Chapter 14Mendel and the Gene Idea

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•One possible explanation of heredity is a “blending” hypothesis▫The idea that genetic material contributed by

two parents mixes in a manner analogous to the way blue and yellow paints blend to make green

•An alternative to the blending model is the “particulate” hypothesis of inheritance: the gene idea▫Parents pass on discrete heritable units, genes

What genetic principles account for the transmission of traits from parents to offspring?

•Gregor Mendel▫Mendel used the scientific

approach to identify two laws of inheritance

•Mendel discovered the basic principles of heredity by breeding garden peas

•Vocabulary▫Character: a heritable

feature, such as flower color▫Trait: a variant of a

character, such as purple or white flowers

•Mendel chose to track▫Only those characters that varied in an

“either-or” manner Ex: Flower color trait is either purple or white,

there is no intermediate•Mendel also made sure that

▫He started his experiments with varieties that were “true-breeding” all successive generations display only the

desired trait Ex: A purple-flowered plant is self-pollinated

and all the offspring have purple flowers

Pollen transferred from white flower to stigma of purple flower

anthersremoved

all purple flowers result

Mendel’s work

F1

P

F2

self-pollinate

•Bred pea plants▫cross-pollinate two

true breeding parents (P) hybridization P = parental

▫raised seed & then observed traits (F1) Hybrid offspring F = filial

▫allowed offspring to self-pollinate & observed next generation (F2)

F2generation

3:175%purple-flower peas

25%white-flower peas

Looking closer at Mendel’s work

P

100%F1generation(hybrids)

100%purple-flower peas

Xtrue-breedingpurple-flower peas

true-breeding white-flower peas

self-pollinate

Where didthe whiteflowers go?

Whiteflowers cameback!

•Mendel reasoned that▫In the F1 plants, only the purple flower factor

was affecting flower color in these hybrids▫Purple flower color was dominant, and white

flower color was recessive• Mendel observed the same

pattern▫ In many other pea plant

characters

Table 14.1

Mendel’s Experiments and Observations•Allowed Mendel to deduce two

fundamental laws of heredity:1. Law of Segregation2. Law of Independent Assortment

Mendel’s Model•Mendel developed a hypothesis

▫To explain the 3:1 inheritance pattern that he observed among the F2 offspring

•Four related concepts make up this model1. Alternative versions of genes (alleles)2. Each Allele is represented twice3. If two alleles differ, the dominant one is

expressed4. Two alleles segregate during meiosis

What did Mendel’s findings mean?•Traits come in alternative versions

▫purple vs. white flower color▫alleles

different alleles vary in the sequence of nucleotides at the specific locus of a gene

some difference in sequence of A, T, C, G

purple-flower allele & white-flower allele are two DNA variations at flower-color locus

different versions of gene at same location on homologous chromosomes

Traits are inherited as discrete units•For each characteristic, an organism

inherits 2 alleles, 1 from each parent▫diploid organism

inherits 2 sets of chromosomes, 1 from each parent

▫homologous chromosomes▫A genetic locus is actually represented

twice, one on each homolog of a pair of chromosomes Two alleles may be identical or different

What did Mendel’s findings mean?

•Some traits mask others ▫purple & white flower colors are

separate traits that do not blend purple x white ≠ light purple purple masked white

▫dominant allele functional protein masks other alleles

▫recessive allele allele makes a

malfunctioning proteinhomologouschromosomes

I’ll speak for both of us!

wild typeallele producingfunctional protein

mutantallele producingmalfunctioningprotein

Fourth, the law of segregation• Law of segregation

▫during meiosis, alleles segregate homologous chromosomes separate

▫each allele for a trait is packaged into a separate gamete

▫An egg or sperm only receives one of the two alleles present in the somatic cell

PP

P

P

ppp

p

PpP

p

Law of Segregation•Which stage of

meiosis creates the law of segregation?

Whoa!And Mendeldidn’t even knowDNA or genesexisted!

Metaphase 1

Genotype vs. phenotype•Difference between how an organism

“looks” & its genetics▫phenotype

description of an organism’s trait the “physical”

▫genotype description of an organism’s genetic

makeup

Explain Mendel’s results using…dominant & recessive …phenotype & genotype F1

P X

purple white

all purple

Making crosses•Can represent alleles as letters

▫flower color alleles P or p▫true-breeding purple-flower peas PP▫true-breeding white-flower peas pp

PP x pp

PpF1

P X

purple white

all purple

•Mendel’s law of segregation, probability and the Punnett square

•Try a cross: Pp x Pp P Generation

F1 Generation

F2 Generation

P p

P p

P p

P

p

PpPP

ppPp

Appearance:Genetic makeup:

Purple flowersPP

White flowerspp

Purple flowersPp

Appearance:Genetic makeup:

Gametes:

Gametes:

F1 sperm

F1 eggs

1/21/2

Each true-breeding plant of the parental generation has identicalalleles, PP or pp.

