Genetics terms to know
alleles
The different forms of a gene. Y and y are different FORMS of alleles for a gene
that determines seed color. Alleles occupy the same locus, or position, on
chromosomes.
autosomal
A locus on any chromosome but a sex chromosome. Not sex-linked.
co-dominant alleles
Two different alleles at a locus are responsible for different phenotypes, and both
alleles affect the phenotype of the heterozygote. For example, consider the
situation where there are three alleles A,B, and O that determine human blood
type. Three possible genotypes are AA, BB, OO that correspond to the
phenotypes of blood type A, B, and O respectively; Two other genotypes are AO
and BO that correspond to blood types A and B, respectively because the O allele
is recessive, The remaining genotype is AB, corresponding to blood type AB.
Both the A and B alleles contribute to the phenotype of the heterozygote. Thus the
alleles A and B are said to be co-dominant.
complete linkage.
Complete linkage describes the inheritance patterns for 2 genes on the same
chromosome when the observed frequency for crossover between the loci is zero.
dioecious
Organisms produce only one type of gamete; i.e. humans
dominant trait.
A trait expressed preferentially over another trait.
Drosophila melanogaster
The fruit fly, a favorite organism for genetic analysis.
epistasis.
One gene masks the expression of a different gene for a different trait.
F1 generation
Offspring of a cross between true breeding plants, homozygous for the trait of
interest
F2 generation
Offspring of a cross involving the F1 generation.
genotype
The genetic constitution of an organism with respect to a trait. For a single trait on
an autosome, an individual can be homozygous for the dominant trait,
heterozygous, or homozygous for the recessive trait. Yellow seeds are dominant,
but yellow seeded plants could have a genotype of either YY or Yy.
hemizygous
If there is only one copy of a gene for a particular trait In a diploid organism, the
organism is hemizygous for the trait, and will display a recessive phenotype. Xlinked genes in fly or human males are hemizygous.
heterozygous
Differing alleles for a trait in an individual, such as Yy.
homologous chromosomes
The pair of chromosomes in a diploid individual that have the same overall
genetic content. One member of each homologous pair of chromosomes in
inherited from each parent.
homozygous
Both alleles for a trait are the same in an individual. They can be homozygous
dominant (YY), or homozygous recessive (yy).
hybrid
heterozygous; usually referring to the offspring of two true-breeding
(homozygous) individuals differing in the traits of interest.
incomplete dominance
Intermediate phenotype in F1, parental phenotypes reappear in F2. The flowers of
the snapdragon plant can be red, pink, or white. Color is determined at a single
locus. The genotype RR results in red flowers and rr results in white flowers. The
heterozygote genotype of Rr results in pink flowers. When the heterozygote has a
different, intermediate phenotype compared to the homozygous dominant or
homozygous recessive individuals, this is said to be incomplete dominance.
lethal alleles.
Mutated genes that are capable of causing death.
linkage.
genes that are inherited together on the same chromosome. Three inheritance
patterns are possible: non-linkage, Partial linkage, and complete linkage.
mendel's law of independent assortment of alleles.
Alleles of different genes are assorted independently of one another during the
formation of gametes.
mendel's law of segregation
Alleles segregate from one another during the formation of gametes.
monoecious
Organisms produce both male and female gametes; i.e. garden pea.
monohybrid cross.
Cross involving parents differing in only one trait.
mutation
Change in the DNA sequence of a gene to some new, heritable form. Generally,
but now always a recessive allele.
non-linkage.
Non-linkage describes the inheritance patterns for 2 genes on the same
chromosome, when the expected frequency for crossover between the loci is at
least one. The observed inheritance patters for non-linked genes on the same
chromosome is the same as for 2 genes on different chromosomes.
partial linkage.
Partial linkage describes one of the inheritance patterns for 2 genes on the same
chromosome, when the expected frequency for crossover between the loci is
greater than zero but less than one. From partial linkage analysis we can learn
about the order and spacing of genes on the same chromosome.
phenotype
The physical appearance of an organism with respect to a trait, i.e. yellow (Y) or
green (y) seeds in garden peas. The dominant trait is normally represented with a
capital letter, and the recessive trait with the same lower case letter.
pleiotropic.
