Transcript genetics, 021816 - Biology East Los Angeles College

Biology Review
Genetics
http://evolution.berkeley.edu
Note
Much of the text material is from, “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 are noted when they are used.
2
Outline
•
•
Patterns of inheritance
Beyond Mendel
3
Patterns of Inheritance
http://www.southwesternexposure.com
4
http://kentsimmons.uwinnipeg.ca
Gregor Mendel
1822 - 1884
5
Gregor Mendel
•
Gregor Mendel was first to analyze patterns of inheritance in a systematic, scientific manner.
•
During the 1860s, he deduced the fundamental principles of genetics by
breeding garden peas in an abbey garden in Brunn, Austria, which is
now part of the Czech Republic.
•
He was strongly influenced by physics, mathematics, and chemistry in
applying experimental techniques and mathematics to the study of pea
plants and inheritance.
•
Mendel’s work, along with that of his (unknown) contemporary, Charles
Darwin, is a classic in science.
6
Inherited Characteristics
•
Mendel postulated in a paper published in 1866 that parents pass on
factors to their offspring that are responsible for inherited characteristics.
•
He found that these factors retain their uniqueness from generation to
generation—these factors are what we now call genes.
•
Mendel’s work is a major foundation of modern biology and genetics,
and provides the biological mechanism for natural selection postulated
by Darwin.
Postulate = to make a claim; to assume or assert a truth.
7
Pea flowers
http://upload.wikimedia.org
http://upload.wikimedia.org
Pea Plants
Pea pods
8
Why Study Pea Plants?
•
Mendel chose garden peas because they exist in readily distinguishable varieties and are easy to grow.
•
He could also strictly control the transfer of pollen for fertilization to
produce offspring.
•
The breeding cycle is short, so he could study many generations in a
short period of time.
9
Fertilization
•
Pea plants can self-fertilize when the pollen from the stamens settle
on the stigma of the same flower.
•
Mendel could assure self-fertilization by covering the flower with a
bag so that no pollen grains from other pea plants could reach the
stigma.
•
He controlled cross-fertilization (crosses) by pollinating other pea
plants using a small brush.
•
Using these methods, the precise parentage of the offspring could
be determined.
10
Pea Plant Characteristics
Seed shape
Seed color
Flower
position
Pod shape
Pod color
Stem
heighth
http://mac122.cu.ac.jp
Flower color
Dominant is to the left and recessive is to the right for each
of the seven characteristics that Mendel studied.
11
Monohybrid Cross
P generation (true-breeding varieties): purple flowers x white flowers
Fertilization
F1 generation: purple flowers x purple flowers
Fertilization
F2 generation: 3/4 purple flowers and 1/4 white flowers
12
Genotype and Phenotype
•
Mendel’s experiment led to a conclusion that have been confirmed
many times by biologists and geneticists:
An organism’s appearance does not always reveal its inherited
traits, or genetic composition.
•
The physical traits of an organism are its phenotype, and its genetic
makeup is its genotype.
13
Mendel’s Hypothesis
1.
Alternative forms of alleles, what we now call genes, determine phenotype or inherited characteristics.
2.
For each inherited characteristic, an organism has two alleles, one
from each parent.
3.
An egg and sperm each carries an allele for each inherited characteristic, which are paired during fertilization.
4.
For each allele pair, the one that is fully expressed in the phenotype
is the dominant allele, and the one that has no noticeable effect is the
recessive allele.
Dominant alleles are represented by uppercase letters and
recessive alleles by lowercase letters.
14
Punnett Square
The Punnett square is a visual
tool for showing all combinations
of alleles of an inherited
characteristic.
Parent 2
P
p
P
PP
Pp
p
Pp
pp
Parent 1
Clockwise rotation by 45o
P
Parent 1
P
PP
p
Pp
Pp
pp
Reginald C. Punnett (1875-1967)
http://www.epidemiology.ch
p
Parent 2
PP—purple flowers
Pp—purple flowers
pp—white flowers
15
Principle of Segregation
•
Mendel found the same type of inheritance pattern occurred for all
seven characteristics of peas that he studied.
