AP Biology, Chapter 15
The Chromosomal Basis of Inheritance

Summary
Introduction

RELATING MENDELISM TO CHROMOSOMES
	Mendelian inheritance has its physical basis in the behavior of chromosomes during 
	sexual life cycles
		1. Explain how the observations of cytologists and geneticists provided the basis for the 
		chromosomal theory of inheritance.
			a. Chromosomal theory of inheritance = genes are stably arranged on 
			chromosomes
			b. Both genes and chromosomes:
				i. In pairs in diploid cells
				ii. Separate in meiosis
				iii. Unite again in fertilization
	Morgan traced a gene to a specific chromosome: science as a process
		2. Describe the contributions that Walter Sutton, Theodor Boveri, and Thomas Hunt 
		Morgan made to current understanding of chromosomal inheritance.
			a. Sutton
				i. Demonstrated Mendel's laws in grasshoppers
				ii. Suggested meiotic separation accounted for Mendel's laws
			b. Boveri
				i. Studied sea urchins
				ii. Showed sperm and eggs are 1N
				iii. Showed that a complete set of chromosomes is required for 
				development - each kind of chromosome is unique
				iv. Suggested Mendel's factors are carried by chromosomes
			b. T.H. Morgan
				i. Gathered overwhelming evidence
				ii. Identified dozens of new Dropsophila mutations
				iii. Demonstrated linkage by extensive crossing
				iv. Demonstrated sex-linkage: a particular gene on a particular 
				chromosome
		3. Explain why Drosophila melanogaster is a good experimental organism.
			a. Prolific breeders
			b. Generation time = 2 weeks
			c. 2N = 8; chromosomes easily distinguishable
	Linked genes tend to be inherited together because they are located on the same 
	chromosome
		4. Define and compare linked genes and sex-linked genes. Explain why the inheritance of 
		linked genes is different from independent assortment.
			a. Comparison
				i. Linked genes are located on the same chromosome
				ii. Sex-linked are on the X chromosome
			b. Genes on the same chromosome tend to separate together, not randomly 
	Independent assortment of chromosomes and crossing over produce genetic 
	recombinants
		5. Distinguish between parental and recombinant phenotypes.
			a. Dihybrid cross with linked genes
				i. P: b+b+ vg+vg+ x bb vgvg
				ii. F1: all are b+b vg+vg
				iii. Testcross: b+b vg+vg x bb vgvg
			b. Testcross results
				i. If they assort independently: 
					1/4 b+b vg+vg
					1/4 b+b vgvg
					1/4 bb vg+vg
					1/4 bb vgvg
				ii. They don't = linkage
					965 b+b vg+vg
					206 b+b vgvg
					185 bb vg+vg
					944 bb vgvg
			c. Explanation
				i. The b+ vg+ and b vg from the P generation tended to stay together
				and gave b+b vg+vg and bb vgvg, respectively, the parental types
				ii. The chromosome can recombine to for b+ vg and b vg+ and those give 
				b+b vgvg and bb vg+vg, respectively, the recombinant types
			d. Generic definitions
				i. Parental types result from the original parental combination of alleles
				ii. Recombinant types result from rarer, new combinations 
		6. Explain why linked genes do not assort independently.
			a. Linked genes are part of the same molecule
			b. Separated as a single object in anaphase I	
	Geneticists use recombination data to map a chromosome's genetic loci
		7. Explain how crossing over can unlink genes.
			a. In crossing over chromosomes trade segments
			b. Alleles on traded segments become linked in new combinations
		8. Explain how Sturtevant created linkage maps.
			a. Mated flies until he had pure b+b+ cn+cn+ vg+vg+ and bb cncn vgvg
			b. Made the trihybrid: b+b+ cn+cn+ vg+vg+ x bb cncn vgvg  b+b cn+cn vg+vg 
			c. Set up a three-point testcross: b+b cn+cn vg+vg x bb cncn vgvg
			d. Results
				i. Parental types: b+b cn+cn vg+vg and bb cncn vgvg
				ii. Single cross over (SCO) recombinant types
					. bb cn+cn vg+vg and bb cn+cn vg+vg
					. bb cncn vg+vg and b+b cn+cn vgvg
				iii. Double cross over (DCO) recombinant types
					. bb cn+cn vgvg x b+b cncn vg+vg
		9. Define map unit.
			a. Distance giving 1% recombinants
		10. Explain why Mendel did not find linkage between seed color and flower color.
			a. 50 map units = 50% recombinants = 1:1 ratio of parental to recombinant
			b. Same ratio as independent assortment
			c. Widely separated linked genes show independent assortment
		11. Explain how genetic maps are constructed for genes located far apart on a 
		chromosome.
			a. Gaps are filled in with newly discovered genes
			b. Overlapping mappable segments are connected 
		12. Explain the impact of multiple crossovers between loci.
			a. Multiple crossovers cause underestimation of distance
		13. Explain what additional information cytological maps provide over linkage maps.
			a. Crossover frequencies are not uniform along the chromosome
			b. Cytological maps locate genes with respect to physical features

