Download 1.Mendelian Patterns of Inheritance

Title
Chapter 11
Mendelian
Patterns of
Inheritance
Capt. Piyapol Anubuddhangkura
B.S. (1st class honors cum gold
medal) in Genetics,
M.S. in Biophysics
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• Heredity, the transmission of genetic information
from parent to offspring, generally follows predictable
patterns in organisms.
• Genetics, the science of heredity, studies both genetic
similarities and genetic variation, the differences,
between parents and offspring or among individuals
of a population.
• The science of genetics explains the
stability of inheritance and also variations
between offspring from one generation to
the next.
• An understanding of inheritance patterns
has always been important to agriculture,
animal husbandry, and medicine.
• The Blending Concept of
Inheritance 
• In blending inheritance, male and female gametes
supposedly contained fluids that blended together
during reproduction to produce hybrid offspring with
features intermediate between those of the mother and
father.
• The fact that dominance can occur was not consistent
with the notion of blending inheritance.
• The Blending Concept of
Inheritance 
• However, the theory did not
always explain observed
inheritance patterns. 
– Charles Darwin: If
populations contained only
intermediate individuals and
normally lacked variations,
how could diverse forms
evolve?
• Mendel’s Particulate Theory
of Inheritance
Mendel’s results also argued against
blending inheritance in a more
compelling way. Once two fluids have
blended, it is very difficult to imagine
how they can separate.
Why Mendel??
• He was one of the first scientists to apply mathematics
to biology.
• He was a careful, deliberate scientist who followed
the scientific method very closely and kept very
detailed, accurate records.
• The very reason his theory is termed “particulate”
theory is that it is based on the existence of minute
particles or hereditary units we now called genes.
• Mendel chose the garden pea, Pisum sativum, as his
experimental material.
Fig. 11.2a
• Why garden pea?
–
–
–
–
Easy to cultivate
Short generation time
Could be cross-pollinated
Many varieties available
Fig. 11.2b
• In contrast to his predecessors, Mendel
studied the inheritance of relatively simple
and discrete traits that were not subjective
and were easy to observe.
• In his crosses, Mendel observed either
dominant or recessive characteristics but
no intermediate ones.
Fig. 11.2
• Law of Segregation
– Mendel chose varieties that differed in only one trait.
– If the blending theory of inheritance were correct, the
cross should yield offspring with an intermediate
appearance compared to the parents. 
– He performed reciprocal crosses. 
– When Mendel allowed the F1 plants to self-pollinate, ¾
of the F2 generation were tall and ¼ were short, a 3:1
ratio.
Fig. 11.3
Monohybrid cross:
parents are hybrids in
one way.
Today, we know
that the expected
phenotypic
results of a
monohybrid
cross are always
3:1.
Therefore, the F1
plants were able
to pass on a factor
for shortness.
• Widow’s Peak and Straight Hairline
– W = Widow’s peak (dominant allele)
– w = Straight hairline (recessive allele)
• The law of segregation states the following:
– Each individual has two factors for each trait.
– The factors segregate during the formation of
gametes.
– Each gamete contains only one factor from each
pair of factors.
– Fertilization gives each new individual two factors
for each trait.
• In Mendel’s cross, the original parents (P generation)
were true-breeding; therefore, the tall plants had two
alleles for tallness (TT), and the short plants had two
alleles for shortness (tt).
• When an organism has two identical alleles we say it
is homozygous.
• After cross-pollination, all the individuals of the
resulting F1 generation had one allele for tallness and
one for shortness (Tt). The allele expressed is the
dominant allele.
• When an organism has two different alleles at a gene
locus, we say that it is heterozygous.
• Mendel’s Cross as Viewed by Classical Genetics
– Stem length in peas is controlled by a single gene.
– This gene occurs on a homologous pair of chromosomes
at a particular location is called the gene locus. 
– Alternative versions of a gene are called alleles. 
– The dominant allele is so named because of its ability to
mask the expression of the recessive allele.