A single gene determines more than one phenotype for an organism.
Purebred.
Belonging to a group of organisms that can produce offspring having only
one form of a trait in each generation.
recessive trait.
The opposite of dominant. A trait that is preferentially masked.
reciprocal cross
Using male and female gametes for two different traits, alternating the source of
gametes.
sex chromosomes
Sex determination is based on sex chromosomes
sex-linked.
A gene coded on a sex chromosome, such as the X-chromosome linked genes of
flies and man.
test cross
Generally a cross involving a homozygous recessive individual. When a single
trait is being studies, a test cross is a cross between an individual with the
dominant phenotype but of unknown genotype (homozygous or heterozygous)
with a homozygous recessive individual. If the unknown is heterozygous, then
approximately 50% of the offspring should display the recessive phenotype.
true-breeding
Homozygous for the true-breeding trait.
wild-type allele
The non-mutant form of a gene, encoding the normal genetic function. Generally,
but not always a dominant allele.
Transmission of Genes--Mendelian Genetics
In the early 1800s, there was a new theory that organisms were made of cells, and that
visible traits were somehow passed from generation to generation. Gregor Mendel, a
monk interested in plant breeding, set out to answer some of the difficult questions that
these new theories posed. First, did both parents contribute to the offspring equally?
(remember how big the egg is compared to the sperm).
Were traits in the offspring the result of blending of traits from the parents or did
traits remain the same?
Mendel carefully selected an organism in which to answer these questions. He thought it
should have the following characteristics:
--visible traits
--capable of both self and cross fertilization
--offspring must also be fertile so that further crosses can be done
Mendel chose the pea plant to do his experiments, and tested the varieties he had to make
sure the traits he had selected remained the same and easily identifiable after selffertilization.
Then, over the next 8 years, he used some 28,000 plants to test his hypotheses!
Mendel did 7 kinds of crosses by fertilizing the flowers of a plant that produced (for
example) wrinkled seeds when self-fertilized with the pollen of a plant that normally
produced smooth seeds. He then harvested the seeds from the cross-fertilized plant, and
recorded their appearance. This generation was the first generation, called the F1. The
next year, he planted the F1 seeds, let them grow into plants and allow them to selffertilize. Then he collected those seeds (the second generation, F2) and recorded their
appearance (phenotype)
What he saw was very interesting. In the F1 generation, in all of his crosses, only one of
the parental traits was visible. However, when he planted the F1 seeds and let them selffertilize, he now saw both original parental traits. In other words, one trait seemed
dominant over another .
Mendel started out by doing crosses in which only one trait was followed, for example,
seed shape (smooth or wrinkled) or flower position (at top of plant or along the stem of
the plant). His conclusions:
1. Traits remained unchanged from parent to offspring
2. Traits did not blend together, they were distinct (wrinkled or smooth, not something in
between)
3. Traits were inherited as if they were separate units.
4. Some traits appeared to mask other traits. He called the trait that was visible in the F1
generation the dominant trait, and the trait that was not present in F1 but resurfaced again
in F2, the recessive trait.
5. Two plants could have the same phenotype (smooth), but when self-fertilized, could
produce either smooth and wrinkled, or just smooth. Thus the appearance of an organism
(phenotype) did not always match its genetic makeup (genotype). He called "true
breeding" plants homozygous--they had two copies of the same allele. The other variety,
which could produce two kinds of traits in the next generation, is called heterozygous
(two different alleles).
Mendel reasoned that female and male must contribute equally to the offspring, and that
if they did, the offspring must contain one gene from the mother and one from the father
(he called them factors at the time).
The principle of segregation--Mendel's 1st Law
Members of a gene pair must separate or segregate during gamete formation. We've
already talked about how this happens (meiosis), now here is the practical demonstration
of how it happens for specific genes. An individual with genotype Ss will make two
kinds of gametes, those containing S and those containing s.
Independent assortment and inheritance of two genes; pedigree analysis
The principle of independent assortment--Mendel's 2nd Law
The segregation of each chromosome is independent of the segregation of any other
chromosome. In other words, the principle of segregation applies to each chromosome
independently. The practical application of this law is the following: say you are looking
at two different traits on two different chromosomes (smooth or wrinkled seeds and
yellow or green seed color). An offspring has an equally likely chance of inheriting any
of the possible combinations of the alleles on these chromosomes.
