits sometimes ‘skip’ a generation? Mendel deduced: True breeding: hold information for only a single trait F1: possess information for both traits ‘Dominant’ trait is one that appears ‘Recessive’ trait is suppressed Mendel saw many such relationships Mendelian Inheritance

6. How can an organism possess information for two different traits? 1) organisms possess 2 ‘genes’ for a trait 2) specific information is called an ‘allele’ Mendel’s “Principle of Segregation” Each trait is inherited as a pair of alleles, which separate in the gametes and recombine upon fertilization What are three possible combinations of alleles? 2 dominants = ‘homozygous dominant’ 1 dom & 1 rec = “heterozygous’ 2 recessives = ‘homozygous recessive’ What is Phenotype vs Genotype? -- genetic information vs its physical expression Round ‘R’ Wrinkled ‘r’ A dominant allele Is designated with uppercase Letter. A recessive allele with the corresponding lower case letter GenotypePhenotype RR round Rr round rr wrinkled Question Mendelian Inheritance

7. r r Rr Rr R R Rr Rr R r RR Round Rr Round R r Rr Round rr wrinkled How can a Punnett square be used to predict the outcomes of crosses? Genotypes of gametes are placed on borders P F1 RR X rr = all Rr True breeding traits must have a homozygous genotype F1 X F1 = F2 Rr X Rr Only the homozygous recessive genotype will yield the recessive phenotype Ratio of genotypes= 1:2:1 Ratio of phenotypes= 3:1 Crosses that examine 1 gene at a time are called “monohybrid” Mendelian Inheritance

8. What are the characteristics of Autosomal Recessive traits and disorders? Carried on non-sex chromosomes Phenotype can skip generations People can be a carrier And many disorders, e.g. Cystic fibrosis & Tay Sachs Question freckles hexadactyly Mendelian Inheritance

9. What are the characteristics of Autosomal Dominant traits and disorders? Also on non-sex chromosomes Phenotype does not skip generations 50 or 100% of children will get trait And Various disorders, e.g. Huntingtons Question Cleft chin Mendelian Inheritance

10. How does meiosis explain Mendel’s Principle of Segregation? Key questions: • Where do a pair of alleles exist in the cell? 2) When does separation of alleles occur? 3) When does recombination occur? Probability yields 3:1 ratio in phenotypes Mendelian Inheritance

11. What is Mendel’s ‘Principle of Independent Assortment’? Alleles for one trait sort independently of the alleles for a different trait --illustrated by a Dihybrid Cross Gamete genotypes Gamete genotypes Question 1 Question 2 Mendelian Inheritance

12. How can the outcomes of ‘multiple-hybrid’crosses be predicted mathematically? Ratios of ‘multiple-hybrid’ crosses are the product of the ratios of monohybrid crosses RrYy x RrYy Rr x Rr = ¾ Round : ¼ wrinkled Yy x Yy = ¾ Yellow : ¼ green (¾R_ : ¼rr) x (¾Y_ : ¼yy)___ 9/16 : 3/16 : 3/16 : 1/16 R_Y_ R_yy rrY_ rryy Rnd Yel Rnd Grn Wrk Yel Wrk Grn In a cross of RrYy x RrYY what is the expected frequency of “rrYy”? ¼ x ½ = ⅛ How does meiosis explain Mendel’s Principle of Independent Assortment? Question Mendelian Inheritance

13. HSHC HS HS Straight HS HC Wavy HS HC HS HC Wavy HC HC Curly Why do inheritance patterns sometimes not follow normal Mendelian ratios? How is Incomplete Dominance different from ‘normal’ dominance? -- heterozygote has intermediate phenotype e.g. Human hair form -- two alleles: HS – straight and HC – curly In a mating of heterozygotes, what is expected frequency of hair styles among children? Other examples: Pea flower color (see book) Chicken “Naked neck” allele homozygote NA NA -- normal neck feathers homozygote Na Na -- lack neck feathers heterozygote NA Na -- reduced # of feathers Mendelian Inheritance

