Chapter 15 The Chromosomal Basis of Inheritance Timeline • • • • 1866- Mendel's Paper 1875- Mitosis worked out 1890's- Meiosis worked out 1902- Sutton, Boveri et. al. connect chromosomes to Meiosis. • Parents are two true-breeding pea plants • Parent 1 Yellow, round Seeds (YYRR) • Parent 2 Green, wrinkled seeds (yyrr) These 2 genes are on different chromosomes. Draw meiosis to determine the resulting gametes of parent 1. How do the resulting gametes connect to Punnett squares? • F1: YyRr x YyRr • What are the predicted phenotypic ratios of the offspring? • ¾ yellow ¾ round • ¼ green ¼ wrinkled ¼ (green) x ¼ (wrinkled) = 1/16 green, wrinkled 9:3:3:1 phenotypic ratio First Experimental Evidence to connect Mendelism to the chromosome • Thomas Morgan (1910) • Chose to use fruit flies as a test organism in genetics. • Allowed the first tracing of traits to specific chromosomes. Fruit Fly • Drosophila melanogaster • Early test organism for genetic studies. Reasons • • • • • Small Cheap to house and feed Short generation time Many offspring 3 pairs of Autosomes • 1 pair of sex chromosomes Examples • Wild type is most common, NOT dominant or recessive • Recessive mutation: • w = white eyes • w+ = red eyes • Dominant Mutation • Cy = Curly wings • Cy+ = Normal wings Morgan Observed: • A male fly with a mutation for white eyes. Morgan crossed • The white eye male with a normal red eye female. • Male ww x Female w+w+ The F1 offspring: • All had red eyes. • This suggests that white eyes is a _________? • Recessive. • F1= w+w • What is the predicted phenotypic ratio for the F2 generation? F1 X F1 = F2 • Expected F2 ratio - 3:1 of red:white • He got this ratio, however, all of the white eyed flies were MALE. • Therefore, the eye color trait appeared to be linked to sex. Morgan discovered: • Sex linked traits. • Genetic traits whose gene are located on the sex chromosome Fruit Fly Chromosomes • Female • XX Male XY • Presence of Y chromosome determines the sex • Just like in humans! Morgan Discovered • There are many genes, but only a few chromosomes. • Therefore, each chromosome must carry a number of genes together as a “package”. Sex-Linked Problem • A man with hemophilia (a recessive, sexlinked, x-chromosome condition) has a daughter of normal phenotype. She marries a man who is normal for the trait. • A. What is the probability that a daughter of this mating will be a hemophiliac? • B. That a son will be a hemophiliac? • C. If the couple has four sons, what is the probability that all four will be born with hemophilia? • Original Man - XhY • Daughter - must get the dad’s X chromosome XHXh (normal phenotype, so she’s a carrier) • Daughter’s husband XHY (normal phenotype) • A. daughter must get XH from the dad. 0% (50% carrier, 50% homo dom.) • B. son must get Y from dad. 50% chance to be hemophiliac • C. ½ x ½ x ½ x ½ = 1/16 Linked Genes • Traits that are located on the same chromosome. • Result: • Failure of Mendel's Law of Independent Assortment. • Ratios are different from the expected Example: • Body Color - gray dominant • b+ - Gray • b - black • Wing Type - normal dominant • vg+ - normal • vg – vestigial (short) Example b+b vg+vg X bb vgvg Predict the phenotypic ratio of the offspring Show at board b+b x bb vg+vg x vgvg ½ gray ½ black ½ normal ½ vestigial ----------------------------------------------------¼ gray normal, ¼ gray vestigial, ¼ black normal, ¼ black vestigial 1:1:1:1 phenotypic ratio Conclusion • Most offspring had the parental phenotype. Both genes are on the same chromosome. • What do you expect to happen if they’re on the same chromosome? (draw chromosomes) • bbvgvg parent can only pass on b vg • b+b vg+vg can pass on b+ vg+ or b vg b+b vg+vg - Chromosomes (linked genes) Crossing-Over • Breaks up linkages and creates new ones. • Recombinant offspring formed that doesn't match the parental types. • Higher recombinant frequency = genes further apart on chromosome If Genes are Linked: • Independent Assortment of traits fails. • Linkage may be “strong” or “weak”. • Strong Linkage means that 2 alleles are often inherited together. • Degree of strength related to how close the traits are on the chromosome. Genetic Maps • Constructed from crossing-over frequencies. • 1 map unit = 1% recombination frequency. • Can use recombination rates to ‘map’ chromosomes. • Comment - only good for genes that are within 50 map units of each other. Why? • Over 50% gives the same phenotypic ratios as genes on separate chromosomes Genetic Maps • Have been constructed for many traits in fruit flies, humans and other organisms. Sex Linkage in Biology • 1. 2. 3. 4. Several systems are known: Mammals – XY and XX Diploid insects – X and XX Birds – ZZ and ZW Social insects – haploid and diploid Chromosomal Basis of Sex in Humans • X chromosome - medium sized chromosome with a large number of traits. • Y chromosome - much smaller chromosome with only a few traits. Human Chromosome Sex • Males - XY Females - XX • Comment - The X and Y chromosomes are a homologous pair, but only for a small region at one tip. SRY • Sex-determining Region Y chromosome gene. • If present - male • If absent - female • SRY codes for a cell receptor. Sex Linkage • Inheritance of traits on the sex chromosomes. • X- Linkage (common) • Y- Linkage (very rare if exists at all) Males • Hemizygous - 1 copy of X chromosome. • Show ALL X traits (dominant or recessive). • More likely to show X recessive gene problems than females. X-linked Disorders • • • • Color blindness Duchenne's Muscular Dystrophy Hemophilia (types a and b) Immune system defects Samples of X-linked patterns: X-linked Patterns • Trait is usually passed from a carrier mother to 1/2 of sons. • Affected father has no affected children, but passes