First, let's write out the genotype of the starting parents., the dominant alleles will be
uppercase, recessive will be lowercase (so a smooth yellow is SS YY and a wrinkled
green is ss yy). Just as before, we will have segregation of the two alleles, but now we
will have independent assortment of each chromosome as well (this should sound
familiar; remember when we talked about meiosis, I said that when homologous
chromosomes lined up at the metaphase plate in meiosis 1, the copy from "mom" and the
copy from "dad" can be on either side of the plate).
So if we look at the gametes that each parent can produce, it's pretty easy for the first
generation: S, Y for the smooth yellow (one kind of gamete) and
s,y for the wrinkled green (one kind of gamete).
Thus, combining a gamete from each parent, all the offspring will be Ss Yy
In the next generation, there are 4 possibilities for gametes:
S, Y
S, y
s, Y
s, y
What you need to be able to do:
You should be able to do a Punnett Square and understand how to generate gametes
given a genotype. For example, if the genotype is Ss, the gametes will be S and s
In a monohybrid cross, the genotypic ratios are 1:2:1 (e.g.) TT, Tt, tt, and the
phenotypic ratios are 3:1 (e.g. 3 tall: 1 short).
In a dihybrid cross, the phenotypic ratios are 9:3:3:1 (e.g. round and yellow, round and
green, wrinkled and yellow, wrinkled and green). These ratios are true for the
transmission of every gene.
PROBABILITY
To calculate the chance that some particular genotype or phenotype will result from a
certain cross, one has to understand probability.
Probability: the chance that something will happen. The chance you will roll a 4 on a 6sided die is 1/6.
Independent events are multiplied together: the chance that you will roll two
consecutive 4s is 1/6 x 1/6= 1/36
Dependent events are added together: in a cross between two heterozygous parents, the
chance that an offspring will be either Rr or RR is 1/2 + 1/4 = 3/4
We can use probability to determine the chance of getting a particular genotype and
phenotype from a starting set of parents.
EXAMPLE: The brother (Michael) of the mother-to-be (Ellen) has sickle cell anemia.
This meant that the parents of Michael and Ellen had to both be carriers, Aa. Michael
had to be aa. Ellen can be either Aa or AA. There is a 2/3 chance that she is Aa. If she
is Aa, she has a 1/2 chance of passing on the a allele to her child. So you multiply 2/3 x
1/2, giving an overall chance of 1/3 that the child will be a carrier. This also means that
there is a 2/3 chance that she is NOT a carrier (since the overall probability of any event
happening must add up to 1).
You can also work through the problem to determine the chance that her child will not be
a carrier (but it's more complicated!). Back to the beginning, there is a 1/3 chance that
Ellen is AA. If she is AA, there is a chance of 1 (100%) that her child will not be a
carrier (so a 1/3 chance the daughter is not a carrier). But, if she IS a carrier (2/3 chance),
there is still a 1/2 chance that her daughter will NOT inherit the allele, so that means there
is an additional 1/3 chance the daughter will not be a carrier. Add the two 1/3s together
to get 2/3. You add because the initial event of whether Ellen is AA or Aa is a dependent
event.
Variations and Extensions of Mendel's laws
Multiple Alleles
Most of the time, there are more than two alleles of every gene. We've talked so far just
about examples in which there are two alleles for a gene, one being recessive and one
being dominate. When thinking about the inheritance of multiple alleles, you must
remember that it is possible to inherit any 2 out of however many there are in your
parents' genomes. The other complication that arises from multiple alleles is that some
alleles may not be completely dominant or recessive. This fact leads us into a discussion
about instances in which a person's phenotype differs from what you might expect from
straight Mendelian inheritance.
Definition of dominance
dominance: protein encoded for by dominant allele is visible in a dominant fashion in the
phenotype. A dominant allele encodes for a particular kind of protein. The other allele
does not make this protein at all or makes a non-functional protein, or makes a slightly
different protein. Ex. "B" allele encodes for pigment that makes eye brown. "b" allele
does not make this pigment. In absence of the eye color pigment, the eye is blue. In
presence of eye color pigment, the eye is brown. Traits are said to be inherited in an
autosomal dominant fashion if the gene is on an autosome (chromosomes 1-22, but not
X or Y) and is required in only one copy to see the effect, or autosomal recessive if two
copies are required to see the effect (more on this later).
