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Extending Mendelian Genetics
1. Complete Dominance
2. Incomplete
Dominance
3. Codominance
4. Polygenic
5. Pleiotropic
6.
7.
8.
9.
Sex-linked
Epistasis
Collaboration
Complementary genes
10.Genomic Imprinting
11.Extranuclear genes
Other vocab:
•Penetrance
•Expressivity
• Because an allele is dominant does not
necessarily mean that it is more common in a
population than the recessive allele.
• For example, polydactyly, in which individuals are
born with extra fingers or toes, is due to an allele
dominant to the recessive allele for five digits per
appendage.
• However, the recessive allele is far more prevalent
than the dominant allele in the population.
• 399 individuals out of 400 have five digits per
appendage.
• The heterozygous F1 offspring of Mendel’s
crosses always looked like one of the
parental varieties because one allele was
dominant to the other
• Incomplete dominance- where heterozygotes
show a distinct intermediate phenotype, not
seen in homozygotes.
• This is not blended inheritance because the traits
are separable (particulate) as seen in further
crosses.
• Offspring of a cross between heterozygotes will
show three phenotypes: both parentals and the
heterozygote.
• The phenotypic and genotypic ratios are identical,
1:2:1.
Flower color of snapdragons
• White-flowered plant
X Red-flowered
produces all pink F1.
• Self-pollination of the
F1 offspring produces:
.
-25% white,
-25% red,
-50% pink
“not blended inheritance
because the traits are
separable”
Incomplete Dominance
Codominance- two alleles affect the
phenotype in separate, distinguishable ways.
Most genes have more than two alleles in a
population. (Multiple alleles)
• The ABO blood groups in humans are
determined by three alleles, IA, IB, and i.
• Both the IA and IB alleles are dominant to the i allele
• The IA and IB alleles are codominant to each other.
• Because each individual carries two alleles,
there are six possible genotypes and four
possible blood types.
• Surface oligosaccharides
• A or B or none
Genotype
Phenotype
IOIO
Type O
IAIO
Type A
IAIA
Type A
IB IO
Type B
IB IB
Type B
IAIB
Type AB
• Matching compatible blood groups is critical for
blood transfusions because a person produces
antibodies against foreign blood factors.
• If the donor’s blood has an A or B oligosaccharide
that is foreign to the recipient, antibodies in the
recipient’s blood will bind to the foreign molecules,
cause the donated blood cells to clump together, and
can kill the recipient.
• IA IA or IA i are type A -type A oligosaccharides on the surface
• IB IB or IB i are type B - type B oligosaccharides on the surface
• IA IB are type AB -
both types on the surface
• ii are type O -
neither oligosaccharide on the surface
Dominance/recessiveness
relationships have three
important points
1. They range from complete dominance, though
various degrees of incomplete dominance, to
codominance.
2. They reflect the mechanisms by which specific
alleles are expressed in the phenotype and do not
involve the ability of one allele to subdue
another at the level of DNA.
3. They do not determine or correlate with the
relative abundance of alleles in a population.
Ability of one single gene to affect an organism
in several ways.
• Ex: In chickens, frizzle trait- malformed feathers
• Malformed feather cannot keep chicken warm, resulting in
changes in several organ systems
• Ex: Coloration in Siamese cats.
• Allele responsible for light-body/dark extremities is the same
allele that is responsible for cross-eyed.
• Ex: Marfan syndrome in humans.
• Single defective gene results in abnormalities of the eyes, the
skeleton, and the some blood vessels.
The genes that we have covered so far affect
only one phenotypic character.
• Most genes are pleiotropic, affecting more
than one phenotypic character.
• For example, the wide-ranging symptoms of sicklecell disease are due to a single gene.
Greek for “stopping”
In epistasis, a gene at one locus alters the
phenotypic expression of a gene at a second locus.
• For example, in mice and many other mammals, coat
color depends on two genes.
• One, the epistatic gene, determines whether pigment
will be deposited in hair or not.
• Presence (C) is dominant to absence (c).
• The second determines whether the pigment to be
deposited is black (B) or brown (b).