the trait on to all daughters who will be carriers for the trait. Comment • Watch how questions with sex linkage are phrased: • Chance of children? • Chance of males? Can Females be color-blind? • Yes, if their mother was a carrier and their father is affected. Y-linkage • Hairy ear pinnae. • Comment - new techniques have found a number of Y-linked markers that can be shown to run in the males of a family. • Ex: Jewish priests Sex Limited Traits • Traits that are only expressed in one sex. • Ex – prostate Sex Influenced Traits • Traits whose expression differs because of the hormones of the sex. • These are NOT on the sex chromosomes. • Ex. – beards, mammary gland development, baldness Baldness • Testosterone – the trait act as a dominant. • No testosterone – the trait act as a recessive. • Males – have gene = bald • Females – must be homozygous to have thin hair. Barr Body • Inactive X chromosome observed in the nucleus. • Way of determining genetic sex without doing a karyotype. Lyon Hypothesis • Which X inactivated is random. • Inactivation happens early in embryo development by adding CH3 groups to the DNA. • Result - body cells are a mosaic of X types. Examples • Calico Cats. • Human examples are known such as a sweat gland disorder. Calico Cats • XB = black fur • XO = orange fur • Calico is heterozygous, XB XO. Question? • Why don’t you find many calico males? • They must be XB XOY and are sterile. Chromosomal Alterations • Changes in number. • Changes in structure. Number Alterations • Aneuploidy - too many or too few chromosomes, but not a whole “set” change. • Polyploidy - changes in whole “sets” of chromosomes. Nondisjunction • When chromosomes fail to separate during meiosis • Result – cells have too many or too few chromosomes which is known as aneuploidy Meiosis I vs Meiosis II • Meiosis I – all 4 cells are abnormal • Meiosis II – only 2 cells are abnormal Aneuploidy • Caused by nondisjunction, the failure of a pair of chromosomes to separate during meiosis. Types • Monosomy: 2N - 1 • Trisomy: 2N + 1 Turner Syndrome • 2N - 1 or 45 chromosomes Genotype: X_ or X0. • Phenotype: female, but very poor secondary sexual development. Characteristics • • • • • Short stature. Extra skin on neck. Broad chest. Usually sterile Normal mental development except for some spatial problems. Question • Why are Turner Individuals usually sterile? • Odd chromosome number. • Two X chromosomes need for ovary development. Homework • • • • Read Chapter 15 (Hillis – 8) Genetics Lab Report – today No class Feb. 4 and 5 Chapter 15 – Thurs. 2/7 Other Sex Chromosome changes • Kleinfelter Syndrome • Meta female • Supermale Kleinfelter Syndrome • 2N + 1 • Genotype: XXY • Phenotype: male, but sexual development may be poor. Often taller than average, mental development fine, usually sterile. Meta female • 2N + 1 or 2N + 2 • Genotype: XXX or XXXX • Phenotype: female, but sexual development poor. Mental impairment common. Super male • 2N + 1 or 2N + 2 • Genotype: XYY or XYYY • Phenotype: male, usually normal, fertile. Trisomy events • Trisomy 21: Down's Syndrome • Trisomy 13: Patau Syndrome • Both have various physical and mental changes. Question? • Why is trisomy more common than monosomy? • Fetus can survive an extra copy of a chromosome, but being hemizygous is usually fatal. Question? • Why is trisomy 21 more common in older mothers? • Maternal age increases risk of nondisjunction. Polyploid • Triploid= 3N • Tetraploid= 4N • Usually fatal in animals. Question? • In plants, even # polyploids are often fertile, why odd # polyploids are sterile. Why? • Odd number of chromosomes can’t be split during meiosis to make spores. Structure Alterations • • • • Deletions Duplications Inversions Translocations Translocations Result • Loss of genetic information. • Position effects: a gene's expression is influenced by its location to other genes. Cri Du Chat Syndrome • Part of p arm of #5 missing. • Good survival, but low birth weight and slow gain. • Severe mental impairment. • Small sized heads common. Cri Du Chat Syndrome Philadelphia Chromosome • An abnormal chromosome produced by an exchange of portions of chromosomes 9 and 22. • Causes chronic myeloid leukemia. Parental Imprinting of Genes • Gene expression and inheritance depends on which parent passed on the gene. • Usually caused by different methylations of the DNA. Example: • Prader-Willi Syndrome and Angelman Syndrome • Both lack a small gene region from chromosome 15. • Male imprint: Prader-Willi Female imprint: Angelman Cause: • Imprints are "erased" in gamete producing cells and re-coded by the body according to its sex. • Gametes are methylated to code as “male “ or “female”. Result • Phenotypes don't follow Mendelian Inheritance patterns because the sex of the parent does matter. Extranuclear Inheritance • Inheritance of genes not located on the nuclear DNA. • DNA in organelles. • Mitochondria • Chloroplasts Result • Mendelian inheritance patterns fail. • Maternal Inheritance of traits where the trait is passed directly through the egg to the offspring. Chloroplasts • Gives non-green areas in leaves, called variegation. • Several different types known. • Very common in ornamental plants. Variegation in Violets African Variegated Examples Mitochondria • • • • Myoclonic Epilepsy Ragged Red-fiber Disease Leber’s Optic Neuropathy All are associated with ATP generation problems and affect organs with high ATP demands. Comment • Cells can have a mixture of normal and abnormal organelles. • Result - degree of expression of the maternal inherited trait can vary widely. Summary • Know about linkage and crossing-over. • Sex chromosomes and their pattern of inheritance. Summary • Be able to work genetics problems for this chapter.