•
For a true-breeding variety, one parental trait disappears in the F1
generation and then reappears in one-fourth of the F2 generation.
•
The underlying mechanism is known as Mendel’s principle of segregation.
16
Principle of Segregation (continued)
•
The principle conveys that pairs of alleles segregate—or separate—
during meiosis, and the fusion of gametes at fertilization creates allele
pairs once again.
•
Research over the past ~150 years has shown the principle applies to
all sexually-reproducing organisms for non-linked genes (more about
this later).
17
Homologous Chromosomes
•
A pair of chromosomes, as we discussed in the lecture on reproduction, is homologous—one is from the female parent and one is from
the male parent.
•
A homologous pair has the same alleles (such as for flower color) at
the same locus, or location, on the chromosomes.
Locus = singular; loci = plural.
18
Homologous Chromosomes
(continued)
P
s
C
P
s
c
PP
ss
Cc
Homozygous
for the
dominant allele
Homozygous
for the
recessive allele
Heterozygous
Genotypes:
Homo- = same
Hetero- = different
Genes are shown as three banded colors on the chromosome fragments.
The letters for the three gene loci are arbitrary and are only used to convey
the concepts.
19
Principle of Independent Assortment
•
What would result from a dihybrid cross, the mating of parents differing
in seed shape and seed color?
•
Mendel found the yield ratios in the F2 generation were the same as if
seed shape and color were studied as separate monohybrid crosses.
•
Mendel’s principle of independent assortment states that each pair of
alleles segregates independently of other pairs of alleles during gamete
formation.
•
This is true for genes that are not linked, which Mendel fortunately happened upon in his work with pea plants.
20
Testcross
•
A testcross involves mating an organism of unknown genotype with a
known, homozygous recessive organism (Pp).
•
The unknown genotype is determined by observing the F2 yields and
inferring the parentage.
•
Mendel used the method to confirm if he had true-breeding varieties
of pea plants.
•
Testcrosses are still used by geneticists to determine unknown genotypes.
p
?
Parent 1
Parent 2
Observe
p
?
Observe
Observe
Observe
21
Can you create an example of a testcross?
22
Probability
•
The segregation of allele pairs during gamete formation (meiosis)
and the reforming of allele pairs during fertilization follow the rules
of probability.
•
The same rules apply to tossing a coin, rolling a die, and drawing
playing cards.
•
Just as in probability experiments, Mendel found that he needed to
obtain large sample sizes of F1 and F2 offspring since random variation exists.
Morgan Silver Dollar minted in 1895 (tails)
http://z.about.com
23
Probability Visualized
Pp—female
Pp—male
Meiosis
F1 genotypes
Egg (P or p)
Sperm (P or p)
(Random chance in fertilization)
http://www.rpi.edu
P 1/2
1/2 P
1/2
F2 genotypes
PP
1/4
p
Pp
1/4
p
Pp
1/4
pp
1/4
1/2
Yields:
PP = 1/4
Pp = 1/4 + 1/4 = 1/2
pp = 1/4
24
Complex Genetic Problems
•
The results for the rule of multiplication work out the same as for a
Punnett square.
•
The outcomes of trihybrid crosses involving three different characteristics can be calculated using probability rules.
•
In comparison, it would be difficult to analyze a trihybrid cross using
the Punnett tool.
•
Complex genetic problems are typically solved by applying rules of
probability to the principles of segregation and independent assortment.
25
Inheritance of Human Traits
•
Mendel’s principles apply to the inheritance of a number of human
traits including those we will discuss next.
•
Each of these traits is the result of simple dominant-recessive inheritance at one gene locus (position).
•
The genetic basis of some human characteristics, such as eye color
and hair color, are not as well understood since multiple gene loci are
involved.