Fig. 11.4
The process of meiosis
gives an explanation
for Mendel’s law of
segregation, and why
only one allele for
each trait is in a
gamete.
• Genotype Versus Phenotype
– The word genotype refers to the alleles an individual
receives at fertilization.
• TT = homozygous dominant
• tt = homozygous recessive
• Tt = heterozygous
– The word phenotype refers to the physical appearance of
the individual.
– The phenotype is dependent upon the genotype of the
individual.
Table 11.1
Fig. 11.5
Mendel’s
Law of
Independent
Assortment
The law of
independent
assortment applies
only to alleles on
different
chromosomes.
The F1 plants
showed both
dominant
characteristics.
The F1 cross is
known as a
dihybrid cross.
• The law of independent assortment states the
following:
– Each pair of factors segregates (assorts)
independently of the other pairs.
– All possible combinations of factors can occur
in the gametes.
Fig. 12A
• In 1902, American biologist Walter Sutton
and German biologist Theodor Boveri
independently pointed out the connection
between Mendel’s segregation of alleles and
separation of homologous chromosomes
during meiosis. This connection developed
into the chromosome theory of inheritance,
which stated that inheritance can be explained
by assuming that genes are linearly arranged
in specific locations along the chromosomes.
• Mendel’s Laws of Probability
– The Punnett square allows us to easily calculate the
chances, or the probability, of genotypes and phenotypes
among the offspring. 
– The product rule of probability tells us that we have to
multiply the chances of independent events to get the
answer.
– The sum rule of probability tells us that when the same
event can occur in more than one way, we can add the
results.
– Another useful concept is the statement that “chance has
no memory.”
Fig. 11.6
– The probable results of 3:1 or 9:3:3:1 tell us the probable
phenotypic ratio among the offspring, but not the chances
for each possible phenotype.
• How could we know that an F1 plant of a one-trait
cross is a heterozygous?
• How could we know that a tall pea plant is a
homozygous or heterozygous?
• Testcrosses
– To confirm that the F1 plant of his one-trait crosses were
heterozygous , Mendel crossed his F1 generation plants
with true-breeding, short (homozygous recessive) plants.
– One-Trait Testcross
– Two-Trait Testcross
Fig. 11.7
Mendel
reasoned that
half the
offspring should
be tall and half
should be short,
producing a 1:1
phenotypic
ratio.
Today, a one-trait
testcross is used
to determine if an
individual with
the dominant
phenotype is
homozygous
dominant (TT) or
heterozygous
(Tt).
Page 197
Two-Trait Testcross
Homozygous recessive for both traits
L = long wings
G = gray bodies
l = vestigial (short) wings
g = black bodies
• If the test fly is homozygous dominant for both traits
with the genotype LLGG, it will form only one
gamete: LG.
 All the offspring from the proposed cross will have
long wings and a gray body.
• If the test fly is heterozygous for both traits with the
genotype LlGg, it will form four different types of
gametes: LG, Lg, lG, lg. 
Page 197
Four different offspring
The expected phenotypic ratio for this type of two-trait cross
(heterozygous for two traits × recessive for both traits) is
always 1:1:1:1.
• Backcross
– Backcross is the mating of a hybrid organism (offspring
of genetically unlike parents) with one of its parents or
with an organism genetically similar to the parent. The
backcross is useful in genetics studies for isolating
(separating out) certain characteristics in a related group
of animals or plants.
Pedigree analysis most often identifies three modes of singlelocus inheritance: autosomal dominant, autosomal recessive,
and X-linked recessive.
Pedigree Conventions
Pedigree analysis most often identifies
three modes of single-locus
inheritance: autosomal dominant,
autosomal recessive, and X-linked
recessive
• Mendel’s Laws and Human Genetic Disorders
– These traits are controlled by a single pair of alleles on
the autosomal chromosomes.
• Autosomal Patterns of Inheritance
– When a genetic disorder is autosomal dominant, the
normal allele (a) is recessive, and an individual with the
alleles AA or Aa has the disorder.
– When a genetic disorder is autosomal recessive, the
normal allele (A) is dominant, and only individuals with
the alleles aa have the disorder.
