Biology II
Chapter 13 Notes
Based upon
their observities form ornamental plant breeding, biologists of the 19th
century realized that both parents contribute to the characteristics of
offspring. Before Mendel, the favored
explanation of heredity was the blending theory.
Blending
theory of heredity- Pre-Mendelian of heredity proposing that heredity material
from each parent mixes in the offspring once blended like two liquids in
solution, the hereditary material is inseparable and the offspring’s traits are
some intermediate between the parental types.
According to this theory:
- Individuals of a population should
reach a uniform appearance after many generations
- Once hereditary traits are
blended, they can no longer be separated out to appear again in later
generations
This blending
theory of hereditary was inconsistent with the observations that:
- Individuals in a population
do not reach a uniform appearance;
inheritable variation among individuals is generally preserved
- Some inheritable traits skip one generation
only to reappear in the next
Modern
genetics began in the 1860’s when Gregor Mendel, an Augustinian monk,
discovered the fundamental principles of heredity. Mendel’s great contribution to modern genetics was to replace the
blending theory of hereditary with the particles theory of hereditary.
Particulate
theory of heredity- Gregor Mendel’s theory that parents transmit to their
offspring discrete inheritable factors (now called genes) that remain as
separate factors from one generation to the next.
I. Mendel brought
an experimental and quantitative
approach to genetics: science
as a process
While attending the University of Vienna
from
1851-1853, Mendel was influenced by two
professors:
o
Doppler,
a physicist, trained Mendel to apply a
quantitative experimental approach to the study of natural phenomena.
o
Unger,
a botanist, interested Mendel in the causes of inheritable variation in plants.
These experiences inspired Mendel to use key
elements of the scientific process in the
study
of heredity. Unlike most nineteenth century
biologists, he used a quantitative approach
to
his experimentation.
In 1857, Mendel was living in an Augustinian
monastery, where he bred garden peas in the
abbey
garden.
He probably chose garden peas as his
experimental organisms because:
o
They
were available in many easily distinguishable varieties.
o
Strict
control over mating was possible to ensure the parentage of new seeds. Petals
of the pea flower enclose the pistil and stamens,
which prevents cross-pollination.
Immature stamens can be removed to prevent
Self-pollination.
Mendel hybridized pea
Plants by transferring pollen from one flower to
another with an artist’s brush.
Character=Detectable inheritable
feature of an
organism.
Trait=Variant of an inheritable
character.
Mendel
chose characters in pea plants that
differed
in
a relatively clear-cut manner. He chose
seven
characters,
each of which occurred in two alternative forms:
1.
Flower
color (purple or white)
2.
Flower
position (axial or terminal)
3.
Seed
color (yellow or green)
4.
Seed
shape (round or wrinkled)
5.
Pod
shape (inflated or constricted)
6.
Pod
color (green or yellow)
7.
Stem
length (tall or dwarf)
True
breeding=always
producing offspring with the same traits
as the parents when the parents are
self-fertilized.
Mendel
started his experiments with true-breeding
plant
varieties, which he hybridized (cross-pollinated) in experimental crosses.
o
The
true-breeding parental plants of such a
cross are called the P generation (parental).
o
The
hybrid offspring of the P generation as the
F1 generation
(first
filial).
o
Allowing
F1 generation plants to self-pollinate, produces the next
generation, the F2
Generation ( second filial).
Mendel
observed the transmission of selected traits
for
at least three generations and arrived at two
principles
of heredity that are now known as the law
of segregation and the law of independent assortment.
II. According to the law of
segregation, the two
alleles for a character are packaged into
separate gametes.
When Mendel crossed true-breeding plants
with
different character traits, he found that
the
traits did not blend.
o
Using
the scientific process, Mendel designed
experiments in which he used large sample sizes
and kept accurate quantitative records of the
results.
o
For
example, a cross between true-breeding
varieties, one with purple flowers and one with
white flowers, produced F1 progeny (offspring)
with only purple flowers.
Hypothesis: Mendel hypothesized that if the
inheritable factor for white flowers had been
lost, then a cross between F1 plants
should produce only purple-flowered plants.
Experiment: Mendel allowed the F1 plants to
self-pollinate.
Results: There were 705 purple-flowered and 224 white-flowered plants in
the F2 generation-a ratio of 3:1.
The inheritable factor for
white flowers was not lost, so the hypothesis was
rejected.
Conclusions: From these types of experiments
and observations, Mendel concluded that since
the inheritable factor for white flowers was not
lost in the F1 generation, it must have been masked by the presence
of the purple-flower factor. Mendel’s
factors are now called
genes; and in Mendel’s terms,
purple flower is
the dominant
trait and white flower is the
recessive trait.
Mendel
repeated these experiments with the other six characters and found similar 3:1
ratios in the
F2
generations. From these observations he
developed a hypothesis that can be divided into four parts:
1. Alternative forms of genes are responsible
for variations in inherited characters.
o
For
example, the gene for flower color
in pea
plants exists in two alternative
forms; one
for purple color and one for
white
color.
o
Alternative
forms for a gene are now
called alleles.
