Transcript lecture 11, part 1, beyond mendel, 042809c

Beyond Mendel
Lecture 11, Part 1
Nicholas, Alexandra, and Children
http://img.dailymail.com.uk
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Much of the text material in the lecture notes is from our textbook,
“Essential Biology with Physiology” by Neil A. Campbell, Jane B.
Reece, and Eric J. Simon (2004 and 2008). I don’t claim authorship.
Other sources were sometimes used, and are noted.
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Outline
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Complex inheritance patterns
Incomplete dominance
Co-dominance
Pleiotropy
Polygenic inheritance
Chromosomal basis of inheritance
Linked genes and recombination
Sex-linked genetic disorders
Words and terms to know
Possible test items
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Complex Inheritance Patterns
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Mendel’s work explains how genes are passed down through generations
based on simple rules of probability.
Although his principles apply to all sexually-reproducing organisms, they
do not explain all patterns of genetic inheritance.
The principles of segregation and independent assortment fail to explain
inherited physical characteristics that can exist in more than two clear-cut
variants.
Inheritance patterns can be complex, as will be discussed in this lecture.
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Snapdragons
http://www.elliotbaker.com
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Incomplete Dominance
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In Mendel’s pea plants, the F1 hybrids looked like one of the parents
because the dominant alleles had the same effect on the organism’s
phenotype.
In other organisms, F1 hybrids can have an appearance between that
of the two parents.
When red snapdragons and white snapdragons are crossed, all of the
F1 hybrids have pink flowers.
In the F2 offspring, the genotype ratios are 1:2:1, just as we found for
pea plants.
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Punnett Squares—Snapdragons
R
Red flowers
r
Rr
R
Rr
F1 generation
r
Rr
Yields
All are pink flowers (Rr)
Rr
R
Pink flowers
F2 generation
R
RR
r
Rr
r
Rr
rr
White flowers
Pink flowers
Genotypic ratio
1 RR : 2 Rr : 1 rr
Phenotypic ratio
1 red : 2 pink : 1 white
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High Cholesterol
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High cholesterol, known medically as hypercholesterolemia, is the result of
a recessive allele (h).
Homozygous dominant individuals (HH) do not have this disorder.
Heterozygous individuals (Hh)—about one in 500 people—have blood
cholesterol levels about twice normal.
Homozygous recessive individuals (hh)—about one in a million people—
have much higher elevated cholesterol levels (about five times normal).
Cholesterol can build-up in the arteries and lead to blockages, a condition
known as atherosclerosis.
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Punnett Squares—Cholesterol Levels
Parent 1
H
Hh
HH
HH
HH
Diet and exercise can
also affect cholesterol
levels
H
h
hh
h
Parent 2
Hh
h
H
h
hh
H
HH
H
HH
h
Cholesterol levels:
HH—low
Hh—moderately high
hh—very high
H
H
hh
h
hh
hh
h
Hh
H
Hh
h
Hh
Hh
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LDL Crystals
False color electron micrograph
www.scienceclarified.com
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Low-Density Lipoproteins
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Low-density lipoproteins (LDL) are cholesterol-containing molecules in
the blood.
The H allele is responsible for the production of LDL receptors in the cell
membrane that enable the cells to uptake and breakdown cholesterol.
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Genetic Basis
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The HH genotype assures a full complement of LDL receptors—the LDL
levels are generally within normal limits.
The Hh genotype has about one-half the normal number of LDL receptors—
LDL levels are twice as high as in the HH genotype.
The hh genotype lacks LDL receptors, allowing LDL to accumulate at very
high levels.
Cholesterol-lowering drugs, such as the statins, can be effective in treating
high cholesterol.
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Human Blood
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So far, we have discussed inheritance patterns involving two alleles (one on
each homologous chromosome pair).
Multiple alleles also exist for certain phenotypes, such as for the ABO blood
groups in humans.
http://www.cleoconference.org•
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Blood Types
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The human blood phenotypes are A, B, AB, and O.