26
Dominant Phenotype
•
Dominant refers to the expression of alleles in a homologous gene
pair.
•
Dominant does not imply that a phenotype is necessarily more common than a recessive phenotype.
•
For example, freckles are the result of a dominant allele but they are
not common in the general population.
27
Handedness and Cerebral Specialization
Handedness is not the result of
a single gene, and is not fullyunderstood.
Right-handed—the left hemisphere
contains the processing areas for
verbal and mathematical abilities.
Left-handed—the right hemisphere
often contains the areas for verbal
and math abilities.
Einstein’s brain, from the medical journal,
The Lancet
http://www.answers.com
28
Family Pedigree
•
Geneticists, for obvious reasons, are unable to control the matings
of humans, unlike researchers working with pea plants or other organisms.
•
Instead, they analyze the results of matings in humans that already
occurred.
29
Family Pedigree (continued)
•
A geneticist collects as much information as possible about a family’s
history for a phenotype.
•
The information is assembled into a upside-down, tree structure known
as a family pedigree.
•
The geneticist uses the concepts of dominant and recessive alleles and
the principle of segregation for analyzing family pedigree to determine if
an inheritance pattern exists.
30
Case Study
•
A classic study was the construction of family pedigrees for a rare type
of deafness on Martha’s Vineyard, a once-remote island off the coast of
Massachusetts.
•
This form of deafness results from a homozygous recessive genotype
(which we will call, dd).
•
Family members with a heterozygous genotype (Dd) are not deaf, but
they are carriers of the disorder.
•
Members with a homozygous dominant genotype (DD) are neither deaf
nor carriers.
31
http://ma.water.usgs.gov
Martha’s Vineyard
http://www.mass.gov
Martha’s
Vineyard
The isolation of Martha’s Vineyard help foster marriages between close
relatives between about 1700 and 1900. The frequency of deafness was
high since there was little exchange of alleles with outsiders.
32
Punnett Square
The appearance of deafness from generation-to-generation on Martha’s
Vineyard can be solved using either a 2 x 2 Punnett square or the rule of
multiplication.
D
Mother
D
DD
d
Dd
d
Father
Dd
dd
Which offspring of two heterozygous parents (Dd) will be deaf
and which will be carriers?
33
Family Pedigree for Deafness
http://www.myops.org
A sketch of a family pedigree showing inheritance of deafness.
Females are shown by circles and males by squares.
Deafness is indicated by dark symbols representing an allele pattern of dd.
Hearing is indicated by light symbols representing an allele pattern of DD or Dd.
34
Inheritance Patterns
•
The hereditary deafness observed on Martha’s Vineyard is one of
over a thousand genetic disorders of dominant or recessive traits
controlled by single genes.
•
These disorders have simple inheritance patterns just like the traits
Mendel studied in pea plants.
•
The genes are all located on the autosomes—that is, chromosomes
other than X and Y in the 23rd set.
35
Inbreeding
•
Mating of close relatives—called inbreeding—can produce offspring
who are homozygous for a harmful recessive trait because the allele
is more likely to be encountered.
•
Many societies have taboos and laws to forbid marriages between
close relatives.
•
The legal prohibitions may have first formed from observations that
still-births and birth defects are more common when two parents are
closely-related.
36
Inbreeding (continued)
https://g6n.wikispaces.com
Some small and isolated groups of animals, such as cheetahs, show
the detrimental effects of inbreeding, which could lead to their extinction.
http://lh6.ggpht.com
•
37
Likelihood of Genetic Disorders
•
People who share recent common ancestors are more likely to carry
the same alleles than unrelated people.
•
Due to increased mobility in modern societies, it is relatively unlikely
that two carriers of a rare and harmful allele will meet and have children.
38
Recessive Disorders
•
Human genetic disorders are usually recessive, and they they can
range in severity from relatively harmless to life-threatening.