• The black allele is dominant to the brown allele.
• An individual that is cc has a white (albino) coat
regardless of the genotype of the second gene.
• A cross between two black mice that are
heterozygous (BbCc) will follow the law of
independent assortment.
• However, unlike the
9:3:3:1 phenotype
offspring ratio
of an normal Mendelian
experiment, the ratio is
nine black, three brown,
and four white. 9:3:4
One gene masks another gene
• Polygenic inheritance- the additive effects of
two or more genes on a single phenotypic
character.
• Quantitative characters- characteristic with a
continuum.
• For example, skin color in humans is controlled by at
least three different genes.
• Imagine that each gene has two alleles, one light and
one dark, that demonstrate incomplete dominance.
• An AABBCC individual is dark and aabbcc is light.
• A cross between two AaBbCc individuals
(intermediate skin shade) would produce
offspring covering a wide range of shades.
• Individuals with
intermediate skin shades
would be the most likely
offspring, but very light
and very dark individuals
are possible as well.
• The range of phenotypes
forms a normal
distribution.
• In addition to their role in determining sex, the sex
chromosomes, especially the X chromosome, have
genes for many characters unrelated to sex.
• If a sex-linked trait is due to a recessive allele, a
female will have this phenotype only if
homozygous.
• Heterozygous females will be carriers.
• Because males have only one X chromosome
(hemizygous), any male receiving the recessive
allele from his mother will express the trait.
• The chance of a female inheriting a double dose of
the mutant allele is much less than the chance of a
male inheriting a single dose.
• Therefore, males are far more likely to inherit sexlinked recessive disorders than are females.
• Several serious human disorders are sex-linked.
• Duchenne muscular dystrophy affects one in
3,500 males born in the United States.
• Affected individuals rarely live past their early 20s.
• This disorder is due to the absence of an X-linked gene
for a key muscle protein, called dystrophin.
• The disease is characterized by a progressive weakening
of the muscles and a loss of coordination.
• Although female mammals inherit two X
chromosomes, only one X chromosome is active.
• Therefore, males and females have the same
effective dose (one copy ) of genes on the X
chromosome.
• During female development, one X chromosome per
cell condenses into a compact object, a Barr body.
• This inactivates most of its genes.
• The condensed Barr body chromosome is
reactivated in ovarian cells that produce ova.
• Mary Lyon, a British geneticist, has demonstrated
that the selection of which X chromosome to form
the Barr body occurs randomly and independently
in embryonic cells at the time of X inactivation.
• As a consequence, females consist of a mosaic of
cells, some with an active paternal X, others with
an active maternal X.
• After Barr body formation, all descendent cells have the
same inactive X.
• If a female is heterozygous for a sex-linked trait,
approximately half her cells will express one allele and
the other half will express the other allele.
• In humans, this mosaic pattern is evident in women
who are heterozygous for a X-linked mutation that
prevents the development of sweat glands.
• A heterozygous woman will have patches of normal
skin and skin patches lacking sweat glands.
Similarly, the orange and black pattern on
tortoiseshell cats is due to patches of cells
expressing an orange allele while others have
a nonorange allele.
Collaboration
• When two genes interact to produce a novel phenotype
• Ex: Comb shape in chickens.
• R=rose comb
• r= single comb
• P= pea comb
• p=single comb
• RP=walnut
(collaboration)
Rose
Single
Pea
Walnut
Complementary Genes
Mutually dependent.
The expression of each depends upon the alleles of the other.
Type of epistatic interaction
Ex: Flower color in sweet peas.
Dominate alleles- A&B code for an enzyme that catalyzes
two separate reactions in the production of purple pigment.
In order for the purple to be produced, both reactions
must take place. ( if missing A-no purple, if missing B-no
purple)
In squash, color is recessive to no color
at one allelic pair. This recessive allele
must be expressed before the specific
color allele at a second locus is
expressed. At the first gene white colored
squash is dominant to colored squash,
and the gene symbols are W=white and
w=colored. At the second gene yellow is
dominant to green, and the symbols used
are G=yellow, g=green. If the dihybrid is
selfed, three phenotypes are produced in
a 12:3:1 ratio. The following table
explains how this ratio is obtained.