Exceptions to Mendel's laws
Dominant lethality
A good example of homozygous dominant lethality is the Mexican Hairless dog (fig 5.1).
The highly prized hairless phenotype is inherited in an autosomal dominant fashion, such
that a genotype of Hh is hairless. However, if you cross two hairless dogs together, you
get 1/4 dead offspring (HH), and the ratio of the remaining is 2 hairless:1 hairy, an
obvious departure from the expected Mendelian ration of 3:1. But it is still Mendelian
inheritance, it just doesn't look it, because when a dog gets two copies of the dominant
allele, it dies. To avoid this lethality, breeders cross their Hh Hairless dogs to hairy dogs
(powderpuffs) hh, so that half of the offspring are hairless (Hh) and half are hairy (hh).
There are examples of this in other animals, too. Therefore, if you see a skewed
Mendelian ratio, this is one possibility to consider as an explanation--lethality when
homozygous dominant.
BLOOD TYPES
Co dominance: when two alleles are equally dominant, both are expressed
Blood type is a good example to explain both multiple alleles and codominance. Blood
type is actually defined by what kind of antigens you have on the surface of your blood
cells. An antigen is a protein, and an antibody is another protein manufactured by your
immune system that recognizes specific antigens. Your immune system fights disease or
infection by making antibodies against things that are unfamiliar to the body, then uses
the antibodies to grab these foreign objects and destroy them. Red blood cells have
antigens on their surface, and there are two different kinds of antigens that they can
express, A and B.
There are three alleles for blood type, IA, IB, i. IA and IB are codominant, and i
(sometimes referred to as IO, is recessive). If you are genotype IA/IB, you have both A
and B antigens on the surface of your blood cells. If you are IA/IA or IA/i, you have only
A antigen. If IB/IB or IB/i, only B antigen. If you are i/i, you have neither.
Your body normally makes antibodies to the antigen that is not present on your blood
cells. So, if you have antigen A on your blood cells, your body makes antibodies to B. If
your body sees the B antigen, it will make antibodies to B and get rid of it. This is why
blood transfusions must be of the same blood type. Individuals with blood type AB
(called the "universal recipients") can receive any blood type because they have both
antigens present. That means their immune system will not make antibodies to either of
these antigens. Therefore, they can theoretically receive any blood type. Unfortunately,
there are a lot of other antigens on the surface of blood cells in addition to A and B, so
matching blood type very closely is actually important. Individuals with blood type O do
not have any antigens on the surface of their blood cells, and thus could act as "universal
donors", again with the caveat mentioned above.
Incomplete dominance
In incomplete dominance, the effect of the dominant allele is modified by the presence of
the recessive allele. Snapdragons: R encodes for red pigment protein. r does not encode
for red pigment. In absence of red pigment, flower is white. With one dose of R, have
some red pigment, flower is pink. With two doses of R, have lots of red pigment, flower
is red. Pink F1s self fertilized make 1:2:1 red, pink, white, demonstrating the incomplete
dominance again.
A less obvious example of incomplete dominance in humans is with the sickle cell
anemia allele. Carriers of the sickle cell anemia allele are not actually affected by the
disease, but they do have affected blood cells (erythrocytes) in their blood stream. When
both traits (wild type and affected) are seen, the individual is said to have Sickle "trait"
rather than sickle cell anemia. This is not a great example of incomplete dominance
because technically there should be a blending of the phenotype. In this case, you
actually have two phenotypes of blood cells. However, it is not an example of codominance because carriers do not have the disease.
Pleiotropy
GENETIC DISORDERS
A defect in a single gene can lead to many effects on the body. This occurs when a single
protein plays a role in many different systems in the body. Thus the symptoms of a single
disease may first be thought to be the symptoms of different diseases.
Tourette's Syndrome--blinking, tics, grimaces, tapping, barking, and uncontrollable
swearing, etc (autosomal dominant). Tourette's is also not completely penetrate, so that
some people with the dominant allele do not show any traits.
