Human Pedigrees

Etymologically speaking, pedigree comes from a French word pie de grue which means
crane’s foot. During the 15th to 19th century, the first pedigree analysis was used to trace the
hereditary pattern of the disease called hemophilia. Queen Victoria of England with his chronicler,
constructs the Queen’ family tree pedigree. Later, in 1845, Pliny Earle, a genealogist constructed
a pedigree of a family with colorblindness.

Today, the word pedigree means a pattern of a family tree showing the phenotypes of the trait
to predict and analyze the inherited traits. Pedigree uses signs and symbols that correspond to
a specific trait or meaning. Figure 4 shows signs and symbols in a pedigree.

Figure 4. Pedigree symbols.

(Image retrieved from:

Lewis, R. (2015). Human genetics: Concepts and applications. 11th Edition. McGraw-Hill Education.)
 Extensions and Modification of
Mendelian Inheritance
Module Overview

There are many ways in which two alleles of a single gene may govern a trait's outcome. In this
module, we will discuss the different types of Mendelian inheritance patterns. It includes the
patterns of dominance, the lethal and multiple alleles, the X-linked inheritance, and the sex-limited
and sex-influenced inheritance.

Lesson 2.1: The Patterns of Dominance

Learning Outcomes
Differentiate law of dominance, the law of segregation, and the law of independent
assortment.
Compare and contrast incomplete dominance, codominance, and overdominance.
Predict the possible result in crossing two alleles.

Discussion

Reminiscing Mendel’s Laws

In our previous module, we discussed Mendel’s first three postulates: the unit factors of
pairs, the law of dominance, and the law of segregation. We have learned that genes are present
on homologous chromosomes. The homologous chromosomes segregate from each other and
assort (arrange) independently with segregating chromosomes during gamete formation.
Mendel’s first three postulates, including the law of independent assortment, help us understand
the fundamental principles of gene transmission from parent to offspring.

Mendelian inheritance involves a single gene with two different alleles. The alleles show
a simple dominant-recessive relationship. It is inheritance patterns that follow or obey the law of
segregation and the law of independent assortment. To further understand the extension and
modification of Mendelian inheritance, let us have a short recap of dominance, the law of
segregation, and the law of independent assortment.
Law of Dominance

In a cross of parents that are pure for opposing traits, only one form of the trait will give
the impression in the next generation. All the offspring will be heterozygous and express only the
dominant trait. For instance, if we cross a dominant tall plant (TT) to a recessive dwarf/short plant
(tt), the genotypic result will be all alike (Tt). The phenotypic result will also be all alike (Tall plant),
as shown in Figure 5.

Figure 5. Applying the law of dominance.

Law of Segregation

During the formation of gametes (eggs or sperms), the two alleles are responsible for a trait
separate from each other. Alleles for a trait are then recombined at fertilization, producing the
genotype for the traits of the offspring. When we say fertilization, it is a process of combining
the male gamete (sperm cell) with the female gamete (egg cell) to produce a fertilized egg or
cell called a zygote. In applying the law of segregation, the male and female gametes will
combine and produces possible offspring, as shown in the figure below.
Figure 6. Applying the law of segregation.

Law of Independent Assortment

The law of independent assortment states that different genes and their alleles are
inherited independently within sexually reproducing organisms. Considering the two genes on
different chromosomes, the inheritance of one does not influence the chance of inheriting the
other. Independent assortment results from the random alignment of chromosome pairs during
metaphase I and meiosis, as shown in the figure below. It can be illustrated using dihybrid
crosses.

Figure 7. Applying the law of independent assortment

Image retrieved from:

https://www.kindpng.com/imgv/hTixxTT_principle-of-independent-assortment-mendels-law-of-inheritance/
 Figure 8 sums up and shows the law of segregation and the law of independent
assortment.

Figure 8. Segregation and independent assortment

Image retrieved from:

https://biologydictionary.net/law-of-independent-assortment/

Inheritance Pattern of Dominance

There are many ways in which two alleles of a single gene may govern the outcome of a
trait. In this lesson, we will first talk about the patterns of dominance, which includes incomplete
dominance, codominance, and overdominance. These patterns are examined with two goals in
mind: understanding the relationship between the molecular expression of a gene and the trait
itself; and the outcome of crosses.

