34 | Genetics

3 Genetics

UNIT SPECIFICS
Through this unit we have discussed the following aspects:
● Mendel's laws and Concept of allele
● Gene mapping and Gene interaction
● Mitosis and Meiosis
● Concept of recessive and dominance
● Concept of mapping of phenotype to genotype
● Single gene disorders in humans
● Concept of complementation using genetics
The practical applications of the topics are discussed for generating further curiosity and
creativity as well as improving problem solving capacity.
Besides giving a large number of multiple choice questions as well as questions of short and
long answer types marked in two categories following lower and higher order of Bloom's
taxonomy, assignments through a several numerical problems, a list of references and suggested
readings are given in the unit so that one can go through them for practice. It is important to note
that for getting more information on various topics of interest some QR codes have been provided
in different sections which can be scanned for relevant supportive knowledge.
After the related practical, based on the content, there is a “Know More” section. This section
has been carefully designed so that the supplementary information provided in this part becomes
beneficial for the users of the book. This section mainly highlights the initial activity, examples of
some interesting facts, analogy, history of the development of the subject focusing the salient
observations and finding, timelines starting from the development of the concerned topics up to the
recent time, applications of the subject matter for our day-to-day real life or/and industrial

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applications on variety of aspects, case study related to environmental, sustainability, social and
ethical issues whichever applicable, and finally inquisitiveness and curiosity topics of the unit.
RATIONALE
To convey that “Genetics is to biology what Newton’s laws are to Physical Sciences”. Mendel’s
laws, Concept of segregation and independent assortment. Concept of the allele. Gene mapping,
Gene interaction, Epistasis. Meiosis and Mitosis be taught as a part of genetics. Emphasis is to be
given Not to the mechanics of cell division nor the phases but how genetic material passes from
parent to offspring. Concepts of recessiveness and dominance. Concept of mapping of phenotype
to genes. Discuss the single gene disorders in humans. Discuss the concept of complementation
using human genetics.
PRE-REQUISITES
Biology: (Class XI and XII)
UNIT OUTCOMES
List of outcomes of this unit is as follows:
U3-O1: Gives overview about Genetics, Heredity, Mendel’s law and Concept of allele
U3-O2: Explain gene mapping, gene interaction and Epistasis
U3-O3: Describe Meiosis and Mitosis from genetics point of view
U3-O4: Understanding chromosomal abnormalities and single gene disorder
U3-O5: Defining the concept of complementation using human genetics

EXPECTED MAPPING WITH COURSE OUTCOMES

Unit-3 (1- Weak Correlation; 2- Medium correlation; 3- Strong
Outcomes Correlation)
CO-1 CO-2 CO-3 CO-4 CO-5
U3‐O1 - 2 3 - -
U3‐O2 - 1 3 - -
U3‐O3 - 2 3 - -
U3‐O4 - - 3 - -
U3‐O5 - - 3 - -

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3.1 INTRODUCTION TO GENETICS