Page 197
Which pattern of inheritance do you suppose to
represent an autosomal dominant/recessive
characteristic?
Fig. 11.8
Inbreeding
This person is
significantly
heterozygous
increases the
because
she
chances of children
inheriting
two
has a child
copies of a
that
is harmful
potentially
affected.
recessive allele.
Fig. 11.9
This person is heterozygous because he
has a child that is unaffected.
• Autosomal Recessive Disorders
– Methemoglobinemia
• Individuals with methemoglobinemia are unable to clear the
abnormal blue protein from their blood, causing their skin to
appear bluish-purple in color.
• Enzyme tests indicated that the blue Fugates lacked the enzyme
diaphorase, coded by a gene on chromosome 22. The enzyme
normally converts methemoglobin back to hemoglobin.
• Methemoglobin is hemoglobin that has been oxidized from the
ferrous (Fe++) to the ferric (Fe+++) state, thus unable to bind
oxygen. The NADH-methemoglobin reductase enzyme reduces
methemoglobin to hemoglobin. Methemoglobinemia results
from either inadequate enzyme activity or too much
methemoglobin production.
– Cystic Fibrosis
• CF patients exhibit a number of characteristic symptoms, the
most obvious being extremely salty sweat.
• In children with CF, the mucus in the bronchial tubes and
pancreatic ducts is particularly thick and viscous, interfering
with the function of the lungs and pancreas.
• CF is caused by a defective chloride ion channel that is encoded
by the CFTR allele on chromosome 7.
• It is hoped that other novel treatments, such as gene therapy,
may be able to correct the defect by placing a normal copy of
the gene in patients to replace the faulty ones.
• To explain the persistence of the mutated CFTR allele in a
population, it has been suggested that those heterozygous for
CF are less likely to die from potentially fatal diseases, such as
cholera.
– Niemann-Pick Disease
• In infants, a persistent jaundice, feeding difficulties, an
enlarged abdomen, and pronounced mental retardation may
signal to a medical professional that the child has NiemannPick disease.
• Type A and B forms of Niemann-Pick disease are caused by
defective versions of the same gene located on chromosome 11.
This gene codes for acid sphingomyelinase, an enzyme that
normally breaks down a lipid called sphingomyelin.
• Affected individuals accumulate lipid droplets within cells of
the liver, lymph nodes, and spleen.
• The abnormal accumulation of lipids causes enlargement of the
abdomen.
• Autosomal Dominant Disorders
– Osteogenesis Imperfecta
• Osteogenesis imperfecta is an autosomal dominant genetic
disorder that results in weakened, brittle bones.
• Osteogenesis imperfecta leads to a defective collagen I that
causes the bones to be brittle and weak.
• Collagen has many roles, including providing strength and
rigidity to bone and forming of framework for most of the
body’s tissues.
• Because the mutant collagen can cause structural defects even
when combined with normal collagen I, osteogenesis
imperfecta is generally considered to be dominant.
• Currently, the disorder is treatable with a number of drugs that
help to increase bone mass, but these drugs must be taken longterm.
Osteogenesis imperfecta Type V Adult X-Ray
Ramana Murthy Reddicharla
Skull of an Egyptian child of the 22nd dynasty (945-716 BCE) who suffered from
osteogenesis imperfecta, a.k.a. "brittle bone syndrome" (British Museum)
– Hereditary Spherocytosis
• The abnormal spherocytosis protein is unable to perform its
usual function, causing the affected person’s red blood cell to
adopt a spherical shape.
• Hereditary spherocytosis exhibits incomplete penetrance, so not
all individuals who inherit the mutant allele will exhibit the
trait.
– Huntington Disease
• Huntington disease is a devastating neurological disease caused
by the inheritance of a single dominant allele.
A large number of individuals either had a sequence designated as
J, K, or L. Only the sequence of bases designated as L appears in
all the individuals with Huntington disease.
huMan TraiTs
• Follow Mendelian laws
– Albinism (autosomal, recessive), webbed fingers (autosomal,
dominant), short-limbed dwarfism (autosomal, dominant)
• Multiple Allelic Traits
– If three or more alleles for a given locus exist within the
population, we say that locus has multiple alleles.