Incomplete (Partial) Dominance

After discovering the Mendelian inheritance laws, the term incomplete dominance (partial
dominance) was proposed by the German botanist named Carl Correns. Carl Correns continued
research about genetics and experimented on Four 0’clock flowers. Correns’s experiment leads
to the discovery of incomplete dominance. Incomplete dominance is a pattern responsible for
variations in different life forms leading to enhanced and better reforms through the genetics
used by humans.
 In incomplete dominance, a heterozygous individual does not entirely show or express a
dominant allele. Instead, it shows a phenotype intermediate (the result in heterozygotes who
inherit both alleles) of the phenotypes of the dominant and recessive alleles. It partially shows or
expresses the phenotypes of the dominant allele and the recessive allele, where one allele for a
specific trait is not completely expressed as dominant or recessive over its pair allele. Instead,
the dominant allele is expressed in a reduced ratio. In-plant, for instance, if we cross a Four O’clock
plant producing red flowers (CR CR, where C indicates “color” and R superscripts indicates red) to
another Four O’clock plant with white flowers (CWCW, where C indicates “color” and W superscripts
indicates white), the offspring will have pink flowers. Why? It is because some red pigment is
produced in the first filial generation (F1 generation) intermediate-colored pink flowers. Neither
red nor white flower is dominant, as shown in Figure 9. Generally, this happens when the two
alleles for a given gene produce proteins, but one protein is not functional.

Figure 9. Incomplete dominance of four O'clock plant in a first filial generation.

Suppose the Four O’clock plant with pink flowers (CRCW) will undergo self-fertilization. In
that case, the resulting second filial generation (F2 generation) will be 1 red flower, 2 pink flowers,
and 1 white flower shown in Figure 10.
 Figure 10. Incomplete dominance of four O'clock plant in a second filial generation

Clear-cut cases of incomplete dominance, which result in the intermediate expression of

the overt/open phenotype, are relatively uncommon. However, even when complete dominance
seems apparent, careful examination of the gene product, rather than the phenotype, often
reveals an intermediate level of gene expression. An example is the human biochemical disorder
called Tay-Sachs disease (a genetic mutation in the HEXA gene on chromosome 15), in which
homozygous recessive individuals are severely affected with a fatal lipid storage disorder, and
neonates (newborn child) die during their one to three years of life. There is almost no activity of
the responsible enzyme hexosaminidase in afflicted individuals, which is normally involved in lipid
metabolism. Heterozygotes, with only a single copy of a mutant gene, are phenotypically normal,
but express only about fifty percent (50%) of the enzyme activity in a homozygous normal
individual. However, Tay-Sachs disease will be fully expressed to its offspring when his/her
partner is also carriers of that mutant gene.
Codominance

Codominance pertains to the genetic pattern in which gene products from the two alleles
in a heterozygote are both expressed. Which means, the two alleles are expressed (multiple
alleles) in heterozygous individuals. An example of codominance is the ABO blood group, which
is based on the expression of codominant alleles. We can determine blood types by using the
patterns of molecules on the surfaces of red blood cells. Most of these molecules are proteins
embedded in the plasma membrane bonded with sugars that extend from the cell surface. The
sugar is the antigen, which is the molecule that the immune system recognizes.

➢ People who belong to blood group A have an allele that encodes an enzyme that adds a
final piece to a certain sugar to produce antigen A. Their plasma contains an antibody B.
➢ In people with blood type B, the allele and its encoded enzyme are slightly different, which
causes a different piece to bond to the sugar, producing antigen B, and their plasma
contains an antibody A.
➢ People who belong to blood group AB have both antigen types (A and B), and they have
no antibodies in their plasma.
➢ People with blood type O reflect the third allele of this gene yet. This means that they miss
one DNA nucleotide, but this changes the encoded enzyme in a way that removes the
sugar chain from the final piece, as shown in Figure 11. A blood type O person lacks both
antigen A and B, but have antibodies A and B in their plasma.

