Chapter 9 ppt

Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings

Purebreds and Mutts–A Difference of Heredity

• Purebred dogs

– Variation?

– Selective breeding?


• Mutts, or mixed breed dogs on the other hand

– Genetic variation? More? …less? Why?


• Modern Experimental Genetics

– Gregor Mendel’s quantitative experiments with pea plants

Petal

CarpelStamen

Figure 9.2 BFigure 9.2 A


• Mendel crossed? ..bred? …pea plants that differed in certain characteristics

• WHY?

– And traced traits from generation to generation

WHY?


• Mendel hypothesized that there are alternative forms of genes

– The units that determine heritable traits

Flower color

Flower position

Seed color

Seed shape

Pod color

Pod shape

Stem length

Purple White

Axial Terminal

Round Wrinkled

Inflated Constricted

Tall Dwarf

GreenYellow

Green Yellow


Mendel’s Law’s:

1)Dominance

2)Segregation From his experimental data

– Mendel deduced that an organism has two genes (alleles) for each inherited characteristic

P generation(true-breedingparents)

F1 generation

F2 generation

Purple flowers White flowers

All plants havepurple flowers

Fertilizationamong F1 plants(F1 F1)

of plantshave purple flowers

34 of plants

have white flowers

14


• For each characteristic

– An organism inherits two alleles, one from each parent

– Hmmm…does this remind you of anything we studied? …what? Be Specific!


• Mendel’s law of segregation

– Predicts that allele pairs separate from each other during the production of gametes

Figure 9.3 B

P plants

Gametes

Genetic makeup (alleles)

Gametes

F1 plants(hybrids)

F2 plants

PP pp

All P All p

All Pp

Sperm

12 P

P

P

p

p

PP Pp

Pp pp

EggsGenotypic ratio1 PP : 2 Pp: 1 pp

Phenotypic ratio3 purple : 1 white

12 p


Recal….Homologous chromosomes bear the two alleles for each characteristic

• Alternative forms of a gene

– Reside at the same locus on homologous chromosomes

Genotype: PP aa BbHeterozygous

P a b

P a B

Gene loci

Recessiveallele

Dominantallele

Homozygousfor thedominant allele

Homozygousfor therecessive allele


• Mendel’s law of independent assortment

– States that alleles of a pair segregate independently of other allele pairs during gamete formation

Hypothesis: Dependent assortment Hypothesis: Independent assortment

RRYY rryy

Gametes Gametes

RRYY rryy

RrYy RrYy

RY ry ryRY

Sperm Sperm

RY ry

ry

RY

ry

Ry

ry

RY

RRYY

RrYY

RRYy

RrYy

RrYY

rrYY

RrYy

rrYy

RRYy

RrYy

RRyy

Rryy

RrYy

rrYy

Rryy

rryy

RY ry ryRY

Actual resultscontradict hypothesis

Actual resultssupport hypothesis

Yellowround

Greenround

Yellowwrinkled

Greenwrinkled

Eggs

P generation

F1 generation

F2 generation

Eggs

12

12

12

12

14

14

14

14

14

14

14

14

916

316

316

116


• An example of independent assortment

• Punnett Squares, Probablility & Predicting F1 & F2

Black coat, normal visionB_N_

Black coat, blind (PRA)B_nn

Chocolate coat, normal visionbbN_

Chocolate coat, blind (PRA)bbnn

Blind Blind

9 black coat, normal vision

3 black coat,blind (PRA)

3 chocolate coat, normal vision

1 chocolate coat, blind (PRA)

BbNn BbNn

PhenotypesGenotypes

Mating of heterozygotes(black, normal vision)

Phenotypic ratioof offspring

Figure 9.5 BPRA: Progressive Retinal Atrophy


Geneticists a testcross to determine unknown genotypes

• The offspring of a testcross, a mating between an individual of unknown genotype and a homozygous recessive individual

Testcross:

Genotypes

Gametes

Offspring

B_ bb

Two possibilities for the black dog:

BB or Bb

B B b

b Bb b Bb bb

All black 1 black : 1 chocolate


Mendel’s laws reflect the…..

RULES OF PROBABILITY

• Inheritance follows the rules of probability

Could you use a test cross to determine if an organism was true breeding or pure breeding? How?


