Chromosomal Inheritance II

Outline

• Incomplete Dominance, Codominance, and Multiple Allelism

• Interaction of genes

• Pedigree Studies

• Genetics and Ethics

Extending Mendel’s Rules• Incomplete dominance

– heterozygotes have an intermediate phenotype

• Codominance– Heterozygotes displays the phenotype of both alleles

• multiple allelism– Multiple distinct genes versions (i.e., alleles) are present

in the population

• polymorphism – Multiple distinct phenotypes are present in a population

Multiple Alleles and Polymorphism

• ABO blood group in humans are determined by three alleles : IA, IB, and i.

IA

IB

i

A

B

none(a) The three alleles for the ABO blood groups and their associated carbohydrates

Allele Carbohydrate

GenotypeRed blood cellappearance

Phenotype(blood group)

IAIA or IA i A

BIBIB or IB i

IAIB AB

ii O

(b) Blood group genotypes and phenotypes

Pleiotropy• A gene that influences many traits rather than just one is

pleiotropic.– Marfan Syndrome (FBN1): defective fibrillinlimbs, spinal chord, heart– Cystic fibrosis (CFTR): defective salt transportlungs, pancreas,

sebacious glands, etc.

Lung(s)pancreas

healthy

CF

Antagonistic pleiotropy

• Some effects are good; some are bad

• Sickle cell anemia (hemoglobin B)– Codominant trait– HBB/HBB; HBB/hbb; hbb/hbb

Healthy Unhealthy ???

HBB/hbb

Mild sickle cell disease

Malaria protection

Fig. 14-UN2

Degree of dominance

Complete dominanceof one allele

Incomplete dominanceof either allele

Codominance

Description

Heterozygous phenotypesame as that of homo-zygous dominant

Heterozygous phenotypeintermediate betweenthe two homozygousphenotypes

Heterozygotes: Bothphenotypes expressed

Multiple alleles

Pleiotropy

In the whole population,some genes have morethan two alleles

One gene is able toaffect multiplephenotypic characters

CRCR CRCW CWCW

IAIB

IA , IB , i

ABO blood group alleles

Sickle-cell disease

PP Pp

Example

Fig. 14-12

BbCc BbCc

Sperm

EggsBC bC Bc bc

BC

bC

Bc

bc

BBCC

1/41/4

1/41/4

1/4

1/4

1/4

1/4

BbCC BBCc BbCc

BbCC bbCC BbCc bbCc

BBCc BbCc

BbCc bbCc

BBcc Bbcc

Bbcc bbcc

9 : 3 : 4

• A gene at one locus

alters the phenotypic expression of a gene at a second locus

• Coat color in mice– pigment color (B for

black; b for brown)– Pigment deposit (C

for color; c for no color)

Epistasis

Discrete vs. Quantitative Traits• Discrete traits.

– seed color in peas—no intermediate phenotypes• Quantitative traits

– Traits that fall into a continuum• Frequencies

– form a bell-shaped curve (normal distribution) for a population.

A phenotype distribution that forms a bell-shaped curve. Normal distribution—bell-shaped curve

Quantitative Traits Result from the Action of Many Genes

Wheat kernel color is a quantitative trait. Hypothesis to explain inheritance of kernel color

Parentalgeneration

F1generation

F2generation

1 1

6 6

151520

aa bb cc(pure-line white)

AA BB CC(pure-line red)

Aa Bb Cc(medium red)

Self-fertilization

Eggs

Sperm

Phenotypes:Number ofdark-skin alleles: 0 1 2 3 4 5 6

1/646/64

15/6420/64

15/646/64

1/64

1/8

1/8

1/8

1/8

1/8

1/8

1/8

1/8

1/81/8

1/81/8

1/81/8

1/81/8

AaBbCc AaBbCc

Polygenic Inheritance• Traits that vary in the

population along a continuum

• Additive effect of 2+ genes on a single phenotype

• Skin color in humans is an example of polygenic inheritance

DescriptionRelationship amonggenes

Epistasis One gene affectsthe expression ofanother

Example

Polygenicinheritance

A single phenotypiccharacter isaffected bytwo or more genes

BbCc BbCc

BCBC

bC

bC

Bc

Bc

bc

bc

9 : 3 : 4

AaBbCc AaBbCc

Applying Mendel’s Rules to Humans

• Humans terrible genetic models– Generation time is too long– Parents produce relatively few offspring– Breeding experiments are frowned upon

• Human disorders follow 5 patterns1) Autosomal dominant 2) Autosomal recessive3) X-linked recessive 4) X-linked dominant5) Y-linked

• Pedigrees (family trees) – analyze the human crosses that already exist.

KeyMale

Female

AffectedmaleAffectedfemale

Mating

Offspring, inbirth order(first-born on left)

Human Pedigree Reports

Fig. 14-15b

1st generation(grandparents)

2nd generation(parents, aunts,and uncles)

3rd generation(two sisters)

Widow’s peak No widow’s peak

Is a widow’s peak a dominant or recessive trait?

Ww ww

Ww Wwww ww

ww

wwWw

Ww

wwWW

Wwor

Autosomal Recessive Traits• If a phenotype is due to an autosomal recessive allele

– trait = homozygous – parents (w/o trait) = heterozygous carriers.

• Carriers carry the allele and transmit it even though they do not exhibit the phenotype.

Carrier male Carrier female

Affectedmale

Affectedfemale

I

II

III

IV

Each

row

repr

esen

ts a

gen

erati

on

Carriers (heterozygotes) are indicated with half-filled symbols

Autosomal or Sex-Linked trait?• Equally often in males and females

– likely to be autosomal. • Males more likely to have the trait

– usually X-linked.• Hemophilia is an example of an X-linked trait resulting from a

recessive allele.Queen Victoria Prince Albert

Female carrier of hemophilia allele

I

II

III

IV

Affected male

Frequency of Dominant Alleles• Not necessarily more common (NOT always “WT”)

• one baby out of 400 in the United States is born with extra fingers or toes• Dominant allele; uncommon occurrence

• In this example, the recessive allele is far more prevalent than the population’s dominant allele

What are the Societal Implications of this Knowledge?

Fetal Testing• Tests to determine in utero if a child has a

disorder.• 14th to 16th week of pregnancy• Blood or amniocentesis

• Fetal tests can reveal a serious disorder• Trisomy 21, 18, etc.

• Some testing after birth• eg Type I diabetes

http://www.youtube.com/watch?v=qA25_fiyh_E&feature=related

• Science of “improving the genetic stock” of humans• Old Testament • Plato’s Republic (description of the

ideal society )

• Francis Galton• “National Eugenics Laboratory”• Experimental studies of heredity

• Twins

• Karl Pearson• The higher birth rate of the poor • Supplant by "higher" races

Eugenics

US Propaganda and Policy• The Immigration Act of 1924

– quota for different nationalities – perceived tendencies towards crime etc.

• Forced Sterilization

• Nazi Germany• The Aryan Nation and the Holocaust

• Human races • Ill-founded concept• Populations with overlapping gene pools. • No major difference in the genome sequence

Eugenics and the Third Reich