Mendelian genetics

Mayukh Banerjee
In most of the somatic cells of all diploid organisms, two haploid set
of chromosomes are present.

Each chromosome of a matching pair are called “homologues”.

Homologous chromosomes are similar in that they consist of alleles

of same genes on identical positions or loci.

However, the homologues are not identical, because the alleles of a

gene may vary (i.e. same gene, different version).

When identical alleles are present on each of the two homologous

chromosomes, then the individual is said to be Homozygous with
respect to the particular trait controlled by that particular allele.

When different alleles are present on each of the two homologous

chromosomes, then the individual is said to be Heterozygous with
respect to the particular trait controlled by that particular allele.

If two different alleles of a gene are present in a cell, the phenotype

of only one will be expressed, while the other will be suppressed.
Dominance refers to the non-linear relationship between different forms
(alleles) of a gene and the resultant phenotype.

The key concept of dominance is that the heterozygote is

phenotypically identical to one of the two homozygotes.

The homozygous trait seen also in the heterozygous individual is called

the ‘dominant’ trait.

Recessive refers to an allele that does not produce a characteristic effect

when present with a dominant allele. Alternatively, it a trait that is
expressed only when the determining allele is present in the
homozygous condition.

Ex: The gene controlling sees shape in Pea (Pisum sativum) has two
alleles; one codes for round seeds (R), the other for wrinkled seeds (r).
The seeds are round when homozygous for R (i.e. RR), while they are
wrinkled if homozygous for r (i.e. rr). The heterozygotes (i,.e. Rr) are
round. Thus, the allele for round seeds (R) is dominant over the allele
for wrinkled seeds (r), which happens to be the recessive allele.
 Homologous
Chromosomes

Allele for Allele for

Round Seed (R) Wrinkled Seed (r) Homologous for Round Seed (RR)

Homologous for Wrinkled Seed (rr) Heterozygous (Rr)

 Mendel’s First Law (Law of Segregation)

Mendel’s Experiments

Parental Cross F1Phenotype F2 Phenotypic Ratio F2Ratio

Round x Wrinkled 5474 Round:
Round 2.96:1
Seed 1850 Wrinkled
Yellow x Green 6022 Yellow:
Yellow 3.01:1
Seeds 2001 Green
Red x White Flowers Red 705 Red:224 White 3.15:1
Tall x Dwarf Plants Tall l787 Tall:227 Dwarf 2.84:1

Mendel’s Observations:
1. All F1 progenies always exhibit one particular trait.
2. F2 progenies had a mixed population of individuals in the ratio of ~ 3:1.
Mendel’s Explanations
 Mendel’s Conclusions

• The hereditary determinants are of a particulate nature.

• Each parent has one pair of these particulate determinants in each

somatic cell for each trait studied. One of these determinants must
be dominant (i.e., will exhibit its character in spite of the presence
of the other determinant), whereas, the other must be recessive
(i.e., will nor express its character if present in combination with
the dominant determinant). The F1 from a cross of two pure lines
contains one allele for the dominant phenotype and one for the
recessive phenotype.

• One member of the pair segregates into a gamete, thus each

gamete only carries one member of the determinant pair.

• Gametes unite at random creating new random combinations of

these determinants.

allele pairs separate or segregate during gamete formation, and randomly unite at
fertilization.
Backcross - The cross of an F1 hybrid to one of the homozygous parents; for
pea plant height the cross would be Tt x TT or Tt x tt; most often, though a
backcross is a cross to a fully recessive parent.

Testcross - The cross of any individual to a homozygous recessive parent;

used to determine if the individual is homozygous dominant or
heterozygous.
 Exceptions to Law of Segregation

Any phenomenon in which two alleles of a gene does not express a typical dominant-
recessive relationship will lead to a deviation from the law of segregation.

1. Codominance: A condition in which the alleles of a gene pair in a

heterozygote are fully expressed thereby resulting in offspring
with a phenotype that is neither dominant nor recessive.
Ex: ABO blood group system. A person having A allele and B allele
will have a blood type AB because both the A and B alleles are
codominant with each other.