The phenotypic effects of some
mammalian genes depend on whether they
were inherited from the mother or the
father (imprinting)
• For some traits in mammals, it does depend on which
parent passed along the alleles for those traits.
• The genes involved are not sex linked and may or may not lie
on the X chromosome.
Genomic Imprinting
• Expression depends on inheritance- mother or father
• Cause of several genetic disorders
• Prader-Willi syndrome
• A deletion on chromosome 15.
• Mental retardation, obesity, short stature, small hands
• father
• Angelman syndrome
• A deletion on chromosome 15.
• Spontaneous laughter, jerky movements, mental deficiencies.
• mother
• Fragile X syndrome
• Abnormal X chromosome.
The difference between the disorders is due to
genomic imprinting.
• In this process, a gene on one homologous
chromosome is silenced, while its allele on the
homologous chromosome is expressed.
• The imprinting status of a given gene depends
on whether the gene resides in a female or a
male.
• The same alleles may have different effects on
offspring, depending on whether they arrive in the
zygote via the ovum or via the sperm.
• In the new generation,
both maternal and
paternal imprints are
apparently “erased” in
gamete-producing cells.
• Then, all chromosomes
are reimprinted
according to the sex of
the individual in which
they reside.
• In many cases, genomic imprinting occurs when
methyl groups are added to cytosine nucleotides on
one of the alleles.
• Heavily methylated genes are usually inactive.
• The animal uses the allele that is not imprinted.
• In other cases, the absence of methylation in the
vicinity of a gene plays a role in silencing it.
• The active allele has some methylation.
• Several hundred mammalian genes, many critical
for development, may be subject to imprinting.
• Imprinting is critical for normal development.
• Found in Mitochondria and chloroplasts.
• Linked to some rare and severe inherited diseases.
• Defects in Mito. DNA reduces the amt of ATP a
cell can make.
• Affects nervous and musculature systems.
• Ones that need the most energy
• Always inherited from the mother.
3. Extranuclear genes exhibit a nonMendelian pattern of inheritance
• Not all of a eukaryote cell’s genes are located in the
nucleus.
• Extranuclear genes are found on small circles of
DNA in mitochondria and chloroplasts.
• These organelles reproduce themselves.
• Their cytoplasmic genes do not display Mendelian
inheritance.
• They are not distributed to offspring during meiosis.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• Karl Correns first observed cytoplasmic genes in
plants in 1909.
• He determined that the coloration of the offspring
was determined only by the maternal parent.
• These coloration patterns are due to genes in the
plastids which are inherited only via the ovum, not
the pollen.
Fig. 15.16
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• Because a zygote inherits all its mitochondria only
from the ovum, all mitochondrial genes in
mammals demonstrate maternal inheritance.
• Several rare human disorders are produced by
mutations to mitochondrial DNA.
• These primarily impact ATP supply by producing
defects in the electron transport chain or ATP synthase.
• Tissues that require high energy supplies (for example,
the nervous system and muscles) may suffer energy
deprivation from these defects.
• Other mitochondrial mutations may contribute to
diabetes, heart disease, and other diseases of aging.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Penetrance
• The frequency (expressed as a percent) with which
individuals of a given genotype manifest at least
some degree of a specific mutant phenotypes.
Expressivity
• Range of expression of mutant gene
“Nature vs. Nurture”
• Phenotype depends on environment and genes.
• A single tree has leaves that vary in size, shape, and
greenness, depending on exposure to wind and sun.
• For humans, nutrition influences height, exercise
alters build, sun-tanning darkens the skin, and
experience improves performance on intelligence
tests.
Multifactorial Characters
The product of a genotype is generally not a
rigidly defined phenotype, but a range of
phenotypic possibilities, the norm of reaction,
that are determined by the environment.
• Norms of reactions are broadest for polygenic
characters.
• For these multifactorial
characters, environment
contributes to their
quantitative nature.
