Chapter : Genetics
The Classic Approach
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Mendel working in his garden
Pea Plants!
Gregor Mendel
• Gregor Mendel combined his farmer’s skills with his
training in mathematics.
• Mendel’s law of segregation states that each individual
has two factors (called genes today) for each trait.
• Alternative forms of a gene having the same position
on a pair of homologous chromosomes and affecting
the same trait are now referred to as alleles.
• Today we know that alleles occur at the same
loci (position) on a chromosome.
• The factors segregate during the formation of
the gametes and each gamete has only one
factor from each pair.
• Fertilization gives each new individual two
factors again.
Gene locus (locus = location)
The Inheritance of a Single Trait
• A capital letter indicates a dominant allele,
which is expressed when present.
• An example is W for widow’s peak.
• A lowercase letter indicates a recessive allele,
which is only expressed in the absence of a
dominant allele.
• An example is w for continuous hairline.
Widow’s peak
Genotype and Phenotype
• Genotype refers to the genes of an individual
which can be represented by two letters or by a
short descriptive phrase.
• Homozygous means that both alleles are the
same; for example, WW stands for homozygous
dominant and ww stands for homozygous
recessive.
• Phenotype refers to the physical appearance of
the genotype!
Gamete Formation
•
•
•
•
(sperm and eggs)
Because homologous pairs separate during
meiosis, a gamete has only one allele from each
pair of alleles.
If the allelic pair is Ww, a gamete would contain
either a W or a w, but not both.
Ww represents the genotype of an individual.
Gametes are represented by W or w.
One-Trait Crosses
(let’s breed!)
• In one-trait crosses, only one trait such as type
of hairline is being considered.
• When performing crosses, the original parents
are called the parental generation, or the P
generation.
• All of their children are the filial generation, or F
generation.
• Children are monohydrids when they are
heterozygous for one pair of alleles.
• If you know the genotype of the parents, it is
possible to determine the gametes and use a
Punnett square to determine the phenotypic
ratio among the offspring.
• When a monohybrid reproduces with a
monohybrid, the results are 3 : 1.
• This ratio is used to state the chances of a
particular phenotype.
• A 3 : 1 ratio means that there is a 75% chance
of the dominant phenotype and a 25% chance
of the recessive phenotype.
Monohybrid cross
One-Trait Crosses and Probability
• Laws of probability alone can be used to
determine results of a cross.
• The laws are:
• (1) the probability that two or more
independent events will occur together is
the product of their chances occurring
separately, and
• (2) the chance that an event that can
occur in two or more independent ways is
the sum of the individual chances.
• In the cross of Ww x Ww, what is the
chance of obtaining either a W or a w from
a parent?
• Chance of W = ½, or chance of w = ½
• The probability of these genotypes is:
• The chance of WW = ½ x ½ = ¼
• The chance of Ww = ½ x ½ = ¼
• The chance of wW = ½ x ½ = ¼
• The chance of ww = ½ x ½ = ¼
• The chance of widow’s peak (WW, Ww,
wW) is ¼ + ¼ + ¼ = ¾ or 75%.
The One-Trait Testcross
• It is not always possible to discern a
homozygous dominant from a
heterozygous individual by inspection of
phenotype.
• A testcross crosses the dominant
phenotype with the recessive phenotype.
• If a homozygous recessive phenotype is
among the offspring, the parent must be
heterozygous.
One-trait testcross
The Inheritance of Many Traits
• Independent Assortment
• The law of independent assortment states
that each pair of alleles segregates
independently of the other pairs and all
possible combinations of alleles can occur
in the gametes.
• This law is dependent on the random
arrangement of homologous pairs at
metaphase.
Segregation and independent
assortment
Two-Trait Crosses
• In two-trait crosses, genotypes of the
parents require four letters because there
is an allelic pair for each trait.
• Gametes will contain one letter of each
kind in every possible combination.
• When a dihybrid reproduces with a
dihybrid the results are 9 : 3 : 3 : 1.
Dihybrid cross
Two-Trait Crosses and Probability
• It is possible to use the two laws of
probability to arrive at a phenotypic ratio
for a two-trait cross without using a
Punnett square.