Genetics is the branch of biology that deals with the study of genetic variation, genes, and heredity.
Genetics and its concepts had been observed for centuries, however, it was scientifically studied
by Gregor Mendel. Genetics is the study of inheritance on several levels of comprehension, from
molecules to populations. Genetics is central to contemporary biology, making its comprehension
crucial for all life sciences scholars. Numerous areas of daily living are profoundly influenced by
the field. The food we consume and the clothing we wear are derived from species that have been
genetically modified. On the basis of fundamental genetic discoveries, the causes of significant
human diseases are being uncovered, and treatments are being devised. The management of
human health is increasingly dependent on genetic and genomic information. Genetics is a growth
field since these effects will likely increase over the future decades.
3.1.1 Past, modern and future genetics
The Importance and role of genetics: We all have genes that have an effect on our life. They have an
impact on our height, weight, hair colour, and skin pigmentation. They affect our susceptibility
to several diseases and ailments and even contribute to our intelligence and character. Genes are
vital to our being and identity. Although genetics is a relatively recent discipline, individuals have
understood the heritable nature of traits and "practised" genetics for millennia. When humans
began to apply genetic principles to the domestication of plants and animals, agriculture began to
flourish. Today, the principal crops and animals used in agriculture have undergone considerable
genetic modifications to significantly enhance their yields and give numerous desirable
properties, including resistance to disease and pests, specific nutritional attributes, and harvest-
facilitating characteristics. Today, a large amount of the food produced worldwide is derived from
genetically modified corn, soybeans, and other crops. Numerous medications and food additives
are also produced in the pharmaceutical business by fungus and bacteria that have been
genetically modified to be effective makers of these chemicals. Commercially generated growth
hormones, insulin, and clotting factor are now created by genetically modified bacteria.
Additionally, genetics plays an important part in medicine. Physicians acknowledge numerous
diagnostic tests have been made possible by the emergence of fundamental insights into
molecular genetics. Without a good understanding of genes and genetic approaches, the study of
practically any discipline of biology or medicine is insufficient.
Evolution of Genetic Variation: On Earth, a vast variety of life forms and characteristics inhabit
virtually every imaginable area. All life has a common ancestor thus this diversity has developed
during the past four billion years. Adaptation is another defining characteristic of life; many
species are exquisitely adapted to their surroundings. The history of life is a chronicle of the
emergence of new forms of life, the extinction of old forms, and the transformation of existing
forms. Diversification and adaption of life are the results of evolution, which is merely genetic
change over time. Evolution is a two-step process: first, genetic variants develop at random, and
then the frequency of certain variants grows or decreases. Therefore, genetic variety is the basis
of all evolutionary change and, eventually, the basis of all known life. Understanding the past,
present, and future of life is dependent on genetics, the study of genetic diversity.
Divisions of Genetics: Genetics has traditionally been split into three key subfields: transmission
genetics, molecular genetics, and population genetics. Transmission genetics involves the

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fundamental principles of genetics and how features are transmitted from one generation to the
next. This field examines the connection between chromosomes and heredity, as well as the
arrangement of genes on chromosomes and gene mapping. Molecular genetics is concerned with
the chemical composition of the gene itself, including how genetic information is encoded,
duplicated, and expressed. It consists of the cellular processes of replication, transcription, and
translation which transfer genetic information from one molecule to another and gene regulation
the mechanisms that control the expression of genetic information. Population genetics
investigates the genetic makeup of groups of individuals belonging to the same species
(populations) and how that genetic makeup varies over time and space. Population genetics is
essentially the study of evolution because evolution involves genetic change. Population genetics
focuses on the collection of genes present in a population.
3.1.2 Heredity and principles of heredity
As the twentieth century has unfolded, the new science of genetics has come to occupy an increasingly
important position at the centre of the science of life. It is claimed that the origin of the science
of genetics can be traced to one man - Gregor Mendel (1822-1884), raised in German-speaking
Silesia, who entered the Augustinian order in the Monastery of Brünn, Moravia, and taught high
school science, also finding time to conduct experiments in the hybridization of plants, before
becoming abbot of his monastery. Mendel's research with pea plants is what made him most
famous.

Fig. 3. 1 Gregor Johann Mendel 'Father of Genetics’

(Source: 5.10 Mendel’s Experiments and Laws of Inheritance – Human Biology (under creative commons licenses)
On numerous occasions, it has been noted that family members have certain similar qualities, such as
facial features, skin tones, etc. Why is this so? Why does a child resemble their mother in certain
aspects and their father in others? In qualities that run-in families, hereditary variables, such as
the genetic material a person inherits from his or her parents, have a role. All animals and plants
share the same traits. Heredity, or the transmission of character qualities from one generation to
the next, is the phenomenon of offspring inheriting their parents' characteristics. On the
chromosomes are the genes responsible for the inheritance of characteristics. In addition, it has
been observed that although while offspring receive qualities from their parents, they are unique
and possess traits that distinguish them from their parents. Variations relate to these differences
between progeny and parents. Genetics is the study of heredity and genetic variation from a
scientific perspective.

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The primary objective of biotechnology is to modify living organisms or alter their genetic composition
in order to develop products that improve the quality of life for humans. Understanding genetics
and the inheritance of traits is essential for using biotechnological techniques to change genes.
To alter a trait, it is necessary to identify the genetic components (genes and their allelic forms at
the population level) that influence the trait. The principles will be covered in this chapter.