2.
For each character, an
organism inherits two
alleles, one
from each parent.
o
Mendel
deduced that each parent
contributes one “factor,” even though he
did not know about chromosomes or
meiosis.
o
We
now know that Mendel’s factors are
genes.
Each genetic locus is represented
twice in diploid organisms, which have
homologous pairs of chromosomes, one set
for each parent. Homologous loci may
have the same allele as in Mendel’s true-
breeding organisms or they may differ as
in
the F1 hybrids.
3.
If the two alleles differ,
one is fully
expressed
(dominant allele); the other is
completely
masked (recessive allele).
o
Dominant
alleles are designated by a
capital
letter: P=purple flower color.
o
Recessive
alleles are designated by
lowercase
letter: p=white flower color.
4.
The two alleles for each
character segregate
during gamete
production.
o
Without
any knowledge of meiosis, Mendel
deduced that a sperm cell or ovum carries only one
allele for each inherited
characteristic, because allele pairs separate
(segregate) from each other during
gamete production.
o
Gametes
of true-breeding plants will all carry the same allele. If different alleles are present in the parent, there is
a 50% chance that a gamete will receive the
dominant allele, and a 50% chance that it
will receive the recessive allele.
o
This
sorting of alleles into separate gametes is known as Mendel’s law of segregation.
Mendel’s
law of segregation=Allele pairs segregate
during
gamete formation (meiosis), and the paired
condition
is restored by the random fusion of gametes at fertilization.
o
This
law predicts the 3L1 ratio observed in the F2 generation of a
monohybrid cross.
o
F1
hybrids (Pp) produce two classes of gametes when allele pairs segregate
during gamete
formation. Half receive a
purple-flowered allele(P)and the other half the white-flower allele(p).
During self-pollination, these two
classes
of gametes unite randomly. Ova containing
purple-flower alleles have equal
chances of
being fertilized by sperm carrying purple-
flower alleles or sperm carrying
white-
flower alleles.
o
Since
the same is true for ova containing
white-flower alleles, there are four equally likely
combinations of sperm and ova.
The
combinations resulting from a genetic cross may be predicted by using a Punnett Square.
The F2 progeny would include:
o
One-fourth
of the plants with two alleles
for purple flowers.
o
One-half
of the plants with one allele for purple flowers and one allele for white
flowers. Since the purple flower
Allele is dominant, these plants have purple
flowers.
o
One-fourth
of the plants with two alleles
White flower color, which will have white flowers
since no dominant allele is present.
The
pattern of inheritance for all seven of the
characteristics
studied by Mendel was the same:
one
parental trait disappeared in the F1 generation and reappeared in
one-fourth of the F2 generation.
A. Some Useful Genetic
Vocabulary
Homozygous=having two identical
alleles for a
given trait (e.g. PP or pp).
o
All
gametes carry that allele
o
Homozygotes
are true-breeding.
Heterozygous=having two different
alleles for a
trait(e.g. Pp).
o
Half
of the gametes carries one allele(P)and the remaining half carries the other(p)
o
Heterozygotes
are not true-breeding.
Phenotype=An organism’s expressed
traits(e.g. purple or white flowers).
o
In
Mendel’s experiment above, the F2 generation had a 3:1 phenotypic ratio of plants with purple
flowers to plants with
White flowers.
Genotype=An organism’s genetic
makeup (e.g. PP, Pp, or pp).
o
The
genotypic ratio of the F2
generation was 1:2:1 (1PP:2 Pp:1 pp).
B. The Testcross
Because some alleles are dominant over others,
the genotype of an organism may not be
apparent.
For example:
o
A
pea plant with purple flowers may be either
Homozygous dominant(PP)or heterozygous(Pp).
Testcross=The breeding of an organism
of unknown
genotype with a homozygous recessive.
o
For
example, if a cross between a purple-flowered plant of unknown genotype (P__)
produced only purple-flowered plants, the
parent was probably homozygous dominant since
a PP x pp cross produces all purple-flowered
progeny that are heterozygous (Pp).
o
If
the progeny of the testcross contains both
purple and white phenotypes, then the purple-
flowered parent was heterozygous since a Pp x pp
cross produces Pp and pp progeny in a 1:1 ratio.
III. According to the law of
independent
assortment, each pair of alleles segregates
into gametes independently
Mendel deduced the law of segregation
from
experiments with monohybrid crosses, breeding
experiments that used parental varieties
differing in a single trait. He then
performed crosses between parental
varieties
that differed in two characters or dihybrid
crosses.
Dihybrid cross=A mating between
parents that
Are heterozygous for two characters
(dihybrids).
o
Mendel
began his experiments by crossing true-breeding parent plants that differed in
two
characters such as seed color (yellow or green) and
seed shape (round or wrinkled).