• The Mule of Multiplication, OR …the Product Rule

– Calculates the probability of two independent events

• The Rule of Addition

– Calculates the probability of an event that can occur in alternate ways

Figure 9.7

F1 genotypes

Bb female

Formation of eggs

F2 genotypes

Bb male

Formation of sperm

B b

BB B B b

b b B b b

12

12

12

12

14

14

14

14


• Family pedigrees

– Can be used to determine individual genotypes

DdJoshuaLambert

DdAbigailLinnell

D ?JohnEddy

D ?HepzibahDaggett

D ?Abigail

Lambert

ddJonathanLambert

DdElizabeth

Eddy

Dd Dd dd Dd Dd Dd dd

Female MaleDeafHearing

Figure 9.8 BComet Hale Bopp seen from path to Lambert’s Cove Beach…Martha’s Vineyard


CONNECTION

9.9 Many inherited disorders in humans are controlled by a single gene

• Some autosomal disorders in humans

Table 9.9


Parents

Offspring

Sperm

NormalDd

NormalDd

D d

Eggs

D

d

DDNormal

DdNormal(carrier)

DdNormal(carrier)

ddDeaf

Figure 9.9 A

Recessive Disorders• Most human genetic disorders are recessive


Dominant Disorders• Some human genetic disorders are dominant• http://www.youtube.com/watch?v=zS7vCd8KQIA• http://en.wikipedia.org/wiki/Human_genetics#Autosomal_dominant_inheritance

Figure 9.9 B


CONNECTION

New technologies can provide insight into one’s genetic legacy

• New technologies

– Can provide insight for reproductive decisions

http://www.gaucherdisease.com/


Amniocentesis Chorionic villus sampling (CVS)

Ultrasoundmonitor

Fetus

Uterus

Amnioticfluid

Fetalcells

Severalweeks

Biochemicaltests

Severalhours

Fetalcells

Uterus

Cervix

Suction tube insertedthrough cervix to extracttissue from chorionic villi

Needle insertedthrough abdomen toextract amniotic fluid

Centrifugation

Ultrasoundmonitor

Fetus

Placenta

Chorionicvilli

Karyotyping

Placenta

Cervix

Fetal Testing• Amniocentesis and chorionic villus sampling (CVS)

– Allow doctors to remove fetal cells that can be tested for genetic abnormalities


Fetal Imaging• Ultrasound imaging

– Uses sound waves to produce a picture of the fetus


NON-MENDELIAN INHERITANCE

Genotype = Phenotype?

1)What does this mean?

2)Mendel’s principles are valid for all sexually reproducing species

3)D’OH…. genotype often does not dictate phenotype in the simple way his laws describe


Incomplete Dominance?

When an offspring’s phenotype is in between the phenotypes of its parents, it exhibits incomplete dominance.

P generation

F1 generation

F2 generation

RedRR

Gametes

Whiterr

Gametes

Sperm

Eggs

PinkRr

R

R

R

r

rR

r

r

RedRR

PinkrR

PinkRr

Whiterr

12

12

12

12

12

12

Genotypes:

HHHomozygous

for ability to makeLDL receptors

HhHeterozygous

hhHomozygous

for inability to makeLDL receptors

Phenotypes:

LDL

LDLreceptor

Cell

Normal Mild disease Severe disease

Figure 9.12 B


Multiple Alleles!!

• In a population

– Multiple alleles often exist for a characteristic


• The ABO blood type in humans

– Involves three alleles of a single gene

• The alleles for A and B blood types are codominant

– And both are expressed in the phenotype

Figure 9.13

BloodGroup(Phenotype) Genotypes

AntibodiesPresent inBlood

Reaction When Blood from Groups Below Is Mixed withAntibodies from Groups at Left

O A B AB

O

A

B

AB

ii

IAIA

orIAi

IBIB

orIBi

IAIB

Anti-AAnti-B

Anti-B

Anti-A

—


Pleiotropy: A single gene may affect many phenotypic characteristics•Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets.

PKU (phenylketonuria) Symptoms:mental retardation reduced hair skin pigmentation,

…caused by any of a large number of mutations in a single gene that codes for the enzyme (phenylalanine hydroxylase), which converts the amino acid phenylalanine to tyrosine, another amino acid.

