Patterns of inheritance

Chapter 9

The first genetics research “lab” was a monk’s abbey garden

The same genetic defect that causes sickle-cell disease can also protect you against malaria

In certain isolated communities, one out of 100 boys is born with the genetic defect that causes Duchenne muscular dystrophy

Intermarriage caused the disease hemophilia to spread through the royal families of Europe

Genetic testing

TESTING YOUR BABY

Allows expectant parents to test for possibilities in their unborn childIncludes amniocentesis and CVSHas risks associated with it

Wild type traits are traits most commonly found in nature

HERITABLE VARIATION AND PATTERNS OF INHERITANCE

Various traits exist in organisms

These traits are usually inherited in particular patterns

Parents:

Wild-type Wild-type

Parents:

Wild-type Sky-blue

Offspring: All Wild-typeFirst-generationoffspring:

All wild-type

MatingsSecond-generationoffspring: 3/4

Wild-type

and 1/4

Sky-blue

(a) Offspring from the mating of two wild-type birds

(b) Two generations of offspring from the mating of a wild-type with a sky-blue bird

Gregor MendelWas the first person to analyze patterns of inheritanceDeduced the fundamental principles of genetics

Mendel studied garden peas

In an Abbey Garden

These plant are easily manipulatedThese plants can self-fertilize

Stamen

Carpel

Mendel carried out some cross-fertilization

Removed stamens from purple flower

1

2

3

Transferred pollenfrom stamens ofwhite flower tocarpel of purpleflower

4Planted seedsfrom pod

Pollinated carpelmatured into pod

White

Stamens

Carpel

Parents(P)

Purple

Offspring(F1)

He also created true-breeding varieties of plants

Mendel then crossed two different true-breeding varieties, creating hybrids

Mendel performed many experiments

Mendel’s Principles of Segregation

He tracked several characteristics in pea plants from which he formulated several hypotheses

Dominant Recessive

WhitePod shape Inflated Constricted

Flower position

Pod Color

Dominant Recessive

Flower color Purple

Axial Terminal

Green Yellow

Tall Dwarf

Seed shape Round Wrinkled

Seed color Yellow GreenStem length

A monohybrid cross is a cross between parent plants that differ in only one characteristic

Monohybrid CrossesP Generation(true-breedingparents)

All plants havepurple flowers

Fertilizationamong F1 plants(F1 F1)

F2 Generation

3/4 of plantshave purpleflowers

1/4 of plantshave white flowers

Purple flowers

Whiteflowers

F1 Generation

(a) Mendel’s crosses tracking one characteristic (flower color)

Mendel developed four hypotheses from the monohybrid crossThere are alternative forms of genes, now called allelesFor each characteristic, each organism has two genesGametes carry only one allele for each inherited characteristicAlleles can be dominant or recessive

An explanation of Mendel’s results, including a Punnett square

P plants

Gametes

Genetic makeup (alleles)PP

p

F1 plants:(hybrids)

Gametes

All Pp

1/2

pp

All P All

P 1/2

P

p

PP

Pp Pp

F2 plants:Eggs Sperm

p

P

Phenotypic ratio3 purple : 1 white

Genotypic ratio1 PP : 2 Pp : 1 pp

(b) Explanation of the results in part (a)

p

pp

PhenotypeAn organism’s physical traits

GenotypeAn organism’s genetic makeup

Purple and white sweet pea flowers

Principle of segregation: Pairs of alleles segregate (separate) during gamete formation; the fusion of gametes during fertilization pairs alleles once again

Using a Punnett square derive the phenotypes and genotypes in the F1 and F2 generations (from self-fertilization of F1) of the following crosses between true-bred plants

P:Tall (TT) x Dwarf (tt)

F1:

F2:

Round x Wrinkledseeds (RR) seeds (rr)

F1:

F2:

Homologous chromosomes

Genetic Alleles and Homologous Chromosomes

Have genes at specific lociHave alleles of a gene at the same locus

Homologous chromosomes:Gene loci

P a b Recessiveallele

Genotype:

P a B

Dominantallele

PP aa Bb

Homozygousfor thedominant allele

Homozygousfor therecessive allele

Heterozygous

HomozygousWhen an organism has identical alleles for a geneHeterozygous

When an organism has different alleles for a gene

Two hypotheses for gene assortment in a dihybrid cross

Mendel’s Principle of Independent Assortment

Dependent assortmentIndependent assortment

Hypothesis: (a) Dependent assortment (b) Independent assortment

P Generation

RRYY rryy RRYY rryy

Gametes RY ry Gametes RY ry

F1 Generation RrYy RrYy

Eggs Sperm1/2

ry

1/2RY

1/2

RY

1/2 ry

Actual resultscontradict hypothesis

1/4

ry

1/4

Ry1/4

rY1/4

RY 1/4RY

1/4

Eggs Sperm

rY

1/4Ry

1/4ry

RRYY

RrYY RrYY

RRYy rrYY RRYy

RrYy RrYy RrYy RrYy

rrYy RRyy rrYy

Rryy Rryy

rryy

Actual resultssupport hypothesis

9/16

Yellow round

3/16

Green round

3/16

Yellowwrinkled

1/16Greenwrinkled

F2 Generation

Mendel’s principle of independent assortment

Each pair of alleles segregates independently of the other pairs during gamete formation