From previous monohybrid crosses, Mendel knew that
yellow seed(Y)was dominant to green (y),
and that round(R)was dominant to wrinkled (r).
o
Plants
homozygous for round yellow seeds (RRYY) were crossed with plants homozygous
for
Wrinkled green seeds (rryy).
o
The
resulting F1 dihybrid progeny were heterozygous for both traits
(RrYy) and had round yellow seeds, the dominant phenotypes.
o
From
the F1 generation, Mendel could not tell if the two characters were
inherited
Independently or not, so he allowed the F1
progeny to self-pollinate. In the
following
Experiment, Mendel considered two alternate
Hypotheses:
Hypothesis
1: If the two characters segregate
together, the F1 hybrids
can only produce the
same two
classes of gametes(RY and ry) that
they received from the parents, and the F2
progeny will show a 3:1 phenotypic ratio.
Hypothesis 2: If the two characters segregate
independently,
the F1 hybrids will produce four
classes of gametes (RY, Ry, rY,ry), and
the F2
progeny
will show a 9:3:3:1 ratio.
Experiment: Mendel performed a dihybrid cross by allowing
self-pollination of the F1 plants
(RrYy x RrYy).
Results: Mendel categorized the F2 progeny and
determined a ratio of 315:108:101:32, which approximates 9:3:3:1.
These results were repeatable. Mendel performed similar dihybrid crosses
with all
seven characters in various combinations and
found the same 9:3:3:1 ratio in each case.
He also noted that the ratio for each individual
gene pair was 3:1, the same as that for a monohybrid cross.
Conclusions: The experimental results supported the hypothesis
that each allele pair
Segregates
independently during gamete formation.
This
behavior of genes during gamete formation is referred to as Mendel’s law of independent assortment.
Mendel’s
law of independent assortment=Each allele
pair
segregates independently of other gene pairs during gamete formation.
IV. Mendelian inheritance
reflects rules of
Probability
Segregation and independent assortment of
alleles during gamete formation and fusion
of
gametes at fertilization are random
events.
Thus, if we know the genotypes of parents,
we
can predict the most likely genotypes of
their
offspring by using the simple laws of
probability.
o
The
probability scale ranges from 0 to 1; an
event that is certain to occur has a probability of
1, and an event that is certain
not to occur has a probability
of 0.
o
The
probabilities of all possible outcomes for
An event must add up to 1.
o
For
example, when tossing a coin or rolling a six-sided die:
Event Probability Tossing heads with a two-headed coin
1 1 + 0 = 1 Tossing tails with a Two-headed coin
0 Tossing heads with a
1/2 normal coin ½ + ½ = 1 Tossing tails with a
1/2 normal coin Rolling 3 on a six-
1/6 sided die 1/6 + 5/6 =
1 Rolling a number
5/6 other than 3
Random events
are independent of one another.
o
The outcome
of a random event is unaffected by the outcome of previous such events.
o
For example,
it is possible that five successive tosses of a normal coin will produce five
heads; however the probability of heads on the sixth toss is still ½.
Two basic
rules of probability are helpful in solving genetics problems: the
rule of multiplication and the rule of addition.
A. Rule of
Multiplication
Rule of multiplication=The
probability that
independent events will occur
simultaneously
is the product of their individual
probabilities. For example:
Question: In a Mendelian cross between pea
plants that are heterozygous for flower
color
(Pp), what is the probability that the
offspring
will be homozygous recessive?
Answer:
Probability that an egg from the F1
(Pp) will
receive a p allele = ½.
Probability that a sperm from the F1
will
receive a p allele = ½.
The overall probability that two recessive
alleles will unite at fertilization:
½ x ½ = ½ .
This rule
also applies to dihybrid crosses. For
example:
Question: For a dihybrid cross, YyRr x YyRr,
what is the probability of an F2 plant
having the
having the genotype YYRR?
Answer:
Probability that an egg from a YyRr parent
will
Receive the Y and R alleles = ½ x ½ = ¼ .
Probability that a sperm from a YyRr parent
will
receive the Y and R alleles= ½ x ½ = ¼ .
The overall probability of an F2
plant having the
genotype YYRR: ¼ x ¼ = 1/16.
B. Rule of
Addition
Rule of addition=The probability of
an event
that can occur in two or more independent
ways
is the sum of the separate probabilities of
the
different ways. For example:
Question: In a Mendelian cross between pea
plants that are heterozygous for flower
color
(Pp), what is the probability of the
offspring
being a heterozygote?
Answer: There are two ways in which a
Heterozygote may be produced: the dominant
allele (P) may be in the egg and the
recessive
allele (p) in the sperm, or the dominant
allele
may be in the sperm and the recessive in
the
egg.
Consequently, the probability that the
offspring will be heterozygous is the sum
of the
probabilities of those two possible ways:
Probability that the dominant allele will
be in
the egg with the recessive in the sperm is
½ x ½
= ¼ .
Probability that the dominant allele will be
in
the sperm and the recessive in the egg is ½
x ½
=1/4.
Therefore, the probability that a
heterozygous
offspring will be produced is ¼ + ¼ =1/2.
C. Using Rules of Probability to Solve
Genetics
Problems
The rules of
probability can be used to solve
complex genetics problems. For example,
Mendel crossed pea varieties that differed in
three characters (trihybrid crosses).