3.2 MENDEL'S LAWS OF INHERITANCE

In the middle of the 19th century, advancements were made in understanding inheritance. After seven
years of hybridization study on garden peas, Gregor Mendel (Fig. 3.1) formulated the rules of
heredity in living creatures (1856–1863). Mendel's research on inheritance patterns initiated the
application of statistical analysis and mathematical reasoning to biological problems. Greater
accuracy in the data he gathered. In addition, the validation of his beliefs by research on
successive generations of his test plants proved that his findings were theoretical conjectures and
general rules of inheritance.
Mendel studied garden pea plant characteristics that were displayed as two opposite phenotypes, such
as tall or dwarf plants or yellow or green seeds. As a result, he was able to formulate a fundamental
set of inheritance rules that other scientists used to explain the complexity and diversity of natural
data. Mendel tested artificial pollination and cross-pollination on a variety of pure-bred pea lines.
A true-breeding line is one that exhibits steady trait inheritance and expression over numerous
generations after having experienced continual self-pollination. Mendel chose fourteen true-
breeding pea plant varieties, pairing them in ways that were identical but for one feature that was
different. Smooth or wrinkled seeds, yellow or green seeds, inflated (full) or constricted green or
yellow pods, tall or dwarf plants, violet or white blossom colour, and axial or terminal flower
location were some of the contrasting features chosen (Fig. 3.2).

Fig. 3. 2 Contrasting Traits Studied by Mendel in Pea plant

(Source: [Link] under
Creative Commons licenses

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Why did Mendel choose the Pea plant for his experiments?
1. The pea plant is simple to grow and maintain.
2. They are naturally self-pollinating, but also capable of cross-pollination.
3. Due to the fact that it is an annual plant, multiple generations can be studied in a short amount of
time.
4. It contains contrasting characters

3.3 LAWS OF INHERITANCE PROPOSED BY MENDEL:

Mendel structured his experiments in a way that he would observe one pair of contrasting characters at
one time. He began his experiments using purebred lines for contrasting characters. He cross-
pollinated two pure lines for contrasting characters and the resultant offspring were called the F1
generation (also called the first filial generation/ monohybrid cross). The F1 generations were
then self-pollinated which gave rise to the F2 generation the of second filial generation or dihybrid
cross. These two experiments lead to the formulation of Mendel's laws known as laws of
inheritance which are:
● Law of Dominance
● Law of Independent Assortment
● Law of Segregation
3.3.1 Law of Dominance
The first law of inheritance is known as Mendel's law. Only the dominant trait in the phenotypic will be
passed down to hybrid offspring, in accordance with the law of dominance. Recessive
characteristics are those alleles that are suppressed, whereas dominant traits are those alleles that
control the trait. (Fig. 3.3)

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Fig. 3. 3 Law of Dominance

(Source: [Link]

"When parents with pure, contrasting traits are crossed together, only
one form of trait appears in the next generation. The hybrid offspring
will exhibit only the dominant trait in the phenotype."

According to the law of dominance, only one of the contrasting features of the parents will be displayed
in the F1 generation, and both parents' traits will be expressed in the F2 generation in a 3:1 ratio.
A recessive trait is one that is suppressed while a dominant trait is one that is displayed in the F1
generation. The law of dominance essentially states that the dominant trait always dominated or
masked the recessive traits. The Mendel experiment can be used to explain this law.
A monohybrid cross is created when two monohybrid traits are combined (TT and tt). Here, identical
plants that only differed by one character were crossed. Mendel started with a pair of pea plants
that had two distinct features, one tall and the other dwarf, for the monohybrid cross. Cross-
pollination between tall and dwarf plants produced tall plants, known as F1 progeny. Dominant
traits are those that are manifested in the phenotype, whereas recessive traits are those that are
not. He then carried out further studies on the self-pollination of F1 offspring plants. Due to the
3:1 ratio of tall to short plants produced as a result, the law of segregation was formed.

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3.3.2 Law of Independent Assortment

Also known as Mendel’s second law of inheritance, it states that a pair of traits segregate
independently of another pair during gamete formation. As the individual heredity factors assort
independently, different traits get equal opportunities to occur together.
Let us now consider a dihybrid cross between homozygous round shape and yellow colour (RRYY)
seeded pea plant with a homozygous wrinkled and green colour (rryy) seeded pea plant. All F1
progeny were round seeded having yellow colour. In this following example which traits are
dominant, and which are recessive? In F1 progeny, as all plants were round and yellow seeded,
it clearly showed that they are dominant over wrinkled and green seeded traits. The result of F2
generation upon selfing is explained in Fig. 3 in which a ratio of 9:3:3:1 of offspring with 9 round
yellow, 3 wrinkled yellow, 3 round green, and 1 wrinkled green (9:3:3:1) is observed. Since two
pairs of contrasting characters are included in such crosses, hence they are called dihybrid crosses.
Based upon such observations on dihybrid crosses, the third principle of inheritance, i.e., Law of
Independent Assortment was proposed. (Fig. 3.4)

