Patterns of InheritanceChapters 14 and 15

A. P. Biology

Liberty Senior High School

Mr. Knowles

How do you make a giraffe?

X

G. camelopardalis

Early Ideas of Genetics• Saw patterns of inheritance in people and

domesticated plants and animals.• Bizarre chimeras explained variation- not

true – heredity occurs within species.• Thought traits were “blended” from

parents.• Traits are transmitted directly- explained

by a seed “gonons” (Hippocrates) or “humuculus” (Leewenhoek)

Gregor Mendel (1866)

Wrinkled

Smooth

Pea Color

Why Peas (Pisum sativum)?• Many varieties or strains of plant.• These strains are true-breeding or pure

– produce the same trait generation after generation.

• The strains can be hybridized or strains crossed (T. A. Knight, 1790s).

• Can be self-fertilized or cross-fertilized.

Table 14.1

• First, alternative versions of genes– Account for variations in inherited characters, which

are now called alleles

Figure 14.4

Allele for purple flowers

Locus for flower-color gene

Homologouspair ofchromosomes

Allele for white flowers

Gene

LocusBrown Allele

Blue Allele

Homologous Chromosomes

ACGTAC

ACGGCT

Some Terms• Locus (i)- position on a chromosome

where a gene is located.• Alleles- alternative forms of a gene.

Different genetic information for a protein.

• Phenotype- “form that is shown”- physical appearance of a trait.

• Genotype- the sum of an organism’s alleles.

Phenotype versus Genotype

Figure 14.6

3

1 1

2

1

Phenotype

Purple

Purple

Purple

White

Genotype

PP(homozygous)

Pp(heterozygous)

Pp(heterozygous)

pp(homozygous)

Ratio 3:1 Ratio 1:2:1

Some Terms• Dominant Allele- an allele whose

expression is readily seen; affects the phenotype more.

• Recessive Allele-an allele whose expression is less seen; affects the phenotype less.

• Homozygous- organism with two identical alleles at the same locus.

• Heterozygous- organism with two different alleles at one locus.

Summary of Mendel’s Crosses• A cross between homozygous

dominant X homozygous recessive, F1 progeny are all heterozygous, and resemble the homozygous dominant parent in phenotype.

• Two alternative alleles of a gene segregate randomly.

A Testcross

Figure 14.7

Dominant phenotype,unknown genotype:

PP or Pp?

Recessive phenotype,known genotype:

pp

If PP,then all offspring

purple:

If Pp,then 1⁄2 offspring purpleand 1⁄2 offspring white:

p p

P

P

Pp Pp

PpPp

pp pp

PpPpP

p

p p

APPLICATION An organism that exhibits a dominant trait,such as purple flowers in pea plants, can be either homozygous forthe dominant allele or heterozygous. To determine the organism’sgenotype, geneticists can perform a testcross.

TECHNIQUE In a testcross, the individual with theunknown genotype is crossed with a homozygous individualexpressing the recessive trait (white flowers in this example). By observing the phenotypes of the offspring resulting from this cross, we can deduce the genotype of the purple-flowered parent.

RESULTS

Testcross (Backcross)• How can you tell if an organism

with a dominant phenotype is a Het. or Homo.?

• To determine whether an individual is a Het or Homo., cross the individual with a known homozygous recessive- Testcross.

Summary of Mendel’s Crosses• If cross or self-fertilize the F2 generation,

the result is a 3:1 ratio. • Crosses with individuals that are

heterozygous at one locus-Monohybrid Cross.

• The two alternative alleles segregate independently from one another and are distinct- Law of Segregation.

Law of Segregation• Alternative forms of a gene (alleles) are

discrete and do not blend in Hets.

• Alleles independently assort from each other into gametes.

• Each gamete has an equal probability of receiving either allele.

Do different genes also segregate independently?

• Examine crosses which involve two genes. (Ex. seed shape and seed color). Fig. 13.16, p. 282.)

• Crosses with individuals heterozygous at two different loci- Dihybrid Crosses.

• Genes assort independently in the F2 with a 9:3:3:1 ratio.

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

Eggs

YR 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.

A dihybrid cross:– Illustrates the inheritance of two characters

• Produces four phenotypes in the F2 generation

Figure 14.8

Law of Independent Assortment

• Genes located on different chromosomes assort independently of one another- Independent Assortment.

How would separate genes located close to one another

on a chromosome be inherited?

Linked Genes-do not assort independently.

Was Mendel lucky?

Non-Mendelian Inheritance

Complex Patterns of Inheritance: How Genes

Interact

Incomplete Dominance• Red (CRCR) X White (CWCW)

Snapdragons

• F1 generation are all pink (CRCW)

• F2 generation is 1 red:2 pink:1 white

• Not blending, parental phenotype is recovered in the F2.

Incomplete Dominance

Red (CRCR) X White (CWCW)

Roan (CRCW)

Codominance• MN Blood Type: a single gene

locus (B) at which two alleles (M and N) are possible.

Genotype Phenotype

BM BM M blood group

BN BN N blood group

BM BN MN blood group

Codominance

• The MN phenotype is not intermediate between M and the N phenotypes.