Depending on the mutation involved, this results in reduced or zero conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body. PKU is totally benign if a diet free from phenylalanine is maintained


A single characteristic may be influenced by many genes

• Polygenic inheritance: Creates a continuum of phenotypes

http://www.athro.com/evo/inherit.html

In humans three genes involved in eye color are known. They explain typical patterns of inheritance of brown, green, and blue eye colors. However, they don't explain everything. Grey eye color, Hazel eye color, and multiple shades of blue, brown, green, and grey are not explained. The molecular basis of these genes is not known. What proteins they produce and how these proteins produce eye color is not known. Eye color at birth is often blue, and later turns to a darker color. Why eye color can change over time is not known. An additional gene for green is also postulated, and there are reports of blue eyed parents producing brown eyed children (which the three known genes can't easily explain [mutations, modifier genes that supress brown, and additional brown genes are all potential explanations]).

The known Human Eye color genes are: EYCL1 (also called gey), the Green/blue eye color gene, located on chromosome 19 (though there is also evidence that another gene with similar activity exists but is not on chromosome 19). EYCL2 (also called bey1), the central brown eye color gene, possibly located on chromosome 15. EYCL3 (also called bey2), the Brown/blue eye color gene located on chromosome 15. EYCL3 probably involves mutations in the regulatory region just before the OCA2 gene (which produces a protein that is expressed in melanocytes). A second gene for green has also been postulated. Other eye colors including grey and hazel are not yet explained. We do not yet know what these genes make, or how they produce eye colors. The two gene model (EYCL1 and EYCL3) used above explains only a portion of human eye color inheritance. Both additional eye color genes and modifier genes are almost certainly involved


The environmental affects many characteristics

• Many traits are affected, in varying degrees

– By both genetic and environmental factors


• Genetic testing can detect disease-causing alleles

• Predictive genetic testing – May inform people of their risk for developing genetic

diseases– http://www.wired.com/wiredscience/2009/03/

designerdebate/– http://www.geneticsandsociety.org/article.php?id=4561

Designer Babies?


THE CHROMOSOMAL BASIS OF INHERITANCE

Chromosome behavior accounts for Mendel’s laws

• The structure and assembly of a eukaryotic chromosome: http://www.youtube.com/watch?v=gbSIBhFwQ4s

• Genes are located on chromosomes

– Whose behavior during meiosis and fertilization accounts for inheritance patterns


• The chromosomal basis of Mendel’s laws

All round yellow seeds(RrYy)

Metaphase Iof meiosis

(alternative arrangements)

Anaphase Iof meiosis

Metaphase IIof meiosis

Gametes

F1 generation

F2 generation

Fertilization among the F1 plants

(See Figure 9.5A)

1

4 RY

1

4ry

R

R

R

R RR

R

y

Y

Y

Y

Y Yy Y Y

r

r

y

R

Y

r

y

R r r r r

rr

y

r

Y

R

y

r

Y

R

y

1

4rY

1

4 Ry

9 : 3 : 3 : 1

y y y

yY


Genes on the same chromosome tend to be inherited together

• Certain genes are linked

– They tend to be inheritedtogether because they reside close together onthe same chromosome

Experiment

Explanation: linked genes

PpLI PpLILong pollen

Observed PredictionPhenotypes offspring (9:3:3:1)

Purple longPurple roundRed longRed round

Parentaldiploid cellPpLI

Most gametes

Mostoffspring Eggs

3 purple long : 1 red roundNot accounted for: purple round and red long

Meiosis

Fertilization

Sperm

284212155

215717124

P I

P L

P L

P L

P L

P L

P I

P L P I

P I

P L

P I

P I

P I

P I

P L

Purple flower

Figure 9.19

Trait A Trait BDominant or Recessive

References

Blond hair Blue eyes both recessive [5]

Flexibility Anxiety disorderA is recessive B is dominant

[6]

Large ears broad nose both dominant [7]


Crossing over produces new combinations of alleles??? HOW?

• Crossing over can separate linked alleles

– Producing gametes with recombinant chromosomes

A B

a b

Tetrad Crossing over

A B

A b

a b

a B

Gametes


• Thomas Hunt Morgan

– Performed some of the early studies of crossing over using the fruit fly Drosophila melanogaster


Thomas Hunt Morgan• Morgan began working seriously with Drosophila in 1907.