Gametes (circles) each contain only one allele for the flower-color gene. In this case, every gamete produced by one parent has the same allele.

Union of the parental gametes produces F1 hybrids having a Pp combination. Because the purple-flower allele is dominant, allthese hybrids have purple flowers.

When the hybrid plants producegametes, the two alleles segregate, half the gametes receiving the P allele and the other half the p allele.

3 : 1

Random combination of the gametesresults in the 3:1 ratio that Mendelobserved in the F2 generation.

This box, a Punnett square, shows all possible combinations of alleles in offspring that result from an F1 F1 (Pp Pp) cross. Each square represents an equally probable product of fertilization. For example, the bottomleft box shows the genetic combinationresulting from a p egg fertilized bya P sperm.

Genotypes • Homozygous = same alleles = PP, pp

▫ True-breeding, all sperm/egg contain P • Heterozygous = different alleles = Pp

▫ ½ sperm/egg contain P other ½ contains p

homozygousdominant

homozygousrecessive

heterozygousHow do you determine the genotype of an individual withwith a dominant phenotype?

Can’t tellby lookin’at ya!

Test cross•Breed the dominant phenotype —

the unknown genotype — with a homozygous recessive (pp) to determine the identity of the unknown allele

ppis itPP or Pp?

x How does that work?

PP pp

How does a Test cross work?

p p

P

P

p p

P

p

Pp pp

x x

Pp

Pp Pp

Pp

100% purple

Pp

pp

Pp

50% purple:50% white or 1:1

pp

Am I this?

Or am I this?

The Law of Independent Assortment•Mendel derived the law of segregation

▫By following a single trait•The F1 offspring produced in this cross

▫Were monohybrids, heterozygous for one character Crossing two heterozygotes is a monohybrid

crossx

Pp Ppx

F1

The Law of Independent Assortment•Mendel identified his second law of

inheritance▫By following two characters at the same time

See color & seed shape•Crossing two, true-breeding parents

differing in two characters▫Produces dihybrids in the F1 generation,

heterozygous for both characters

xYYRR yyrr

P

Y = yellowR = round

y = greenr = wrinkled

• How are two characters transmitted from parents to offspring?▫ As a package?▫ Independently?

• A dihybrid cross▫ Illustrates the inheritance of two characters

• Produces four phenotypes in the F2 generation

YYRRP Generation

Gametes YR yr

yyrr

YyRrHypothesis ofdependentassortment

Hypothesis ofindependentassortment

F2 Generation(predictedoffspring)

1⁄2 YR

YR

yr

1 ⁄2

1 ⁄2

1⁄2 yr

YYRR YyRr

yyrrYyRr

3 ⁄4 1 ⁄4

Sperm

Eggs

Phenotypic ratio 3:1

YR1 ⁄4

Yr1 ⁄4

yR1 ⁄4

yr1 ⁄4

9 ⁄163 ⁄16

3 ⁄161 ⁄16

YYRR YYRr YyRR YyRr

YyrrYyRrYYrrYYrr

YyRR YyRr yyRR yyRr

yyrryyRrYyrrYyRr

Phenotypic ratio 9:3:3:1

315 108 101 32 Phenotypic ratio approximately 9:3:3:1

F1 Generation

EggsYR Yr yR yr1 ⁄4 1 ⁄4 1 ⁄4 1 ⁄4

Sperm

RESULTS

CONCLUSION The results support the hypothesis of independent assortment. The alleles for seed color and seed shape sort into gametes independently of each other.

EXPERIMENT Two true-breeding pea plants—one with yellow-round seeds and the other with green-wrinkled seeds—were crossed, producing dihybrid F1 plants. Self-pollination of the F1 dihybrids, which are heterozygous for both characters, produced the F2 generation. The two hypotheses predict different phenotypic ratios. Note that yellow color (Y) and round shape (R) are dominant.

Figure 14.8 9:3:3:1

What’s going on here?•If genes are on different chromosomes…

▫how do they assort in the gametes?▫together or independently?