2. Incomplete Dominance: Incomplete dominance is a form of inheritance

in which one allele for a specific trait is not completely dominant
over the other allele. This results in an intermediate phenotype.
Ex: In cross-pollination experiments between red and white
snapdragon plants, the resulting offspring are pink. The dominant
allele that produces the red color is not completely expressed over
the recessive allele that produces the white color.
 In both codominance and incomplete dominance both alleles are
expressed. How they're expressed is different.

Co-dominance is when both alleles are expressed separately. Human

blood type is a good example of this. The A and B alleles are both
expressed, so an individual gets the AB blood type.

In incomplete dominance, the phenotype resembles a sort of

blending of the two alleles. That is, a cross between an allele for red
petals and allele for white petals, result in pink petals.

In codominance, both alleles are equally expressed in heterozygote,

whereas, in incomplete dominance, both the alleles are expressed
but unequally leading to different degrees of intermediate
phenotype.

So, what would be the observation, if A and B alleles in Blood grouping system were in
incomplete dominance and the alleles for red and pink petals were codominant?
Individuals would neither have A blood group nor B blood group, but something
intermediate to both.

Flower would have had white and red splotches .

 Segregation distorters

Segregation distorters are chromosomal factors that promote their

inheritance by preventing the production of functional gametes
carrying their allelic alternative in heterozygous individuals. A
segregation distortion gene produces a distortion in normal
segregation in favor of itself, so that chromosomes bearing this gene
are over-represented in an organism's offspring. This phenomenon
in general is also called meiotic drive.

Because of their advantage in segregation, distorters can spread

through-out populations and eventually become fixed without
providing any advantage in fitness to their carriers. They thus
represent an example of non-adaptive selection. When located on a
sex chromosome and expressed in the heterogametic sex,
segregation distorters induce a sex-ratio bias in the progeny.
The system could work as follows:
Two tightly linked loci mainly control the process:
• a recognition locus
• a distortion locus.
The recognition locus has a particular recognition sequence, and the
distorter allele produces a protein that binds to the recognition locus.
If it is a 'distorter' recognition sequence, there is no effect. If it binds to
any other recognition sequence, it prevents the chromosome from
entering sperm. This produces a distortion in favor of chromosomes
containing the segregation distortion gene.

Ex: The segregation distorter gene was first found in fruitfly

(Drosophila) stocks from Wisconsin and Baja California. More than
90% of offspring from male heterozygotes have the segregation
distorter gene because the sperm containing other genes fail to
develop.
 Mendel’s second Law (Law of independent assortment)

Mendel also performed crosses in which he followed the segregation of

two genes simultaneously. His aim was to determine if any
relationship/interaction existed between different allelic pairs.

Mendel’s Experiments

Parental Cross F1Phenotype F2 Phenotypic Ratio F2Ratio

Yellow, Round,
Yellow, Round Seed
Yellow, Yellow, Wrinkled,
x Green, Wrinkled 9:3:3:1
Round Green, Round,
Seed
Green, Wrinkled
Mendel’s Explanations
Seed Color: Yellow = G; Green = g
Seed Shape: Round = W; Wrinkled = w
 Female Gametes
GW Gw gW gw
GGWW  GGWw  GgWW  GgWw 
GW (Yellow, (Yellow, (Yellow, (Yellow,
round) round) round) round)
GGWw  GGww  GgWw  Ggww 
Gw (Yellow, (Yellow, (Yellow, (Yellow,
round) wrinkled) round) wrinkled)
GgWW  GgWw  ggWW 
ggWw 
gW (Yellow, (Yellow, (Green,
(Green,
round) round) round)
GgWw  Ggww  ggWw  ggww 
Male gw (Yellow, (Yellow, (Green, (Green,
Gametes round) wrinkled) round) wrinkled

Round Yellow: G_W_ = 9; wrinkled Yellow: G_ww = 3;

Round green: ggW_ = 3; wrinkled green: ggww = 1
 Mendel’s Conclusions

during gamete formation the segregation of the alleles of one allelic pair is independent of
the segregation of the alleles of another allelic pair
 epistasis
Epistasis: An interaction between nonallelic genes, an interaction in
which one gene suppresses the expression of another.

Thus, epistasis is the masking of the expression of a gene at one

position in a chromosome, or locus, at one or more genes at other
positions.