• But despite much effort and the breeding of successive generations, Morgan initially failed to detect a single mutation. "Two years work wasted," he lamented to one visitor to his laboratory. "I have been breeding those flies for all that time and I've got nothing out of it."(Harrison, R.G., "Embryology and Its Relations")

• April 1910 he suddenly had a breakthrough…one male fly with white : How did this white eye color originate? What determines eye color?

• Morgan bred this white-eyed (mutant) male to a red-eyed (wild-type) virgin sister and found that white-colored eyes are inherited in a special way. In the first generation of brother-sister mating, labeled F1, there were only red-eyed offspring, suggesting that red eye color is dominant and that white eye color is recessive. To prove this idea Morgan carried out brother-sister matings with the next generation (F2) and found that the offspring followed the expected Mendelian ratio for a recessive trait: three red-eyed flies to every one white-eyed fly. With these experiments Morgan started a tradition, which continues to this day, whereby he named the gene "white" by the result of its mutation. But then came a surprise. He had expected there would be an equal number of males and females with white eyes, but it turned out that all the female flies had red eyes; only males had white eyes, and, even more, only some of them displayed the trait. Morgan realized that white eye color is not only recessive but is also linked in some way to sex.


Morgan…continued• By 1910, it was already known that chromosomes occur in pairs and that Drosophila had four pairs of chromosomes. Several decades earlier, these thread-shaped structures had been seen under a microscope to be located in the nucleus, but nobody knew their function. Morgan later was to describe them in the following terms:

•"The egg of every species of animal or plant carries a definite number of bodies called chromosomes. The sperm carries the same number. Consequently, when the sperm unites with the egg, the fertilized egg will contain the double number of chromosomes. For each chromosome contributed by the sperm there is a corresponding chromosome contributed by the egg, i.e., there are two chromosomes of each kind, which together constitute a pair." (Morgan, T.H. et al., The Mechanism of Mendelian Heredity) When Morgan turned to examining the fruit fly's chromosomes under the microscope, he immediately appreciated that not all four pairs of chromosomes were always identical. In particular, whereas female flies had two identical-looking X chromosomes, in the male the X chromosome was paired with a Y chromosome, which looks different and is never present in the female.

• Morgan deduced that a male must inherit the X chromosome from his mother and Y from his father, and he immediately spotted a correlation between these sex-linked chromosomes and the segregation of the factors determining eye color. When the mother was homozygous and had two copies of the gene for red eyes, the male offspring invariably had red eyes, even if the father had white eyes. But when the mother had white eyes, the male offspring did too, even if the father's eyes were red. In contrast, a female fly gets one X chromosome from each parent, and if one passed along an X chromosome with a gene for red eyes, the offspring had red eyes because the color is dominant over white. Only when both parents gave her an X chromosome with a gene for white eyes did she display the recessive trait. From these observations, Morgan concluded that the allele-producing eye color must lie on the X chromosome that governs sex. This provided the first correlation between a specific trait and a specific chromosome.


• Morgan’s experiments

– Demonstrated the roleof crossing over in inheritance

Figure 9.20 C

Experiment

Gray body,long wings(wild type)

GgLI

Female

Black body,vestigial wings

ggll

Male

Offspring

Gray long

965 944 206 185

Black vestigial Gray vestigial Black long

Parentalphenotypes

Recombinantphenotypes

Recombination frequency = = 0.17 or 17%391 recombinants

2,300 total offspring

Explanation

GgLI(female)

ggll(male)

G L

g l

g l

g l

G L g l G l g L g l

Eggs Sperm

G L g l

g l g l g l g l

LglG

Offspring


Geneticists use crossover data to map genes

• Morgan and his students

– Used crossover data to map genes in Drosophila



• Recombination frequencies

– Can be used to map the relative positions of genes on chromosomes.

Mutant phenotypes

Shortaristae

Blackbody(g)

Cinnabareyes(c)

Vestigialwings(l)

Browneyes

Long aristae(appendageson head)

Gray body(G)

Redeyes(C)

Normalwings(L)