SEX CHROMOSOMES
	Intro
	The chromosomal basis for sex varies with the organism
		14. Explain how sex is genetically determined in humans and the significance of the SRY 
		gene.
			a. Humans: XX, female; XY, male 
				i. Grasshoppers: X-, male; XX, female
				ii. Birds: ZZ, male; ZW, female
				iii. Bees: haploid, male; diploid, female
			b. Intact SRY gene is required for the formation of testes
			c. SRY is Y-linked
	Sex-linked genes have unique patterns of inheritance
		15. Explain why sex-linked diseases are more common in human males.
			a. Sex-linked genes are on the X chromosome
			b. Y chromosome is mainly non-homologous
			c. Most genes on the X chromosome are not paired
		16. Describe the inheritance patterns and symptoms of color blindness, Duchenne 
		muscular dystrophy, and hemophilia.
			a. Color blindness; sex-linked recessive
				i. Some types: red, green, and red-green
				ii. Difficulty distinguishing reds and/or greens
			b. Duchenne muscular dystrophy; sex-linked recessive
				i. Progressive weakening of muscles
				ii. Rarely live past early 20s
				iii. Lack the protein dystrophin, a link between the cytoskeleton and cell 
				membrane
			c. Hemophilia; sex-linked recessive
				i. Lack one of the blood proteins required for clotting
				ii. Controlled by injections of recombinant clotting factor
		17. Describe the process of X inactivation in female mammals. Explain how this 
		phenomenon produces the tortoiseshell coloration in cats.
			a. Human cells require a single active copy of the X chromosome
			b. In females, after embryonic development, one remains condensed, the Barr 
			body
			c. Inactivation involves DNA methylation
			d. This inactivation is random
			e. Sex-linked heterozygous genes randomly turned off create a mosaic 
			phenotype
			f. In cats, calico is such a phenotypic mosaic 

ERRORS AND EXCEPTIONS IN CHROMOSOMAL INHERITANCE
	Intro
	Alterations of chromosome number or structure cause some genetic disorders
		18. Distinguish nondisjunction, aneuploidy, trisomy, triploidy, and polyploidy. Explain how 
		these major chromosomal changes occur and describe the consequences.
			a. Nondisjunction
				i. Failure of homologous chromosomes to separate 
				properly singly or complete spindle or cytokinetic failure
				ii. Each chromosome has many genes, pleiotropic effects
				iii. Altered ratios of genes disrupt function
			b. Types
				i. Aneuploidy: abnormal chromosome number
				ii. Trisomy: one extra chromosome; three of one type
				iii. Monosomy: one missing chromosome; only one of one type						iv. Triploidy: three sets of chromosomes; 3N
				v. Polyploidy: many sets of chromosomes
		19. Distinguish deletions, duplications, inversions, and translocations.
			a. Chromosomal mutations all result from breakage and rejoining
				i. Many genes may be involved; ratio and pleiotropic effects
				ii. Points of breakage and rejoining may be damaged; mutation
			a. Types
				i. Deletions: loss of a section of a chromosome
				ii. Duplications: doubling of a section
				iii. Inversions: flipping over asection
				iv. Translocations: a piece of a chromosome becomes attached to a non-
				homologous chromosome
		20. Describe the type of chromosomal alterations implicated in the following human 
		disorders: Down syndrome, Klinefelter's syndrome, extra Y, triple-X syndrome, Turner 
		syndrome, cri du chat syndrome, and chronic myelogenous leukemia.
			a. Down syndrome: trisomy 21
			b. Klinefelter's syndrome: XXY
			c. Extra Y: XYY
			d. Triple-X syndrome: XXX
			e. Turner syndrome: XO
			f. Cri du chat syndrome: deletion from chromosome 5
			g. Chronic myelogenous leukemia: 22  9 translocation
	The phenotypic effects of some genes depend on whether they are inherited from the 
	mother or the father (imprinting)
		21. Define genomic imprinting and provide evidence to support this model.
			a. Example: a specific deletion from chromosome 5
				i. Inherited from the mother: Angelman syndrome
				ii. Inherited from the father: Prader-Willi syndrome
			b. Genes showing imprinting
				i. Usually inactivated by methylation
				ii. Usually are required in embryonic development
				iii. Must be present as one active copy
			c. After development unimprinted; germ line cells perform methylation
	Extranuclear genes exhibit a non-Mendelian pattern of inheritance
		22. Give some exceptions to the chromosome theory of inheritance. Explain why 
		extranuclear genes are not inherited in a Mendelian fashion and how they can contribute 
		to disease.
			a. DNA isn't just found on large chromosomes in the nucleus
				i. Mitochondria and chloroplasts have small circular chromosomes
				ii. Prokaryotes and some eukaryotes may carry variable numbers of 
				plasmids
			b. Not included in the mitotic or meiotic spindle
				i. Segregated randomly by cytokinesis
				ii. In organisms with dimorphic gametes, mitochondria and chloroplasts 
				come from the mother
			c. Mitochondrial defects affect high energy tissues: mitochondrial myopathy
			d. Also implicated in diabetes, heart disease, Alzheimer's, aging