LECTURE 27-28

CHAPTER 9b

MENDEL
Part 2
 Human Genetics
Traits are called Mendelian
when there is a simple dominant/recessive
relationship and they are controlled by a single
autosomal gene (not X or Y).

The inheritance of many human traits follows

Mendels principles and the rules of probability.

Dominant traits include freckles, widows peak,

free earlobes, cleft chin, dimples, really hairy
forearms, hyperextension, curly hair,
and tongue rolling.

Dominant traits are not necessarily normal or

more common.

Figure 9.12
 Cystic fibrosis: recessive trait
2 copies of the cystic fibrosis mutation
Affects about 30,000 Americans excessive salt secreted by sweat glands
thick mucus

many organ systems are involved

lungs and bronchial tubes clogged

hard to breathe, prone to infection

decreased fertility

digestive enzymes trapped, break down pancreas

poor nutrition and slow growth

The CF gene product is the CFTR protein frequency Aa (US)

Cystic Fibrosis Transmembrane Regulator 1/25 European-Americans
1/46 Hispanics-Americans
CFTR is located in the plasma membrane 1/60 African-Americans
of certain gland cells and regulates the 1/150 Asian-Americans
flow of chloride ions
1 copy of the cystic fibrosis mutation
resistant to typhoid
Sickle-Cell Anemia: Recessive Trait
Sickle-cell anemia is an autosomal recessive trait in which
the protein hemoglobin is defective
Affected individuals cannot properly transport oxygen to their tissues

Ss

not

Ss
Normal red blood cell Sickled red blood cell

Irregular shape
causes blockage
of capillaries
 The sickle-cell allele is particularly common among people of
African descent
Carriers (Ss) are resistance to malaria
and thus were more likely to survive and have babies
Heterozygote advantage

Close match between

distribution of sickle-cell
allele and malaria
 Understanding Mendelian inheritance allows
you predict the probability of having an affected child

Lots of problems like these occur on

MCATs, DATs and Biology GREs !!!!

Do the checkpoint problems

and Self Quiz in chapter 9

Two phenotypically normal parents

have a child who is deaf due to a
rare autosomal recessive mutation.
What is the chance that their next child
will be deaf?
Figure 9.9

Parents are both phenotypically normal carriers (heterozygotes)

There is a 1/2 chance their child will be a carrier
and 1/4 chance child will be affected.
(not considered a carrier even though they carry two mutants alleles

If they KNOW their child can hear, what is the chance that the child is a carrier?
Ellen and Michaels parents
must be heterozygous

Kate and Brad have a child named Michael who is affected

with a rare autosomal recessive form of deafness. Their
other child Ellen has normal hearing.
What is the chance that Ellen has a child who is a carrier of
the recessive allele?
 S s

S DD Dd

s
Dd dd
Ellen and Michaels parents
must be heterozygous

Ellen is not affected and

cannot be dd

Probability Ellen is a carrier = 2/3

Probability child inherits sickle cell allele =
Probability child carries sickle cell allele from Ellen
= 2/3 x 1/2 = 1/3
Huntingtons Disease: Dominant Trait

Huntingtons disease is an autosomal dominant trait that

causes progressive deterioration of brain cells
It is a fatal disease
However, it persists in
human populations because
it has a late onset

50% of children
are at risk
http://www.ncbi.nlm.nih.gov
click on OMIM in middle of top banner
Online Mendelian Inheritance in Man
Search by name of disease
 Gender in humans determined initially by the Y chromosome

Human X chromosomes has more

than 1000 protein-encoding genes
most have nothing to do with sex determination

Human Y chromosomes has only 100 genes

play large role in sex determination

Figure 9.29
 X-linked recessive
color blindness
red-green 8% of US males
blue autosomal dominant

Mutations in specific opsin

genes, cone defect

Figure 9.30
Figure 9.31
 Some X-linked recessive traits
Trait Phenotype

Color blindness cant see red

cant see green

Hemophilia inability to form blood clots

missing factor VIII or factor IX

Ichthyosis brown scaly skin, missing enzyme that removes cholesterol from skin

G-6-P dehyd deficiency fatal anemia with exposure to certain foods and drugs
Homozygous females and hemizygous males resistant to malaria

Muscular dystrophy Duchennes, fatal muscle wasting

Some X-linked dominant traits

not very many disorders

Congenital Generalized Hypertrichosis Werewolf?

 VARIATIONS ON MENDELS PRINCIPLES
Mendels principles describe the transmission of the genes
and are valid for all sexually reproducing species

However, often the genotype does not dictate the phenotype in the
simple way Mendels principles describe

Mendelian segregation of alleles can be disguised by a variety of

factors.
These variations are not exceptions to Mendels Principles

Chromosomal linkage
Sex linkage

Incomplete dominance Be able to define these!

