©2000 timothy g. standish matthew 18:11 11for the son of man is come to save that which was lost

©2000 Timothy G. Standish

Matthew 18:11

11For the Son of man is come to save that which was lost.


Chromosomal Basis Chromosomal Basis of Inheritanceof Inheritance

Timothy G. Standish, Ph. D.


Introduction- Gregor MendelIntroduction- Gregor MendelFather of classical genetics.Born 1822 to peasant family in the Czech

village of Heinzendorf, part of the Austro-Hungarian empire at the time.

Austrian Augustinian monk (Actually from Brunn which is now in the Czech Republic).


Gregor Mendel - EducationGregor Mendel - EducationStudied mathematics in Olmutz college.Attended University of Vienna 1851 - 1853.

Influenced by:– Franz Unger, a plant physiologist who believed

new species could come about via hybridization.– Christian Doppler, physicist who discovered

the Doppler effect. Sharpened his math skills.


Gregor Mendel - WorkGregor Mendel - Work

Studied peas which he grew in a garden outside of the Abbey where he lived starting 1856 (3 years prior to publication of Origin of Species).

Showed that the traits he studied behaved in a precise mathematical way and disproved the theory of "blended inheritance."


Gregor Mendel - Work Cont.Gregor Mendel - Work Cont.Published rules of transmission of genes in 1866

(handwritten in German, not Latin!). Work was totally ignored.

Mendel’s work was rediscovered in 1900 by three botanists:– Carl Correns (Germany)– Erich von Tschermak (Austria)– Hugo de Vries (Holland)


3 Reasons Mendel’s Work 3 Reasons Mendel’s Work Was IgnoredWas Ignored

Mendel was not on the ballBiologists didn’t know

mathematicsLack of independent

supporting discoveries


Reasons Mendel’s Reasons Mendel’s Work Was Ignored:Work Was Ignored:

1) Mendel was not on the ball1) Mendel was not on the ball

Wrote in an obscure journal (Proceedings of the Natural History Society of Brunn).

Wrote in German, not Latin.Mendel was not well known and did not

persevere in his attempt to push his ideas.



2) Biologists didn’t know math2) Biologists didn’t know mathBiologists didn’t understand math very well.Biologists were interested in the explaining

the transmission of continuous traits like height, esp. after publication of Origin of Species in 1859. Mendel suggested that inherited characteristics were discrete units (discontinuous).



3) Lack of independent supporting 3) Lack of independent supporting discoveries:discoveries:

There was no physical element in which Mendel’s inherited particles could be identified.

By the turn of the century, chromosomes had been discovered (physical particles) and biologists were better at math.


Chromosomes:Chromosomes:The Physical Basis of InheritanceThe Physical Basis of Inheritance

1866 Mendel published his work1875 Mitosis was first described1890s Meiosis was described1900 Mendel's work was rediscovered1902 Walter Sutton, Theodore Boveri and

others noted parallels between behavior of chromosomes and alleles.


Chromosomal Theory Chromosomal Theory of Inheritanceof Inheritance

Genes have specific loci on chromosomes.

Chromosomes undergo segregation (meiosis) and independent assortment,

Thus alleles of genes are independently assorted.


E

n

e

N

Chromosomal Theory Chromosomal Theory of Inheritanceof Inheritance

e

N

E

n

Father

Mother

N

eE

n

N

E

n

e e

n

E

N

e

n

E

N

e

n

E

N

e

N

E

n

Telophase II

Replication

Telophase IProphase I

Crossing Over


En

eN

en

EN

Sperm e ne NE nE N

EggsIndependent AssortmentIndependent Assortment

n

E

e

N

e

n

N

E

n

Ee

n

e

NN

E

EeNnEeNNEENnEENN

EennEeNnEEnnEENn

eeNneeNNEeNnEeNN

eenneeNnEennEeNn

As long as genes are on different chromosomes, they will assort independently


E

A a

e

Two Genes On One Two Genes On One ChromosomeChromosome

Telophase II

Father

Mother

e

a

E

A

Telophase I

A

eE

A

E

a

e

a

E

A A

e E

a a

e

Replication

e

a

E

A

Prophase I

E

AA a

e

a

As long as genes on the same chromosome are located a long distance apart, they will assort independently due to crossing over during Prophase I of meiosis


Thomas Hunt MorganThomas Hunt Morgan First to associate a trait (gene) with a chromosome. Worked with fruit flies (Drosophila melanogaster) Why fruit flies?

– Short generation time (≈ 2 weeks)– Survive and breed well in the lab– Very large chromosomes in some cells– Many aspects of phenotype are genetically controlled.