Blind Blind

PhenotypesGenotypes

Black coat,normal vision

B_N_

Black coat,blind(PRA)

B_nn

Chocolate coat,normal vision

bbN_

Chocolate coat,blind (PRA)

bbnn

Mating of heterozygotes(black, normal vision)Phenotypic ratioof offspring

9 black coat,normal vision

3 black coat,blind (PRA)

BbNnBbNn

3 chocolate coat,normal vision

1 chocolate coat,blind (PRA)

(a)

(b)

A testcross is a mating between

Using a Testcross to Determine an Unknown Genotype

An individual of unknown genotype andA homozygous recessive individual

Testcross:

Genotypes P_ pp

Two possibilities for the purple flower:

PP Pp

Gametes

P

P P p

Pp p Pp pp

Offspring All purple 1 purple : 1 white

The rule of multiplication

The Rules of Probability

The probability of a compound event is the product of the separate probabilities of the independent events

F1 GenotypesB b female B b male

Formation of eggs Formation of sperm

1/2

B B1/2

b

1/2B B

1/4(1/2 1/2)

1/2

b

b B

1/4

B b

1/4

b b

1/4F2 Genotypes

What is the probability of a ‘bb’ offspring from a Bb x Bb cross?

P: Bb x Bb

Gametes: B (½) b (½) B (½) b (½)

F1: bb½ * ½ = ¼

What are the chances of getting a ‘Bb’ outcome from a Bb x Bb cross?

P: Bb x Bb

Gametes: B (½) b (½) B (½) b (½)

F1: Bb Bb½*½ = ¼ and ½*½ =

¼

¼ + ¼ = ½

Two organisms have the genotype AaBbCc. What is the probability that an offspring with genotype aabbcc will be produced from their cross?

AaBbCc x AaBbCc aabbcc

*** A trihybrid cross is equivalent to three monohybrid crosses****

Aa x Aa: probability of ‘aa’ offspring = ½ * ½ = ¼

Bb x Bb: probability of ‘bb’ offspring = ½ * ½ = ¼

Cc x Cc: probability of ‘cc’ offspring = ½ * ½ = ¼

Thus, probability of an ‘aabbcc’ offspring= ¼*¼*¼ = 1/64

Mendel’s principles apply to the inheritance of many human traits

Family PedigreesDominant TraitsRecessive Traits

Freckles No freckles

Widow’s peak Straight hairline

Free earlobe Attached earlobe

A family pedigreeShows the history of a trait in a familyAllows researchers to analyze human traits

JoshuaLambert

AbigailLinnell

JohnEddy

HepzibahDaggett

AbigailLambert

JonathanLambert

ElizabethEddy

Female MaleDeaf

Hearing

DdJoshuaLambert

DdAbigailLinnell

D_JohnEddy

D_HepzibahDaggett

D_AbigailLambert

ddJonathanLambert

DdElizabeth

Eddy

Dd Dd dd Dd Dd Dd dd

Female MaleDeaf

Hearing

Many human traits

Human Disorders Controlled by a Single Gene

Show simple inheritance patternsAre controlled by genes on autosomes

Most human genetic disorders are recessive

Recessive Disorders

Individuals can be carriers of these diseases

Parents: NormalDd

NormalDd

D DEggs Sperm

d d

Offspring:

DDNormal

DdNormal

(carrier)

DdNormal

(carrier)

ddDeaf

Some human genetic disorders are dominant

Dominant Disorders

Achondroplasia is a form of dwarfism

• Karyotyping and biochemical tests of fetal cells and molecules can help people make reproductive decisions– Fetal cells can be obtained through amniocentesis

Fetal testing can spot many inherited disorders early

in pregnancy

AmnioticfluidFetus(14-20weeks)

Placenta

Amnioticfluidwithdrawn

Centrifugation

Fetalcells

Fluid

Uterus

Cervix Cell culture

Severalweeks later Karyotypin

g

Biochemicaltests

Chorionic villus sampling is another procedure that obtains fetal cells for karyotyping

Fetus(10-12weeks)Placenta

Chorionic villi

Suction

Several hourslater

Fetal cells(from chorionic villi)

Karyotyping

Some biochemical tests

Examination of the fetus with ultrasound is another helpful technique

• Genetic testing can be of value to those at risk of developing a genetic disorder or of passing it on to offspring