Codominance• A,B,O Blood Type: a specific

locus (I) at which there are three common alleles (A, B, and O). They are modifying enzymes. They modify cell surface glycolipids.

Codominance in Blood Types

Enzyme Function

A adds a galactosamine

B adds a galactose

O does not add anything

A, B, O, AB Blood TypesGenotype Phenotype

IAIA or IAIO + galactosamine,

Blood Type A

IBIB or IBIO + galactose

Blood Type B

IAIB + both Blood Type AB

IOIO neither added, Type O

Distribution of O Allele

Distribution of A allele

Distribution of B allele

A “Typical” Antibody

Compatible Blood Groups• Donors and recipients must have matching

cell surface molecules.

• If not “self,” the recipient will produce proteins called antibodies to agglutinate (clump together) the donated blood cells.

• The foreign cell surface molecule is an antigen.

Agglutination Reactions

A Blood

B Blood

Agglutination Reactions

AB Blood

O Blood

Agglutination for the Rh or D Antigen

Rh Positive Blood

Rh Negative Blood

Blood Group CompatibilityBlood Type Antibodies Produced

A anti-B

B anti-A

AB neither antibody (universal recipient)

O anti-A and anti-B

(universal donor)

Rh Factor in Humans• Rh Blood Group: another cell surface

marker on RBC’s controlled by > 7 closely linked genes.

Genotype Phenotype

R R or R r cell surface marker (about are Rh+ 85%)

rr lack molecule, Rh-

Rh Factor in Humans• What happens when an Rh- female X Rh+ male?

• Offspring is possibly Rh+.

• If fetal Rh+ RBCs cross the placenta and treated as a foreign antigen.

• Anitbodies (IgG) cross the placenta and agglutinate fetal RBC’s- erythroblastosis fetalis

• Treat with Rhogam: anit-Rh antibodies and prevent maternal immune response.

Erythroblastosis fetalis

Genetic Diseases can be Mendelian Dominant or

Recessive

Autosomal Dominant Diseases• Homozygotes and Heterozygotes

can be phenotypically the same- both show disease phenotype.

• Lethal dominant diseases are less common. Why?

Autosomal Dominant Diseases

• Familial Hypercholesterolemia- most common; 1:500; 19p13.2-p13.1

• Huntington’s Disease- production of an inhibitor of brain cell metabolism; degeneration of nervous system at middle age; lethal dominant; 1:10,000; 4p16.3

Familial Hypercholesterolemia

QuickTime™ and aGIF decompressor

are needed to see this picture.

The Solution-Balloon Angioplasty

A Stent

Marfan Syndrome- Dominant Mutation

• Marfan’s Syndrome- mutation in the fibrillin gene (glycoprotein in connective tissue).

Marfan’s Sufferer?

Mitral Valve Prolapse

Baby with Osteogenesis Imperfecta

Osteogenesis Imperfecta-autosomal dominant

Gene for Neurofibromatosis Type 2

Neurofibromatosis-Autosomal Dominant

Joseph Merrick-N. F. or Proteus Syndrome?

Baby with Achondroplasia

Achondroplasia- autosomal dominant

• Affects in 1:10,000.

• Heterozygotes have dwarf phenotype.

• Homozygosity is lethal.

Polydachtyly -dominant mutation at 13q21-q32, occurs only 1/400)

Autosomal Recessive Diseases

• Heterozygotes are phenotypically normal, called carriers.

• Only the homozygous recessive alleles are diseased.

• Lethal Recessive Diseases are more common. Why?

Cystic fibrosis-Autosomal Recessive• Most common Caucasian genetic disease-1:

2500 affected; 1:25 are carriers.

• Mutation in a chloride channel protein (CFTR).

• Leads to high [Cl-]in extracellular fluid.

• Causes mucus to become thicker than normal-favors bacterial infections.

• Untreated condition- death by fifth year.

Molecular Mechanisms of CF

C F Lung

Tay-Sachs Disease• Recessive lethal allele-dysfunctional

hexosaminidase A; unable to metabolize gangliosides (lipids of the CNS).

• Lipids accumulate--> lead to neuron death and eventual death.

• Affects 1: 3600 European Jews.• Only the homozygotes are affected and

die.

Tay-Sachs Diseased Tissue

Tay-Sachs Disease-Autosomal Recessive

• Why are only the homozygous people affected? In other words, why is this disease recessive?

• Answer: the Heterozygote produces about 1/2 the normal amount of enzyme--> they are phenotypically normal.

Genetic Diseases are Codominant at the Molecular Level

• Sickle-cell Disease: a single amino acid change at #6 (Glu-->Val) in the 146 a.a. chain of hemoglobin.

• Mutant form of hemoglobin deforms the RBCs at low [O2].

• Multiple Symptoms: anemia, clumping and clogging of RBCs (heart failure and CV disease), spleen and kidney damage.