Mendelian Inheritance in Humans
1.Pedigree analysis reveals Mendelian
patterns in human inheritance
2.Technology is providing news tools
for genetic testing and counseling
Introduction
• While peas are convenient subjects for
genetic research, humans are not.
• The generation time is too long, fecundity too low,
and breeding experiments are unacceptable.
• Yet, humans are subject to the same rules
regulating inheritance as other organisms.
• New techniques in molecular biology have led
to many breakthrough discoveries in the
study of human genetics.
1.Pedigree analysis reveals Mendelian patterns
in human inheritance
• Geneticists analyze the results of matings that have already occurred.
• Create pedigrees.
• Analyze- can collect information across generations.
A pedigree can help us understand the past and to predict the future.
• For example: occurrence of widows peak (W) is
dominant to a straight hairline (w).
• The relationship among alleles can be integrated with
the phenotypic appearance of these traits to predict
the genotypes of members of this family.
Determining pattern of inheritance from a
pedigree.
• Autosomal
• dominant
• recessive
• Sex-linked
•X
•Y
Autosomal-Dominant
SEX-LINKED-X
SEX-LINKED-Y
1. Both sexes
2. All
generations
Autosomal
-Dominant
1. Both sexes
2. Skips generations
Autosomal
-Recessive
????
• Mitochondrial
2. Technology is providing new tools for
genetic testing and counseling
• A preventative approach to simple Mendelian
disorders is sometimes possible.
• The risk that a particular genetic disorder will occur
can sometimes be assessed before a child is
conceived or early in pregnancy.
• Many hospitals have genetic counselors to provide
information to prospective parents who are
concerned about a family history of a specific
disease.
Amniocentesis
• Tests in utero if a child has a particular disorder.
• Can be used beginning at the 14th to 16th week of
pregnancy.
• Fetal cells extracted from amniotic fluid are cultured and
karyotyped to identify some disorders.
• Other disorders can be identified from chemicals in the
amniotic fluids.
• A second technique, chorionic villus sampling (CVS)
can allow faster karyotyping and can be performed as
early as the 8th to 10th week of pregnancy.
• This technique extracts a sample of fetal tissue from the
chrionic villi of the placenta.
• This technique is not suitable for tests requiring amniotic
fluid.
• Other techniques, ultrasound and fetoscopy, allow
fetal health to be assessed visually in utero.
• Both fetoscopy and amniocentesis cause
complications in about 1% of cases.
• These include maternal bleeding or fetal death.
• Therefore, these techniques are usually reserved for
cases in which the risk of a genetic disorder or other
type of birth defect is relatively great.
• If fetal tests reveal a serious disorder, the parents
face the difficult choice of terminating the
pregnancy or preparing to care for a child with a
genetic disorder.
• Recently developed tests for several disorders can
distinguish between normal phenotypes in
heterozygotes from homozygous dominants.
• The results allow individuals with a family history
of a genetic disorder to make informed decisions
about having children.
• However, issues of confidentiality, discrimination,
and adequate information and counseling arise.
• Some genetic tests can be detected at birth by
simple tests that are now routinely performed in
hospitals.
• One test can detect the presence of a recessively
inherited disorder, Phenylketonuria (PKU).
• This disorder occurs in one in 10,000 to 15,000 births.
• Individuals with this disorder accumulate the amino
acid phenylalanine and its derivative phenypyruvate in
the blood to toxic levels.
• This leads to mental retardation.
• If the disorder is detected, a special diet low in
phenyalalanine usually promotes normal development.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• One such disease is cystic fibrosis, which strikes
one of every 2,500 whites of European descent.
• One in 25 whites is a carrier.
• The normal allele codes for a membrane protein that
transports Cl- between cells and the environment.
• If these channels are defective or absent, there are
abnormally high extracellular levels of chloride that
causes the mucus coats of certain cells to become
thicker and stickier than normal.
• This mucus build-up in the pancreas, lungs, digestive
tract, and elsewhere favors bacterial infections.