Question: What is the probability that a
trihybrid cross between two organisms with the
genotypes AaBbCc and AaBbCc will produce an
offspring with the genotype aabbcc?
Answer: Because segregation of each allele is
an independent event, we can treat this as
three
separate monohybrid crosses:
Aa x Aa:
probability for aa offspring = ¼
Bb x Bb:
probability for bb offspring = ¼
Cc x Cc:
probability for cc offspring = ¼
The probability that these independent
events
will occur simultaneously is the product of
their independent probabilities (rule of
multiplication). So the probability that the
offspring will be aabbcc is:
¼ aa x ¼ bb x ¼ cc = 1/64
For another
example, consider a trihybrid cross of garden peas, where:
Flower
Color
Purple: PP, Pp White: pp Seed Color Yellow: YY, Yy Green: yy Seed Shape Round: RR, Rr Wrinkled: rr
Character Trait &
Genotype
Question: What fraction of offspring from the
following cross of garden peas, would show
recessive phenotypes for at least two of the
three traits?
PpYyRr x Ppyyrr
Answer: First list those genotypes that are
homozygous recessive for at least two
traits,
(note that this includes the homozygous
recessive for all three traits). Use the rule
of multiplication to
calculate the probability
that offspring would be one of these
genotypes.
Then use the rule of addition to calculate the
probability that two of the three traits
would
be homozygous recessive.
Genotypes with at least two Probability
Homozygous recessives of genotype
ppyyRr ¼ x ½ x ½ =
1/16
ppYyrr ¼ x ½ x ½ =
1/16
Ppyyrr ½ x ½ x ½ =
2/16
Ppyyrr ¼ x ½ x ½ =
1/16
ppyyrr ¼ x ½ x ½ =
1/16
= 6/16 or
3/8
chance
of
two
recessive
traits
V. Mendel
discovered the particulate behavior of
genes:
a review
If a seed is planted from the F2 generation
of a
monohybrid cross, we cannot predict
with
absolute certainty that the plant grow to
produce white flowers (pp). We can
say that
there is a ¼ chance that the plant will have
white flowers.
- Stated in statistical terms: among
a large sample of F2 plants, 25% will have white
flowers.
- The larger the sample size, the
closer the results will conform to predictions.
Mendel’s
quantitative methods reflect his understanding of this statistical feature of
inheritance. Mendel’s laws of segregation and independent
assortment are based on the premise
that:
- Inheritance is a consequence of
discrete factors (genes) that are passed on from
generation
to generation.
- Segregation and assortment are
random events and thus obey the simple laws of probability.
VI.
The
relationship between genotype and
Phenotype is
rarely simple
As Mendel
described it, characters are determined by one gene with two alleles; one
allele completely
dominant over
the other. There are other patterns
of
inheritance not described by Mendel, but his laws of segregation and
independent assortment can be extended to these more complex cases.
A. Incomplete
Dominance
In cases of incomplete dominance, one allele is
not
completely dominant over the other, so the
heterozygote has a phenotype that is
intermediate
between the phenotypes of the hemozygotes.
Incomplete dominance=Pattern of
inheritance in
which the dominant phenotype is not fully
expressed in the heterozygote, resulting in
a
phenotype intermediate between the
homozygous
dominant and homozygous recessive.
- For example, when red
snapdragons(RR) are crossed with white snapdragons(rr), all F1 hybrids
(Rr) have pink flowers. (The
heterozygote produces half as much red pigment as the homozygous
red-flowered plant.)
- Since the heterozygous can be
distinguished
from
homozygotes by their phenotypes, the phenotypic and genotypic ratios from a
mono-
hybrid
cross are the same-1:2:1.
- Incomplete dominance is not support for the
blending
theory of inheritance, because alleles
maintain
their integrity in the heterozygote and segregate during gamete formation. Red and
white
phenotypes reappear in the F2 generation.
B. What Is a
dominat Allele?
Dominance/recessiveness relationships among
alleles vary in a continuum from complete
dominance on one end of the spectrum
to
codominance on the other, with various
degrees of
incomplete dominance in between these
extremes.
Complete
dominance=Inheritance
characterized by an allele that is fully expressed in the phenotype of
a heterozygote and
that masks the phenotypic expression of the recessive allele, state in which
the phenotypes of the heterozygote and dominant
homozygote are
indistinguishable.
Codominance=Inheritance characterized
by full expression of both alleles in the heterozygote.
o
For
example, the MN blood-group locus codes
for the production of surface glycoproteins
on the red blood cell. In this system, there
are three blood types: M, N, and MN.
o
The
MN blood type is the result of full
phenotypic expression of both alleles in the
heterozygote; both molecules, M and N, are
produced on the red blood cell.