DrosophilaDrosophila Nomenclature Nomenclature

+ = Wild type, phenotype in nature (i.e., red eyes and round wings)

Mutants are alternatives to the wild type Fruit fly genes are named after the mutant Dominant mutations are capitalized (i.e., Hairless or

H and Bar or B) Recessive mutants are named using lower case

letters (i.e., black or b and white or w)


DrosophilaDrosophila Mutations Mutations


More More DrosophilaDrosophila Mutations Mutations

ebony body ee

Wild Type ++

white eyes ww


Sex DeterminationSex Determination Two ways in which sex can be determined: Environment:

Turtles - Temperature of development Some fish - Social structure

Chromosomes - Three methods: XO - Haploid/diploid, i.e., bees, haploid males diploid females ZW - Heterogametic (ZW) females, homogametic (ZZ) males, i.e.,

birds XY - Heterogametic (XY) males, homogametic (XX) females, i.e.,

humans and Drosophila


X-Chromosome Human and X-Chromosome Human and DrosophilaDrosophila Genes Are Easy To Find Genes Are Easy To Find In humans and Drosophila, males are XYThus males are haploid for the X

chromosomeBecause of this, recessive genes on the X

chromosome show up far more commonly in male than female phenotypes


Morgan’s Discovery Of An X-Morgan’s Discovery Of An X-Linked Linked DrosophilaDrosophila Gene Gene

A white-eyed male was discovered

X+ X+

X+Y

Xw X+

XwY

X+ Xw

X+

Y

Xw X+

X+Y

Xw X+

X+Y

X+ X+

Xw

Y

X P

X F1

F2

1/21/4 1/4


The Key To Morgan’s DiscoveryThe Key To Morgan’s Discovery The key to Morgan’s discovery was the observation that all

the white-eyed individuals in the F2 generation were males

Without this vital data on the association of white eyes with being male, the gene for white eyes could have been seen as a simple recessive trait on an autosome

This illustrates the importance of recording all the data possible and being alert to the possibility of interesting things being present in the data

“Fate favors the prepared mind” (Louis Pasteur)


Human X-linked Recessive Human X-linked Recessive GenesGenes

Brown enamel - Tooth enamel appears brown rather than white

Hemophilia - Two types:– A - Classic hemophilia, deficiency of blood-

clotting factor VIII

– B - Christmas disease, deficiency of blood-clotting factor IX


X-linked Recessive GenesX-linked Recessive GenesRelated to SightRelated to Sight

Coloboma iridis - A fissure in the eye’s iris Color Blindness - Two types:

– Deutan - Decreased sensitivity to green light– Protan - Decreased sensitivity to red light

Congenital night blindness - Not due to a deficiency of vitimin A

Microphthalmia - Eyes fail to develop Optic atrophy - Degeneration of the optic nerves


Variation In Chromosome Variation In Chromosome Number - PolyploidyNumber - Polyploidy

Polyploid individuals have more than two sets of chromosomes

Many important commercial plants are polyploid:– Roses– Navel oranges– Seedless watermelons

Polyploid individuals usually result from some sort of interruption during meiosis

Pro or Metaphase I

Interruption

of meiosis

Metaphase II

2n Gametes

+ 1n Gamete

3n Zygote


Variation In Chromosome Variation In Chromosome Number - AneuploidyNumber - Aneuploidy

Polyploid humans are unknown, but individuals with extra individual chromosomes are known.

Having extra chromosomes or lacking some chromosomes is called aneuploidy

Aneuploid individuals result from nondisjunction during meiosis

Metaphase I Anaphase IZygote

+

Zygote

+


Aneuploidy In HumansAneuploidy In Humans Most human aneuploids spontaneously abort The most viable variations in chromosome number are those that deal with

the sex chromosomes: XO - Turner’s Syndrome - Phenotypically females XXX…- “Super” females XYY… - “Super” Males - On average tend to be larger and less intelligent XXY - Klinefelter’s Syndrome - Phenotypically male Of the non-sex chromosome aneuploids, Down’s Syndrome, extra

chromosome 21, tends to be the most viable Down’s Syndrome is more common in children of mothers who gave birth

after age 40


Gene DosageGene DosageThere seem to be elegant mechanisms for

maintaining the correct dosage of genetic material in each cell

When aneuploidy causes a change in the relative dose of one chromosome, problems result

Another way in which dosage of genetic material can be changed is via macromutations


MacromutationsMacromutations Four major types of Macromutations are recognized:

1 Deletions - Loss of chromosome sections

2 Duplications - Duplication of chromosome sections

3 Inversions - Flipping of parts of chromosomes

4 Translocations - Movement of one part of a chromosome to another part


Macromutation - DeletionMacromutation - Deletion

ChromosomeCentromere

A B C D E F G H

Genes

E F

A B C D G H


A B C D E F E F G H

Macromutation - DuplicationMacromutation - DuplicationChromosome

Centromere

A B C D E F G H

Genes

E F

Duplication


Macromutation - InversionMacromutation - InversionChromosome

Centromere

A B C D F E G H

Genes

A B C D E F G H

Inversion


Macromutation - TranslocationMacromutation - Translocation

A B E F C D G H

CentromereChromosome

Genes

A B C D E F G H


The Lyon HypothesisThe Lyon Hypothesis Having extra chromosomes causes problems (e.g.,

Down’s Syndrome) Men have only one X chromosome and they are

normal (at least they think so) Women have two X chromosomes and they are normal Mary Lyon proposed that the extra dosage of X

chromosome that women have is compensated for by turning off one of the X chromosomes.