• The results for two separate monohybrid
crosses are as follows:
• Probability of widow’s peak = ¾
• Probability of short fingers = ¾
• Probability of straight hairline = ¼
• Probability of long fingers = ¼
• The probabilities for the dihybrid cross:
• Probability of widow’s peak and short
fingers = ¾ x ¾ = 9/16
• Probability of widow’s peak and long
fingers = ¾ x ¼ = 3/16
• Probability of straight hairline and short
fingers = ¼ x ¾ = 3/16
• Probability of straight hairline and long
fingers = ¼ x ¼ = 1/16
The Two-Trait Testcross
• A testcross is done when it is not known
whether a dihybrid individual is
homozygous dominant or heterozygous for
both or one of the traits under
consideration.
• A cross of a person heterozygous for both
traits with a homozygous recessive person
produces a 1 : 1 : 1 : 1 ratio.
Two-trait testcross
• Pedigree charts represent males as
squares and females as circles.
• Recessive and dominant alleles have
different patterns of inheritance.
• Genetic counselors construct pedigree
charts to determine the mode of
inheritance of a condition.
Autosomal recessive pedigree
chart
Autosomal dominant pedigree chart
Autosomal Recessive Disorders
• Tay-Sachs Disease
• Tay-Sachs disease is common among
United States Jews of central and eastern
European descent.
• An affected infant develops neurological
impairments and dies by the age of three
or four.
• Tay-Sachs results from a lack of
hexosaminidase A and the storage of its
substrate in lysosomes.
Cystic Fibrosis
• Cystic fibrosis is the most common lethal
genetic disorder among Caucasians.
• A chloride ion transport protein is defective in
affected individuals.
• Normally when chloride ion passes through
a membrane, water follows.
• In cystic fibrosis patients, a reduction in
water results in a thick mucus which
accumulates in bronchial passageways and
pancreatic ducts.
Cystic fibrosis therapy
Phenylketonuria (PKU)
• Individuals with phenylketonuria lack an
enzyme needed for the normal metabolism
of phenylalanine, coded by an allele on
chromosome 12.
• Newborns are regularly tested for elevated
phenylalanine in the urine.
• If the infant is not put on a phenylalaninerestrictive diet in infancy until age seven
when the brain is fully developed, brain
damage and severe mental retardation
result.
Autosomal Dominant Disorders
• Neurofibromatosis
• Small benign tumors, made up largely of
nerve cells, occur under skin or on various
organs.
• The effects can range from mild to severe,
and some neurological impairment is
possible; this disorder is variably
expressive.
• The gene for this trait is on chromosome
17.
Huntington Disease
• Individuals with Huntington disease
experience progressive degeneration of
the nervous system and no treatment is
presently known.
• Most patients appear normal until middle
age.
• The gene coding for the protein huntingtin
contains many more repeats of glutamines
than normal.
Huntington disease
Polygenic inheritance
Skin Color
• The inheritance of skin color, determined
by an unknown number of gene pairs, is a
classic example of polygenic inheritance.
• A range of phenotypes exist and several
possible phenotypes fall between the two
extremes of very dark and very light.
• The distribution of these phenotypes
follows a bell-shaped curve.
Polygenic Disorders
• Many human traits, like allergies,
schizophrenia, hypertension, diabetes,
cancers, and cleft lip, appear to be due to
the combined action of many genes plus
environmental influences.
• Many behaviors, such as phobias, are also
likely due to the combination of genes and
the effects of the environment.
Multiple Allelic Traits
• Inheritance by multiple alleles occurs
when more than two alternative alleles
exist for a particular gene locus.
• A person’s blood type is an example of a
trait determined by multiple alleles.
• Each individual inherits only two alleles for
these genes.
ABO Blood Types
• A person can have an allele for an A
antigen (blood type A) or a B antigen
(blood type B), both A and B antigens
(blood type AB), or no antigen (blood type
O) on the red blood cells.
• Human blood types can be type A (IAIA or
IA i), type B (IBIB or IBi), type AB (IAIB), or
type 0 (ii).
Inheritance of blood type
Incompletely Dominant Traits
• Codominance means that both alleles are
equally expressed in a heterozygote.
• Incomplete dominance is exhibited when
the heterozygote shows not the dominant
trait but an intermediate phenotype,
representing a blending of traits.
• Such a cross would produce a phenotypic
ratio of 1 : 2 : 1.
Incomplete dominance
Sickle-Cell Disease
• Sickle-cell disease is an example of a
human disorder controlled by incompletely
dominant alleles.
• Sickle cell disease involves irregular, sickle
shaped red blood cells caused by abnormal
hemoglobin.
• HbA represents normal hemoglobin; and HbS
represents the sickled condition.
• HbAHbA individuals are normal; HbSHbS
individuals have sickle-cell disease and
HbAHbS individuals have the intermediate
condition called sickle-cell trait.