Fig. 3. 4 Law of Independent Assortment

(Source: [Link] under Creative Commons licenses

3.3.3 Law of Segregation

The law of segregation states that during the production of gametes, two copies of each hereditary
factor segregate so that offspring acquire one factor from each parent. In other words, allele
(alternative form of the gene) pairs segregate during the formation of gamete and re-unite
randomly during fertilization. This is also known as Mendel’s third law of inheritance.

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When Mendel cross pollinated a pure (homozygous) tall pea plant with a pure dwarf pea plant, he
noticed that the progeny of first generation (First filia or F1 generation, which was raised by
collecting the seeds produced from this cross) were all tall. The dwarf phenotype was missing.
What happened to the dwarf trait? When the said F1 offspring were self-pollinated to raise F2
generation, surprisingly both tall and dwarf plants appeared in the ratio of 3:1 (3 tall and dwarf).
Since Mendel designed this experiment by considering only one contrasting trait, i.e., tall and
dwarf, this cross is called monohybrid cross. Interestingly, in all such monohybrid crosses
involving other contrasting pair of characters carried out by Mendel, similar ratio of
approximately 3:1 was obtained in F2 generation. These results prompted Mendel to propose that
each individual has two factors for each character (trait) and that one factor (which was later
named as gene) was inherited from each parent through gametes.
This is the reason that the dwarf feature which was not there in F1 generation was found in F2. Hence,
F1 tall plants are heterozygotes as they contain two different alleles (Tt). As F1 plants are
heterozygous tall (Tt), this indicates that the tall allele (T) is dominant over dwarf allele (t). Thus,
dwarf allele (t) is recessive to tall allele (T). Understanding of these crosses can be well
understood by the graphical representation developed by Reginald C. Punnett, a British geneticist.
Using Punnett Square, we can easily calculate the probability of all possible genetic combinations
or genotypes.
We can see in (Fig. 3.5), that when plants in F1 heterozygous progeny were self-pollinated as they
produced 'T' and 't' gametes, the progeny revealed three genotype combinations; TT, Tt, tt in a
ratio of 1:2:1 respectively. Here we learnt that through Punnett Square by using mathematics, we
can easily calculate the probability of genotype (genetic make-up) and phenotype (morphological
or observable traits) of future progeny. This clearly shows that the phenotypic ratio of a
monohybrid cross is 3:1 and the genotypic ratio is 1:2:1.

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Fig. 3. 5 Segregation of height character in pea plant

(Source: [Link]

3.4 CONCEPT OF ALLELE

Each gene has two alternative versions known as alleles. When two identical alleles for a characteristic
are present in an individual, they are called homozygous alleles. When two different alleles for a
trait are present, they are called heterozygous alleles.
Any one of two or more genes that may alternately appear at a specific location (locus) on a chromosome
is known as an allele, also known as an allelomorph. Alleles may exist in pairs or there may be
several alleles influencing how a certain trait is expressed (phenotype). The genotype of an
organism is made up of the alleles it possesses in combination. The genotype of an organism is
referred to as homozygous or heterozygous depending on whether the paired alleles are the same
or different. In a heterozygous pairing, a dominant allele will take precedence over a recessive
allele's features. However, some alleles may be co-dominant, which means that neither one

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operates as dominant or recessive. The human ABO blood group system serves as an illustration;
people with type AB blood have one allele for A and one for B. Type O people fall into this
category.
The majority of characteristics are determined by more than two alleles for a particular gene encoding
a characteristic. Multiple variants of the allele may occur; nevertheless, a diploid individual can
only carry two alleles of a gene. During the generation of haploid gametes, only one will bind to
the assigned gene location during meiosis. Additionally, some features are governed by many
gene locations. Both possibilities increase the number of implicated alleles. All genetic qualities
result from interactions between alleles. Mutation, crossing over, and environmental variables
alter the frequency of phenotypes (and consequently their alleles) in a population. For instance,
alleles carried by individuals with high fitness (meaning they successfully reproduce and pass on
their genes to their kids) are more likely to endure in a population than alleles carried by
individuals with lower fitness, which are gradually lost over time.