The letters refer to two carbohydrates, known as A and B, on the surface
of red blood cells (RBCs).
RBCs may contain one carbohydrate (A or B), both carbohydrates (AB),
or neither (O).
Compatible blood types are critical for transfusion of blood from a donor
to a recipient.
If a recipient receives a foreign type (A or B), antibodies in the recipient’s
blood bind to the foreign carbohydrate, causing RBCs to clump together.
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Blood Group Compatibility
http://cache.eb.com
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The Three Alleles
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The four blood types result from combinations of three alleles, IA, IB, and
i.
IA produces carbohydrate A, IB produces carbohydrate B, and i produces
neither.
One of each of the alleles (IA, IB, and i) is inherited from each parent.
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Combinations of Alleles
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The IA and IB alleles are dominant to the i allele.
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The six combinations are:
IA *IA and IA*i have type A blood.
– IB *IB and IB*i have type B blood.
– IA* IB have type AB blood where both alleles are expressed.
– i *i have type O blood, with neither the A nor B carbohydrate present.
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Co-Dominance
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In co-dominance, both alleles are expressed, such as in the AB blood
type.
Co-dominance is different from incomplete dominance, the expression
of an intermediate trait (such as we saw in modestly-elevated levels of
blood cholesterol levels)
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Blood Type Predictor
http://www.testsymptomsathome.com
Try calculating these combinations using your knowledge of
Mendel’s principles, Punnett squares, and the alleles, IA, IB, and i.
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Blood Donor Programs
http://www.hhs.gov
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Whole blood
Platelets
National Marrow Donor Program (http://www.marrow.org)
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Pleiotropy
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So far, the examples have involved one or more genes that specify one
hereditary characteristic.
In other instances, a gene can specify a number of characteristics, which
is known as pleiotropy.
A well-known type of pleiotropy in humans is the genetic disorder, sicklecell disease.
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Sickle-Cell Disease
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Hemoglobin in red blood cells transports oxygen to the body’s tissues.
In sickle-cell disease, abnormally-shaped hemoglobin molecules are
produced.
Sickle-cell disease is a homozygous recessive disorder—the allele (ss)
must be present on both homologous chromosomes.
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Physical Effects
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In sickle-cell disease, the hemoglobin molecules tend to link together and
crystallize.
This can especially happen when the blood’s oxygen content is low due to
high altitude, overexertion, or respiratory ailments.
When hemoglobin crystallizes, the red blood cells deform to a sickle shape,
leading to a number of cascading symptoms.
http://trc.ucdavis.edu
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Sickled Red Blood Cells
http://www.nhlbi.nih.gov
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Cascading Symptoms
Breakdown of red
blood cells (RBCs)
Clumping of sickled
RBCs and clogging
of small blood
vessels
Accumulation of
sickled RBCs in the
spleen
Physical weakness
Heart failure
Spleen damage
Heart failure
Pain and fever
Anemia
Brain damage
Other organ damage
Secondar y Effec ts
Anemia
Brain damage
Other organ damage
Impaired mental
function
Impaired mental
function
Pneumonia and
other infections
Paralysis
Rheumatism
Kidney failure
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Incidence
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The disease kills about 100,000 people world-wide each year.
About one in ten African Americans is heterozygous (Ss) for the gene, but it
is rare in other ancestries.
It is the most common inherited disorder among African Americans, affecting about one in 500 newborn.
Although no cure exists, blood transfusions and certain drugs may relieve
some of the symptoms.
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Polygenic Inheritance
• Mendel studied genetic characteristics that occur on an ‘either-or’ basis.
• Many characteristics, such as human skin color, vary along a continuum
in the general population.
• Polygenic inheritance is the additive effects of two or more genes on a
single phenotype characteristic.
• This is the converse of pleiotropy, where a single gene can affect several
phenotype characteristics.