Genetic testing can detect disease-causing alleles

Dr. David Satcher, former U.S. surgeon general, pioneered screening for sickle-cell disease

Some patterns of genetic inheritance are not explained by Mendel’s principles

BEYOND MENDEL

In incomplete dominance F1 hybrids have an appearance in between the phenotypes of the two parents

Incomplete Dominance in Plants and PeopleP Generation

RedRR

Whiterr

Gametes R r

F1 Generation PinkRr

Gametes 1/2 R 1/2 r

1/2 R 1/2 REggs Sperm

1/2r1/2r

F2 Generation

RedRR

PinkrR

PinkRr

Whiterr

Incomplete dominance in carnations: red, pink, white

HypercholesterolemiaIs a human trait that is incompletely dominant

LDL (carriescholesterol)

LDL receptor(mops up LDL)

Cell

Genotypes:NormalHH

Mild diseaseHh

HeterozygousHomozygousfor ability to make

LDL receptors

Severe diseasehh

Homozygousfor inability to make

LDL receptors

The ABO blood groups in humans are examples of multiple alleles

Two of the human blood type alleles exhibit codominance

Discovered by Karl Landsteiner (1930 – Nobel Prize in Physiology and Medicine)

Multiple Alleles and Blood Type

–Both alleles are expressed in the phenotype

Blood Antibody AntigenType Genotype (serum) (RBC)

AB IAIB - AgA, AgB

A IAIA, IAi B AgA -

B IBIB, IBi A - AgB

O ii AB - -

Blood group identification

Blood grouping

Antibody

Pleiotropy is the impact of a single gene on more than one characteristic

Pleiotropy and Sickle-Cell Disease

Sickle-cell disease is an example

RBC: normal and sickle shaped(x 9,620)

Individual homozygousfor sickle-cell allele

Sickle-cell (abnormal) hemoglobin

Abnormal hemoglobin crystallizes,causing red blood cells to become sickle-shaped

Sickled cells

Breakdown ofred blood cells

Accumulation ofsickled cells in spleen

Physicalweakness Anemia

Heartfailure Pain and

feverBraindamage

Damage to other organs

Clumping of cellsand clogging of

small blood vessels

Spleendamage

Impairedmentalfunction

ParalysisPneumoniaand otherinfections

Rheumatism Kidneyfailure

Polygenic inheritance is the additive effects of two or more genes on a single phenotype

Polygenic InheritanceP Generation

aabbcc(very light)

AABBCC(very dark)

F1 Generation

AaBbCc AaBbCcF2 Generation

Eggs Sperm

Inheritance of coat color in mice: Cross between heterozygous yellow mice give a 2:1 ratio instead of a

3:1 ratio

Many human characteristics result from a combination of heredity and environment

The Role of Environment

The chromosome theory of inheritance states that

THE CHROMOSOMAL BASIS OF INHERITANCE

Genes are located on chromosomesThe behavior of chromosomes during meiosis and fertilization accounts for inheritance patterns

P Generation Yellow-round seeds(YYRR)

Meiosis

FertilizationGametes

Green-wrinkled seeds(yyrr)

F1 Generation

Principle of Segregation: Follow the long chromosomes (carrying R and r) taking either the left or right branch.

All roundyellow seeds

(RrYy)Principle of IndependentAssortment: Follow both the Long and the short chromosomes.

The R and r alleles segregate in anaphase I of meiosis.

Meiosis

Metaphase I(alternativearrangements)

They are arranged in either of two equally likely ways at metaphase I.

Only one longchromosome endsup in each gamete.

MetaphaseII

They assortindependently, giving four gamete types.

GametesFertilizationrecombines the r And R alleles at random. Fertilization among the F1 plants

Fertilizationresults in the9:3:3:1 phenotypicratio in the F2generation.

F2 Generation

In 1908, British biologists discovered an inheritance pattern inconsistent with Mendelian principles

Gene Linkage

Experiment:

Purple flower

PpLl PpLl

Long Pollen

This inheritance pattern was later explained by linked genes, which are

Genes located on the same chromosomeGenes that are typically inherited together

(b) Explanation: Linked genes

Parentaldiploid cellPpLl

Meiosis

Fertilization

Sperm

Mostoffspring

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

Mostgametes

Egg

Two linked genes

Genetic Recombination: Crossing Over and Linkage Maps

Can give rise to four different gamete genotypesCan sometimes cross over

(c) Explanation: Crossing over

Tetrad

Crossing over

Parental-type gametesRecombined gametesFertilization

Purple round

Red long

Among the offspring, some with recombinant phenotypes

Early studies of crossing over were performed using the fruit fly Drosophila melanogaster

Wild type(gray body, long wings, red eyes)

Variant(black body, short wings, cinnabar eyes)

