AP Biology Chapter 15 Notes The Chromosomal Basis of Inheritance I. Chapter 15.1: Mendelian inheritance has its physical basis in the behavior of chromosomes. a. Chromosome theory of inheritance: i. Mendelian genes have specific loci on chromosomes, and it is the chromosomes that undergo segregation and independent assortment. 1. The process of meiosis accounts for homologous chromosomes segregation of the alleles at each genetic locus to different gametes. 2. Behavior of non- homologous chromosomes accounts for independent assortment of alleles for two or more genes located on different chromosomes. b. Morgan s Experimental Evidence: Scientific Inquiry i. Thomas Hunt Morgan: provided first solid evidence associating a specific gene with a specific chromosome 1. Embryologist 2. Early 20 th century 3. Columbia University 4. Chromosomes are the location of Mendel s heritable factors. c. Morgan s Choice of Experimantal Organisms: i. Drosophila melanogaster 1. Fruit flies 2. Prolific and frequent breeders(every two weeks producing 100 s of offspring) 3. Has four pairs of chromosomes a. Can be distinguished with a light microscope b. 3 pairs of autosomal chromosomes c. 1 pair of sex chromosomes i. males= XY ii. females = XX ii. Morgan s flies: 1. Spent about a year collecting fruit flies 2. Found a mutant variety: a. Single male with white eyes (instead of red) i. Red eyes = wild type ii. White eyes = mutant type 3. Morgan symbolized his fruit flies alleles for a giving character by taking the symbol from the mutant (non- wild type) a. Example: i. White eyes = w
4. wild type (red eyes) is symbolized by a superscript (+) a. red eyes = w + d. Correlating Behavior of a Gene s alleles with Behavior of a Chromosome pair: i. Morgan mated white eye male with red eye female 1. F1 were red eyes 2. Suggested that red eye is dominant ii. Morgan then mated the F1: 1. F2 Results: 3:1 Mendelian ratio (3 red: 1 white) iii. He also observed that the white eye only showed up in males 1. All F2 females had red eyes 2. Half F2 males had red eyes and half had white eyes iv. Morgan concluded that eye color was linked to sex 1. White eyes was exclusively located on the X chromosome with no corresponding allele present on the Y chromosome 2. Single copy of the w allele would confer white eyes a. There can be no w+ allele to offset the w because males have only one X. 3. The female could only have white eyes if ww, but since all of Morgan s males in F1 were red eye so the F2 females where all red eye. v. Morgan determined that specific genes are carried on specific chromosomes. vi. Morgan also determined that genes located on sex chromosomes exhibit unique inheritance patterns. II. Chapter 15.2: Linked genes tend to be inherited together because they are located near each other on the same chromosome. a. Linked Genes: genes located on the chromosome that tend to be inherited together in genetic crosses b. How Linkage Affects Inheritance: i. Another of Morgan s experiments: 1. Body color and wing size: each have two different phenotypes 2. Wild type = gray bodies and normal wings (b+_, vg+_) 3. Mutant type = black body and vestigial wings (bbvgvg_ 4. Morgan first mated true breeding wild types with black, vestigial winged ones a. b+b+vg+vg+ x bbvgvg i. F1 = b+b vg+vg ii. All wild type phenotype 5. He then crossed female dihybrids with true breeding males a. b+bvg+vg (female) x bbvgvg (male) = test cross
i. phenotypes depend on the female ii. he scored 2300 offspring iii. he observed much higher proportion of the parental phenotypes than would be expected iv. Morgan concluded that body color and wing size are usually inherited together because the genes for these characteristics are on the same chromosome. v. If this always was the case, no non- parental phenotypes would be observed vi. Both of the non parental phenotypes were observed which suggests that body color and wing size are only partially linked b. Genetic recombination: the production of offspring with combinations of traits differing from those found in either parent. c. Genetic Recombination and Linkage: i. Chromosomal basis of recombination d. Recombination of Unlinked Genes: Independent Assortment of Chromosomes: i. Phenotypes that match parental phenotypes are called parental types: 1. As opposed to non- parental types. a. Example: crossing YyRr X yyrr yields: i. YyRr- parental type ii. Yyrr- parental type iii. Yyrr- non parental type iv. yyrr- non parental type 2. offspring that have new combinations or are non parental types are called recombinant type. a. If 50% of the offspring are recombinant types then geneticists say that there is a 50% frequency of recombination i. This percentage is found on any two genes that are located on different chromosomes. ii. Recombination frequency is related to distance between genes 1. The further apart two genes are the higher probability that a crossover will occur between them and therefore the higher the recombination frequency
