THE CHROMOSOMAL BASIS OF INHERITANCE 1. A. Background 1. Genetics 1860’s—Mendel proposed that discrete inherited factors segregate and assort independently.

CHAPTER 15

THE CHROMOSOMAL BASIS OF INHERITANCE

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A. Background1. Genetics

1860’s—Mendel proposed that discrete inherited factors segregate and assort independently during gamete formation

2. Cytology1875—Cytologists worked out process of mitosis1890’s—Cytologists worked out process of meiosis

3. Genetics1900—Correns, von Tschermak, and de Vries independently discovered Mendel’s work

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I. Concept 15.1: Behavior of Chromosomes

4. Cytology and Genetics1902—2 areas converge as Walter Sutton, Theodor Boveri,

and others noticed parallels between the behavior of Mendel’s factors and the behavior of chromosomes:

Chromosomes and genes both present in pairs in diploid cells.

Homologous chromosomes separate and allele pairs segregate during meiosis.

Fertilization restores the diploid condition for both.5. Chromosomal Theory of Inheritance is based on these

observations. According to this theory: Mendelian factors (genes) are located on

chromosomes. Chromosomes segregate and assort independently

during meiosis3

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1. Walter Flemming (1882)First to observe chromosomes in nuclei of dividing

salamander cellsCalled process “mitosis”

2. August Weismann (1887)Each gamete has half the number of chromosomes as a

fertilized egg.Proposed that a special division process reduced the

chromosome number by one half

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B. Contributions to the Chromosomal Theory

3. Theodore Boveri (1888)Determined that chromosomes were essential for fertilization

and developmentDiscovered the centrioleActually observed meiosis in cells of Ascaris

4. Walter Sutton (1902)Found relationship between meiosis and Mendel’s lawsPredicted gene linkage

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5. Thomas Hunt Morgan (1910) Began experiments with Drosophila melanogaster (fruit fly) Discovered X-linked (sex linked) inheritance Discovered sex determination (X and Y chromosomes) Provided convincing evidence that Mendel’s factors are

located on chromosomes

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1. Reasons for using Drosophila Easy to raise Produce a large number of offspring Short life cycle (2 weeks) Mutants easily recognized Only 4 pairs of chromosomes (3 pr. of autosomes, 1 pr.

of sex chromosomes XX female, XY male)

C. Morgan and Drosophila

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2. Sex-linked Traits Wild type—normal character phenotype

Ex: w+-red eyes Mutant phenotype

-alternatives to wild type-due to mutations in wild type gene

Ex: w-white eyes Discovered by Morgan Refers to genes on the X chromosome From this experiment, Morgan deduced that:

a. Eye color is linked to sex. b. The gene for eye color is located on the X

chromosome.

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EXPERIMENT

PGeneration

GenerationF1 All offspring

had red eyes

Fig. 15-4b

RESULTS

GenerationF2

Experiment:

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3. Morgan’s finding of the correlation between a particular trait and an individual’s sex provided support for the chromosome theory of inheritance

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Heterogametic sex—produces 2 kinds of gametes which determine the sex of offspring

Homogametic sex—produces 1 kind of gamete with respect to sex chromosome

In humans and some other animals, there is a chromosomal basis of sex determination

Each gamete has only 1 sex chromosome.

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II. Concept 15.2 Sex-Linked Genes

A. The Chromosomal Basis of Sex1.In humans and other mammals, there are two varieties

of sex chromosomes: a larger X chromosome and a smaller Y chromosome

2.Only the ends of the Y chromosome have regions that are homologous with the X chromosome

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A. The Chromosomal Basis of Sex3. The SRY gene on the Y chromosome codes for the development of testes

SRY- Sex determining Region of Y◦ -The presence of this gene on the Y chromosome◦ codes for the development of testes. In the absence of ◦ this gene, the gonads develop into ovaries

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B. Systems of Sex Determination1. X-Y Mammals, humans, Drosophila ♂--heterogametic (XY) ♀--homogametic (XX) Y chromosome determines sex of offspring