Studies using DrosophilaDeveloped a method for mapping gene lociResulted in linkage maps

Chromosomeg l

17%

9% 9.5%

Recombination frequencies

cBlack body Cinnabar eyes Short wings

• Certain genes are linked– They tend to be inherited together because they reside close together on the same chromosome

Genes on the same chromosome tend to be inherited

together

• Crossing over is more likely to occur between genes that are farther apart– Recombination frequencies can be used to map the relative positions of genes on chromosomes

Geneticists use crossover data to map genes

gChromosome

c

17%

9% 9.5%

l

Alfred H. Sturtevant, seen here at a party with T. H. Morgan and his students, used recombination data from Morgan’s fruit fly crosses to map genes

A partial genetic map of a fruit fly chromosome

Shortaristae

Blackbody(g)

Cinnabareyes(c)

Vestigialwings(l)

Browneyes

Long aristae(appendageson head)

Graybody(G)

Redeyes(C)

Normalwings(L)

Redeyes

Mutant phenotypes

Wild-type phenotypes

Sex chromosomes

SEX CHROMOSOMES AND SEX-LINKED GENES

Influence the inheritance of certain traits

Sex chromosomes

Sex Determination: Human and Fruit Flies

Are designated X and YDetermine an individual’s sex

Male FemaleSomaticcells

22+X

Sperm

22+Y

22+X

44+XX

44+XY

Egg

MaleFemale

44+XY

44+XX

Other systems of sex determination exist in other animals and plantsThe X-O system, where O stands for absence of sex chromosome

The Z-W system, where sex is determined by the egg

Chromosome number

• All genes on the sex chromosomes are said to be sex-linked- In many organisms, the X chromosome carries

many genes unrelated to sex - Were discovered in fruit flies, eye color is a sex-linked characteristic

Sex-linked genes exhibit a unique pattern of

inheritance

Male and female fruit flies Drosophila

Female withwild type eye

Male with mutantwhite eye

Their inheritance pattern reflects the fact that males have one X chromosome and females have two

These figures illustrate inheritance patterns for white eye color (r) in the fruit fly, an X-linked recessive trait

Female Male Female Male Female Male

XrYXRXR

XRXr

XRY

XR Xr

Y

XRXr

XR

Xr XRXR

XR

Y

XRY

XrXR XRY

XrY

XRXr

XR

Xr

Xr

YXRXr

XrXr XRYXrY

XrY

R = red-eye alleler = white-eye allele

Inheritance patterns of a sex-linked geneFemaleXRXR

MaleXrY

All females inherittwo X chromosomes,one from each parent.

All males inheritone X chromosome,always from themother.

R = red-eye alleler = white-eye allele

FemaleXRXr

MaleXRY

Female

Male

FemaleXRXr

MaleXrY

Female

Male

(b) Heterozygous female red-eyed male

(c) Heterozygous female white-eyed male

(a) Homozygous red-eyed female white-eyed male

A number of human conditions result from sex-linked (X-linked) genes

Sex-Linked Disorders in Humans

Red-green color blindness

Is characterized by a malfunction of light-sensitive cells in the eyes

Hemophiliais a blood-clotting disease

QueenVictoria

Albert

Alice Louis

Alexandra CzarNicholas IIof Russia

Alexis

Duchenne muscular dystrophyIs characterized by a progressive weakening and loss of muscle tissue

Sex chromosomes

EVOLUTION CONNECTION:THE TELLTALE Y CHROMOSOME

Influence the inheritance of certain traits

The Y chromosome of human males is only about one-third the size of the X chromosome

Scientists believe that X and Y were once a fully homologous pairMajor episodes of change have rearranged pieces of the Y chromosome

Researchers recently used comparisons of Y DNA to confirm that the Lemba tribe in Africa descended from ancient Jews

Mendel’s Principle of Segregation

SUMMARY OF KEY CONCEPTS

Alleles

Meiosis Fertilization

Diploid cell(contains pairedalleles, alternateforms of a gene)

Haploid gametes(allele pairsseparate)

Diploid zygote(contains pairedalleles)

Using a Testcross to Determine an Unknown Genotype

Phenotype:

Genotype:Recessive

pp

Phenotype:

All dominant 1 dominant : 1 recessive

Conclusion: Unknown parentwas PP

Unknown parentwas Pp

or

DominantP?

Incomplete Dominance in Plants and People

Dominantphenotype

RR

Recessivephenotype

rr

Intermediate phenotype(incomplete dominance)

Rr

Pleiotropy and Sickle-Cell Disease

Singlegene

PleiotropyMultipletraits

Polygenic Inheritance

Multiple genes

Polygenicinheritance Single trait

(e.g., skin color)

Sex Determination in Humans and Fruit Flies

Male

44+XY

Somaticcells

Female

44+XX