3.5 GENE MAPPING

As the distance between 2 genes increases, the crossing over will be more and hence more will be
recombinants. The greater the distance between linked genes greater the chance of crossing over
and the greater will be the number of recombinants. The unit of gene distance is cM
(CentiMorgan) or mu (Map units). If the recombination frequency is 1% = 1cM distance between
two genes on the chromosome. The highest possible frequency is 50% (In the case of Mendelism)
which means the genes are either on 2 extreme ends of chromosomes or on different
chromosomes.
For Example,
Suppose, two genes (A and B) are located on the same chromosome. An AA BB individual is crossed
to an aa bb individual to produce Aa Bb offspring. The AaBb offspring are then test-crossed to
aa bb individuals. Let us assume this produces a total of 400 offspring. Among these 325 offspring
are parental and 75 are recombinant.
F2 Progeny: ABab = 160, abab = 165, Abab = 36 and aBab = 39
With the help of the above data, we can calculate the recombination frequency and map distance in the
following way:
= (36+39/36+39+160+165) x 100
= 18.8 cm

The genes are approximately 18.8 cm apart.

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3.6 GENE INTERACTION

Genetic interaction is the set of functional associations between genes. One such relationship is epistasis,
which is the interaction of non-allelic genes in which the effect of one gene is masked by another
gene, either causing the effect to be suppressed or resulting in the production of a new phenotype.

3.6.1 Epistasis
Epistasis is a circumstance where the expression of one gene is modified (e.g., masked, inhibited or
suppressed) by the expression of one or more other genes. Genes can either work together to
create a new characteristic or mask one another so that one is recognized as "dominant." The
phenotype of specific traits is determined by the conditional linkage between two genes. At each
location, there are two alleles that influence phenotypes. They may interact in a way that makes
one gene recessive to a dominant allele of the other, regardless of the genotype of the other gene.
Tables and ratio charts are two other ways to express epistasis. There are four alleles for each of
the two genes, creating a total of 16 potential pairs. There are sixteen phenotypes corresponding
to these sixteen allele combinations. Not all combinations are unique because of the dominant
and recessive traits of the dominant and recessive alleles. To visually represent the 16 potential
allele pairings for four alleles, a 44 chart can be utilised. The colour of many bee species is
demonstrated in the table below. (Fig. 3.6)

Fig. 3. 6 Example of Epistasis in Bee

(Source: [Link]

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3.6.2 Types of Epistasis

There are six common types of epistasis gene interactions: dominant, dominant inhibitory, duplicate
dominant, duplicate recessive, polymeric gene interaction, and recessive.
Dominant epistasis, sometimes referred to as simple epistasis, occurs when a dominant allele suppresses
the expression of both dominant and recessive alleles at a distinct location. Recessive epistasis is
the process through which an expression is hidden by a recessive allele. Some genes have the
ability to stop other genes from being expressed. Due to the gene's role as a suppressor or factor
that prevents the expression of another allele, this phenomenon is known as dominant inhibitory
or suppression epistasis.
Duplicate types of epistasis depend on two loci. Duplicate dominant epistasis, also referred to as
duplicate gene action, occurs when a dominant allele conceals the expression of recessive alleles
at two loci. Duplicate recessive epistasis occurs when a recessive allele conceals the expression
of dominant alleles at two loci. Because both genes are necessary for the right phenotype to exist,
it is often referred to as complementary gene action. The combination of two dominant alleles
that enhances the phenotype or generates a median variation is known as polymeric gene
interaction. Each dominant allele alone results in a physical characteristic that is distinct from the
combined dominant alleles. This results in three phenotypes being produced from just two
dominant alleles. It is clear from this that neither dominant allele is prevailing over the other.
Summer squash can have three different colours: white, yellow, and green. The dominant gene controls
the colour white, the dominant gene G controls the colour yellow, and the recessive genes w and
g control the colour green. In contrast to yellow and green, white is the prevailing colour. Epistatic
refers to the relationship between the dominant and recessive G/g alleles and the dominant white
allele. Following that, this interaction is categorized as simple or dominant epistasis.