• Heterozygotes have an advantage in
malaria-infested Africa because the
pathogen for malaria cannot exist in their
blood cells.
• This evolutionary selection accounts for
the prevalence of the allele among African
Americans.
• Many genetic disorders and other traits
are inherited according to laws first
established by Gregor Mendel.
• Inheritance is often more complex,
providing exceptions to Mendel’s laws but
helping to explain an even wider variety in
patterns of gene inheritance.
Chapter 24 : Chromosomes!
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Amniocentesis
• Amniocentesis uses a needle to extract
amniotic fluid from the uterus of a
pregnant woman from the 14th to 17th
week of pregnancy.
• Up to 400 chromosome and biochemical
problems can be detected by culturing
fetal cells that are in the amniotic fluid.
• There is a slight risk of spontaneous
abortion with this procedure.
Amniocentesis
Chorionic Villi Sampling
• Chorionic villi sampling (CVS) uses a thin
suction tube to sample chorionic cells from
the placenta as early as the fifth week of
pregnancy.
• The cells do not have to be cultured, and
karyotyping can be done immediately.
• CVS carries a slightly greater risk of
spontaneous abortion but can be
performed earlier than amniocentesis.
Chorionic villi sampling
Karyotyping
• Sampled fetal cells are stimulated to
divide in culture medium and another
chemical stops division during metaphase
when chromosomes are highly
condensed.
• The stained cells are photographed and
can be paired based on stained crossbands, and size and shape.
Human karyotype preparation
Normal male karyotype
Down syndrome karyotype
Nondisjunction in meiosis I
Nondisjunction in meiosis II
• Normal development depends on the
presence of two of each kind of
chromosome, but an extra chromosome is
tolerated more than a missing
chromosome.
• The Barr body is an inactive X
chromosome and is seen whenever more
than one X chromosome is present (i.e.,
XX, XXY, XXX).
• Cells of females function with a single
chromosome just as those of males do.
Down Syndrome
• Down syndrome is caused by trisomy 21,
three copies of chromosome 21 as a result
of nondisjunction.
• Symptoms include mental retardation,
short stature, eyelid fold, flatter face, a
palm creases, and stubby fingers, among
others.
• Nondisjunction usually occurred in
producing the mother’s egg and risk
increases at age 40.
Abnormal autosomal chromosome
number
• The genes causing Down syndrome are
located on the bottom third of
chromosome 21.
• In particular, the Gart gene leads to a high
level of purines, which contribute to mental
impairment but may allow future
preventive treatment.
Changes in Sex Chromosome
Number
• The presence of a Y chromosome
determines maleness.
• The SRY gene on the short arm of the Y
produces a testis-determining factor that
begins the development of a male;
otherwise an embryo develops as a female.
• An abnormal number of sex chromosomes
is the result of inheriting to many or too few
X or Y chromosomes.
Turner Syndrome
• Individuals with Turner syndrome are
females that have only one X
chromosome; therefore they are XO.
• They are short, with a broad chest, and
webbed neck.
• They do not undergo puberty or
menstruate, and there is a lack of breast
development.
• Intelligence is normal and individuals can
lead normal lives.
Klinefelter Syndrome
• Individuals with Klinefelter syndrome are
males that have two or more X
chromosomes in addition to a Y
chromosome.
• The Y chromosome drives development as
a male but gonads are underdeveloped
and breasts develop.
• Klinefelter males are usually slow to learn
but are not mentally retarded.
Abnormal sex chromosome
number
Poly-X Females
• A poly-X female has more than two X
chromosomes and extra Barr bodies in the
nucleus.
• An XXX female has a normal phenotype
except there may be menstrual difficulties,
but she is fertile; her children usually have
normal karyotypes.
• Females with XXXX are usually tall and
severely retarded; they may menstruate
normally.
Jacobs Syndrome
• Jacobs syndrome males are XYY which
can only result from nondisjuction during
spermatogenesis.
• They tend to be tall, have persistent acne,
and have speech and reading problems.
• At one time it was suggested that XYY
males were unusually aggressive, but this
was found not to be true.
Deletions and Duplications
• Deletions occur when a single break
causes a lost end piece, or two breaks
result in a loss in the interior.
• An individual who inherits a normal
chromosome from one parent and a
chromosome with a deletion from the other
parent no longer has a pair of alleles for
each trait, and a syndrome can result.
• In Williams syndrome, chromosome 7
loses an end piece and children have a
pixie look and the skin ages prematurely
from lack of the gene that governs elastin
production.