b. Physical basis of recombination between unlinked genes is the random orientation of homologous chromosomes at metaphase I i. This leads to independent assortment of alleles e. Recombination of Linked Genes: Crossing Over: Explaining Morgan s Drosophila Test cross: i. Most offspring were parental types- suggesting that the two genes were on the same chromosome 1. A small number were non- parental type or recombinant type a. Linkage appears to be incomplete b. Crossing over: physical break between genes on the chromosome i. Accounts for recombination of linked genes ii. Occurs during prophase of meiosis I iii. One paternal and one maternal chromatid break at corresponding points and then rejoined 1. Trading places may bring alleles together in new combinations which are distributed to gametes f. Linkage Mapping Using Recombination Data: i. Alfred H. Sturtevant: Student of Morgan who developed a method for constructing a genetic map. 1. Genetic map: an ordered list of the genetic loci along a particular chromosome. a. Determined that recombinant frequencies depend on the distances between genes on a chromosome. b. He assumed crossing over is a random event and thus the chance of crossing over is approximately equal at all points along a chromosome. c. Predictions: i. The farther apart two genes are the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency. d. Reasoning- the farther apart two genes are, the more points between them where crossing over can occur e. He assigned relative positions to genes on the same chromosomes. ii. Gene map based on recombination is a linkage map
1. Linkage map: is based on the assumption that the probability of a crossover between two genetic loci is proportional to the distance separating the loci. a. Created by recombination frequencies obtained from experimental crosses 2. Drosophila genes: a. Body color (b) b. Wing size (vg) c. Cinnabar (cn)- one of many genes affecting eye color i. Cinnabar eyes are a mutant type of bright red eye color, brighter than the wild- type ii. Recombination frequency between cn and b is 9%, between cn and vg is 9.5%, and between b and vg is 17% iii. Frequency of recombination between cn and b and cn and vg is about half as frequent as b and vg. iii. Distances between genes are expressed in map units. 1. One map unit is the equivalent of a 1% recombination frequency. a. Today map units are often called centimorgans b. Genetic map distances = recombinants/ recombinants + parentals X 100 i. Unit is centimorgans 2. Some genes are so far apart on the chromosome that a cross over is almost certain a. Maximum value 50% which is indistinguishable from that for genes on different chromosomes b. These genes are considered to be genetically unlinked c. They assort independently as though they were on different chromosomes d. Example: seed color and flower color for pea plants are actually found on the same chromosome but are so far apart that linkage is not observed in genetic crosses. i. To map genes that are far apart on the chromosome, the recombinant frequencies from crosses involving each of the distant genes and a number of genes lying between then. e. Each chromosome had a linear array of specific gene loci. f. Frequency of crossing over is not actually uniform over the length of the chromosome
III. i. Map units do not correspond to actual physical distances ii. Also does not portray the order of genes on a chromosome but does accurately portray the precise locations of the genes. 3. Cytogenetic maps: locate genes with respect to chromosomal features such as stained bands that can be seen with a microscope. Chapter 15.3: Sex linked genes exhibit unique patterns of inheritance: a. Humans have two varieties of sex chromosomes i. X and Y 1. XX = female 2. XY = male ii. Y chromosomes are much smaller than X and only have short segments at the end of the chromosome that are homologous with the X. 1. These regions allow the X and Y chromosome to pair and behave like homologous chromosomes iii. Sex determination is a 50-50 chance of female or male iv. Three other chromosome systems: 1. X- O system of grasshoppers, cock roaches and some other insects 2. Z- W system of birds, fishes and some insects 3. Haplo- diploid system in bees and ants a. No sex chromosomes v. Anatomical signs of sex begin to emerge in the embryo at two months 1. Before that, the gonads are generic and can develop into ovaries or testes depending on hormonal conditions with in the embryo. a. Presence or absence of Y chromosome determines the sex of the individual b. Gene on the Y chromosome (SRY= sex determining region of Y) codes for the development of the testes c. Many genes are involved in the development of the physiological and anatomical differences between males and females 2. Inheritance of Sex Linked Genes: a. Sex chromosomes have many genes unrelated to sex i. Sex linked genes 1. Fathers can pass sex linked alleles to all of their daughters but to none of their sons