Apparent
dominance/recessiveness relationships
among
alleles reflect the level at which the
phenotype
is studied. For example:
o
Tay-Sachs disease is a rare inherited disease
in humans, only children who are homozygous
recessive for the Tay-Sachs allele have the disease.
o
Brain
cells of Tay-Sachs babies lack a crucial lipid-metabolizing enzyme. Thus, lipids
accumulate in the brain, causing the disease
symptoms and ultimately leading to death.
o
At
the organismal level, since
hetrozygotes are symptom free, it appears that the normal allele is completely
dominant and the Tay-Sachs allele
is recessive.
o
At
the biochemical level, inheritance of
Tay-Sachs seems to be incomplete dominance of the normal allele, since there is
an intermediate phenotype.
Heterozygotes have an enzyme activity level that is intermediate between
individuals homozygous for the normal allele
And individuals with Tay-Sachs Disease.
o
At
the molecular level, the normal
allele and the Tay-Sachs allele are actually codominant.
Heterozygotes produce equal numbers of normal and
dysfunctional enzymes. They lack
disease symptoms, because half the normal amount of
Functional enzyme is sufficient to prevent lipid
accumulation in the brain.
Dominance/recessiveness
relationships among alleles:
o
are
a consequence of the mechanism that determines phenotypic expression, not the
ability of one allele to subdue another at the level
of the DNA.
o
Do
not determine the relative abundance of alleles in a population.
Þ
In
other words, dominant alleles are not
necessarily more common and recessive
alleles more rare.
Þ For example, the allele for
polydactyly is quite rare in the U.S. (1 in 400 births),
Yet it is caused by a dominant allele. (Polydactyly is the condition of having
extra fingers or toes.)
Marilyn
Monroe-What famous sex symbol had six toes
on
each foot?
C. Multiple Alleles
Some genes may have multiple alleles; that is,
more than just two alternative forms of a
gene.
The inheritance of the ABO blood group is an
Example of a locus with three alleles.
Paired
combinations of three alleles produce four
Possible
phenotypes:
o
Blood
type A, B, AB, or O.
o
A
and B refer to two genetically determined
Polysaccharides(A and B antigens)which are
Found on the surface of red blood cells.
There
are three alleles for this gene: IA,
IB and I
o
The
IA allele codes for the production of A antigen, and IB allele codes
for the production of B antigen, and the I allele codes for no antigen
production on the red blood cell (neither A or B)
o
Alleles
IA and IB are codominant since both are expressed in herteozygotes
o
Alleles
IA and IB are dominant to allele I, which is recessive
o
Even
though there are three possible alleles, every person carries only two alleles
which specify their ABO blood type; one allele is inherited from each parent
Sine
there are three alleles, there are six possible genotypes:
|
Blood
Type |
Possible
Genotyes |
Antigens
on the red blood cell |
Anitbodies
in the serum |
|
A |
IAIA
|
A |
Anti-B |
|
B |
IBIB |
B |
Anti-A |
|
AB |
IAIB |
A,B |
----- |
|
O |
ii |
----- |
Anti-A Anti-B |
Foreign
antigens usually cause the immune system to respond by producing antibodies,
globular proteins that bind to the foreign molecules causing a reaction that
destroys or inactivates it. In the ABO
blood system:
o
The
antigens are located on the red blood cell and the antibodies are in the serum
o
A
person produces antibodies against foreign blood antigens (those not possessed
by the individual). These antibodies
react with the foreign antigens causing the blood cells to clump or agglutinate,
which may be lethal
o
For
a blood transfusion to be successful, the red blood cell antigens of the donor
must be compatible with the antibodies of the recipient
D. Pleiotropy
Pleitropy- The ability of a single gene
to have multiple phenotypic effects
o
There
are many heredity in which a single defective genes causes complex sets of
symptoms (e.g. sickle-cell anemia)
o
One
gene can also influence a combination of seemingly unrelated
characteristics. For example, in tigers
and Siamese cats, the gene that controls fur pigmentation also influence the
connections between a cat’s eyes and the brain. A defective gene causes both abnormal and cross-eye condition
E. Epistasis
Different
genes can interact to control the phenotypic expression of a single trait. In some cases. A gene at one locus alters
the phenotypic expression of a second gene, a condition known as epistasis
Epistasis-
(Epi= upon, stasis= standing) Interaction between two nonallelic genes in which
one modifies the phenotypic expression of the other
o
If
one gene suppresses the phenotypic expression of another, the first gene is
said to epistastic to the second
o
If
epistasis occurs between two nonallelic genes, the phenotypic ratio resulting
from a dihybrid cross will deviate from the 9:3:3:1 Mendelian ratio
o
For
example, in mice and other rodents, the gene for pigment deposition © is epistatic
to the gene for pigment (melanin) production.