• An end piece of chromosome 5 produces
cri du chat syndrome where larynx is
abnormal and the infant’s cry is like that of
a cat, the head is small, and there are
facial abnormalities.
Deletion
• Duplication results in a chromosome
segment being repeated in the same
chromosome or in a nonhomologous
chromosome, producing extra alleles for a
trait.
• An inverted duplication in chromosome 15
causes inv dup 15 syndrome with poor
muscle tone, mental retardation, and
related symptoms.
Duplication
Translocation
• Translocation is exchange of chromosomal
segments between two, nonhomologous
chromosomes.
• In a small percent of cases, a translocation
between chromosomes 21 and 14 causes
Down syndrome.
• The tendency for this particular
translocation can run in the family of either
the mother or father of affected individuals.
• Alagille syndrome results from a deletion
of chromosome 20 or a translocation that
disrupts an allele on chromosome 20.
• The symptoms for Alagille syndrome range
from mild to severe, so people may not be
aware they have the syndrome.
Translocation
Inversion
• Inversion involves a segment of a
chromosome being turned 180 degrees;
the reverse sequence of alleles can alter
gene activity.
• Crossing-over between inverted and
normal chromosomes can cause
recombinant chromosomes due to the
inverted chromosome needing to form a
loop to align.
Inversion
X-Linked Alleles
• The key for an X-linked problem shows the
allele attached to the X as in:
• XB = normal vision
• Xb = color blindness.
• Females with the genotype XBXb are
carriers because they appear to be normal
but each son has a 50% chance of being
color blind depending on which allele the
son receives.
• XbXb and XbY are both colorblind.
Cross involving an X-linked allele
X-Linked Disorders
• In pedigree charts that show the inheritance
pattern for X-linked recessive disorders, more
males than females have the trait because
recessive alleles on the X chromosome are
expressed in males.
• A grandfather passes an X-linked recessive
disorder to a grandson through a carrier
daughter.
• X-linked recessive disorders include redgreen color blindness, muscular dystrophy,
and hemophilia.
X-linked recessive pedigree chart
Color Blindness
• Three types of cones are in the retina
detecting red, green, or blue.
• Genes for blue cones are autosomal;
those for red and green cones are on the
X chromosome.
• Males are much more likely to have redgreen color blindness than females.
• About 8% of Caucasian men have redgreen color blindness.
Muscular Dystrophy
• Muscular dystrophy is characterized by the
wasting of muscles.
• The most common form is Duchenne
muscular dystrophy; this is an X-linked
disorder, occurring in 1 of 3,600 males.
• Muscles weaken, frequent falls and
difficulty in rising occur early; death occurs
by age 20.
• Duchenne muscular dystrophy involves the
absence of a protein called dystrophin that
is involved in the release of calcium from
the sarcoplasmic reticulum of muscle cells.
• The lack of dystrophin causes calcium to
leak into the cell, which promotes the action
of an enzyme that dissolves muscle fibers.
• A test is now available to determine the
carriers of Duchenne muscular dystrophy.
Hemophilia
• Hemophilia refers to the lack of one of
several clotting factors that leads to
excessive bleeding in affected individuals.
• Hemophiliacs bleed externally after injury,
but also bleed internally around joints.
• Hemorrhages can be stopped with blood
transfusions or a biotechnology clotting
factor.
Fragile X Syndrome
• Fragile X syndrome is an X-linked genetic
disorder with an unusual pattern of
inheritance.
• Individuals with this syndrome (one in
1,500 males and one in 2,500 females)
have a base triplet repeat (CGG) in a gene
on the X chromosome.
• Children may be autistic or hyperactive
with speech difficulties.
• Adults have large testes if male, and big
protruding ears.
• They are short in stature and the face is
long with a prominent jaw.
• A person with a smaller number of CGG
repeats and minor or no symptoms is said
to have a premutation and can pass it to
their children where the number increases
and the condition is severe.
Linkage group
• The frequency of recombinant gametes
that occurs due to the process of crossingover has been used to map chromosomes.
• Crossing-over data is used to map the
chromosomes of animals, such as fruit
flies, but is limited in mapping human
chromosomes because we do not control
the crosses.
Cross involving linked genes
• Abnormalities arise when humans inherit an
incorrect number of sex chromosomes.
• Traits unrelated to the gender of an
individual are controlled by genes located on
the sex chromosomes.
• Males express X-linked recessive disorders
because they inherit only one X
chromosome.
• Genes that occur on the same chromosome
form a linkage group and tend to be inherited
together.