IV. 2. Mothers can pass sex linked alleles to both sons and daughters ii. Any male possessing a homozygous recessive sex linked allele will express the phenotype of that allele 1. Far more males will have sex linked disorders b. Sex linked disorders: i. Colorblindness ii. Duchenne muscular dystrophy iii. Haemophilia b. X inactivation in female mammals: i. Of the two X chromosomes inherited by females, one of them becomes completely inactive during embryonic development. 1. So males and females have one effective copy of genes that are located on the X chromosome. ii. Barr body: when a X chromosome becomes inactivated, it condenses into a compact object, which lies along the inside of the nuclear envelope. iii. In the ovaries, Barr body chromosomes are reactivated in the cells that give rise to the egg, so all female gametes have an active X. iv. Selection of which X chromosome becomes the Barr body is random and independent. v. Females become a mosaic of two types of cells; those with the active X derived from the mother and those with the active X derived by the father. vi. After a X chromosome is inactivated, all daughter cells of that cell will have the same inactive X. 1. So if a female is heterozygous for a sex linked trait, about half of her cells will express one allele, while the others will express the alternate allele. vii. Example: tortoiseshell cat- mottled coloration in cats 1. Humans can be mosaic in a recessive X- linked mutation that prevents the development of sweat glands. A heterozygous woman would have patches of skin with sweat glands and patches of skin with out. viii. X chromosomes are inactivated by modifications of the DNA, such as the attachment of methyl groups to a nitrogen base. 1. XIST- X- active specific transcript- a gene that is only active on the Barr body chromosome. Chapter 15.4: Alterations of Chromosome Number or Structure Cause Some Genetic Disorders. a. Physical and chemical disturbances and errors during meiosis can damage chromosomes in major ways or alter their number in a cell. i. Often lead to spontaneous abortions
ii. Also leads to genetic defects commonly exhibited by various development disorders. b. Abnormal Chromosome Number: i. Nondisjunction: members of a pair of homologous chromosomes do not move apart properly during meiosis I or sister chromatids during meiosis II. 1. One gamete receives two of the same type of chromosome and another gamete receives no copy. 2. Can also occur during mitosis a. If this occurs early in embryonic development, a large number of the organisms cells will be aneuploids which could have substantial effect on the organism. ii. Aneuploidy- nondisjunction results in an abnormal number of particular chromosomes 1. 2n+ 1 = trisomic- triplicate form of chromosome a. trisomy 21: Downs syndrome- extra chromosome on the 21 st pair. b. Klinefelter syndrome: one in 2000 live births will produce a male with XXY genotype. i. Small testes- individual is sterile ii. Breast enlargement and other female characteristics are present iii. Females with an extra X chromosome (XXX) are normal and can only be distinguished by karyotype 2. 2n 1 = monosomic- singlet form of chromosome a. in both cases the anomaly will be transmitted to daughter cells through mitosis b. Turner Syndrome: females have the XO genotype(occurs 1 in 5000) i. Immature sex organs = sterile ii. Normal intelligence iii. Can be treated with hormones which will produce secondary sex characteristics iii. polyploidy- more than two complete chromosome sets- fairly common in plant kingdom(pinching the flowers off of tomato plants will change the plant from a diploid to triploid 1. triploidy (3n)- three chromosomal sets a. can occur by the fertilization of an unusual diploid egg 2. tetraploidy (4n)- four chromosomal sets a. failure of a 2n zygote to divide after replicating its chromosomes 3. usually normal in appearance
a. genetic balance is not disrupted as much as aneuploidy c. Alterations of Chromosome Structure: i. Deletion: chromosomal fragments lacking a centromere is lost 1. Results in the loss of certain genes 2. Likely to occur during meiosis ii. Duplication: when a deleted fragment becomes attached as an extra segment to a sister chromatid 1. Could also attach to a non sister chromatid of homologous chromosome a. May not be identical 2. Likely to occur during meiosis 3. Tend to have harmful effects iii. Inversion: when a chromosome fragment reattaches to the original chromosome but in the reverse orientation 1. Can alter genotype iv. Translocation: when a chromosome fragment joins a non- homologous chromosome 1. Tend to have harmful affects 2. Can alter genotype d. Disorders Caused by Stucturally Altered Chromosomes: i. Cri du chat - results from specific deletion in chromosome 5 1. mentally retarded 2. small head and unusual features 3. cry sounds like a cat 4. death comes in infancy or early childhood ii. CML: chronic mylogenous leukemia- reciprocal translocation between a large fragment of chromosome 22 and a small fragment of chromosome 9 1. Philadelphia chromosome