YyRr

YR yr

YyRr

Yr yRYR yr

Is it this?

Or this?

Which systemexplains the data?

9/16yellowround

3/16greenround

3/16yellowwrinkled

1/16greenwrinkled

Is this the way it works?YyRr YyRr

YR yr

YR

yr

x

YyRr

Yr yRYR yr

YyRr

YR yr

or

YYRR YyRr

YyRr yyrr

Well, that’sNOT right!

Dihybrid crossYyRr YyRr

YR Yr yR yr

YR

Yr

yR

yr

YYRR

x

YYRr YyRR YyRr

YYRr YYrr YyRr Yyrr

YyRR YyRr yyRR yyRr

YyRr Yyrr yyRr yyrr

9/16yellowround

3/16greenround

3/16yellowwrinkled

1/16greenwrinkled

YyRr

Yr yRYR yr

YyRr

YR yr

or

BINGO!

•Using the information from a dihybrid cross, Mendel developed the law of independent assortment▫Each pair of alleles segregates independently

during gamete formation▫Works for alleles on different chromosomes

(chromosomes that are not homologous) Or genes far apart from each other on the same

chromosome that frequently cross over

Mendel’s 2nd law of heredity

Law of Independent Assortment

Which stage of meiosis creates the law of independent assortment?

Metaphase 1

EXCEPTION If genes are on same

chromosome & close together will usually be inherited

together rarely crossover separately “linked”

The chromosomal basis of Mendel’s laws…

Review: Mendel’s laws of heredity • Law of segregation

▫monohybrid cross single trait

▫each allele segregates into separate gametes

established by Metaphase 1• Law of independent assortment

▫dihybrid (or more) cross 2 or more traits

▫genes on separate chromosomes assort into gametes independently

established by Metaphase 1EXCEPTION linked genes

Concept Check 14.1• A pea plant heterozygous for

inflated pods (Ii) is crossed with a plant homozygous for constricted pods (ii). Draw a Punnett square for this cross.

• Pea plants heterozygous for flower position and stem length (AaTt) are allowed to self pollinate, and 400 of the resulting seeds are plants. How many offspring would be predicted to have terminal flowers and be dwarf?

•Concept 14.2: The laws of probability govern Mendelian inheritance

•Mendel’s laws of segregation and independent assortment▫Reflect the rules of probability

•The multiplication rule▫Finding the probability that two or more

independent events will occur together: Multiply the probability of one event by the

probability of the other even Ex: Probability of 2 offspring from the same

parents are both homozygous recessive?

• Probability in a monohybrid cross▫ Can be determined using this rule

• The rule of addition▫ States that the probability that any one of two or more exclusive events will

occur is calculated by adding together their individual probabilities One or more possibilities that can occur in the same event

Rr

Segregation ofalleles into eggs

Rr

Segregation ofalleles into sperm

R r

rR

RR

R1⁄2

1⁄2 1⁄2

1⁄41⁄4

1⁄4 1⁄4

1⁄2 rr

R rr

Sperm

Eggs

Figure 14.9

• What is the likelihood that an offspring is heterozygote?

• ¼ + ¼ = ½ • What is the

likelihood two offspring from the same parents are both homozygous recessive?

• ¼ x ¼ = 1/16

Solving Complex Genetics Problems with the Rules of Probability•We can apply the rules of probability

▫To predict the outcome of crosses involving multiple characters

•A dihybrid or other multicharacter cross▫Is equivalent to two or more independent

monohybrid crosses occurring simultaneously

•In calculating the chances for various genotypes from such crosses▫Each character first is considered separately

and then the individual probabilities are multiplied together

Concept Check 14.2• For any gene with a

dominant allele C and recessive allele c, what proportions of the offspring from a CC x Cc cross are expected to be homozygous dominant, homozygous recessive and heterozygous?

• An organism with the genotype BbDD is mated to one with the genotype BBDd. Assuming independent assortment of these two genes, write the genotypes of all possible offspring from this cross and use the rules of probability to calculate the chance of each type occurring.