In other words, whether the pigment can be deposited in the fur
determines whether the coat color can be expressed. Homozygous recessive for pigment deposition (cc) will result in
an albino mouse regardless for the genotype at the black/ brown locus (BB, Bb,
or bb):
CC, Cc= Melanin deposition
cc= Albino
BB,Bb= Black coat color
bb= Brown coat color
o
Even
though both genes affect the same character (coat color), they are inherited
separately and will assort independently during gamete formation. A cross between black mice that are
heterozygous for the two genes results in a 9:3:4 phenotypic ratio:
9 Black (B_C_)
3 Brown (bbC_)
4 Albino(_cc)
F. Polygenic Inheritance
Mendel’s
characters could be classified on an either-or basis, such as purple versus
white flower. Many characters, however,
are quantitative characters that vary in a continuum within a population
Quantitative
characters- Characters that vary by degree in a continuous distribution rather
than by discrete (either-or) qualitative differences.
o
Usually,
continuous variation is determined not by one, but by many segregating loci or
polygenic inheritance
Polygenic
inheritance- Mode of inheritance in which the additive effect of two or more
genes determines a single phenotypic character
For
example, skin pigmentation in humans appears to be controlled by at least three
separately inherited genes. The
following is a simplified model for the polygenic inheritance of skin color:
o
Three
genes with the dark-skin allele (A,B,C) contribute one “unit” of darkness to
the phenotype. These alleles are
incompletely dominant over the alleles (a,b,c).
o
An
AABBCC person would be very dark and
an aabbcc person would be very light
o
An
AaBbCc person would have skin of an intermediate shade
o
Because
the alleles have a cumulative effect, genotypes AaBbCc and AABbcc make the same
genetic contribution (three “units”) to skin darkness.
o
Environmental
factors, such as sun exposure, could also affect the phenotype
G. Nature versus
Nature: The Environmental Impact of
Phenotype
Environmental conditions can influence the
phenotypic expression of a gene, so that a single genotype may produce a range
of phenotypes. This
environmentally-induced phenotypic range is the norm of reaction for the genotype.
Norm
of reaction- Range of phenotypic variability produced by a single genotype
under various environmental conditions.
Norms of reaction for a genotype:
o
May
be quite limited, so that a genotype only produces a specific phenotype, such
as the blood group locus that determines ABO blood type
o
May
also include a wide range of possibilities.
For example, an individual’s blood cell count varies with environmental
factors such as altitude, activity level or infection
o
Are
generally broadest for polygenic characters, including behavioral traits
The
expression of most polygenic traits, such as skin color, is multifactorial; that is, it depends upon
many factors- a variety of possible genotypes, as well as a variety of
environmental influences
H. Integrating a Mendelian
View of Heredity and Variation
These patterns of inheritance that are departures
from Mendel’s original description, can be integrated into a comprehensive
theory of Mendelian genetics.
o
Taking
a holistic view, an organism’s entire phenotype reflects its overall genotype
and unique environmental history
o
Medelism
has broad applications beyond it original scope; extending the principles of
segregation and independent assortment helps explain more complex hereditary
pattersn such as epistasis and quantitative characters
VII.
Pedigree analysis Mendelian
patterns in human inheritance
Mendelian inheritance in humans is difficult to
study because:
o
The
human generation time is about 20 years
o
Humans
produce relatively few offspring compared to most other species
o
Well-planned
breeding experiments are impossible
Our
understanding of Mendelian inheritance in humans is based on the analysis of
family pedigrees or the results of matings that have already occurred
Pedigree-
A family tree that diagrams the relationships among parents and children across
generations and that shows the inheritance pattern of a particular phenotypic
character. By convention:
o
Squares
are males and circles are females
o
A
horizontal line connecting a male and female indicates a mating; offspring are
listed below in birth order, from left to right
o
Shaded
symbols indicated individuals showing the trait being traced
Following
a dominant trait (complete dominance).
For example, family member’s genotypes can be deduced from a pedigree
that traces the occurrence of widow’s peak, the expression of a dominant
allele.
o
If
a widow’s peak results from a dominant allele, W , then all individuals that do
not have a widow’s peak hairline must be homozygous recessive (ww). The genotypes
of all recessive can be written on the pedigree
o
If
widow’s peak results from a dominant allele, W, then individuals that have a
widow’s peak hairline must be homozygous dominant (WW) or heterozygous (Ww)
o
If
only some of the second generation offspring have a widow’s peak, then the
grandparents that show the trait must be heterozygous (Ww).
o
Second
generation offspring with widow’s peaks must by heterozygous, because they are
the result of Ww x ww matings
o
The
third generation sister with widow’s peak may be either homozygous dominant
(WW) or heterozygous (Ww), because her parents are both heterozygous
Pedigre
analysis can also be used to:
o
Deduce
whether a trait is determined by a recessive or dominant allele. Using the example above:
The first-born third generation daughter has
attached earlobes. Since both parents
lack the trait, it must not be determined by a dominant allele
o
Predict
the occurrence of a trait in future generations. For example, if the second generation couple decide to have
another child,
What is the probability the child will have a
widow’s peak? From a mating of Ww x Ww:
Probability
of a child being WW= ¼
Probability
of a child being Ww= 2/4
Probability
of widow’s peak= ¾
What is the probability the child will have attached
earlobes? From a mating of Ff x Ff:
Probability
of a child being ff= ¼
What is the probability the child will have a
widow’s peak and attached earlobes? From the cross of WwFf x WwFf, use the rule
of multiplaction
¾
(probability of widow’s peak) x ¼ (probability of attached earlobes)= 3/16
This
type of analysis is important to geneticists and physicians, especially when
the trait being analyzed can lead to a disabling or lethal disorder
VIII.