V. Chapter 15.5: Some inheritance patterns are exceptions to the standard chromosome theory. a. Genomic Imprinting: variation in phenotype is dependent upon which parent, the mother or the father donates the allele. i. Most are found on autosomes not sex chromosomes ii. Most of the time it is safe to assume that the same allele, whether it was inherited from the mother or the father will have the same effect. iii. There are two to three dozen traits in humans where what parent donates the allele does determine its effect. iv. Occurs during the formation of the gametes v. Results In the silencing of one of the alleles of a certain gene vi. Imprints are transmitted to all cells of the body during embryonic development vii. In each generation, old alleles are erased viii. In a given species, an imprinted gene is always expressed the same way 1. A gene imprinted for maternal allele expression is always imprinted for the maternal allele expression, generation after generation. ix. Most imprinted genes are critical for embryonic development even though only a small fraction of mammalian genes are imprinted 1. Example: mice genetically altered to receive both copies of a gene from one parent will die, regardless of where the copies come from(mother or father). 2. Embryos need one active copy, not 2 and not 0. x. Example of gene imprinting: 1. Gene for insulin like growth factor: (Igf2) 2. Needed for normal prenatal growth 3. Only the paternal allele is expressed 4. Crossing wild type mice with dwarf mice(homozygous recessive) 5. The heterozygous offspring differed depending on whether the mutant allele came from the father or the mother 6. When a normal Igf2 gene is inherited from the father, the mice grow to normal size, but when a mutant type allele is inherited from the father, the mice express the dwarf phenotype. a. Father = normal allele, mother =mutant type allele- offspring = normal size b. Father = mutant allele, mother = normal allele, offspring = dwarf size. 7. Example: Fragile X syndrome
a. Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited intellectual disability in boys. b. Fragile X syndrome is caused by a change in a gene called FMR1. A small part of the gene code is repeated on a fragile area of the X chromosome. The more repeats, the more likely there is to be a problem. The FMR1 gene makes a protein needed for your brain to grow properly. A defect in the gene makes your body produce too little of the protein, or none at all. c. Boys and girls can both be affected, but because boys have only one X chromosome, a single fragile X is likely to affect them more severely. You can have fragile X syndrome even if your parents do not have it. A family history of fragile X syndrome, developmental problems, or intellectual disability may not be present. b. Inheritance of Organelles: i. Not all eukaryotic genes are found in nuclear DNA ii. Some are located on the mitochondria, chloroplast and other plant plastids, which have their own DNA = extranuclear genes 1. Contain small circular DNA molecules which code for proteins and RNA. 2. These organelles reproduce themselves and distribute themselves and transmit their genes to daughter organelles 3. These genes are not subjected to mendelian inheritance iii. Karl Correns: studied the inheritance of yellow or white patches on the leaves of green plants. 1. Observed that coloration was determine by the maternal parent(source of seeds that germinate and give rise to offspring) 2. Source of variegation is due to mutations in plastid genes that control pigmentation. 3. The pattern of variegation is determined by the ratio of wild type vs. mutant type plastids in the various tissues. iv. Defects of the proteins found in mitochondria that make up the complexes for electron transport chain and to synthesize ATP can reduce the amount of ATP the cell can make 1. Can cause a number of rare human disorders that affect those parts of the body that need the most energy a. Nervous system and muscles
VI. Mutations in Mitochondrial DNA Cause Several Genetic Diseases in Man: a. Heteroplasmy- when a cell contains both mutant mtdna and wild type mtdna. b. Leber s hereditary optic neuropathy- degeneration of the optic nerve i. Caused by a missense mutation c. Chronic Progressive External Ophthalmoplegia- eye defects d. Kearns- Sayre syndrome- abnormal heart beat and central nervous system degeneration. e. Mitochondrial myopathy- symptoms are weakness, intolerance of exercise and muscle deterioration f. Mitochondrial mutation inherited from the mother may also contribute to some cases of diabetes, heart disease and Altheimers.