Phenocopies
When a trait appears to be inherited, but is actually caused by environment. Ex. limb
defects caused by the drug thalidomide resemble an inherited diseases called
phocomelia..
Practice Questions
1. You cross two true breeding plants together, one with red flowers and one with white.
In the F1 generation, all the flowers are red and white together. What principle is this an
illustration of?
2. If Joe's blood type is AB and his wife Jane is blood type A, what is the chance that
they will have a child with blood type A?
3. There are 10 children in a family. They all carry the allele for polydactly (P), but only
6 of them have polydactly. What is this an example of?
Modes of Inheritance and Drawing Pedigrees
Pedigrees
Drawing a pedigree of inheritance follows several simple rules. Vertical lines represent
generations; horizontal lines at the top of symbols depict relationship (sibling), while
horizontal lines connecting the middle of the symbols depict mating. Squares indicate
males, circles indicate females. Filled in shapes represent individuals who express the
trait under study, while half-shaded shapes indicate individuals who are known to be
heterozygous. Pedigrees are extremely useful for determining the inheritance of traits.
Modes of inheritance
Alleles can be dominant and recessive. Inheritance of alleles, and thus of diseases or
syndromes, also follows dominant or recessive patterns of inheritance. Most diseases are
a result of two copies of a mutated allele, for example: sickle cell anemia. To have the
disease, you have to have two copies of the disease allele, and thus this disease is
inherited in a recessive fashion. If, on the other hand, having one copy of a disease allele
gives the person in question the disease that is said to be a dominantly inherited disease.
Autosomal recessive inheritance Two autosomal recessive diseases we’ve already
mentioned are cystic fibrosis and sickle cell anemia. Cystic fibrosis, remember, is the
disease that affects a protein used to transport chloride across the cell membrane. Have
many affects on the body (pleiotropic) due to thickened mucus throughout the body—
inability of the pancreas to function and respiratory problems, primarily.
Typical pedigree for autosomal recessive inheritance
Characteristics: 1. both parents usually look normal, but are carriers
2. both sexes are affected
3. about 1/4 of the offspring are affected when both parents are
heterozygotes (seen in large families)
4. if both parents are affected parents, 100% of the children are
affected.
Autosomal dominant inheritance—Huntington’s disease (a degenerative disease of the
brain), Marfan’s syndrome (connective tissue defect that affects the aorta—die young
from heart attack (Olympic volleyball star Flo Hyman); fig 4.16; see also fig 4.7).
Characteristics:
1. one parent affected
2. 1/2 children affected when one parent affected is affected
3. 3. both sexes affected
4. tends NOT to skip a generation
Sex Linkage usually refers to the X chromosome because there are very few genes on the
Y chromosome, so don’t usually see examples of Y linkage.
X linked recessive inheritance Examples: hemophilia, red-green color blindness,
muscular dystrophy.
Characteristics:
1. will often appear to skip at least one generation. This happens when a male is affected
by having the recessive allele. He donates this allele to his daughter, and she gets her
other X from her mother, so she is unaffected. However, she’s a carrier , so she now has a
50% chance of passing down the recessive allele X to her son, and then he will show the
disease or trait.
2. Male offspring are not carriers. If they inherit the allele from mom, they are affected
(of course, they are not affected 50% of the time, if they get the other allele). Thus, the
vast majority of the affected individuals are male
3. Daughters are carriers, and rarely show the trait because of the low frequency that they
would inherit two recessive alleles (each parent would have to have the allele).
X linked dominant inheritance Very few diseases are transmitted by this mode-- one is
hypophosphatemia, which causes rickets. In this kind of inheritance daughters inherit the
disease from their father, while the sons do not (since they get the Y chromosome). These
daughters can then pass on to either daughters or sons, but again their sons will only pass
it to their daughters. The pattern of inheritance is thus recognizably different from Xlinked recessive
Characteristics:
1. overall twice as many females as males affected
2. affected males have only affected daughters
3. affected daughters have both sons and daughters that are affected (about 1/2 of
their progeny).
Multifactor Inheritance
So far, we have talked about traits that are determined by one gene.