Ex: Bombay phenotype, involving the ABO blood group system.

Individuals with this phenotype lack a protein called the H antigen
(geno-type hh), which is used to form A and B antigens. Even though
such individuals may have A or B genes, they appear to be blood
group O because they lack the H antigen.
Another well-known example is coat color in mice. Two coat-
color loci are involved. At locus A, color is dominant over albino (lack
of pigment). At locus B, the coat color agouti is dominant over black.
A mouse that is homozygous for the albino gene will show no pigment
regardless of its genotype at the other locus. Thus the A and B loci are
epistatic.
 So, what is the difference between dominance and epistasis?

Dominance involves the interaction of genes at the same locus,

whereas, epistasis involves the interaction of genes at different loci.
 modifiers

Modifier: Genes that have small quantitative effects on the level of

expression of another gene. Instead of masking the effects of
another gene, a gene can modify the expression of a second gene.

Ex: In mice, coat color is controlled by the B gene. The B allele

conditions black coat color and is dominant to the b allele that
produces a brown coat. The intensity of the color, either black or
brown is controlled by another gene, the D gene. At this gene, the
dominant D allele controls full color whereas the recessive d allele
conditions a dilute or faded expression of the color expression at
the B gene. Therefore, if a cross is made among mice that are
BdDd, the following phenotypic distribution will be seen:

9 B_D_ (black)
3 B_dd (dilute black)
3 bbD_ (brown)
1 bbdd (dilute brown)
The D gene does not mask the effect of the B gene, rather it
modifies its expression.
 Molecular basis of dominance

1. In the typical case, the single functional allele makes sufficient

protein to produce a phenotype identical to that of the
homozygote: this is called haplosufficiency. For example, suppose the
standard amount of enzyme produced in the functional
homozygote is 100%, with the two functional alleles contributing
50% each. The single functional allele in the heterozygote produces
50% of the standard amount of enzyme, which is sufficient to
produce the standard phenotype. If the heterozygote and the
functional-allele homozygote have identical phenotypes, the
functional allele is dominant to the non-functional allele.
Ex: This occurs at the albino gene locus: the heterozygote produces
sufficient enzyme to convert the pigment precursor to melanin,
and the individual has standard pigmentation.
2. Alternatively, a single functional allele in the heterozygote may
produce insufficient gene product for proper function, and the
phenotype resembles that of the homozygote for the non-
functional allele. This is called haploinsufficiency. This leads to
dominance of the mutant genotype.

Ex: Haploinsufficiency of telomerase reverse transcriptase which

leads to autosomal dominant dyskeratosis congenita. It is a rare
inherited disorder characterized by abnormal skin
manifestations, which results in bone marrow failure, pulmonary
fibrosis and an increased predisposition to cancer. A mutation in
motif D of the reverse transcriptase domain of the telomerase
protein, hTERT, leads to this phenotype. Thus telomerase dosage
is important for maintaining tissue proliferation.

Dominance of the mutant allele may also happen if its gene

product interferes with the functioning of the gene product of the
normal allele. So, the hererozygote resembles closely the
phenotype of the homozygous for the mutant allele.

Ex: Huntington’s Disease.

3. The intermediate interaction occurs where the heterozygous
genotype produces a phenotype intermediate between the two
homozygotes. Depending on which of the two homozygotes the
heterozygote most resembles, one allele is said to show incomplete
dominance over the other.

Ex: In humans the Hb gene locus is responsible for the chain

protein (HBB) that is one of the two globin proteins that make up the
blood pigment hemoglobin. Many people are homozygous for an
allele called HbA; some persons carry an alternative allele called HbS,
either as homozygotes or heterozygotes. The hemoglobin molecules
of HbS/HbS homozygotes undergo a change in shape that distorts the
morphology of the red blood cells, and causes a severe, life-
threatening form of anemia called sickle-cell anemia. Persons
heterozygous HbA/HbS for this allele have a much less severe form of
anemia called sickle-cell trait. Because the disease phenotype of
HbA/HbS heterozygotes is more similar to but not identical to the
HbA/HbA homozygote, the HbA allele is said to be incompletely
dominant to the HbS allele.
Penetrance: The frequency, under given environmental conditions, with
which a specific genotype is expressed by those individuals that
possess it. In medical genetics, the penetrance of a disease-causing
mutation is the proportion of individuals with the mutation who
exhibit clinical symptoms.
Ex: Achondroplasia is caused by a fully penetrant allele; if the allele is
present, achondroplasia results.