Redeyes

Wild-type phenotypes

Chromosomeg c l

9% 9.5%

17%

Recombinationfrequencies


• The Y chromosome– Has genes for the development of testes

• The absence of a Y chromosome– Allows ovaries to develop


• Other systems of sex determination exist in other animals and plants

22+

XX

22+X

76+

ZW

76+

ZZ

32 16

Figure 9.22 D

Figure 9.22 C

Figure 9.22 B


Sex-linked genes exhibit a unique pattern of inheritance

• All genes on the sex chromosomes

– Are said to be sex-linked

• In many organisms

– The X chromosome carries many genes unrelated to sex


• In Drosophila

– White eye color is a sex-linked trait

Figure 9.23 A


• The inheritance pattern of sex-linked genes

– Is reflected in females and males

Female Male

Sperm

Xr Y

XR

Xr Y XR XR

XR Xr XR YEggs

R = red-eye alleler = white-eye allele

Female Male

Sperm

XR Y

XR

XR Y XR Xr

XR XR XR Y

Eggs

Xr Xr XR Xr Y

Female

Sperm

Xr Y

XR

Xr Y XR Xr

XR Xr XR Y

Eggs

Male

Xr Xr Xr Xr Y

Figure 9.23 B Figure 9.23 C Figure 9.23 D


Genetic Determination of Sex Creates Dosage Problems

In mammals females have 2 X chromosomes, the males only 1

If nothing were done to compensate the females would get a double dose of any gene products from the X chromosome, compared to the dose that males get

Nature solves this problem by shutting down one whole X chromosome in mammalian females

• X chromosome inactivation is called Lyonization after Mary Lyon who discovered it

• Inactive X chromosome appears in condensed state as a Barr body (p. 272, text)

• Inactivation of X chromosomes in different cells is somewhat random

The calico cat is a product of X chromosome inactivation

• Genes for coat color of the cat are on the X chromosome

• One gene produces a black color; its allele produces orange

• To get a calico coat a cat must be heterozygous, with genes for both the orange and the black color

• If the X chromosome with the black gene is inactivated that cell will produce orange

• If the X chromosome with the orange gene is inactivated the cell will produce black

• Inactivation occurs in patches, giving the orange and black coat of the calico


CONNECTION

Sex-linked disorders affect mostly males

• Most sex-linked human disorders

– Are due to recessive alleles

– Are mostly seen in males

Queenvictoria

Albert

Alice Louis

Alexandra CzarNicholas IIof Russia

AlexisFigure 9.24 A Figure 9.24 B


There are about 1,098 human X-linked genes.

Most of them code for something other than female anatomical traits. Many of the non-sex determining X-linked genes are responsible for abnormal conditions such as…

Hemophilia Duchenne Muscular Dystrophy Fragile-X SyndromeSome High Blood PressureCongenital Night BlindnessG6PD DeficiencyRed-Green Color Blindness. Male Pattern Baldness

Mechanism of PRO051 in the restoration of Dystrophin Expression through Exon Skipping.

Normal muscle produces dystrophin, a critical protein, in response to signals encoded in a precise lockstep manner into mRNA. The mRNA is then translated into dystrophin protein. In the muscle of patients with Duchenne muscular dystrophy, mutations in the dystrophin gene lead to the loss of one or more exons. The mRNA splices together the remaining exons; however, the missing pieces lead to errors in translation (frame shift) and loss of production of the dystrophin protein. Intramuscular injection of a small modified DNA molecule can enter Duchenne-affected muscle through abnormal muscle membranes; then enters the nucleus and binds to the dystrophin mRNA. The modified DNA molecule allows the mRNA to skip over the affected exons, and restores the reading frame of the mRNA, for new production of dystrophin. The dystrophin that is produced is not normal but probably retains considerable function.


Mechanism of PRO051 in the Restoration of

Dystrophin Expression through Exon Skipping.

Normal muscle produces dystrophin, a critical protein, in response to signals encoded in a precise lockstep manner into mRNA. The mRNA is then translated into dystrophin protein. In the muscle of patients with Duchenne muscular dystrophy, mutations in the dystrophin gene lead to the loss of one or more exons. The mRNA splices together the remaining exons; however, the missing pieces lead to errors in translation (frame shift) and loss of production of the dystrophin protein. Intramuscular injection of a small modified DNA molecule can enter Duchenne-affected muscle through abnormal muscle membranes; then enters the nucleus and binds to the dystrophin mRNA. The modified DNA molecule allows the mRNA to skip over the affected exons, and restores the reading frame of the mRNA, for new production of dystrophin. The dystrophin that is produced is not normal but probably retains considerable function.


• A male receiving a single X-linked allele from his mother

– Will have the disorder• A female

– Has to receive the allele from both parents to be affected