Complex traits are traits that are determined by more than one gene. These traits are also
usually influenced by non-genetic factors (environment) as well. Many of these traits are
things that seem to "run in the family", such as height, intelligence, alcoholism, etc., but
do not follow . Complex traits can be:
polygenic traits--determined by multiple genes
multifactor traits--determined by one or more genes AND by environment. In these
cases, each gene is being inherited in a Mendelian fashion, but the combination of the
genes produces a variable expression of a certain trait. Thus, overall, you do not see the
typical ratios of single gene inheritance.
Height and skin color are both polygenic and multifactor. If one is deprived of proper
nourishment, one might be short even though one’s genetic makeup predicts tallness.
Environment thus has an effect on realizing the genetic potential. Usually, traits that are
due to multiple genes also are affected by environment.
How to determine how many genes are involved in a trait
When geneticists analyze the frequency with which certain traits appear in the
population, they can determine whether the trait is polygenic or if a single gene produces
it. They do this by plotting the frequency with which a trait is seen against the different
phenotypes of the trait. For example, height . Height in pea plants falls into one of two
categories--dwarf or tall (called discontinuous variation), while height in humans shows a
bell-shaped distribution (continuous variation). This continuous variation, or bell-shaped
curve, is typical of multifactorial traits.
The greater the number of genes involved in a particular trait, the wider the bell curve
because there are more possible combinations.
Correlation coefficients and concordance Geneticists are interested in figuring out how
much of a particular trait is due to genes and how much is due to environment. Usually
this is very hard, because families share similar environments and similar genes.
Other examples of multifactorial traits include fingerprints, skin color, heart disease and
body weight.
Obesity
The individual is more than 20% over the ideal weight. Obesity is associated with other
phenotypes such as high blood pressure, diabetes, stroke, and gallstones. About 1/3 of all
American are obese. Adopted twin studies suggest that there is 75% contribution of
genotype to the phenotype of obesity! This is an impressive correlation, suggesting that
although environment is obviously involved, genetics cannot be ignored.
Some of the genes involved:
a. Leptin: The gene that encodes leptin was identified from a mutant
mouse (that couldn't make leptin). This mouse grew to three times the
size of its normal liter mates. If the obese mice are given the normal leptin
protein, it results in weight loss. Leptin breaks down fats, and helps to
maintain a high rate of metabolism when food intake is reduced. The role
in humans is not yet known.
b. Lipoprotein lipase: The role of this protein is to break down fat deposits
and cholesterol on capillaries (small blood vessels). It is activated by
HDLs (high-density lipoproteins) and breaks down LDLs (low-density
lipoproteins). High HDL levels and low LDL levels are a sign of a healthy
cardiovascular system. Individuals without a functional gene for
lipoprotein lipase have elevated levels of fat and increased numbers of fat
cells, and also are predisposed to heart disease.
Heart disease
ratio of HDL ("good " cholesterol) to LDL ("bad" cholesterol) affects health of the heart.
When there's too much LDL, cholesterol is deposited in the walls of the arteries in the
heart. If too many LDL particles remain deposited, the arteries develop plaques, leading
to atherosclerosis.
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If there are too many LDL particles in your blood, if your liver cells (LDL
receptors) do not break down the LDL quickly enough
If there are too few LDL receptors in your liver, your body's cells become
saturated with cholesterol from the LDL particles.
The role of the high-density lipoproteins (HDLs) is to pick up cholesterol deposited in
your artery walls and transport it to your liver for disposal. This is why a high HDL level
relative to a low LDL level is good. It can help protect you from developing
atherosclerosis. One disease related to LDL uptake is called Familial
hypercholesterolemia. This disease affects cell surface receptors that bind LDLs. When
the cells can't bind the LDLs, they can't get rid of the cholesterol, and there is an
accumulation of cholesterol in the arteries. These individuals often die in there twenties
of heart attacks (occurs in about 1 in a million individuals).
Practice questions
3. It has become fashionable to "blame your genes" for such as nebulous character traits
as infidelity and violence. Can you propose a good argument for why genes can't
necessarily be blamed?
4. What's the difference between dietary cholesterol and blood cholesterol?
5. What's the difference between LDLs and HDLs? Why are one "good" and one "bad"?
6. List one defect that could lead to a higher predisposition for heart attacks.