Figure 11. ABO blood types illustrate codominance

 The A and B alleles are codominant, and both are entirely dominant to the O allele. So,
allele A and allele B are both expressed in a heterozygous individual. Considering that the
genotypes tell us how these interactions happen, to distinguish alleles A, B, and O, we will use the
symbol IA, IA, and i. The I designation stands for isoagglutinin, another term for antigen. People
with blood type A have antigen A on the surface of their red blood cells and may have genotype
IAIA or IAi. People with blood type B have antigen B on their red blood cells' surface and may have
genotype IBIB or IBi. People with the rare blood type AB have both antigens A and B on the surface
of their red blood cells, and they have genotype IAIB. People with blood type O have no antigen,
and they have genotype ii, as shown in Figure 12.

Figure 12. ABO blood group antigens present on red blood cells and IgM antibodies present in the serum

Image retrieved from:

https://en.wikipedia.org/wiki/ABO_blood_group_system

Fiction plots often misuse ABO blood type terminology, assuming that a child’s ABO blood
type must match that of one parent. This is not true because a person with blood type A or B can
be heterozygous. A person who’s genotype IAi and a person who’s genotype IBi can jointly produce
offspring of any ABO genotype or phenotype, as shown in Figure 13.
 Figure 13. Codominance

The IA and IB alleles of the I gene are codominant, but they follow Mendel’s law of
segregation. These Punnett squares follow the genotypes that could result when a person with
type A blood has a child with a person with type B blood.

Overdominance

Overdominance is the phenomenon in which a heterozygous is more vigorous than both

of the corresponding homozygotes. Overdominance, also known as the heterozygous advantage,
is a condition in genetics where the phenotype of the heterozygous lies outside the phenotypical
range of both homozygous parents. It refers to the property of allele to other alleles wherein an
allele shows dominance as it suppresses the expression that dominates the effect of the
recessive allele. Heterozygous individuals that express overdominance have higher fitness than
homozygous individuals. Being a heterozygous individual gives you the best chance of having
offspring and living the best quality of life.

An autosomal recessive disorder called sickle-cell anemia expresses overdominance.

Individuals with Sickle-cell anemia produce an abnormal form of hemoglobin. The two alleles with
normal hemoglobin and abnormal hemoglobin are represented by the symbol HbA and HbS,
respectively.

• HbA represents hemoglobin A, which encodes the normal hemoglobin

• HbS represents hemoglobin B, which encodes the abnormal hemoglobin

A person with homozygous abnormal hemoglobin (HbSHbS individuals) has red blood cells
that deform into a sickle shape under low oxygen tension conditions. Individuals with abnormal
hemoglobin have two significant ramifications:

Sickling of red blood cells shortens its life span.

That will result in anemia (deficiency in red blood cells; in hemoglobins)
 Odd-shaped cells clump
That will partially or completely block capillary circulation.

The sickle-cell allele has been found at a relatively high frequency in the parts of Africa
where malaria is found. Malaria is a human disease that is caused by a protozoan parasite with
the genus Plasmodium. Protozoan parasite (Plasmodium sp.) undergoes its life cycle in two main
parts:

Inside the anopheles’ mosquito

Inside the red blood cells

Red blood cells of heterozygotes are likely to rupture when infected by Plasmodium sp.,
which prevents the propagation of the parasite. Therefore, individuals with heterozygotes red
blood cells (HbAHbS individuals) are better than:

➢ individuals having a homozygote abnormal hemoglobin (HbSHbS individuals) because

they do not suffer from sickle cell anemia.
➢ individuals having a homozygote's normal hemoglobin (HbAHbA individuals) because
they are more resistant to malaria.

At the molecular level, overdominance occurs when two alleles produce slightly different
proteins. The question is, how can these two protein variants produce a favorable phenotype in
the heterozygote? Well, there are three (3) possible explanations for overdominance at the
molecular/cellular level.

• First in line, disease resistance.

• Second, a homodimer formation.
• Lastly, a variation in functional activity.