This turned-off chromosome can be observed as a “Barr Body” in metaphase female nuclei


Consequences of X-Chromosome Consequences of X-Chromosome Dosage CompensationDosage Compensation

During early development, X chromosomes are randomly turned off in female cells

All daughter cells have the same X chromosome inactivated as their parental cell.

Thus, females are a mosaic of patches of cells, some patches expressing the genes on the paternal X chromosome, other patches expressing the maternal X chromosome


Consequences of X-Chromosome Consequences of X-Chromosome Dosage CompensationDosage Compensation

XXXXXXXX

At some point (probably later than the 4-cell stage) half the X chromosomes are turned off

Daughter cells inherit the mother cell’s mixture of off and on X chromosomes

Because of dosage compensation, females are thought to be a mosaic of patches of cells with each patch expressing the same X chromosome, but none expressing both chromosomes

Different patches of cells inherit different act X chromosomes

XXXX

Cell division

XX

Zygote XXXXXXXX


Why Calico Cats Why Calico Cats Are Usually FemaleAre Usually Female

Orange coat color is a sex-linked trait in cats (it is on the X chromosome)

A female cat heterozygous for orange, has skin patches expressing the orange X with the other X chromosome turned off. In other patches the opposite occurs.


Problem 1Problem 1 In Drosophila, vermilion (v) is recessive to red (v+) eyes and miniature (m)

wings are recessive to normal (m+) wings. The following cross was made:

Male v+v+m+m+ x vvmm Female

A What was the phenotype of the F1 generation?

B What F2 phenotypic ratio would you expect?

C If the actual F2 phenotypic numbers were:

– 147 red-eyed normal winged – 49 vermilion-eyed miniature winged, – 2 red-eyed miniature winged, – 2 vermilion-eyed normal winged,

How would you explain this?


Solution 1Solution 1AWhat was the phenotype of the F1 generation?

v+v+m+m+ makes v+m+ gametes

vvmm makes vm gametes

Thus the F1 must be v+vm+m

BWhat F2 phenotypic ratio would you expect?9 red-eyed normal winged (v+_m+_)

3 red-eyed miniature winged (v+_mm)

3 vermilion-eyed normal winged (vvm+_)

1 vermilion-eyed miniature winged (vvmm)


Solution 1 ContinuedSolution 1 ContinuedC If the actual F2 phenotypic numbers were:

– 147 red-eyed normal winged – 49 vermilion-eyed miniature winged, – 2 red-eyed miniature winged, – 2 vermilion-eyed normal winged,

How would you explain this?

mv

m+v+

0.49

0.01

0.49

0.01mv+

m+vmv

m+v+

mv+

m+v

F1 Gametes


Solution 1 ContinuedSolution 1 Continued

0.0001vvm+m+

0.0049vvm+m

0.0049vvm+m

0.2401vvmm

0.01vm+

0.49vm

0.49v+m+

0.01v+m

0.24 vvmm(0.24*200=48)

0.01vm+

0.49vm

0.49v+m+

0.01v+m

0.0049v+vmm

0.0049v+vmm

0.0001v+v+mm

0.0049v+vm+m+

0.2401v+vm+m

0.0001v+vm+m

0.0049v+vm+m+

0.0001v+vm+m

0.2401v+v+m+m+

0.0049v+v+m+m

0.0049v+v+m+m

0.2401v+vm+m

0.01 vvm+_(0.01*200=2)

0.01 v+_mm(0.01*200=2)

0.74 v+_m+_(0.74*200=148)

mv

m+v+

0.49

0.01

0.49

0.01mv+

m+vmv

m+v+

mv+

m+v


Solution 1 ContinuedSolution 1 Continued

Vermilion and miniature winged are closely linked genes on the same chromosome

The distance between vermilion and miniature is 1 centimorgan The reason numbers in the cross do not fit the prediction of 1

centimorgan exactly is that the numbers are the result of chance and thus would not be expected to fit the predicted ratio perfectly

mv

1cM


Problem 2Problem 2 How is the gene tracked in the pedigree shown below

inherited? In other words, what is its mode of inheritance?

A.

?

Answer - Either sex linked recessive (most likely) or autosomal recessive

Use deductive reasoning to solve this problem

Hypothesis 3 - Sex linked dominant

Hypothesis 2 - Autosomal recessive

Hypothesis 1 - Autosomal dominant

Hypothesis 4 - Sex linked recessive

Aa

A_

Aa

Aa

aa

aaaa Aa

aa

A_

aa

aa

A_

A_

A_

A_ A_


Problem 2Problem 2 How is the gene tracked in the pedigree shown below

inherited? In other words, what is its mode of inheritance?

B.

©2000 timothy g. standish matthew 18:11 11for the son of man is come to save that which was lost

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