2. X-O Grasshopper, cricket, roach, and other insects ♂--heterogametic (XO) ♀--homogametic (XX)

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3. Z-WBirds, some fish, some insects—butterflies and moths♀--heterogametic (ZW)♂--homogametic (ZZ)

4. Haplo-diploidyBees and antsHave no sex chromosomes♀--develops from fertilized egg (2n)♂--develops parthenogenetically from unfertilized egg (n)

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C. Inheritance of Sex-Linked Genes1. The sex chromosomes have genes for many characters

unrelated to sex2. A gene located on the X chromosome is called a sex-

linked gene3. Genes on the Y chromosome are called holandric genes

and are found in males only4. In humans, sex-linked usually refers to a gene on the

larger X chromosome5. Sex-linked genes follow specific patterns of inheritance

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6. For a recessive sex-linked trait to be expressed:◦A female needs two copies of the allele◦A male needs only one copy of the allele

7. Sex-linked recessive disorders are much more common in males than in females

8. If a sex-linked trait is due to a recessive allele, a female will express the trait only if she is homozygous.

9. A heterozygous female is a carrier.10. Males only need 1 allele of a sex-linked trait to show

the trait.11. Males are hemizygous (only one copy of a gene is

present in a diploid organism)

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Fig. 15-7

XNXN XnY XNXn XNY XNXn XnY

N= normal color vision

12. Fathers pass sex-linked alleles to only and all of their daughters

XA—Normal geneXa—Sex-linked gene

XAXA—Normal FemaleXAXa—Carrier FemaleXaXa—Affected FemaleXAY—Normal MaleXaY—Affected Male

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13. Mothers can pass sex-linked alleles to both sons and daughters.

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14. If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, whereas males without the disorder will be completely free of the recessive allele

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a. Color Blindness-recessive-can’t distinguish certain colors-red-green most common

b. Duchenne’s Muscular Dystrophy-recessive-atrophy of muscle

c. Hemophilia-recessive-blood fails to clot because of lack of a clotting factor

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15. Examples of Sex-linked Traits

1. Female mammals have only one fully functional X chromosome in diploid cells.

2. Proposed by Mary F. Lyon and known as the Lyon Hypothesis

3. Each of the embryonic cells inactivates one of the two X chromosomes.

4. Inactive X contracts into densely staining object called a Barr Body.

5. Ex:Mosaic coloration of calico catsNormal sweat gland development in humans

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D. X-inactivation in Females

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X-Inactivation in Females

1. Sex-limited Traits◦Appear exclusively in one sex◦Ex: uterine cancer in ♀; prostate cancer in ♂

2. Sex-influenced Traits◦Expression is influenced by presence of ♀ or ♂ sex

hormones◦Acts as a dominant in one sex and recessive in the other◦Ex: ♂--baldness, stomach ulcers;

♀--breast cancer both—length of index finger as compared to ring finger

-dominant in ♂ shorter index finger -dominant in ♀ longer index finger

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E. Other Disorders Associated with Sex

Each chromosome has hundreds or thousands of genes Genes located on the same chromosome that tend to be

inherited together are called linked genes Do not assort independently Dihybrid crosses deviate from expected 9:3:3:1 phenotypic

ratio

III. Concept 15.3: Linked Genes

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A. Genetic Recombination1. Production of offspring with new combinations of

traits different from those combinations found in the parents (crossing over)2. Results from the events of meiosis and random

fertilizationB. Recombination of Unlinked Genes: Independent Assortment

Parental types—progeny that have the same phenotype as one or the other of the parents

Recombinant types—progeny whose phenotypes differ from either parent

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YyRr

Gametes from green-wrinkled homozygousrecessive parent ( yyrr)

Gametes from yellow-roundheterozygous parent (YyRr)

Parental-type

offspring

Recombinantoffspring

yr

yyrr Yyrr yyRr

YR yr Yr yR

Parental Types- offspring that inherit a phenotype that matchesone of the parental phenotypes.