– Some alleles can be identified by the action of certain enzyme or
by some other biochemical feature but do not produce an obvious
phenotype.
– ABO blood type
• IA = A antigen (a glycoprotein) on red blood cells
• IB = B antigen on red blood cells
• i = Neither A nor B antigen on red blood cells
– The possible phenotypes and genotypes for blood type are as
follows:
Phenotype
A
B
AB
O
Genotype
IAIA, IAi
IBIB, IBi
IAIB
ii
– The inheritance of the ABO blood group in humans is an
example of codominance.
– Reproduction between a heterozygote with type A blood
and a heterozygote with type B blood can result in any
one of the four blood types.
 For this reason, DNA fingerprinting is now used to
identify the parents of an individual instead of blood
type.
C > cch > ch > c
• In rabbits, four alleles occur at the locus for coat
color. A C allele causes a fully colored dark gray coat.
The homozygous recessive genotype, cc, causes
albino (white) coat color. These are two additional
allelic variants of the same locus, cch and ch.
• An individual with the genotype cchcch has the
chinchilla pattern, in which the entire body has a light,
silvery gray color.
• The genotype chch causes the Himalayan pattern, in
which the body is white but the tips of the ears, nose,
tail, and legs are colored, like the color pattern of a
Siamese cat.
• Incomplete Dominance and Incomplete Penetrance
– Incomplete dominance is exhibited when the
heterozygote has an intermediate phenotype between that
of either homozygote.
– An example of four-o’clock (Mirabilis jalapa) 
• The reappearance of the three phenotypes in this generation
makes it clear that we are still dealing with a single pair of
alleles.
• A double dose of pigment results in red flowers; a single dose
of pigment results in pink flowers; and because white flowers
produce no pigment, the flowers are white.
Fig. 11.13
When pink four-o’clocks selfpollinate, the results show
three phenotypes. This is only
possible if the pink parents had
an allele for red pigment (R1)
and an allele for no pigment
(R2). Note that alleles involved
in incomplete dominance are
both given a capital letter.
• In complete dominance is not unique to four o’clock,
and additional examples of incomplete dominance are
known in both plants and animals.
• For example, true-breeding white chickens and truebreeding black chickens produce bluish gray
offspring, known as Andalusian blues, when crossed.
Notice that in
these crosses,
the genotypic
and phenotypic
ratios are
identical.
– In some cases, a dominant allele may not always lead to
the dominant phenotype in heterozygote, even when the
alleles show a true dominant/recessive relationship. The
dominant allele in this case does not always determine
the phenotype of the individual, so we describe these
traits as showing incomplete penetrance.
• Polydactyly is inherited in an autosomal dominant manner;
however, not all individuals who inherit the dominant allele
will exhibit the trait.
• Human Examples of Incomplete Dominance
– Familial hypercholesterolemia (FH)
– Cystic fibrosis
• Pleiotropic Effects
– Pleiotropy occurs when a single mutant gene affects two
or more distinct and seemingly unrelated traits.
• Persons with Marfan syndrome have disproportionately long
arms, legs, hands, and feet; a weaken aorta; poor eyesight; and
other characteristics. 
 Due to the production of abnormal connective tissue.
• Cystic fibrosis
• Porphyria
• Sickle-cell disease  
– Although sickle-cell disease is a devastating disorder, it provides
heterozygous individuals with a survival advantage (resistant to the
protozoan parasite that causes malaria).
– Most cases of pleiotropy can be traced to a single
fundamental cause. For example, a defective enzyme
may affect the functioning of many types of cells.
Page 203
• Polygenic Inheritance
– Polygenic inheritance occurs when a trait is governed by two
or more sets of alleles. The individual has a copy of all allelic
pairs, possibly located on many different pairs of
chromosomes.