[Link] penetrance: All individuals who have the disease-causing

mutation have clinical symptoms of the disease. Ex: Achondroplasia.
[Link] penetrant: The trait it produces will almost always be apparent in
an individual carrying the allele. Ex: Retinoblatoma (90% penetrant).
[Link] Penetrance or Reduced penetrance: Some individuals fail to express
the trait, even though they carry the allele. Ex: Polydactyly in human
(<70% penetrant).
[Link] penetrance: An allele with low penetrance will only sometimes
produce the symptom or trait with which it has been associated at a
detectable level. In cases of low penetrance, it is difficult to distinguish
environmental from genetic factors. Ex: Several low-penetrance genes
contribute to cancer risk (penetrance may be as low as 2-5%).
 Compound heterozygosity

The human genome contains two copies of each gene, a paternal and a
maternal allele. A mutation affecting only one allele is
called heterozygous. A homozygous mutation is the presence of the
identical mutation on both alleles of a specific gene. However, when both
alleles of a gene harbor mutations, but the mutations are different, these
mutations are called compound heterozygous. Also called a genetic
compound.

Compound heterozygosity reflects the diversity of the mutation base for

many genetic disorders. In its compound heterozygous forms, the disease
may have lower penetrance. Because the mutations involved are often
less deleterious in combination than would be the case for a homozygous
individual with the classic symptoms of the disease, compound
heterozygotes often become ill later in life, with less severe symptoms.
Expressivity: The relative degree to which a trait caused by a gene is
manifested in an individual. It refers to variations of a phenotype in
individuals carrying a particular genotype.

Ex: Neurofibromatosis is a disease caused by mutations in the

neurofibromin gene. These mutations can cause the Schwann cells in
an affected individual's nervous system to grow into tumors called
neurofibromas, which appear as colored spots or bumps under the
skin. These tumors can result in skeletal abnormalities and
neurological problems. However, not all people who have the mutated
neurofibromin gene are equally affected by this condition. Family
members who carry the same mutated gene can exhibit a range of
symptoms, with some individuals experiencing much more severe
symptoms than others, although they all carry the same allele.
 Relationship between penetrance and expressivity

• Penetrance is a qualitative concept and expressivity is a

quantitative concept.

• Penetrance refers to whether a phenotype is expressed for a

particular genotype, and expressivity refers to the degree to which a
phenotype is expressed when it is expressed.

• Note that expressivity is dependent on penetrance. It is not possible

to measure the degree of expression if a genotype is not expressed as
a phenotype, that is, if the genotype does not penetrate to the
phenotype.

• Penetrance is measured at the population level, whereas,

expressivity is measured at individual level.
A few problems
1. A phenotypic ratio of 3:1 in the offspring of a mating of two
organisms heterozygous for a single trait is expected when:
A. the alleles segregate during meiosis.
B. each allele contains two mutations.
C. the alleles are identical.
D. the alleles are incompletely dominant.
E. only recessive traits are scored.

2. When true-breeding tall stem pea plants are crossed with

true-breeding short stem pea plants, all of the _________
plants, and 3/4 of the __________ plants had tall stems.
Therefore, tall stems are dominant.
A. F1, F2.
B. G1, G2.
C. parental, F2.
D. F2, parental.
E. P1, P2
3. In Mendel's experiments, if the gene for tall (T) plants was
incompletely dominant over the gene for short (t) plants, what would
be the result of crossing two Tt plants?
A. 1/4 would be tall; 1/2 intermediate height; 1/4 short
B. 1/2 would be tall; 1/4 intermediate height; 1/4 short.
C. 1/4 would be tall; 1/4 intermediate height; 1/2 short.
D. All the offspring would be tall.
E. All the offspring would be intermediate.