Recombinant Types or Recombinants- offspring that have new combinations of phenotypes.

P Yy Rr x yyrr (testcross)(yellow, round) (green, wrinkled)

F1 ¼ YyRr ¼ yyrr Parental types 50% ¼ yyRr ¼ Yyrr Recombinant types 50%

When half the progeny are recombinants, there is a 50% frequency of recombination.

A 50% frequency of recombination usually indicates that the two genes are on different chromosomes, because it is the expected result if the two genes assort randomly.

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b—black body vg—vestigial wingsb+--gray body vg+--wild type wings

b+ b vg+ vg x b b vg vg (testcross)(gray, normal wings) (black, vestigial wings)

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C. Recombination of Linked Genes: Crossing OverCrossing Over- accounts for the recombination of linked genes.

b vg Pheno-types

Expectedif genes not

linked

Expected if genes totally linked

Actual

b vg+

b b vg+vg

blacknormal

575 0 206

b+ vg+

b+ b vg+vg

graynormal

575 1150 965

b vg b b vg vg

blackvestigial

575 1150 944

b+ vg

b+ b vg vg

grayvestigial

575 0 185

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Possible Results

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What type of ratios would you expect to see in the testcross offspring if the genes were located on different chromosomes?

What if they were located on the same chromosome and parentalalleles are always inherited together?

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Recombination Frequency (RF) = # recombinants x 100 total # offspring

Proposed by Morgan Process of crossing over during meiosis accounts for the

recombination of linked genes (genes on same chromosome) Crossing over—breakage and exchange of corresponding

segments between homologous chromosomes--results in new allelic combination

Probability of crossing over (recombination) between two genes is proportional to the distance separating those genes

The closer together two genes are, the less likely that a cross over will occur.

Proved by A. H. Sturtevant

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1. Recombination frequencies are used to construct chromosome maps [show locations of genes on a particular chromosome (linear)]

2. Sturtevant constructed chromosome maps for Drosophila using recombination frequencies

3. 1 map unit = 1% recombination frequency (now called centimorgans)

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D. Chromosome Mapping

Recombination Genetic Map- an ordered list of the genetic loci

along a particular chromosome. Linkage Map- a genetic map based on

recombination frequencies. Displays order but not precise location.◦ Distances are expressed in map units- equivalent to 1%

recombination frequency. (Centimorgans)

4. How to use XO (crossover) data to construct a chromosome map:Ex: RF

b vg 17%cn b 9%cn vg 9.5%

a. Establish the distance between the genes with the highest RF

b-----17------------vgb. Determine RF between third gene and first.

cn----9-----bc. Consider the two possible placements of the third gene.

cn----9-----b--------17---------vgor

b---9------cn---8-----vg

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d. Determine the RF between the third gene and the second gene to eliminate the incorrect sequence

b---9------cn-----9.5-----vg 17

--correct sequence b-cn-vg

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5. If linked genes are so far apart on a chromosome that the RF is 50%, they are indistinguishable from unlinked genes that

assort independently. Can map such genes if RF can be determined between those

two genes and intermediate genes.6. Maps from XO data give relative positions of linked genes7. Cytological mapping pinpoints actual location of genes and real

distance between them. May differ from XO maps in distance but not sequence.

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Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders

Meiotic errors and mutagens can cause major chromosomal changes such as altered chromosome numbers or altered chromosomal structure.

A. Alterations of Chromosomal Number1. Nondisjunction

In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis

Results in one gamete receiving two of the same type of chromosome (n+1) and the other gamete receiving

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IV. Concept 15.4: Alternations of Chromosome Number or Structure

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Nondisjunction

2. Aneuploidy Aneuploidy results from the fertilization of gametes in

which nondisjunction occurred Offspring with this condition have an abnormal number of

a particular chromosome a chromosomal aberration in which one or more

chromosomes are present in extra copies or deficient in number

A monosomic zygote has only one copy of a particular chromosome

A trisomic zygote has three copies of a particular chromosome

Ex: Down’s Syndrome or Trisomy 21

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Trisomy 21

3. PolyploidyPolyploidy is a condition in which an organism has more

than two complete sets of chromosomes◦ a chromosomal alteration in which the organism possesses more than two complete chromosome sets.