•
Most people afflicted with recessive disorders are born to parents
who are heterozygous; that is, they are carriers but don’t have the
disorder.
•
As with the rare form of deafness on Martha’s Vineyard, the percentage of affected offspring can be predicted by the matings of the two
parents.
•
Examples of single-gene recessive disorders include albinism, sicklecell disease, Tay-Sachs, phenylketonuria, galactosemia, and cystic
fibrosis.
39
Cystic Fibrosis
Cystic fibrosis is the most common lethal genetic disorder in the United
States.
•
It affects about one in 1,800 European Americans, and is carried as a
recessive allele by about one in 25 people.
•
The disease affects about one in 17,000 African Americans, and about
one in about 90,000 Asian Americans.
http://images.cff.org
•
40
Physical Effects
•
A thick mucus is secreted by lungs, pancreas, and other body organs
in cystic fibrosis.
•
The mucus can interfere with breathing, digestion and liver function,
and can make the person more vulnerable to pneumonia and other
opportunistic bacterial infections.
•
The lives of children afflicted with the disorder can often be extended
with:
Special diets
- Frequent pounding of the chest and back to clear the lungs
- Antibiotics
- Other treatments
-
41
Dominant Disorders
•
Some human disorders are the result of dominant alleles—they
are far less common than those resulting from recessive alleles.
•
One reason for being less common is that dominant alleles also
affect the carrier.
42
Dominant Disorders (continued)
Lethal dominant alleles may kill the embryo, or the afflicted individual
may not live long enough to reproduce.
•
This is in contrast to recessive alleles passed from generation-togeneration by heterozygous carriers who do not exhibit the disorder.
•
A few dominant disorders such as extra or webbed fingers and toes,
are not lethal.
http://keckmedicine.adam.com
•
43
Achondroplasia
•
Achondroplasia is characterized by very short stature, with arms and
legs that are too short for the torso.
•
About one in 25,000 people have this disorder.
•
Only individuals with a single copy of the dominant allele (Aa) have
the disorder because the homozygous genotype (AA) results in the
death of an embryo.
•
A person with achondroplasia has a 50 percent chance (p = 0.50) of
passing the dominant allele to his or her offspring that survive to birth.
•
This pattern can be demonstrated using a Punnett square or the rule
of multiplication.
44
Resources and Support
Top
Little People of America
http://www.flickr.com
http://www.icongrouponline.com
Left
Conference gathering
http://www.ksginfo.org
45
Huntington’s Disease
•
A lethal dominant allele can escape early detection if it does not result
in death until later in life.
•
Huntington’s disease, which causes progressive degeneration of the
nervous system, is not apparent until middle age.
•
Symptoms include uncontrolled movements, memory loss, impaired
judgment, depression, and in later stages, an inability to swallow and
speak.
•
Death usually occurs 10 to 20 years after onset of the first symptoms.
46
Late Appearance of Symptoms
By the time symptoms are evident, the afflicted individual may have
had children—about half will have received the lethal dominant allele.
•
A famous case involved the singer-songwriter, Woody Guthrie, who
died from the disease in 1967, at the age of 55.
•
His children, Nora and Arlo, were at risk for the disease although they
now have passed that point in their lives.
http://www.adliterate.com
•
47
What are some basic differences between recessive and
dominant disorders?
48
Beyond Mendel
The last Russian Czar Nicholas, Alexandra, and Children
http://img.dailymail.com.uk
49
http://www.elliotbaker.com
Snapdragons
50
Incomplete Dominance
•
In Mendel’s pea plants, an F1 hybrid looked like one of the parents
due to the dominant allele.
•
In some organisms, F1 hybrids can express an intermediate phenotype between those of the two parents.
•
For example, when red and white snapdragons are crossed, all of
the F1 hybrids have pink flowers—not red flowers or white flowers.
Allele = an alternative form of a gene (one member of a pair)
that is located at a specific position on a specific chromosome.
