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Chapter 15

Chapter 15. The Chromosomal Basis for Inheritance. Genetics. Late 1800s- Mitosis and Meiosis described Early 1900s- Scientists noticed similarities between chromosome behavior and Mendel’s “heritable factors”

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Chapter 15

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  1. Chapter 15 The Chromosomal Basis for Inheritance

  2. Genetics • Late 1800s- Mitosis and Meiosis described • Early 1900s- Scientists noticed similarities between chromosome behavior and Mendel’s “heritable factors” • Chromosome Theory of Inheritance: genes occupy specific loci on chromosomes and it is the chromosomes which undergo segregation and independent assortment during meiosis • The behavior of chromosomes during meiosis can account for Mendel’s laws of segregation and independent assortment

  3. Genetics The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene

  4. Morgan’s Experimental Evidence • Thomas Hunt Morgan • Experiments with fruit flies provided first evidence associating a specific gene with a specific chromosome • Several characteristics make fruit flies a good organism for genetic studies • Produce many offspring • A generation can be bred every two weeks • Four pairs of chromosomes • Different phenotypes in fly populations • Wild type phenotypes= “normal” trait, most common in the fly populations • Mutant phenotypes= Traits alternative to the wild type

  5. Eye color in fly populations Wild type= red eyes Mutant= white eyes

  6. Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair • In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) • The F1 generation all had red eyes • The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes

  7. EXPERIMENT Morgan determined that the white-eyed mutant allele must be located on the X chromosome PGeneration All offspringhad red eyes. F1Generation RESULTS F2Generation Supported the chromosome theory of inheritance

  8. CONCLUSION Figure 15.4b w w PGeneration X X Y X w w Sperm Eggs F1Generation w w w w w Sperm Eggs w w w F2Generation w w w w w

  9. Sex-Linked Characteristics • Sex chromosomes • Determine sex of offspring • Genes can have other functions too • Mammals= Males have XY chromosomes, Females have XX chromosomes • Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome • Gametes carry one copy of sex chromosome • Females= 100% X • Males= 50% X, 50% Y X Y

  10. Sex-linked genes have unique patterns of inheritance • Sex-linked gene= genes located on sex chromosomes • X chromosome has many genes unrelated to sex • Y chromosome has very few genes • The SRY gene on the Y chromosome codes for a protein that directs the development of male anatomical features • Females- 2 copies of X chromosome • Typical dominant-recessive relationship • Females can be carriers of sex-linked disorders • Males- 1 copy of X chromosome • Only needs one copy of allele to express trait • Sex-linked disorders tend to affect mostly males

  11. Sex-linked genes have unique patterns of inheritance • Cross a white-eyed female fruit fly with a red-eyed male fruit fly • Parent Genotypes= XrXr x XRY Xr Xr XR Y

  12. Sex-linked genes in humans Disorders caused by recessive alleles on the X chromosome in humans • Color blindness (mostly X-linked) • Duchenne muscular dystrophy • Progressive weakening of muscles and loss of coordination • Caused by absence of key muscle protein • Hemophilia • Absence of one or more proteins involved in blood clotting

  13. Red-green colorblindness • Normal vision woman- XNXN • Color-blind woman- XnXn • Woman Carrier- XNXn • Normal vision man- XNY • Color-blind man- XnY XN Xn XN Y

  14. X Inactivation • Mammalian females= one of the two X chromosomes in each cell is randomly inactivated during embryonic development • Inactive X condenses into a Barr body • If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character • Fur color in female mammals

  15. Linked Genes • Each chromosome has hundreds or thousands of genes (except the Y chromosome) • Genes located on the same chromosome that tend to be inherited together are called linked genes • Morgan did other experiments with fruit flies to see how linkage affects inheritance of two characters • Crossed flies that differed in traits of body color and wing size

  16. EXPERIMENT P Generation (homozygous) Figure 15.9-4 Double mutant(black body,vestigial wings) Wild type(gray body, normal wings) b b vg vg b b vg vg Double mutant F1 dihybrid(wild type) TESTCROSS b b vg vg b b vg vg Testcrossoffspring Eggs b vg bvg bvg b vg Wild type(gray-normal) Black-normal Black-vestigial Gray-vestigial bvg Sperm b bvg vg bbvgvg b bvgvg bbvg vg PREDICTED RATIOS : 1 If genes are located on different chromosomes: : 1 1 1 : If genes are located on the same chromosome andparental alleles are always inherited together: 1 0 1 0 : : : RESULTS : 944 185 : 965 : 206

  17. Linked Genes • Morgan found that body color and wing size are usually inherited together in specific combinations (parental phenotypes) • These genes do not assort independently • Must be on the same chromosome • However, nonparental phenotypes were also produced • Genetic recombination:production of offspring with combinations of traits differing from either parent

  18. Genetic Recombination: Unlinked genes • Mendel observed that combinations of traits in some offspring differ from either parent • Parental Types= Offspring with a phenotype matching one of the parental phenotypes • Recombinant types (recombinants)= Offspring with nonparental phenotypes (new combinations of traits) • A 50% frequency of recombination is observed for any two genes on different chromosomes