Many human disorders follow
Mendelian patterns of inheritance
A.Recessively Inherited
Disorders
Recessive
alleles that cause human disorders are usually defective versions of normal
alleles
o
Defective
alleles code for either a malfunctional protein or no protein at all
o
Heterozygotes
can be phenotypically normal, if one copy of the normal allele is all that is
needed to produce sufficient quantities of the specific protein
Recessively
inherited disoders range in severity from nonlethal traits (e.g. albinism) to
lethal diseases (e.g. cystic fibrosis).
Since these disorders are caused by recessive alleles:
o
The
phenotypes are expressed only in homozygotes (aa) who inherit one recessive
allele from each parent
o
Heterozygotes
(Aa) can be phenotypically normal and act as carriers, possibly transmitting
the recessive allele to their offspring (50%)
Most
people with recessive disorders are born to normal parents, both of whom are
carriers
o
The
probability is ¼ that a mating of two carriers (Aa x Aa) will produce a
homozygous recessive zygote
o
The
probability is 2/3 that a normal child from such a mating will be a
heterozygote, or a carrier
Human genetic disorders are not usually evenly distributed among all racial and
cultural groups due to the different genetic histories of the world’s
people. Three examples of such
recessively inherited disorders are cystic fibrosis, Tay-Sachs disease and
sickle-cell disease
Cystic
fibrosis the most common lethal genetic disease in the United States, strikes 1
in every 2,500 Caucasians (it is much rarer in other races)
o
Four
percent of the Caucasian population are carriers
o
The
dominant allele codes for a membrane protein that controls chloride traffic
across the cell membrane. Chloride
channels are defective or absent in individuals that are homozygous recessive
for the cystic fibrosis allele
o
Disease
symptoms result from the accumulation of thickened mucus in the pancreas and
lungs
Tay-Sachs
disease occurs in 1 out of 3,600 births.
The incidence is about 100 times higher among Ashkenazic (centeral
European) Jews than among Sephardic (Mediterranen) Jews and non-Jews
o
Brain
cells of babies with this disease are unable to metabolize gangliosides (a type
of lipid), because a crucial enzyme does not function properly
o
As
lipids accumulate in the brain, the infant begins to suffer seizures, blindness
and degeneration of motor and mental performance. The child usually dies after a few years (by four years).
Sickle-cell
disease is the most common inherited disease among African-Americans. It affect 1 in 400 African-Americans born in
the United States
o
The
disease is caused by a single amino acid substitution in hemoglobin
o
The
abnormal hemoglobin molecules tend to link together and crystallized,
especially when blood oxygen content is lower than normal. This causes red blood cells to deform from
the normal disk-shape to a sickle-shape
o
The
sickled cells clog tiny blood vessels, causing the pain and fever
characterisitics of a sickle-cell crisis
About
1 in 10 African-Americans are heterozygous for the sickle-cell allele and are
said to have sickle-cell trait
o
These
carriers are usually healthy, although some suffer symptoms after an extended
period of low blood oxygen levels
o
Carriers
can function normally because the two alleles are codominant (Heterozygotes
produce not only the abnormal hemoglobin but also normal hemoglobin)
o
The
high incidence of Heterozygotes is related to the fact that in tropical Africa
where malaria is endemic, Heterozygotes have enhanced resistance to malaria
compared to normal Homozygotes. Thus,
Heterozygotes have an advantage over both Homozygotes-those who have sickle
cell disease and those who have normal hemoglobin
The probability of inheriting the same rare harmful allele from both parents,
is greater if the parents are closely related.
Consanguinity=
A genetic relationship that results
from shared ancestry
o
The
probability is higher that consanguineous matings will result in Homozygotes
for harmful rexessives, since parents with recently shared ancestry are more
likely to inherit the same recessive alleles than unrelated persons
o
It
is difficult to accurately assess the extent to which human consanguinity
increases the incidence of inherited diseases, because embryos homozygous for
deleterious mutations are affected so severely that most are spontaneously
aborted before birth
o
Most
cultures forbid marriage between closely related adults. This may be the result of observations and
stillbirths and births defects are more common when parents are closely related
B. Dominantly Inherited
Disorders
Some
human disorders are dominantly inherited
o
For
example, achondroplasia (a type of dwarfism) affects 1 in 10,000 people who are
Heterozygotes for this gene
o
Homozygous
dominant condition results in spontaneous abortion of the fetus, and homozygous
recessives are of normal phenotype (99.9% of the population)
Lethal
dominant alleles are much rather than lethal recessives, because they:
o
Are
always expressed, so their effects are not masked in Heterozygotes
o
Usually
result from new genetic mutations that occur in gametes and later kill the developing
embryo
Late-acting
lethal dominants can escape elimination if the disorder does not appear until
an advanced age age afflicted individuals may have transmitted the lethal gene
to their children. For example,
o
Huntington’s
disease a degenerative disease of the nervous system, is caused by a
late-acting lethal dominant allele. The
phenotypic effects do not appear until 35 to 40 years of age. It is irreversible and lethal once the
deterioration of the nervous system begins
o
Molecular
geneticists have recently located the gene for Huntington’s near the tip of
chromosomes #4
o
Children
of an afflicted parent have a 50% chance of inheriting the lethal dominant
allele. A newly developed test can
detect the Huntington’s allele before disease symptoms appear
C. Multifactorial Disorders
Not
all hereditary diseases are simple Mendelian disorders; that is, disease caused
by the inheritance of certain alleles at a single locus. More commonly, people are afflicted by
multifactorial disorders, disease that have both genetic and environmental
influences
o
Examples
include heart disease, diabetes, cancer, alcoholism and some forms of mental
illness
o
The
hereditary component is often polygenic and poorly understood
o
The
best public-health strategy is to educate people about the role of
environmental and behavioral factors that influence that development of these
diseases
IX.