Normal RBCs

Sickle-Celled RBCs

Sickle-Cell Clumping

Removing Damaged RBC’s by Spleen

Frontal Bossing-Replacing the RBCs

The Genetics of Sickle-CellGenotype Phenotype

A+ A+ normal (9/10)

A+ As Het. Carriers, usually normal, the two alleles are codominant; 1/10; resistance to malaria.

As As severe disease 1/400 African-Americans

Anopheles Mosquito

Malaria in a RBC

Dominance/Recessiveness• Range from Complete---

>Incomplete------->Codominance.

• Reflect the functions of the enzymes encoded by the alleles and not one allele subduing or overpowering another.

• Dominance does not determine the relative frequency of alleles in a population.

And That’s Dominance and Recessiveness!

Other Patterns of Inheritance

Complex Gene Interactions

Multiple Alleles Possible for a Gene

• Incomplete Dominance or Codominance-

• Ex. Coat color in cattle; Red X White ---> Roan

• Ex. ABO blood type; the IA and IB

are equally expressed--> AB blood type.

Pleiotropy• When one gene or allele has multiple

phenotypes (pleion= many).

• Ex. Sickle-cell allele has many symptoms:

Breakdown of RBCs--> Anemia, Heart Failure, Physical Weakness

Clumping of RBCs--> Brain Damage, Kidney and Spleen Damage.

Pleiotropy• Often a gene functions in some other

unknown way.

• Ex. Lucien Cuenot- tried to develop a true-breeding yellow-furred mouse. Y= dominant for yellow fur color.

• Unable to get a YY strain. Why?

Pleiotropic Effects of YYy (Yellow Fur Color,

Dominant)

Y allele

YY (Lethal Development, Recessive)

Epistasis

• When a gene at one locus alters the phenotypic expression of another gene at a second locus.

Epistasis• Ex. Coat Color in Mammals:

One gene, the B locus:

B = black or b = brown

BB or Bb = both black, bb = brown

Another gene, C, deposits pigment into hair

CC or Cc = dominant for color

cc = no pigment deposited, albino

Genetics of Coat Color in Mammals

• What do the offspring of a BbCc X BbCc (dihybrid) cross look like?

• 9 Black : 3 Brown : 4 Albino

• What would Mendel predict?

• 9 : 3: 3 :1

Albinism in Humans

Another Example of Epistasis• R. A. Emerson, 1918, Zea mays

• Crossed two pure-breeding strains that never expressed purple pigment (anthocyanin) in seed coat. All of the F1 plants were purple!

• Crossed these F1 plants--> 56% of F2 purple, 44% were not. How?

Epistasis in Zea maysStarting Molecule (Colorless)

Enzyme 1

Intermediate (Colorless)

Enzyme 2

Anthocyanin (Purple)

Epistasis in Zea mays• Dominant alleles encode functional

enzymes and produce purple pigment.

• Recessive alleles encode nonfunctional enzymes.

• Requires BOTH dominant alleles for the purple phenotype.

Another Example of Epistasis- PTC Tasting

• Can two non-tasters produce a taster child?• Answer: Yes! tt X tt --> Taster Offspring.• I lied! This trait isn’t a simple

dominance/recessive trait.• Research suggests the phenotype is

controlled by two genes.

Polygenic Traits• These are not “either/or” characteristics,

but a continuum or gradation.

• Quantitative Characters-quantitative variation indicates polygenic inheritance- an additive effect of two or more genes on a single phenotypic character.

• Converse of Pleiotropy.

Polygenic Traits• Ex. Skin Color in Humans controlled by at

least three separately inherited genes.

Three Genes: A, B, C, dark-skin alleles, each contribute one “unit” of darkness and are incompletely dominant to the a, b, c alleles.

AABBCC = very dark

aabbcc = very light

Human Skin ColorAaBbCc = intermediate skin color

Alleles have cumulative effect; AaBbCc and AABbcc both make same three unit contribution to darkness.

Cross AaBbCc X AaBbCc

AaBbCc X AaBbCc Skin Coloraabbcc 1/64 Very Light

Aabbcc 6/64

AaBbcc 15/64

AaBbCc 20/64 Intermediate

AABbCc 15/64

AABBCc 6/64

AABBCC 1/64 Very Dark

Polygenic Traits• Quantitative Characteristics- give a

bell-shaped curve, a normal distribution.

• Environmental Factors (sun exposure help smooth the curve also.

• Ex. Height and Weight

Multifactorial Inheritance• Environmental factors interact with genes.

• Genotype may be a phenotypic range or possibilities- norm of reaction for the genotype.

• The variation is due to environmental factors.

Multifactorial Inheritance• The norm of reaction may be

small- Example: ABO Blood type.

• Or it may be very broad- Example: the Number of RBCs--> physical activity, altitude, health, the genes that control cell division.

• Hydrangea Flowers - of the same genotype range in color from purple (alkaline soils) to pink (acidic soils) due to anthocyanin.

• Cardiovascular Disease- ApoE gene (apolipoprotein E) and the angiotensin genes affect cholesterol levels and blood pressure levels--> genetic predisposition + lifestyle factors such as diet, smoking, physical activity.

Some Defects are Multifactorial

The End !