– Each dominant allele has a quantitative effect on the
phenotype, and these effects are additive. Therefore, a
population is expected to exhibit continuous phenotypic
variations. 
– Multifactorial traits are controlled by polygenes subject to
environmental influences.  
• Human Examples of Multifactorial Inheritance
– Human skin color and height are examples of polygenic
traits affected by the environment.
– Eye color is also a polygenic trait.
Fig. 11.15
In polygenic
inheritance, a
number of pairs
of genes control
the trait.
Black dots
and intensity
of blue
shading stand
for the
number of
dominant
alleles.
Orange
shading shows
the degree of
environmental
influences.
The coats of Siamese cats and Himalayan rabbits
have darker tipped ears, nose, paws, etc. due to the
enzyme encoded by an allele which is only active
at the extremities at low temperatures.
– Many human disorders are most likely due to the
combined action of many genes plus environmental
influences.
– In recent years, reports have surfaced that all sorts of
behavioral traits, such as alcoholism, phobias, and even
suicide, can be associated with particular genes.
Cardiovascular disease is more prevalent among those whose
biological or adoptive parents have cardiovascular disease.
Can you suggest environmental reasons for this correlation?
• Sex Determination
Birds, amphibians
Grasshoppers, crickets, cockroaches
Bees, ants, wasps
ZZ (male)
XO
n
ZW (female)
XX
2n
• X-Linked Inheritance
– The X and Y chromosomes in mammals determine the
gender of the individual. In particular, if the Y
chromosome contains an SRY gene, the embryo becomes
a male.
– The term X-linked is used for genes that have nothing to
do with gender, and yet they are carried on the X
chromosome.
– Discovered in the early 1900s by a group at Columbia
University, headed by Thomas Hunt Morgan.
– Fruit flies, Drosophila melanogaster, have the same sex
chromosome pattern as humans.
• Morgan’s Experiment
– Morgan took a newly discovered mutant male with white
eyes and crossed it with a red-eyed female.
Page 205
The expected 3 red-eyed : 1 white-eyed
These results support the chromosome theory of inheritance by
showing that the behavior of a specific allele corresponds exactly
with that of a specific chromosome—the X chromosome in
Drosophila.
• Solving X-Linked Genetic Problems 
– The allele key for an X-linked gene shows an allele
attached to the X:
XR
Xr
=
=
red eyes
white eyes
– The possible genotypes in both males and females are as
follows:
XRXR =
XRXr =
XrXr =
red-eyed female
red-eyed female
white-eyed female
XRY
XrY
red-eyed male
white-eyed male
=
=
Fig. 11.16
Males are
considered
hemizygous
for X-linked
traits, because
a male only
posseses one
allele for the
trait.
The fruit fly has XX
females and XY
males, but the Y does
not determine
maleness; a fruit fly
with only one X
chromosome and no
Y chromosome has a
male phenotype.
Males cannot be
carriers for X-linked
traits.
• Human X-Linked Disorders
– Color Blindness
• The allele for the bluesensitive protein is autosomal,
but the alleles for the red- and
green-sensitive pigments are
on the X chromosome.
– Menkes Syndrome
• The symptoms of Menkes syndrome are due to accumulation of
copper in some parts of the body, and the lack of the metal in
other parts.
– Duchenne Muscular Dystrophy
• The absence of a protein called dystrophin causes the disorder.
• A test is now available to detect carriers of Duchenne muscular
dystrophy.
– Adrenoleukodystrophy (ALD)
• ALD is an X-linked recessive disorder due to the failure of a
carrier protein to move either an enzyme or very long chain
fatty acid into peroxisomes. As a result, these fatty acids are not
broken down, and they accumulate inside the cell and the result
is severe nervous system damage.
• The disease was made famous by the 1992 movie Lorenzo’s
Oil.
– Hemophilia
• There are two common types of hemophilia: Hemophilia A is
due to the absence or minimal presence of a clotting factor
known as factor VIII, and hemophilia B is due to the absence of
clotting factor IX.
• Hemophilia
• Human X-linked dominant trait
– Congenital generalize hypertrichosis