Codominance
Environmental effects
Pleiotropic effects
Polygenic
Epistasis
Incomplete dominance

When an offsprings
phenotypesuch
as flower color in
snapdragons
is in between the
phenotypes of its parents,
it exhibits incomplete
dominance

See Figure 9.18

Incomplete dominance in familial hypercholesterolemia
GENOTYPES:
hh Hh HH
Homozygous Heterozygous Homozygous
for ability to make for inability to make
LDL receptors 1/500 LDL receptors
people!
PHENOTYPES:
LDL

LDL
receptor

Cell
Normal Mild disease Severe disease

Figure 5.2
See Figure 9.19
 Multiple alleles
In a population, multiple alleles often
exist for a characteristic
There are over 1000 alleles of CF

ABO blood group in humans is

determined by gene (I) with 3 alleles
The encoded enzyme adds sugar
molecules to lipids on the surface
of red blood cells
IA adds galactosamine
IB adds galactose
A or B are codominant
i adds neither sugar
The i allele is recessive
to both IA and IB
Figure 9.20
In codominance, like incomplete
dominance, the heterozygote The different combinations of the three
phenotype that is a combination of alleles produces four different phenotypes
that of the two homozygotes
Pleiotropy
Individual homozygous
one gene for sickle-cell allele

many phenotypes Sickle-cell (abnormal) hemoglobin

mutation in one gene
Abnormal hemoglobin crystallizes,
has many symptoms causing red blood cells to become sickle-shaped
or controls several
functions
Sickle cells

see Figure 9.21

Breakdown of red blood Clumping of cells Accumulation of

cells and clogging of sickled cells in spleen
small blood vessels

Physical Heart Brain Damage to other Spleen

weakness Anemia failure Pain and fever organs
damage damage

Impaired Kidney
mental Pneumonia and Rheumatism failure
Paralysis other infections
function
Environmental Effects
Color resembles
The expression of some snowy background
in winter
genes is influenced by
environmental factors,
such as temperature

Some pigment alleles areColor resembles

cold-sensitive tundra background
Arctic foxes make fur in summer

pigment only when the

weather is warm, in the cold
the pigment protein falls apart

Some pigment alleles are

heat-sensitive
 When warm pigment protein falls apart
in Himalayan rabbits or Siamese cats

ice pack
Polygenic Traits and Continuous Variation
In polygenic inheritance there is
one characteristic (i.e. height or
skin color) but many genes.
These genes contribute in a
cumulative way to the phenotype
The result is a gradation in
phenotypes or continuous
variation
Extremes are much
rarer than the
intermediate values

Figure 10.16
Skin Tone is Multifactorial (Polygenic +environment)
Skin color is a phenotype interaction between pigment genes + environment

Melanin production results in skin pigmentation and protects skin from UV

In a genetic sense, race based on skin color has little meaning
over 93% of genetic traits are equally frequent among all racial groups

Three gene model,

seven skin tones.
Epistasis

In 1918, the geneticist R. A. Emerson crossed two true-breeding corn

varieties with white kernels
To his surprise, all F1 plants had purple kernels
The plants of the F2 generation showed a ratio
of 9 purple :

Mendelian genetics predicts a 9:3:3:1 ratio for

independent assortment of two genes

So why is Emersons ratio modified?

 There are two genes
that contribute to
kernel color
B Production of
pigment
A Deposition of
pigment

Either gene can block the

others expression
To produce pigment a
plant must possess at
least one functional
copy of each gene

Epistasis Interaction between two genes where one of

them modifies the phenotypic expression of the other
 Linked Genes
Unlinked genes
Are located on different chromosomes or far apart on same
chromosome
Are inherited independently (independent assortment)

Linked genes
Are located close together on a chromosome
May be inherited together

Homologous recombination (cross over) can separate linked alleles

and produce offspring with recombinant phenotypes

The further apart two linked genes are, the more likely a cross over
with occur between them
 GL gl
GgLl ggll
(female) (male)
gl gl

Crossing over

GL gl Gl gL gl

Sperm

Parental gametes Recombinant gametes

More Frequency
Eggs FERTILIZATION
common is relative
to distance
Offspring
between
genes
GL gl Gl gL
gl gl gl gl

Parental Recombinant
Figure 9.27
Dihybrid testcross Figure 9.25
Gray body, Black body,
long wings short wings
(wild-type) (mutant)
GgLl ggll

Female Male

Results
Offspring
Gray-long Black-short Gray-short Black-long
GgLl ggll Ggll ggLl
_391
2300
= .17
965 944 206 185
Parental phenotypes 83% Recombinant phenotypes 17%

The percentage of recombinant offspring among the total is called the recombination frequency.

17% recombination frequency = 17 map units (mu) or centi Morgans (cM) between G and L
 Linkage Maps
Early studies of crossing over were performed using the
fruit fly Drosophila melanogaster.
Alfred H. Sturtevant, an undergrad student in the lab of
T.H. Morgan, developed a formula for converting
recombinant frequency into an approximation for linear
distances.
A diagram of relative gene locations on a chromosome is a
linkage map.
Human Genome linkage maps were made before our genome
was sequenced.
Linkage analysis is still the workhorse of genetics

Result from crossover between G and L