(http://biology.about.com)•
51
High Cholesterol
•
High cholesterol, or hypercholesterolemia, is the result of a recessive
allele (we will call it “h”).
•
Homozygous dominant individuals (HH) do not have the disorder.
•
Heterozygous individuals (Hh)—about one in 500 people—have blood
cholesterol levels (LDL) about twice normal.
52
High Cholesterol (continued)
Homozygous recessive individuals (hh)—about one in a million people—
have very high elevated LDL cholesterol levels (about five times normal).
•
LDL cholesterol can build-up in the arteries and lead to blockages, a condition known as atherosclerosis.
https://middlepath.com.au
•
53
Low-Density Lipoproteins
•
Cholesterol is a lipid molecule and therefore it is not water-soluble.
•
Low-density lipoproteins (LDL) and high-density lipoproteins (HDL)
are carrier molecules for cholesterol to circulate in the blood.
•
The H allele is responsible for the production of LDL receptors in cell
plasma membranes that enable cells to uptake and breakdown cholesterol.
False color electron micrograph
www.scienceclarified.com
54
Genetic Basis
•
The HH genotype assures a full complement of LDL receptors—LDL
levels in blood circulation are typically within normal limits.
•
The Hh genotype has about one-half the number of LDL receptors on
cells, and LDL levels are twice as high as for the HH genotype.
•
The hh genotype lacks LDL receptors, allowing LDL to accumulate at
very high and dangerous levels in blood circulation.
•
Cholesterol-lowering drugs, such as statins, can be effective in treating high LDL cholesterol.
55
Punnett Squares—Cholesterol Levels
Parent 1
H
Hh
HH
HH
HH
Hh
h
H
h
H
h
hh
h
Parent 2
Diet and exercise can
also affect cholesterol
levels
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
56
Have you had your cholesterol (LDL and HDL) levels
checked?
57
Co-Dominance
•
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.
58
Human Blood
We have discussed inheritance patterns that involve two alleles—
one on each chromosome of a homologous pair.
•
Multiple alleles also exist for certain phenotypes, such as the ABO
blood group in humans.
http://www.cleoconference.org
•
59
Blood Types
•
In the ABO blood group, the human blood phenotypes are A, B, AB,
and O.
•
A and B refer to two carbohydrates (antigens) on the surface of red
blood cells (RBCs).
•
RBCs may contain one carbohydrate (A or B), both carbohydrates (A
and B), or neither (O).
•
The presence or absence of the rhesus factor (Rh) must also be considered in matching blood types—more about this later in the semester.
60
Blood Type Compatibility
•
Compatible blood types are critical for the transfusion of blood from
donor to recipient.
•
If a recipient receives a foreign blood type (A or B), antibodies in the
recipient’s blood bind to the foreign carbohydrate, causing the RBCs
to clump together.
•
Clumping and release of hemoglobin from RBCs damage nephrons,
the filtration mechanism in the kidneys.
61
http://cache.eb.com
RBC Clumping
62
Three Alleles
•
The four ABO blood types result from combinations of three alleles,
IA, IB, and i.
•
IA produces carbohydrate A, IB produces carbohydrate B, and i produces neither carbohydrate.
•
One of each of these three alleles is inherited from the mother and
the father.
63
Combinations of Alleles
•
IA and IB alleles are dominant to the i allele, but co-dominant to each
other.
•
The six combinations are:
IA * IA and IA * i result in type A blood.
– IB * IB and IB * i result in type B blood.
– IA * IB results in type AB blood where both alleles are expressed.
– i * i results in type O blood—neither the A nor the B carbohydrate
is present.
–
64
Blood Type Predictor
http://www.testsymptomsathome.com
Try calculating these combinations using your knowledge of
Mendel’s principles, co-dominance, and the alleles, IA, IB, and i.
65
http://www.hhs.gov
Blood Donor Programs
Whole blood
• Platelets
• National Marrow Donor Program (http://www.marrow.org)
•
66
Do you know your blood type?
67
Pleiotropy
•
So far, the examples have involved one or more genes that determine one hereditary characteristic.
•
In other instances, a gene can specify a number of characteristics,
which is known as pleiotropy.
•
A well-known instance of pleiotropy is the genetic disorder, sickle-cell
disease.
68
Sickle-Cell Disease
•
The hemoglobin molecules in red blood cells (RBCs) transport oxygen to the body’s tissues.
•
In sickle-cell disease, abnormally-shaped hemoglobin molecules are
produced in the bone marrow.
•
The disease is due to a single amino acid mutation (valine substitutes
for glutamic acid).
69
Sickle-Cell Disease (continued)
•
The sickle-shaped RBCs have a greatly reduced oxygen-carrying
capacity.
•
It is a homozygous recessive disorder—the alleles (ss) re present
on the homologous chromosomes.
70
Physical Effects
The abnormally-linked hemoglobin molecules tend to link together and
crystallize.
•
When hemoglobin crystallizes, RBCs deform to a sickle shape, leading
to a number of cascading symptoms.
•
Crystallization is more likely to happen when blood oxygen content is
low due to high altitude, physical overexertion, or respiratory ailments.
http://trc.ucdavis.edu
•
71
http://www.nhlbi.nih.gov
Sickle-Shaped RBCs
72
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
73
Incidence
•
Sickle-cell disease results in the premature deaths of about 100,000
people world-wide each year.
•
About one in ten African Americans is heterozygous (Ss) for the gene.
•
It is the most common inherited disorder among African Americans,
affecting about one in 500 newborn.
•
The disease is rare in other ancestries.
74
Treatment
•
Blood transfusions and certain drugs may relieve some of the symptoms.
•
Bone marrow transplants hold promise, and can help a person lead a
productive, normal life.
75
Can you think of other examples of pleiotropy?
76
Polygenic Inheritance
•
Mendel studied genetic characteristics that occur on an either-or-basis.
•
However, some characteristics, such as human skin color, vary along a
continuum in the general population.
•
Polygenic inheritance involves 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.
77
Skin Color
http:/cache.eb.com
http://anthro.palomar.edu
78
Genetic Basis
•
Let’s say, hypothetically, that skin color is completely determined by
only three genes, each inherited separately.
•
Dark-skin alleles (A, B, and C) each contributes one unit of darkness.
•
Light-skin alleles (a, b, and c) each contributes one unit of lightness.
•
Each dark-skin allele is incompletely dominant to the light-skin alleles.
Units of skin darkness:
A=B=C
Units of skin lightness:
a=b=c
79
Combinations of Alleles
•
A person who has AABBCC would have very dark skin, while a person
who has aabbcc would have very light skin.
•
A person who has AaBbCc would have skin of an intermediate shade.
•
Because the six alleles have a simple additive effect, AaBbCc would
produce the same skin color as AABbcc.
•
Sixty-four genotype combinations are possible in this simplified model,
resulting in seven shades of skin color.
80
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
81
Environmental Factors
•
Many more shades of skin color are possible than the seven depicted in
the model.
•
Intermediate shades of skin color are also determined by environmental
factors such as sunlight exposure.
•
Thus, the genetic basis of skin color is not the entire story no matter how
well the genes are described.
82
Genetics and the Environment
•
Some human phenotypes result from the interaction of genetics and
environment.
•
Some phenotypes, such as eye color, are fully genetically-determined.
•
Other phenotypes, such as height, have an environmental component
(for example, 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.”
83
Penetrance
•
Some dominant alleles are not always consistently expressed in the
phenotype.
•
The probability that a person having a dominant allele will display the
associated phenotype is known as its penetrance.
•
In complete penetrance, the associated phenotype is always displayed
(p = 1.00).
•
In incomplete penetrance, the phenotype may or may not be shown (p
< 1.00).
p = probability, which ranges between 0.00 and 1.00.
84
BRCA1 Gene
•
The BRCA1 gene associated with a rare form of breast cancer is incompletely penetrant.
•
About 70 percent of women with the gene will develop breast cancer
by age 70.
•
Thus, BRCA1 is said to be 70 percent penetrant.
•
Women with the gene should be screened regularly for early detection
of the disease.
85
Expressivity
The degree to which an allele expresses a phenotype can vary from
person-to-person.
•
Polydactyly is a genetic condition where an individual can have more
than ten fingers or toes.
•
This condition shows variable expressivity—some persons with the
allele have additional fully functional fingers or toes while others have
skin tags.
http://upload.wikimedia.org
•
86
Can you describe the differences between penetrance
and expressivity?
87
Chromosomal Basis of Inheritance
•
Mendel published his research in 1866; researchers, were only able to
establish the genetic processes a few decades later.
•
They noticed parallels between chromosomes and Mendel’s inheritance
factors at the beginning of the 20th century.
•
The chromosomal basis of inheritance, a major axiom in biology, began
to emerge.
The axiom states:
1. All genes are located on the chromosomes.
2. The behavior of homologous chromosomes during meiosis
and fertilization accounts for the inheritance patterns from
parents to their offspring.
Axiom = an established rule, principle, or law.
88
Homologous Chromosomes
Electron micrograph (false color image)
http://www.amnh.org
89
Linked Genes
•
Two or more genes located near each other on a chromosome tend to
be inherited together.
•
One instance in Mendel’s work involved flower color and pollen shape
in pea plants.
•
The F2 plants did not show the expected ratio predicted for a dihybrid
cross.
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Linked Genes (continued)
•
The ratio that was observed is the result of crossing-over patterns of
the chromatids during meiosis I.
•
Linked genes that cross-over together produce phenotypes that
cannot be predicted by the principles of segregation and independent
assortment.
91
http://flybase.net
Fruit Flies
Drosophila melanogaster
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Research Uses
•
The fruit fly, Drosophila melanogaster, can be inexpensively raised,
and can produce several generations within a few months.
•
Among other research uses, the fruit fly is used in genetics to map
genes on chromosomes.
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Genetic Recombination
•
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.
•
The crossing-over patterns can be used to determine the relative
location of genes on chromosomes to develop linkage maps.
•
Prior to genome mapping, observation of crossing-over patterns
was the primary method for developing maps of genes residing on
chromosomes.
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Sex-Linked Genes
We briefly discussed the role of the X and Y chromosomes in sexual
differentiation as female or male—more on this later in the semester.
•
The X chromosome also carries genes for characteristics unrelated to
genetic sex.
•
A gene located on the X chromosome is known as a sex-linked gene.
http://www.sanger.ac.uk
•
95
Role of the X Chromosome
•
The X chromosome, due its much larger size, carries many more genes
than the Y chromosome.
•
The X chromosome has what are known as sex-linked genes unrelated
to sexual differentiation.
•
The Y chromosome carries few genes, in large part because it is so
small.
•
Experiments have been conducted with fruit flies to determine how sexlinked genes determine the genotypes and phenotypes of their offspring.
96
Genes on the X Chromosome
•
The X chromosome has somewhere between 900 and 1,200 genes—
many of the genes are involved in human development in both sexes.
•
Only one of the genes (DAX1) is involved in female sexual differentiation.
•
Other genes involved in determining the female phenotype are on the
autosomal chromosomes (the other 22 pairs).
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Genes on the Y Chromosome
•
The SRY gene on the Y chromosome is involved in male sexual differentiation.
•
Other genes on the Y chromosome are involved in male sexual function
and fertility.
•
A Y-linked trait will be expressed if the Y chromosome is present since
the Y chromosome is hemizygous.
•
That is, one copy of the allele is present and passed from the father.
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Genes on the Y Chromosome
(continued)
•
Hairy ears is one of a small number of Y-linked traits that is not related to
sexual function.
•
This allele is said to be incompletely penetrant since not all hairy-eared
men have sons with hairy ears although the allele is passed with the Y
chromosome.
•
The amount of ear hair can vary from slight- to very-hairy due to variable
expressivity.
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Sex-Linked Disorders
•
Some human genetic disorders are the result of recessive alleles on the
X chromosome.
•
A male needs to inherit one of these sex-linked alleles from his mother,
while a female would need one from each parent, a much rarer situation.
•
Thus, males are far more often afflicted by sex-linked disorders, including
red-green color blindness, hemophilia, and Duchenne muscular dystrophy.
100
Rods and Cones
http://www.medgadget.com
Cross-section through
the retina of the human
eye
www.eyedesignbook.com
Electron micrograph of a
small group of rods and
cones.
101
Red-Green Color Blindness
•
Red-green color blindness is a fairly common sex-linked disorder in
males, although its severity can vary (due to variable expressivity).
•
In some affected people, red or green hues may appear to be gray,
while in others, confusion may exist over different shades of these
colors.
•
Red-green color blindness results from the malfunctioning of the red
and green in the retina of the eye.
•
Although males are usually affected, a small number of females may
have the problem if they have the recessive gene on both X chromosomes, which is a rare event.
102
http://www.mediacollege.com
Ishihara Color Plate
What embedded figure do you see?
103
Hemophilia
•
Hemophilia is another sex-linked recessive disorder—it effects are
almost always limited to males since only one copy of the allele is
needed.
•
Persons afflicted with this disorder bleed excessively when bruised or
otherwise injured.
•
Excessive bleeding is due to an abnormal allele on the X chromosome
for producing factors VII and IX that enable blood to clot.
104
http://www.btinternet.com
Victoria, Queen of England
1819-1901
105
A Famous Case Study
•
In the 18th century, hemophilia plagued the royal families of Europe,
who were often closely related through intermarriage.
•
The first royal family member who was known to have hemophilia was
the son of Queen Victoria of England.
•
The allele may have occurred as a spontaneous mutation in one of the
gametes (egg or sperm) of Victoria’s mother or father that was passed
by Victoria to her children.
106
Nicholas and Alexandra
•
Hemophilia was introduced into the royal families of Prussia, Russia,
and Spain through the marriage 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 (Queen Victoria).
107
Nicholas and Alexandra (continued)
•
Alexandra and Nicholas’s son, Alexis, was known to have had hemophilia.
•
The family met a tragic end in the overthrow of the Russian Czar in the
early 20th century.
108
http://bio3400.nicerweb.com
Family Pedigree
Solid-circle-within-a-circle—carrier of X-linked recessive gene.
Blue square—afflicted with hemophilia.
109
Duchenne Muscular Dystrophy
•
•
•
•
Duchenne muscular dystrophy is characterized by a progressive weakening and loss of skeletal muscle.
Almost all cases of this sex-linked genetic disorder involve males for the
same reasons we discussed.
The initial symptoms, including difficulty in standing-up, appear in early
childhood.
The child may require a wheelchair by age 12 due to a continued weakening of skeletal muscles and difficulty in breathing, which is controlled
by skeletal muscles.
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Incidence
•
•
•
•
In the United States, one in 3,500 male newborn is affected by muscular dystrophy.
The rate is much higher in some closed populations such as the Amish.
In one Amish community in Indiana, one out of 100 newborn males has
the disorder.
DNA technology was used to map the gene to the X chromosome.
111
Amish Communities in the United States
Road sign,
southeastern
Pennsylvania
http://www.valpo.edu
http://riversaredamp.files.wordpress.com
112
Pennsylvania Amish Country
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
http://www.baltimoresun.com
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
http://1001arabian.net
http://www.lindamyers.com
113
Have you met anyone who has one of these sex-linked
disorders?
114