•Concept 14.3: Inheritance patterns are often more complex than predicted by simple Mendelian genetics

•The relationship between genotype and phenotype is rarely simple

•The inheritance of characters by a single gene▫May deviate from simple Mendelian patterns

The Spectrum of Dominance •Complete dominance

▫Occurs when the phenotypes of the heterozygote and dominant homozygote are identical

•In incomplete dominance▫The phenotype of F1

hybrids is somewhere between the phenotypes of the two parental varieties

P Generation

F1 Generation

F2 Generation

RedCRCR

Gametes CR CW

WhiteCWCW

PinkCRCW

Sperm

CR

CR

CR

Cw

CR

CRGametes1⁄2 1⁄2

1⁄2

1⁄2

1⁄2

Eggs1⁄2

CR CR CR CW

CW CWCR CW

RR WWRW

Co-dominance•2 alleles affect the phenotype equally &

separately▫not blended phenotype▫human ABO blood groups▫Multiple Alleles: 3 alleles

IA, IB, i IA & IB alleles are co-dominant glycoprotein antigens on RBC IAIB = both antigens are produced

i allele recessive to both

The Relation Between Dominance and Phenotype

•Dominant and recessive alleles▫Do not really “interact”

Dominant alleles do not “subdue” recessive alleles▫Lead to synthesis of different proteins that

produce a phenotype Ex: Tay Sachs Disease: autosomal recessive

inheritance pattern Frequency of Dominant Alleles•Dominant alleles

▫Are not necessarily more common in populations than recessive alleles Ex: Polydactyly: occurs in 1 in 400 births; autosomal

dominant

Pleiotropy•In pleiotropy

▫A gene has multiple phenotypic effects▫Most genes are pleiotrophic

Ex: A genetic disease caused by a single allele has many symptoms associated with it

One gene can affect many characteristics in an organism

Extending Mendelian Genetics for Two or More Genes•Some traits

▫May be determined by two or more genes▫This type of expression includes:1. Epistasis2. Polygenic Inheritance

Epistasis

B_C_B_C_bbC_bbC__ _cc_ _cc

How would you know thatdifference wasn’t random chance?Chi-square test!

•One gene completely masks another gene▫coat color in mice = 2 separate genes

C,c: pigment (C) or no pigment (c)

B,b: more pigment (black=B) or less (brown=b)

cc = albino, no matter B allele

9:3:3:1 becomes 9:3:4

Epistasis in Labrador retrievers• 2 genes: (E,e) & (B,b)

▫pigment (E) or no pigment (e)▫pigment concentration: black (B) to brown (b)

E–B–E–bbeeB–eebb

Polygenic inheritance•Some phenotypes determined by

additive effects of 2 or more genes on a single character▫phenotypes on a continuum▫human traits

skin color height weight intelligence behaviors

enzyme

Skin color: Albinism• However albinism can be

inherited as a single gene trait▫aa = albino

tyrosine melaninalbinism

Environmental effects• Phenotype is controlled by both

environment & genes▫Multifactorial characters

Color of Hydrangea flowers is influenced by soil pH

Human skin color is influenced by both genetics & environmental conditions

Coat color in arctic fox influenced by heat sensitive alleles

Concept Check 14.3• If a man with type AB

blood marries a woman with type O blood, what blood types would you expect in their children?

• A rooster with gray feathers is mated with a hen of the same phenotype. Among their offspring, 15 chicks are gray, 6 are black and 8 are white. What is the simplest explanation for the inheritance of these colors in chickens? What phenotypes would you expect in the offspring of a cross between a gray rooster and a black hen?

Pedigree analysis•Pedigree analysis reveals Mendelian

patterns in human inheritance▫data mapped on a family tree

= male = female = male w/ trait = female w/ trait

Simple pedigree analysis

1 2

3 4 5 6

1 2

3 4 5 6

What’s the likely inheritancepattern?

Genetic counseling•Pedigree can help us understand the past

& predict the future•Thousands of genetic disorders are

inherited as simple recessive traits▫from benign conditions to deadly diseases

albinism cystic fibrosis Tay sachs sickle cell anemia PKU

Recessive diseases• The diseases are

recessive because the allele codes for either a malfunctioning protein or no protein at all▫ Heterozygotes (Aa)

carriers have a normal

phenotype because one “normal” allele produces enough of the required protein

A amale / sperm

A

afem

ale

/ egg

s AA

Aa aa

Aacarrier

carrier disease

Cystic fibrosis (recessive)•Primarily whites of

European descent▫strikes 1 in 2500 births

1 in 25 whites is a carrier (Aa)▫normal allele codes for a membrane protein

that transports Cl- across cell membrane defective or absent channels limit transport of Cl- &

H2O across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract

& causes bacterial infections▫without treatment children die before 5;

with treatment can live past their late 20s

normal lung tissue

Effect on Lungs

Chloride channeltransports salt through protein channel out of cellOsmosis: H2O follows Cl–airway