Technology is providing new
tools for genetic testing and counseling
Genetic
counselors in many hospitals can provide information to prospective parents
concerned about a family history for a genetic disorder
o
This
preventative approach involves assessing the risk that a particular genetic
disorder will occur
o
Risk
assessment includes studying the family history for the disease using Mendel’s
law of segregation to deduce the risk
For
example, a couple is planning to have a child, and both the man and woman had
siblings who died from the same recessively inherited disorder. A genetic counselor could deduce the risk of
their first child inheriting the disease by using the law of probability:
Question: What is the probability that the
husband and wife are each carriers?
Answer:
The genotypic ratio from an Aa x Aa cross is 1 AA:2 Aa:1 aa. Since the parents are normal, they have a
2/3 of being carriers
Question: What is chance of two
carriers having a child with the disease?
Answer:
½ (mother’s chance of passing on the gene) x ½ (father’s chance of
passing on the gene)= ¼
Question:
What is the probability that their firstborn will have the disorder?
Answer:
(Chance that the father is a carrier) x (chance that the mother is a
carrier) x (chances of 2 carriers having a child with the disease)
2/3 x 2/3 x ¼= 1/9
If
the first child is born with the disease, what is the probability that the
second child will inherit the disease?
o
If
the first child is born with the disease, then it is certain that both the man
and the woman are carriers. Thus, the
probability that other children produced by this couple will have the disease
is ¼
o
The
conception of each child is an independent event, because the genotype of one
child does not influence the genotype of the other children. So there is a ¼ chance that any addition
child will inherit the disease
A. Carrier Recognition
Several
tests are available to determine if prospective parents are carriers of genetic
disorders
o
Tests
are currently available that can determine Heterozygous carriers for the
Tay-Sachs allele, cystic fibrosis, and sickle-cell disease
o
Tests
such as these enable people to make informed decisions about having children,
but they could also be abused. Ethical
dilemmas about how this information should be used points to the immense social
implications of such technological advances
B.
Fetal Testing
A
couple that learns they are both carriers for a genetic disease and decide to
have a child can determine if the fetus has the disease. Between the 14th and 16th
weeks of pregnancy, amniocentesis,
can be done to remove amniotic fluid for testing
o
During
amniocentesis, a physician inserts a needle into the uterus and extracts about
10 mL of amniotic fluid
o
The
presence of certain chemicals in amniotic fluid indicated some genetic
disorders
o
Some
tests (including one for Tay-Sachs) are performed on cells grown in culture
from fetal cells sloughed off in the amniotic fluid. These cells can also be karyotyped to identify chromosomal
defects
Chorionic
villus sampling (CVS) is a newer technique during with a physician suctions off
a small amount of fetal tissue from the chorionic villi of the placenta
o
These
rapidly dividing embryonic cells can be karyotyped immediately, usually
providing results in 24 hours- a major advantage over amniocentesis which may
take several weeks. (Amniocentesis
requires that the cells must first be cultured before karyotyping can be done)
o
Another
advantage of CVS is that it can be performed at only 8 to 10 weeks of pregnancy
Other
techniques such as ultrasound and fetoscopy allow physicians to examine a fetus
for major abnormalities
o
Ultrasound
is a non-invasive procedure which uses sound waves to create an image of the
fetus
o
Fetoscopy
involves inserting a thin fiber-optic scope into the uterus
Amniocenteris
and fetoscopy have a 1% risk of complication such as maternal bleeding or fetal
death. Thus, they are used only when risk
of genetic disorder or birth defect is relatively high
C.
Newborn Screening
In
most U.S. hospitals, simple test are routinely performed at birth, to detect
genetic disorders such as phenylketonuria (PKU)
o
PKU
is recessively inherited and occurs in about 1 in 15,000 births in the U.S.
o
Children
with this disease cannot properly break down the amino acid phenylalanine
o
Phenylalanine
and it by-product (phenylpyruvix acid) can accumulate in the blood to toxic
levels, causing mental retardation
o
Fetal
screening for PKU can detect the deficiency in a newborn and retardation can be
prevented with a special diet(low in phenylalanine) that allows normal
development