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Skin Color
http://anthro.palomar.edu
http:/cache.eb.com
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Genetic Basis
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Say, hypothetically, that skin color is controlled by just three genes each
inherited separately.
The dark-skin alleles (A, B, and C) for each gene contributes one unit of
darkness.
Each of these alleles is incompletely dominant to the light-skin alleles (a,
b, and c).
The light-skin alleles (a, b, and c) for each gene contributes one unit of
lightness.
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Combinations of Alleles
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A person who is AABBCC would have very dark skin, while a person who
is aabbcc would have very light skin.
A person who is AaBbCc would have skin of an intermediate shade.
Because the six alleles have a simple additive effect, the combination of
AaBbCc would produce the same skin color as AABbcc.
Sixty-four genotype combinations exist, resulting in seven shades of skin
color.
Units of skin darkness:
A=B=C
Units of skin lightness:
a=b=c
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A Simplified Inheritance Model
P generation
F1 generation
AABBCC x aabbcc
F1 outcomes:
1 intermediate skin shade
F2 generation
F2 outcomes:
Histogram and bellshaped distribution of
skin shades
http://fig.cox.miami.edu
1/64 (very light skin)
6/64
15/64
20/64 (intermediate skin shade)
15/64
6/64
1/64 (very dark skin)
Total = 64/64
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Environmental Factors
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Many more shades of skin color are possible than the seven depicted in
the model.
The genetic description will be incomplete no matter how well the genes
for skin color are defined.
Other shades of skin color can result from the effects of environmental
factors such as exposure to the sun.
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Genetics and the Environment
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Many human characteristics result from the interactions of genetics and
environment.
Some characteristics, such as eye color, are fully genetically determined.
Other characteristics, such as height, have an environmental component
(including diet during childhood).
Human gender identity and sexual orientation are part of the ongoing
debate about the role of genetics versus environment, or ‘nature versus
nurture.’
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Chromosomal Basis of Inheritance
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Mendel published his research in 1866, but researchers were only able to
establish the genetic processes several decades later.
Researchers noticed parallels between chromosomes and Mendel’s inheritance factors at the beginning of the 20th century.
The chromosomal basis of inheritance, an major axiom in biology, emerged.
The axiom states:
All genes are located on the chromosomes.
2. The behavior of homologous chromosomes during meiosis
and fertilization accounts for inheritance patterns from parents
to their offspring.
1.
Axiom = an established rule, principle, or law.
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Homologous Chromosomes, Revisited
Electron micrograph (false color image)
http://www.amnh.org
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Linked Genes
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Two or more genes located close together on a chromosome tend to be
inherited together.
One famous instance involved flower color and pollen shape in pea plants.
The F2 plants did not show the expected ratio predicted for a dihybrid cross.
The observed ratio is supported by examining the crossing-over patterns of
chromatids during meiosis I.
‘Linked genes’ produce phenotypes that cannot be predicted by Mendel’s
principles alone.
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Fruit Flies
http://flybase.net
Drosophila melanogaster
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Genetic Recombination
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The fruit fly, Drosophila melanogaster, is often used in genetics research
because it can be inexpensively grown, and can produce several generations within a few months.
In fruit flies, the results of crossing-over patterns can be used to map the
location of genes on chromosomes.
The farther apart two genes are on homologous chromosomes, the more
likely they will display genetic recombination since there are more points
where crossing-over can occur.
Prior to genome mapping (to be discussed next week) this technique was
the primary method for developing maps of genes that reside on chromosomes.
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Sex-Linked Genes
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In a prior lecture, we discussed the role of the X and Y chromosomes in
sexual differentiation.
The sex chromosomes also contain genes for characteristics unrelated
to genetic sex.
Any gene located on the X or Y chromosome is known as a sex-linked
gene.
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Role of the X Chromosome
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The X chromosome, due to its larger size, contains more genes than the
Y chromosome.