Triploidy (3n) is three sets of chromosomesTetraploidy (4n) is four sets of chromosomes

Polyploidy is common in plants, but not animalsPolyploids are more normal in appearance than aneuploids

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1. Breakage of a chromosome can lead to four types of changes in chromosome structure:

a. Deletion removes a chromosomal segment

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B. Alterations of Chromosomal Structure

b. Duplication repeats a segment

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c. An inversion occurs if the fragment reattaches to the original chromosome in reverse order.

Inversion reverses a segment within a chromosome

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d. A translocation occurs if a chromosomal fragment joins to a nonhomologous chromosome

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2. Crossing over can produce deletions or duplicatons.

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C. Chromosomal Alterations in Human Disease1. Alterations of chromosome number and structure are

associated with some serious disorders2. Some types of aneuploidy appear to upset the genetic balance

less than others, resulting in individuals surviving to birth and beyond

3. These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy

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4. Examples of Autosomal Aneuploidy:a. Down’s Syndrome

Trisomy 21 Related to age of parent Most common birth defect in U. S. (1/700 births)

b. Patau Syndrome Trisomy 13

c. Edward’s Syndrome Trisomy 18

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5. Examples of Sex Chromosome Aneuploidy: (less severe)a. Klinefelter’s Syndrome--Genotype usually XXYb. Extra Y--XYYc. Trisomy X (metafemales)--XXXd. Turner’s Syndrome (monosomy X)--XO

6. Examples of Deletions: a. Cri du chat Syndrome--Deletion on chromosome 5

7. Examples of Translocations:a. Chronic Myelogenous Leukemia (CML)--Portion of

chromosome 22 switched with a fragment of chromosome 9

b. Type of Down’s Syndrome--Translocation from chromosome 21 to chromosome 15

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There are two normal exceptions to Mendelian genetics One exception involves genes located in the nucleus, and the

other exception involves genes located outside the nucleus

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V. Concept 15.5: Exceptions to Chromosome Theory

A. Genomic Imprinting1. For a few mammalian traits, the phenotype depends on

which parent passed along the alleles for those traits2. Such variation in phenotype is called genomic imprinting3. Genomic imprinting involves the silencing of certain genes

that are “stamped” with an imprint during gamete production

4. “a variation in phenotype depending on whether an allele is inherited from the male or female parent.

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V. Concept 15.5: Exceptions to Chromosome Theory

4. It appears that imprinting is the result of the methylation (addition of –CH3) of DNA

5. Genomic imprinting is thought to affect only a small fraction of mammalian genes6. Most imprinted genes are critical for embryonic development

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B. Inheritance of Organelle Genes1. Extranuclear genes (or cytoplasmic genes) are genes

found in organelles in the cytoplasm2. Mitochondria, chloroplasts, and other plant plastids carry

small circular DNA molecules3. Extranuclear genes are inherited maternally because the

zygote’s cytoplasm comes from the egg4. The first evidence of extranuclear genes came from

studies on the inheritance of yellow or white patches on leaves of an otherwise green plant

5. Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems

6. Cytoplasmic genes described in plants by Karl Correns (1909)

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1. Explain the chromosomal theory of inheritance and its discovery

2. Explain why sex-linked diseases are more common in human males than females

3. Distinguish between sex-linked genes and linked genes4. Explain how meiosis accounts for recombinant

phenotypes5. Explain how linkage maps are constructed

You should now be able to:

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6. Explain how nondisjunction can lead to aneuploidy7. Define trisomy, triploidy, and polyploidy8. Distinguish among deletions, duplications, inversions, and

translocations9. Explain genomic imprinting10. Explain why extranuclear genes are not inherited in a

Mendelian fashion

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