14. What is Codominance? -- heterozygote has distinctive phenotype -- combination of alleles yields new trait Tabby gene (T) affects patterning of cat fur TSTS – striping of colored and white hairs = ‘Tabby’ TATA – no striping (hairs are mixed) = ‘Agouti’ TSTA – ‘chinchilla-like’ hair: color-tipped hairs Tabby Agouti chinchilla Question Mendelian Inheritance

15. How can “multiple alleles” for a gene influence inheritance? -- When more than 2 alleles for a trait exist in the population Inheritance of blood type -- involves codominance and multiple alleles Antigens: present on the cells Alleles code for antigens -- 3 alleles in species -- each person can possess only 2 [Given tables such as these, you should be able to fill in missing values] Mendelian Inheritance

16. Inheritance of blood type, con’t. What is the theoretical frequency of genotypes and phenotypes among children of heterozygous-A and a heterozygous-B parents? If a child is heterozygous for B-type blood, what are the possible blood types of the parents? What causes blood type incompatibility? -- role of antibodies Blood type and Paternity If a child has type-O blood, could a man With type-B blood be the father? Explain. IAi IB i Question 1 Question 2 Mendelian Inheritance

17. ONON OOON What is a Lethal Allele? -- homozygous recessive is fatal Overo gene affects hair color pattern in horses Two alleles: ON = normal OO = white OOON X OOON yields ratio of 2 patterned : 1 solid Why? OOOO : lethal aganglionic colon -- absence of nerves in colon ‘Creeper’ gene in birds; CA= ‘Creeper’ allele causes deformed wings and legs; heterozygotes (CNCA) display creeper trait This is impossible: Why? CNCA X CACA OOOO Mendelian Inheritance

18. Sickle-cell anemia: incomplete dominance and lethal allele (Read about this topic in Chapter 13) Cause Genetics HbA: normal allele HbS: abnormal Effects -- ‘SC-anemia’: early death -- ‘SC-trait’: moderate symptoms Consider cross of heterozygotes Why does a lethal allele persist? SC anemia HbAHbS HbA HbS Question 1 Question 2 Mendelian Inheritance

19. How does Sickle cell allele cause the phenotype? Changes in DNA code alter protein structure Chromosomes and Human Genetic Disorders

20. What are the characteristics of Polygenic Inheritance? -- when more than 1 gene contributes to a phenotype e.g., human height, intelligence, eye color, skin color, etc Skin color – A “Gene Dosage” effect Melanin production -- dominant Why variation? No longer reflect long-term phylogenic relationships May be 9 genes involved -- 3 shown Note: this is not albinism Question Mendelian Inheritance

21. Chapter 13 What is a Karyotype? How is a karyotype prepared? 1. Collect & culture cells 2. Treat with mitotic inhibitor 3. Spread out cells and stain 4. Photograph & pair up chromosomes Chronic myeloid leukemia A reciprocal chromosome translocation has occurred between Chromosomes 9 & 22 Chromosomes and Human Genetic Disorders

22. How is sex determined? Does egg or sperm determine the sex of the offspring? What genes are on the sex chromosomes? -- > 1000 on X; many different functions -- < 100 on the Y Why does Y chromosome contain few genes? Study ‘X chromosome inactivation’ in the textbook Chromosomes and Human Genetic Disorders

23. What is unusual about the inheritance of hemophilia? The Romanov family Czar Nicholas and Alexandra Rasputin Chromosomes and Human Genetic Disorders

24. Color responsiveness of different types of cone cells Genes on the X chromosome are said to be ‘sex linked’ Abnormal genes often act as dominants in males and recessive in females. Why? Designation of X-linked genes What is the theoretical frequency of hemophilia among the children of a normal father and a carrier mother? … From a hemophiliac mother? Red-Green Color Blindness ~10% of males; <1% of females XC = normal allele Xc = recessive abnormal Question Ishihara test Question Chromosomes and Human Genetic Disorders

25. How do chromosomal abnormalities affect traits? Nondisjunction and aneuploidy Autosomal aneuplopidy e.g., Down’s syndrome (trisomy 21) -- non-disjunction of chromosomes Sex-chromosome aneuploids X-chromosome nondisjunction -- XO (Turner syndrome) -- XXY (Klinefelter syndrome) Y-chromosome nondisjunction -- XYY male Nondisjunction Chromosomes and Human Genetic Disorders