  19. Gametes from yellow-rounddihybrid parent (YyRr) yr Yr yR YR Gametes from green-wrinkled homozygousrecessive parent (yyrr) yr Yyrr yyrr yyRr YyRr Recombinant offspring Parental-type offspring For unlinked genes, genetic recombination occurs due to the independent assortment of chromosomes

  20. Genetic Recombination: Linked Genes • Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed • He proposed that some process must occasionally break the physical connection between genes on the same chromosome • Crossing over of homologous chromosomes

  21. Gray body, normal wings(F1 dihybrid) Black body, vestigial wings(double mutant) Testcrossparents bvg bvg bvg bvg Replicationof chromosomes Replicationof chromosomes bvg bvg bvg bvg bvg bvg bvg bvg Meiosis I bvg Meiosis I and II bvg bvg bvg Meiosis II Recombinantchromosomes bvg bvg bvg bvg bvg Eggs Sperm

  22. Recombinantchromosomes bvg bvg bvg bvg Eggs 206Gray-vestigial 944Black-vestigial 185Black-normal 965Wild type(gray-normal) Testcrossoffspring bvg bvg bvg bvg bvg bvg bvg bvg bvg Sperm Parental-type offspring Recombinant offspring 391 recombinants2,300 total offspring Recombinationfrequency  100  17% 

  23. Genetic Recombination • Recombinant chromosomes bring alleles together in new combinations in gametes • Random fertilization increases even further the number of variant combinations that can be produced • This abundance of genetic variation is the raw material upon which natural selection works

  24. Mapping the Distance Between Genes Using Recombination Data • Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome • Predicted= farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency

  25. Mapping the Distance Between Genes Using Recombination Data • Linkage map= genetic map of chromosome based on recombination frequencies • Distances between genes can be expressed as map units • 1 map unit (centimorgan)represents a 1% recombination frequency • Map units= relative distance and order, not precise locations of genes

  26. Mapping the Distance Between Genes Using Recombination Data • Genes that are far apart on the same chromosome can have a recombination frequency near 50% • Such genes are physically linked, but genetically unlinked • Behave as if found on different chromosomes • Sturtevant used recombination frequencies to make linkage maps of fruit fly genes • Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes • Cytogenetic maps=positions of genes with respect to chromosomal features

  27. Alteration of Chromosomal Structure Breakage of a chromosome can lead to four types of changes in chromosome structure • Deletion removes a chromosomal segment • Duplication repeats a segment • Inversion reverses orientation of a segment within a chromosome • Translocation moves a segment from one chromosome to another • If occurs in sex cells= congenital disorders • If occurs in somatic cells= non-inherited, can lead to cancer

  28. A B C D E F G H A B C E F G H A B C D E F G H A B C B C D E F G H A B C D E F G H A D C B E F G H A B C D E F G M N O P Q R A B P Q R M N O C D E F H (a) Deletion Figure 15.14 A deletion removes a chromosomal segment. (b) Duplication A duplication repeats a segment. (c) Inversion An inversion reverses a segment within a chromosome. (d) Translocation H A translocation moves a segment from onechromosome to a nonhomologous chromosome. G

  29. Disorders in Humans Caused of Alteration of Chromosome Structure • The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5 • A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood

  30. Disorders in Humans Caused of Alteration of Chromosome Structure • Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes • Portion of chromosome 22 switches places with portion of chromosome 9 • Gene creates a hybrid protein that stimulates cell division, leading to tumors

  31. There are two normal exceptions to Mendelian genetics • One exception involves genes located in the nucleus • Other exception involves genes located outside the nucleus • Extranuclear genes (or cytoplasmicgenes)are found in organelles in the cytoplasm • Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules • In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance

  32. Genes located in nucleus • For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits • This type of variation in phenotype is called genomic imprinting • Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production

  33. Normal Igf2 alleleis expressed. Figure 15.17 Paternalchromosome Maternalchromosome Normal-sized mouse(wild type) Normal Igf2 alleleis not expressed. (a) Homozygote Mutant Igf2 alleleinherited from mother Mutant Igf2 alleleinherited from father Dwarf mouse (mutant) Normal-sized mouse (wild type) Normal Igf2 alleleis expressed. Mutant Igf2 alleleis expressed. Mutant Igf2 alleleis not expressed. Normal Igf2 alleleis not expressed. (b) Heterozygotes

  34. Genes located in nucleus • The difference in mouse size is thought to be caused by imprinting from the methylation (addition of –CH3) of cysteine nucleotides • Genomic imprinting is thought to affect only a small fraction of mammalian genes • Most imprinted genes are critical for embryonic development

  35. Genes located outside of nucleus • Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg • First evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant • Some defects in mitochondrial genes prevent cells from making enough ATP • result in diseases that affect the muscular and nervous systems

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