4. What are the possible blood types of the offspring of a cross between
individuals that are type AB and type O?
A. AB or O
B. A, B, or O
C. A or B
D. A, B, AB, or O
E. A, B, or AB
5. Grey mice were crossed between themselves and in the F1
generation 103 black mice and 197 grey mice were obtained. Does
these results follow Mendel’s first law?

6. In Mendel's experiments, the spherical seed character (SS) is

completely dominant over the dented seed character (ss). If the
characters for height were incompletely dominant, such that TT are
tall, Tt are intermediate and tt are short, what would be the
phenotypes resulting from crossing a spherical-seeded, short (SStt)
plant to a dented-seeded, tall (ssTT) plant?

A. All the progeny would be spherical-seeded and tall.

B. 1/2 would be spherical-seeded and intermediate height; 1/2 would
be spherical-seeded and tall.
C. All the progeny would be spherical-seeded and short.
D. You cannot predict the outcome.
E. All the progeny would be spherical-seeded and intermediate
height.
7. About 70% of Indians perceive a bitter taste from the chemical
phenylthiocarbamide (PTC). The ability to taste this chemical results
from a dominant allele (T) and not being able to taste PTC is the result of
having two recessive alleles (t). Albinism is also a single locus trait with
normal pigment being dominant (A) and the lack of pigment being
recessive (a). A normally pigmented woman who cannot taste PTC has a
father who is an albino taster. She marries a homozygous, normally
pigmented man who is a taster but who has a mother that does not taste
PTC.

• What are the genotypes of the possible children (choose all that apply)?

• What percentage of the children will be albinos?

• What percentage of the children will be non-tasters of PTC?

 8. In the breeding season, male Anole lizards court females by bobbing
their heads up and down while displaying a colorful throat patch.
Assume for this question that both males and females bob their heads
and have throat patches. Assume also, that both traits are controlled
by single locus genes on separate chromosomes. Now, suppose that
anoles prefer to mate with lizards who bob their heads fast (F) and
have red throat patches (R) and that these two alleles are dominant to
their counterparts, slow bobbing and yellow throats. A male lizard
heterozygous for head bobbing and homozygous dominant for the red
throat patch mates with a female that is also heterozygous for head
bobbing but is homozygous recessive for yellow throat patches.

• How many of the F1 offspring have the preferred fast bobbing or red
throat phenotype (assume 16 young)?

• What percentage of the offspring will lack mates because they have
both slow head bobbing and yellow throats?

• What percentage of the offspring will have trouble finding mates

because they lack one of the dominant traits?
9. Wildcat comes in three colors, blue, red, and purple. This trait is
controlled by a single locus gene with incomplete dominance. A
homozygous (BB) individual is blue, a homozygous (bb) individual is red,
and a heterozygous (Bb) individual is purple.

• What would be the genotypes and phenotypes of the offspring if a blue

wildcat were crossed with a red one?

• What are the genotypic and phenotypic ratios of the F2 generation?

10. A naturalist visiting an island in the middle of a large lake observes
a species of small bird with three distinct types of beaks. Those with
short, crushing beaks (BB) consume hard shelled nuts, those with
long, delicate beaks (bb) pick the seeds from pine cones, and those
with intermediate beaks (Bb), consume both types of seeds though
they are not as good at either. Assume that this difference in beak
morphology is the result of incomplete dominance in a single locus
gene. Which mated pair(s) will have the best adapted offspring in a
year in which most of the food available is scarce due to drought?

11. In sweet peas, the two allelic pairs C, c and P, p are known to effect
pigment formation in the flowers. The dominants, C&P, are both
necessary for colored flowers. Absence of either results in white
flowers. A dihybrid plant is crossed to a white one which is
heterozygous at the “C” locus.
a. What is the genotype of the dihybrid plant?
b. What is the genotype of the white plant?
c. What kinds of flowers, colored or white, are to be expected
from the cross above? Include the ratio.
12. Two pairs of alleles are involved in cyanide production in white
clover. Some strains have high cyanide content, others a low one.
When high Strain A was crossed to low Strain B, the F1 all had
high cyanide content. When F1 plants were crossed among
themselves, the following resulted:

High cyanide content: 450 plants

Low cyanide content: 350 plants

Offer an explanation for these results.