• Without treatment, affected children die before five, but
with treatment can live past their late 20’s.
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• Tay-Sachs disease is another lethal recessive
disorder.
• It is caused by a dysfunctional enzyme that fails to
break down specific brain lipids.
• The symptoms begin with seizures, blindness, and
degeneration of motor and mental performance a few
months after birth.
• Inevitably, the child dies after a few years.
• Among Ashkenazic Jews (those from central Europe)
this disease occurs in one of 3,600 births, about 100
times greater than the incidence among non-Jews or
Mediterranean (Sephardic) Jews.
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• The most common inherited disease among blacks
is sickle-cell disease.
• It affects one of 400 African Americans.
• It is caused by the substitution of a single amino acid in
hemoglobin.
• When oxygen levels in the blood of an affected
individual are low, sickle-cell hemoglobin crystallizes
into long rods.
• This deforms red blood cells into a sickle shape.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• This sickling creates a cascade of symptoms,
demonstrating the pleiotropic effects of this allele.
• Doctors can use
regular blood
transfusions to
prevent brain
damage and new
drugs to prevent
or treat other
problems.
Fig. 14.15
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• At the organismal level, the non-sickle allele is
incompletely dominant to the sickle-cell allele.
• Carriers are said to have the sickle-cell trait.
• These individuals are usually healthy, although some
suffer some symptoms of sickle-cell disease under
blood oxygen stress.
• At the molecule level, the two alleles are
codominant as both normal and abnormal
hemoglobins are synthesized.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• The high frequency of heterozygotes with the
sickle-cell trait is unusual for an allele with severe
detrimental effects in homozygotes.
• Interestingly, individuals with one sickle-cell allele have
increased resistance to malaria, a parasite that spends
part of its life cycle in red blood cells.
• In tropical Africa, where malaria is common, the sicklecell allele is both a boon and a bane.
• Homozygous normal individuals die of malaria,
homozygous recessive individuals die of sickle-cell
disease, and carriers are relatively free of both.
• Its relatively high frequency in African Americans
is a vestige of their African roots.
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• Normally it is relatively unlikely that two carriers
of the same rare harmful allele will meet and mate.
• However, consanguineous matings, those between
close relatives, increase the risk.
• These individuals who share a recent common ancestor
are more likely to carry the same recessive alleles.
• Most societies and cultures have laws or taboos
forbidding marriages between close relatives.
• Although most harmful alleles are recessive, many
human disorders are due to dominant alleles.
• For example, achondroplasia, a form of dwarfism,
has an incidence of one case in 10,000 people.
• Heterozygous individuals have the dwarf phenotype.
• Those who are not achodroplastic dwarfs, 99.99% of the
population, are homozygous recessive for this trait.
• Lethal dominant alleles are much less common than
lethal recessives because if a lethal dominant kills an
offspring before it can mature and reproduce, the
allele will not be passed on to future generations.
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• A lethal dominant allele can escape elimination if
it causes death at a relatively advanced age, after
the individual has already passed on the lethal
allele to his or her children.
• One example is Huntington’s disease, a
degenerative disease of the nervous system.
• The dominant lethal allele has no obvious phenotypic
effect until an individual is about 35 to 45 years old.
• The deterioration of the nervous system is irreversible
and inevitably fatal.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• Any child born to a parent who has the allele for
Huntington’s disease has a 50% chance of
inheriting the disease and the disorder.
• Recently, molecular geneticists have used pedigree
analysis of affected families to track down the
Huntington’s allele to a locus near the tip of
chromosome 4.
Fig. 14.15
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• While some diseases are inherited in a simple
Mendelian fashion due to alleles at a single locus,
many other disorders have a multifactorial basis.
• These have a genetic component plus a significant
environmental influence.
• Multifactorial disorders include heart disease, diabetes,
cancer, alcoholism, and certain mental illnesses, such a
schizophrenia and manic-depressive disorder.
• The genetic component is typically polygenic.
• At present, little is understood about the genetic
contribution to most multifactorial diseases
• The best public health strategy is education about the
environmental factors and healthy behavior.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings