14.1.
Mendelism and the Genotype
A. Incomplete Dominance and Codominance
1. Incomplete dominance: offspring show traits intermediate
between two parental phenotypes.
a. Red and
white-flowered four o'clocks produce pink-flowered offspring.
b.
Incomplete dominance has a biochemical basis; level of gene-directed protein
production may
be between that of the two homozygotes.
c. One
allele of a heterozygous pair only partially dominates expression of its
partner.
d. This does
not support a blending theory; parental phenotypes reappear in F2 generation.
2. Codominance is a
pattern of inheritance in which both alleles of a gene are expressed.
a. A person
with AB blood has both A and B antigens on their red blood cells.
b. With
codominance, both alleles produce and effective product.
B. Genes That Interact
1. More than one pair of genes may interact to produce the phenotype.
2. Epistasis: absence
of expected phenotype as a result of masking expression of one gene pair by the
expression
of another gene pair.
a. The
homozygous recessive condition masks the effect of a dominant allele at another
locus.
b. Crossing
sweet pea plants produces purple; F2 generation has a 9:7 rather than 9:3:3:1
dihybrid
ratio; explained by homozygous recessive blocking production of a metabolic
enzyme.
c. Albino
animals inherit allelic pair (aa) preventing production of
melanin, expression of eye, hair, color.
C. Pleiotropy
1. Pleitropy: a single gene exerts an effect on many aspects of
an individual's phenotype.
a. Marfan
syndrome: a mutant gene is unable to code for production of a normal protein,
fibrillin.
b. Results
in the inability to produce normal connective tissue.
c.
Individuals with Marfan syndrome tend to be tall and thin with long legs, arms,
and fingers; are
nearsighted; and the wall of their aorta is weak.
d. From his
lanky frame and other symptoms, Abraham Lincoln may have had Marfan syndrome.
D. Multiple Alleles
1. There may be more than two alleles for one locus, but each individual
inherits only tow alleles.
2. A multiple allele system is
peppered moths has three possible alleles for wing color in order of
dominance: M
> M' > m; therefore, there are three
possible phenotypes.
3. The ABO system of human blood
type involves three alleles (A, B, and O).
4. As a result, there are four
possible phenotypes or blood types: A, B, AB, and O.
E. Polygenic Inheritance
1. Polygenic inheritance occurs when a trait is controlled by
several allelic pairs at different loci.
2. Allelic pairs at different loci
on a chromosome or on different chromosomes all control one trait.
3. Gene alleles can be contributing
or non-contributing.
4. Contributing alleles have an addictive
effect, resulting in quantitative variations.
5. Examples include seed color in
wheat and skin color and height in humans.
6. Polygenic traits are subject to
environmental effects that cause intermediate phenotypes; so they
produce
continuous variations whose frequency distribution forms a normal (bell-shaped)
curve.
F. Environment and the Phenotype
1. Both genotype and environment affect phenotype; relative importance of both
influences vary.
2. Aquatic environment (above and
below water level) influences the phenotype of water buttercup,
Ranunculus
peltatus.
3. Temperature can affect the
phenotypes of some plants (e.g., primroses) and animals
(e.g.,
Siamese cats, Himalaya rabbits).
14.2.
Mendelism and Chromosomes
A. Chromosomal Theory of Inheritance
1. Genes are located on chromosomes; behavior of
chromosomes during mitosis was described in
1875 and for
meiosis, in 1890's.
2. Chromosome theory independently
proposed in 1902 by Theodor Boveri and Walter S. Sutton.
3. Accounts for the similarity of
chromosomal behavior during meiosis and fertilization.
4. Theory is supported by the
following observations:
a. Both
chromosomes and factors (now called alleles) are paired in diploid cells.
b.
Chromosomes and alleles of each pair separate during meiosis so gametes have
one-half.
c.
Chromosomes and alleles of separate independently; gametes contain all
combinations.
d.
Fertilization restores diploid chromosome number and paired condition for
alleles in zygote.
B. Sex Chromosomes
1. In most animal species, chromosomes can be categorized as two types:
a. Autosomes
are non-sex chromosomes that are the same number and kind between sexes.
b. Sex
chromosomes determine if the individual is male or female.
2. Sex chromosomes in the human
female are XX; those of the male are XY.
3. Males produce X-containing and
Y-containing gametes; therefore males determine the sex of offspring.
4. Besides genes that determine sex,
sex chromosomes carry many genes for traits unrelated to sex.
5. X-linked gene is
any gene located on X chromosome; used to describe genes on X chromosome that
are missing
on the Y chromosome.
C. X-Linked Alleles
1. Work with fruit flies by Thomas Hunt Morgan (Columbia University) confirmed
genes were on chromosomes.
a. Fruit
flies are cheaply raised in common laboratory glassware.
b. Females
only mate once and lay hundreds of eggs.
c. Fruit fly
generation time is short, allowing rapid experiments.
2. Experiments involved fruit flies
with XY system similar to human system.
a. Newly
discovered mutant male fruit fly had white eyes.
b. Cross of
white-eyed male with dominant red-eyed female yield expected 3:1 red-to-white
ratio;
however, all white-eyed flies were males!
c. An allele
for eye color on the X but not Y chromosome supports the results of the cross.
d. Behavior
of allele corresponds to chromosome, confirming chromosomal theory of
inheritance.
3. X-Linked Problems
a. X-linked
alleles are designated as superscripts to X chromosome.
b.
Heterozygous females are carriers; they do not show the trait but
can pass it on.
c. Males are
never carriers but express the one allele on the X chromosome.
d. One form
of color-blindness is X-linked recessive.
D. Linkage Groups
1. Fruit flies have four pairs of chromosomes to hold thousands of genes;
Sutton concluded each
chromosome must
hold many genes.
2. All alleles on a chromosome form
a linkage group that stays together except when crossing over.
3. Crossing-over causes recombinant
gametes and at fertilization, recombinant phenotypes.
4. Linked alleles do not obey
Mendel's laws because they tend to go into the gametes together.
5. Crosses involving linked genes do
not give same results as unlinked genes.
6. Heterozygote forms only two types
of gametes and produces offspring with only two phenotypes.
E. Chromosome Mapping
1. Percentage of recombinant phenotypes measures distance between genes to map
the chromosomes.
2. Linked genes indicate the
distance between genes on the chromosomes.
3. If 1% of crossing-over equals one
map unit, then 6% recombinants reveal 6 map units between genes.
4. If crosses are performed for
three alleles on a chromosome, only one map order explains map units.
5. Humans have few offspring and a
long generation time, and it is not ethical to designate matings;
therefore
biochemical methods are used to map human chromosomes.
14.3.
Chromosomal Mutations
A. Mutations
1. Changes in chromosomes or genes that pass to offspring if they occur in
gametes.
2. Mutations increase
the amount of variation among offspring.
3. Chromosomal mutations include
changes in chromosome number and structure.
B. Changes in Chromosome Number
1. Monosomy occurs when and individual has only one of a
particular type of chromosome.
2. Trisomy occurs when and
individual has three of a particular type of chromosome.
3. Nondisjunction is
the failure of chromosomes to separate; it is more common during meiosis I than
meiosis II;
it can occur in mitosis.
4. Monosomy and trisomy occur in
plants and animals; in autosomes of animals, it is generally lethal.
5. Nonlethal human monosomies and
trisomies include the following:
a. Turner syndrome:
monosomy where the individual has single X chromosome.
b. Down
syndrome is most common trisomy among humans; it involves chromosome 21.
6. Polyploidy:
offspring end up with more than two complete sets of chromosomes.
a. Terms
indicate how many sets of chromosomes are present (triploids [3n], tetraploids
[4n], etc.).
b.
Polyploidy does not increase variation in animals; judging from trisomies, it
would be lethal.
c.
Polyploidy is a major evolutionary mechanism in plants; probably involved in
47% of flowering
plants including major crops.
d.
Hybridization in plants can result in doubled number of chromosomes; an even
number of chromosomes
can undergo synapsis during meiosis; successful polyploidy results in a
new species.
C. Changes in Chromosomal Structure
1. Environmental factors including radiation, chemicals, and viruses, can cause
chromosomes to break;
if the broken
ends do not rejoin in the same pattern, this causes a change in chromosomal
structure.
2. Inversion: a
segment that has become separated from the chromosome is reinserted at the same
place
but in
reverse; the position and sequence of genes are altered.
3. Translocation: a
chromosomal segment is removed from one chromosome and inserted into another,
nonhomologous chromosome. Translocation heterozygotes usually have reduced
fertility due to
production
of abnormal gametes.
4. A deletion is a
type of mutation in which an end of a chromosome breaks off or when two
simultaneous
breaks lead
to the loss of a segment.
a. Even if
only one member of pair of chromosomes is affected, a deletion can cause
abnormalities.
b. Cri du
chat syndrome is deletion in which an individual has a small head, is mentally
retarded, has
facial abnormalities, and abnormal glottis and larynx resulting in a cry
resembling that of a cat.
5. A duplications is a
doubling of a chromosomal segment.
a. A broken
segment from one chromosome can simply attach to its homologue.
b. Unequal
crossing-over may occur.
6. Multiple copies of genes can
mutate differently and provide additional genetic variation for a species.
14.4 A.
Karyotypes
1. Human somatic (body) cells have 22 pairs of autosomes, one pair of sex
chromosomes; total of 46.
2. Karyotypes shows
chromosomes paired according to size, shape, and appearance in metaphase.
a. To view
chromosomes, cells are treated and photographed just prior to dividing.
b.
Chromosomes are then sorted and arranged by homologous pairs, often by computer
imaging.
c. Members
of a pair have the same size, shape, and banding pattern.
d.
Chromosomes in a karyotype are aligned from largest to smallest.
e. A
karyotype can be used to diagnose chromosomal abnormalities.
3. Sex chromosomes of
a normal male are X and Y; a normal female has two X chromosomes.
4. All chromosomes besides X and Y
are autosomes.
5. To view chromosomes of an unborn
child, cells must be sampled from an embryo.
a. Chorionic
villi sampling removes a small tissue sample from the embryo side of the
placenta.
b.
Amniocentesis uses a long needle to extract fetal cells floating in the
amniotic fluid.
B. Nondisjunction
1. Nondisjunction during meiosis causes an abnormal chromosome
number in gametes produced.
2. Nondisjunction is a failure of
one or more chromosomes to separate.
3. Nondisjunction can occur when
homologous chromosomes fail to separate during meiosis I or
when
daughter chromosomes fail to separate during meiosis II.
4. Results in gametes with either
two few (n - 1) or too many (n + 1) chromosomes.
5. If abnormal gametes fertilize
normal gametes, a monosomy (2n - 1) or trisomy (2n
+ 1) results.
6. A syndrome is the
set of symptoms that occur with a medical condition.
C. Down Syndrome
1. Down syndrome is most common autosomal trisomy,
involves chromosome 21.
2. Most often, Down syndrome results
in three copies of chromosome 21 due to nondisjunction during gametogenesis.
a. In 23% of
cases, the sperm had the extra chromosome 21.
b. In 5% of
cases, there is translocation with chromosome 21 attached to chromosome 14;
this translocation
could have
occurred generations earlier and is not age-related.
3. Chances of a woman having Down
syndrome child increase with age.
4. Chorionic villi sampling testing
or amniocentesis and karyotyping detects a Down syndrome child.
5. Down syndrome child has tendency
for leukemia, cataracts, faster aging, and mental retardation.
6. Gart gene, located on bottom
third of chromosome 21, leads to high level of purines and is associated
with mental
retardation; future research may lead to suppression of this gene.
D. Abnormal Sex Chromosomal Inheritance
1. Turner (XO) syndrome females have only one sex chromosome, and
X.
a. Turner
females are short, have broad chest and webbed neck.
b. Ovaries
of Turner females never become functional; therefore, do not undergo puberty.
2. Klinefelter syndrome
males have one Y chromosome and two or more X chromosomes.
a. Affected
individuals are sterile males; testes and prostate are underdeveloped.
b.
Individuals have large hands and feet and long arms and legs.
3. Triplo-X females
have three or more X chromosomes.
a. There is
no increased femininity; most lack any physical abnormalities.
b. There is
an increased risk of having triplo-X daughters of XXY sons.
c. May
experience menstrual irregularities, including early onset of menopause.
4. XYY males with Jacob
syndrome have two Y chromosomes instead of one.
a. Results
from nondisjunction during meiosis II.
b. Usually
taller than average; suffer from persistent acne; tend to have lower
intelligence.
c. Earlier
claims that XYY individuals were likely to be aggressive are not correct.
E. Fragile X Syndrome
1. X chromosome is nearly broken; most often found in males.
2. As children: hyperactive or
autistic; delayed speech; account for part of higher proportion of males
in institutions
for mentally retarded.
3. As adults: large testes,
unusually protruding ears.
4. Occurs in females, but symptoms
are less severe.
5. Passes from symptomless male
carrier to grandson.
6. Traced to excessive repeats of
base triple CGG (cytosine, guanine, guanine); up to 230 copies compared
to normal
6-to-50 copies.
14.5.
Autosomal Genetic Disorders
A. Predicting Offspring
1. Genetic disorders are medical conditions caused by alleles inherited from
parents.
2. Males are designated by squares,
females by circles; shaded circles and squares are affected individuals;
line between
square and circle represents a union; vertical line leads to offspring.
3. A carrier is a
heterozygous individual who has no apparent abnormality but can pass on an
allele for a
recessively
inherited genetic disorder.
4. Autosomal dominant and autosomal
recessive alleles have different patterns of inheritance.
a.
Characteristics of autosomal dominant disorders
1) Affected children usually have an affected parent.
2) Heterozygotes are affected. Two affected parents can produce unaffected
child; two unaffected parents
will not have affected children.
b.
Characteristics of autosomal recessive disorders
1) Most affected children have normal parents since heterozygotes have a normal
phenotype.
2) Two affected parents always produce and affected child.
3) Close relatives who reproduce together are more likely to have affected
children.
5. Chance has no memory; each child
born to heterozygous parents has a 25% chance of having a disorder
regardless
of prior siblings' conditions.
B. Autosomal Dominant Disorders
1. Neurofibromatosis
a. This is
an autosomal dominant disorder that affects one in 3,000 people (or 100,000 in
U.S.).
b. Affected
individuals have tan skin spots at birth, which develop into benign tumors.
c.
Neurofibromas are lumps under the skin comprised of nerve cells or other cell
types.
d. Most case
symptoms are mild, patients live a normal life; sometimes symptoms are severe:
1) skeletal deformities, including a large head;
2) eye and ear tumors that can lead to blindness and hearing loss; and
3) learning disabilities and hyperactivity.
4) Such variation is called variable expressivity.
e. Gene that
codes for neurofibromatosis is huge; includes three smaller nested genes.
1) It was discovered in 1990 on chromosome 17.
2) It is a tumor-suppressor gene active in controlling cell division.
3) When it mutates, a benign tumor results.
2. Huntington Disease
a. This is
also an autosomal dominant disorder that affects one in 20,000 people.
b. It leads
to progressive degeneration of brain cells, which in turn causes severe muscle
spasm,
personality disorders, and death in 10 -15 years from onset.
c. Most
appear normal until they are of middle age and already have had children who
might carry
the gene; occasionally, first signs of the disease are seen in teenagers or
even younger.
d. The gene
for Huntington disease is located on chromosome 4.
e. Gene
contains many repeats of base triple CAG (cytosine, adenine, guanine); normal
persons have
11-34 copies; affected persons have 42-120 or more copies.
f. Severity
and time of onset of associated disorders depend on number of triplet repeats.
g.
Apparently, persons most at risk are those inheriting the gene from their
fathers.
1) Genomic imprinting is hypothesis that risk varies by source of
gene (sex of parent).
2) Genes may be imprinted differently during formation of sperm and egg.
C. Autosomal Recessive Disorders
1. Cystic Fibrosis
a. This is
most common lethal genetic disease in Caucasians in U.S.
b. About 1
in 20 Caucasians is a carrier, and about 1 in 2,500 births has this disorder.
c. Involves
production of viscous form of mucus in the lungs and pancreatic ducts.
1) Resultant accumulation of mucus in the respiratory tract interferes with gas
exchange.
2) Digestive enzymes must be mixed with food to supplant the pancreatic juices.
d. New
treatments have raised average life expectancy to 17-28 years.
e. Chloride
ions (Cl-) fail to pass plasma membrane proteins.
f. Since
water normally follows Cl-, lack of water in the lungs causes thick mucus.
g. Cause is
mutated gene on chromosome 7; attempt to insert gene into nasal epithelium has
had
limited success and restores about 25% of Cl- ion transport ability.
h. Genetic
testing for adult carriers and fetuses is possible.
2. Tay-Sachs Disease
a. Usually
occurs among Jewish people in the U.S. of central and eastern European descent.
b. Symptoms
are not initially apparent; infant's development begins to slow at 48 months,
neurological
and psychomotor difficulties become apparent, child gradually becomes blind and
helpless, develops
seizures, eventually becomes paralyzed, dies by age of three or four.
c. Results
from lack of enzyme hexosaminidase A (Hex A) and subsequent storage of its
substrate,
glycosphingolipid, in lysosomes.
d. Primary
sites of storage are cells of the brain; accounts for progressive
deterioration.
e. No
treatment or cure; prenatal diagnosis is by amniocentesis and chorionic villi
sampling.
3. Phenylketonuria (PKU)
a. PKU
occurs 1 in every 5,000 births; it is most common inherited disease of nervous
system.
b. Lack of
enzyme needed to metabolize amino acid phenylalanine results in accumulation of
the amino
acid in nerve cells of the brain; this impairs nervous system development.
c. PKU is
caused by a mutated gene on chromosome 12.
d. Now
newborns are routinely tested in hospital for high levels of phenylalanine in
the blood.
e. If infant
has PKU, child is placed on diet low in phenylalanine until brain is fully
developed near age 7.
E. Beyond Simple Mendelian Inheritance
1. Polygenic Inheritance
a. Polygenic
inheritance occurs when one trait is governed by two or more sets of alleles.
b. Dominant
alleles have a quantitative effect on the phenotype: each adds to the effect.
c. Result is
a continuous variation in phenotypes: a bell-shaped curve.
d. A hybrid
cross for skin color provides a range of intermediates.
e. Includes
cleft lip, clubfoot, hypertension, diabetes, schizophrenia, allergies and
cancers.
f.
Behavioral traits including suicide, phobias, alcoholism, and homosexuality may
be associated
with particular genes but are not likely completely predetermined.
2. Multiple Alleles
a. Occur
where a gene has three or more alternative expressions (alleles).
b. The ABO
system of human blood type is a multiple allele system.
1) Two dominant alleles (A and B) code for presence of A and B antigens on red
blood cells.
2) Also includes recessive allele (o) coding for no A or B antigens on red
blood cells.
3) As a result, there are four possible phenotypes (blood types): A, B, AB, and
O.
c. The Rh
factor is inherited independently from the ABO system; the Rh+ allele is
dominant.
3. Sickle-cell disease
is a blood disorder controlled by incompletely dominant alleles.
a.
Codominance occurs when alleles are equally expressed in a heterozygote.
b. HbA
HbA individuals are normal; HbS HbS have sickle-cell
trait.
c. With
sickle-cell disease, red blood cells are irregular in shape (sickle-shaped)
rather than biconcave,
due to abnormal hemoglobin that the cells contain.
d. Due to
irregular shape, sickle-shaped red blood cells clog vessels and break down;
results in poor
circulation, anemia, low resistance to infection, hemorrhaging, damage to
organs, jaundice, and pain
of abdomen and joints.
e. Persons
heterozygous for sickle-cell (HbAHbS) are usually asymptomatic
unless stressed.
f. In
malaria regions of Africa, infants heterozygous (HbAHbS) for
sickle-cell allele have better chance
of surviving; malaria parasite dies as potassium leaks from sickled cells.
g. Bone
marrow transplants pose high risks; other research focuses on fetal hemoglobin,
etc.
14.6 Sex-linked Genetic Disorders
A. Sex Chromosomes
1. Traits controlled by alleles on sex chromosomes are sex-linked.
2. Since Y chromosome is smaller,
most sex-linked genes are on the X chromosome.
B. X-Linked Recessive Disorders
1. Males receive X-linked traits from mother, source of male's only X
chromosome.
2. If female shows a recessive
sex-linked trait, her father must have it and her mother is carrier.
C. Some Disorders Are X-Linked
1. Color Blindness
a. Can X-linked
recessive disorder involving mutations of genes coding for green or red
sensitive cone
cells, resulting in inability to perceive green or red, respectively.
b. The
possible genotypes for color blindness are as follows:
1) XB XB = a female who has normal color vision;
2) XBXb = a carrier female who has normal color vision;
3) XbXb = a female who is color blind;
4) XBY = a male who has normal color vision; and
5) XbY = a male who is color blind.
2. Duchenne Muscular Dystrophy
a. Duchenne
muscular dystrophy is most common form; characterized by wasting away of
muscles,
eventually leading to death; it affects one out of every 3,600 male births.
b. X-linked
recessive disease involves a mutant gene that fails to produce protein
dystrophin.
c. Symptoms
(e.g., waddling gait, toe walking, frequent falls, difficulty in rising) soon appear.
d. Muscle
weakens until individual is confined to wheelchair; death usually occurs by age
20.
e. Affected
males are rarely fathers; the gene passes from carrier mother to carrier
daughter.
f. Lack of
dystrophin caused calcium ions to leak into muscle cells; this promotes action
of an enzyme
that dissolves muscle fibers.
g. As body
attempts to repair tissue, fibrous tissue forms and cuts off blood supply.
h. Test
detects carriers of Duchenne muscular dystrophy; treatments are under research.
3. Hemophilia
a. About one
in 10,000 males is a hemophiliac with impaired ability of blood to clot.
b.
Hemophilia has tow types: Hemophilia A is due to absence of clotting factor IX;
Hemophilia B is
due to absence of clotting factor VIII.
c.
Hemophiliacs bleed externally after an injury and also suffer internal bleeding
around joints.
d.
Hemorrhages stop with transfusions of blood (or plasma) or concentrates of
clotting protein.
e.
Hemophiliacs were at high risk of AIDS if receiving blood or using blood
concentrate to replace clotting factors.
f. Factor
VIII is now available as a genetic engineering product.
g. Of Queen
Victoria's 26 offspring, 5 grandsons had hemophilia, 4 granddaughters were
carriers.
D. Some Traits are Sex-influenced
1. Some genes not located on the X or Y chromosome are expressed differently in
the two sexes.
2. Male pattern baldness is caused
by an autosomal allele that is dominant in males and due to presence
of
testosterone.