Thus, the X chromosome has more sex-linked genes unrelated to sexual
differentiation.
Experiments have been conducted with fruit flies to determine how sexlinked genes determine the genotypes and phenotypes of their offspring.
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Sex-Linked Disorders
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Some human genetic disorders result from recessive alleles located on the
X chromosome.
A man need only inherit one of these sex-linked alleles from his mother,
while a woman would need one from each parent, a much rarer situation.
Sex-linked disorders include red-green color blindness, hemophilia, and
Duchenne muscular dystrophy.
Males are most afflicted by these disorders.
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Rods and Cones
Electron Micrograph
http://www.medgadget.com
Cross-section through
the retina of the human
eye
www.eyedesignbook.com
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Red-Green Color Blindness
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Red-green color blindness is a common sex-linked disorder, especially in
males.
The disorder results from the malfunctioning of cones (color receptors) in
the retina of the eye.
In some affected people, red or green hues may appear to be gray, and in
others, confusion may exist over different shades of these colors.
Although males are usually affected, a small number of females may have
similar problems.
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Ishihara Color Plate
http://www.mediacollege.com
What embedded figure do you see?
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Hemophilia
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Hemophilia is a sex-linked recessive disorder—it usually affects males.
Individuals with the disorder bleed excessively when injured because of an
abnormal allele on the X chromosome for production of platelets that
enable blood clotting.
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Victoria, Queen of England
http://www.btinternet.com
1819-1901
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A Famous Case Study
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In the 18th century, hemophilia plagued the royal families of Europe, who
were often closely related through intermarriage.
The first royal family member who had hemophilia was the son of Queen
Victoria of England.
The allele may have occurred by a mutation in one of the gametes of
Victoria’s mother or father, which was passed by Victoria to her son.
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The Royal Lineage
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Hemophilia was introduced into the royal families of Prussia, Russia, and
Spain through the marriage of two of Victoria’s daughters, who carried the
recessive gene.
Queen Victoria’s granddaughter, Alexandra, was married to the last Czar
of Russia, Nicholas.
Through an analysis of family pedigree it was later demonstrated that
Alexandra was a carrier of the recessive gene, as were her mother and
grandmother.
Alexandra and Nicholas’s son, Alexis, had hemophilia—the family met a
tragic end in the overthrow of the czar and White Russia in the early 20th
century.
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http://www.ndpteachers.org
Family Pedigree
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Duchenne Muscular Dystrophy
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Duchenne muscular dystrophy is characterized by progressive weakening
and loss of muscle tissue.
Almost all cases of this sex-linked genetic disorder involve males.
The first symptoms, usually involving difficulty in standing-up, appear in
early childhood.
The child may require a wheelchair by age 12 due to continued weakening
of the muscles and difficulty in breathing.
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Amish Communities
http://riversaredamp.files.wordpress.com
Road sign,
southeastern
Pennsylvania
http://www.valpo.edu
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Incidence
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In the United States, one in 3,500 male newborn are affected, but the rate
can be much higher in some historically-closed populations such as the
Amish.
In an Amish community in Indiana, one out of 100 male new-born has the
disorder.
DNA technology enabled the mapping of the gene to the X chromosome.
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Pennsylvania Amish Country
http://www.yodersamishhome.com
http://welshwilderness.files.wordpress.com
http://www.plainandsimplequilts.com
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Words and Terms to Know
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ABO blood groups
Co-dominance
Chromosomal basis of inheritance
Duchenne muscular dystrophy
Environmental factors
Hemophilia
High cholesterol
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Incomplete dominance
Pleiotropy
Polygenic inheritance
Red-green color blindness
Sex-linked disorders
Sex-linked genes
Sickle-cell disease
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Possible Test Items
1. Describe the differences between incomplete genetic dominance and
co-dominance.
2. Describe the differences between pleiotropy and polygenic inheritance.
3. Describe two sex-linked genetic disorders including causes, symptoms,
and prognosis.
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