Cl–

H2O

Cl–

H2O

mucus secreting glands

bacteria & mucus build up

thickened mucus

hard to secrete

normal lungs

cystic fibrosis

cells lining lungs

Cl– channel

Tay-Sachs (recessive)• Primarily Jews of eastern European (Ashkenazi)

descent & Cajuns (Louisiana)▫strikes 1 in 3600 births

100 times greater than incidence among non-Jews

▫non-functional enzyme fails to breakdown lipids in brain cells fats collect in cells destroying their function symptoms begin few months

after birth seizures, blindness &

degeneration of muscle & mental performance

child usually dies before 5yo

Sickle cell anemia (recessive)•Primarily Africans

▫strikes 1 out of 400 African Americans high frequency

▫caused by substitution of a single amino acid in hemoglobin

▫when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods deforms red blood cells into

sickle shape sickling creates pleiotropic

effects = cascade of other symptoms

Sickle cell phenotype•2 alleles are codominant

▫both normal & mutant hemoglobins are synthesized in heterozygote (Aa)

▫50% cells sickle; 50% cells normal▫carriers usually healthy▫sickle-cell disease

triggered under blood oxygen stress exercise

Dominantly Inherited Disorders• Some human disorders

▫Are due to dominant alleles▫Dominant alleles that cause lethal disease are much

less common ▫Ex: achondroplasia: a form of dwarfism that is lethal

when homozygous for the dominant allele▫What is the chance that two married dwarves with

achondroplasia would have a child who was of normal height?

Heterozygote advantage• Malaria

▫single-celled eukaryote parasite spends part of its life cycle in red blood cells

• In tropical Africa, where malaria is common:▫homozygous dominant individuals die of malaria▫homozygous recessive individuals die of sickle

cell anemia▫heterozygote carriers are relatively free of both

reproductive advantage• High frequency of sickle

cell allele in African Americans is vestige of African roots ������

Aa x aa

Inheritance pattern of Achondroplasia

a a

A

a

A a

A

a

Aa x Aa

Aa

aa aa

Aa

50% dwarf:50% normal or 1:1

AA

aa

Aa

67% dwarf:33% normal or 2:1

Aa

lethal

dominantinheritance

dwarf dwarf

Huntington’s chorea (dominant) • Dominant inheritance

▫repeated mutation on end of chromosome 4

mutation = CAG repeats glutamine amino acid repeats in protein one of 1st genes to be identified

▫build up of “huntingtin” protein in brain causing cell death

memory loss muscle tremors, jerky movements

“chorea” starts at age 30-50 early death

10-20 years after start

Multifactorial Disorders•Many human diseases

▫Have both genetic and environment components

•Examples include▫Heart disease, cancer, diabetes, and

alcoholism▫The hereditary component of these diseases

is polygenic

Genetic Testing and Counseling Based on Mendelian Genetics and Probability Rules•Genetic counselors

▫Can provide information to prospective parents concerned about a family history for a specific disease

•Using family histories▫Genetic counselors help couples determine the

odds that their children will have genetic disorders

Tests for Identifying Carriers•For a growing number of diseases

▫Tests are available that identify carriers and help define the odds more accurately

▫Tests are available for Tay-Sachs, Sickle Cell Anemia, and Cystic Fibrosis

sequence individual genes

Fetal & Newborn Testing• In amniocentesis

▫ The liquid that bathes the fetus is removed and tested• In chorionic villus sampling (CVS)

▫ A sample of the placenta is removed and tested(a) Amniocentesis

Amnioticfluidwithdrawn

Fetus

Placenta Uterus Cervix

Centrifugation

A sample ofamniotic fluid canbe taken starting atthe 14th to 16thweek of pregnancy.

(b) Chorionic villus sampling (CVS)

FluidFetalcells

Biochemical tests can bePerformed immediately onthe amniotic fluid or lateron the cultured cells.

Fetal cells must be culturedfor several weeks to obtainsufficient numbers forkaryotyping.

Severalweeks

Biochemicaltests

Severalhours

Fetalcells

Placenta Chorionic viIIi

A sample of chorionic villustissue can be taken as earlyas the 8th to 10th week ofpregnancy.

Suction tubeInserted throughcervix

Fetus

Karyotyping and biochemicaltests can be performed onthe fetal cells immediately,providing results within a dayor so.

Karyotyping