3.7 MITOSIS AND MEOSIS

Handmade graphic depictions of mitotic chromosomes by Walther Flemming and meiotic chromosomes
by Walter Sutton provided an early record of the physical path of chromosomes
during cell division. The physical movement of chromosomes could then be correlated with cells'
patterns of genetic inheritance. (The idea that genes were carried on cytological structures is now
known as the chromosome theory) Using such methods, researchers determined that
although mitosis and meiosis are both forms of cell division, the results of these processes are
actually quite different.
3.7.1 Gene Transmission in Mitosis
Somatic cells undergo mitosis, which means that all cell types whose function is not the generation of
gametes go through this process. Each chromosome is duplicated before each mitotic division,
resulting in a full set of chromosomes in the nucleus of each new cell after division. Indeed, due
to the inheritance of the same chromosome set and the same biological milieu, each succeeding
duplicate cell will have the same genetic makeup as its parent, barring random mutations. This
works well for repairing damaged tissue as well as for embryonic growth and expansion. (Fig.
3.7)

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Fig. 3. 7 The progressive and regressive phases of cell division

(Source: [Link]
All mitotic progenies are genetically similar because the genes found in the duplicate chromosomes are
passed down to each succeeding cellular generation. There are, however, certain exceptions. For
instance, spontaneous mutations that occur during mitotic division can lead to genetic differences
in clonal species like bacteria. Furthermore, chromosomes can replicate several times without a
cell division taking place in between. For instance, this happens in the cells of the salivary glands
of Drosophila larvae, where there is a high metabolic requirement. When compared to the
chromosomes in other Drosophila cells, these chromosomes, known as polytene chromosomes,
are enormous. Without any cytokinesis, these chromosomes replicate by going through the first
stages of mitosis, where the same cell includes dense configurations of duplicate chromosomes
placed side by side that resemble thick rope-like strands. These chromosomes are thought to be
hyper-replicated in order to facilitate the quick and abundant production of certain proteins that
support larval growth and metamorphosis.

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3.7.2 Gene Transmission in Meiosis

Fig. 3. 8 Different phases involved in Meiosis

(Source: [Link]
Walther Flemming witnessed spermatozoa go through meiosis in 1882, but he thought it was mitosis.
Flemming did note, however, that during spermatozoan production, chromosomes occur in pairs,
in contrast to normal cell division. This finding, together with Sutton's laborious chromosome
counting throughout the development of grasshopper sperm cells in 1902, proved beyond a doubt
that cell division in gametes involved more than just mitosis. Sutton proved that the number of
chromosomes was reduced during reductive division, also known as the division of spermatozoan
cells. Sutton found that as a result of this process, each gamete contained half the genetic
information of the original cell. A short while later, J. Farmer, B., and J. Meiosis, often known as
this process, is the primary mechanism by which plants and animals produce gametes, according
to E. S. Moore (Farmer & Moore, 1905).
More than anything else, Sutton's study has had the biggest impact by supporting Mendel's principle of
independent assortment. Sutton observed that there was never a consistent maternal or paternal
side to the cell division and that the location of each chromosome at the midline during metaphase
was unpredictable. Each chromosome was therefore independent of the others. As a result, when
the parent cell divided into gametes, each daughter cell's set of chromosomes may have included
a combination of the parental features, however, this combination may not have been the same as
in other daughter cells. (Fig. 3.8). To demonstrate this idea, think about the variation resulting
from just three fictitious chromosomal pairs, as shown in the example below (Hirsch, 1963). One
maternal and one paternal homologue make up each pair. The maternal chromosome is denoted

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by capital letters, whereas the paternal chromosome is denoted by lowercase letters in this
sentence:
● Pair 1: A and a
● Pair 2: B and b
● Pair 3: C and c
When these chromosome pairs are reshuffled through the independent assortment, they can
produce eight possible combinations in the resulting gametes:
A B C, A B c, A b c, A b C, a B C, a B c, a b C, a b c

3.8 CONCEPT OF MAPPING PHENOTYPE TO GENOTYPE

The relationship between the genotype, the genetic instructions encoded into a genome, and phenotype,
the macroscopic realization of such instructions, remains mostly uncharted. In addition, tools able
to uncover the connection between the phenotype with a specific set of responsible genes are still
under definition. In one of the studies related to this, the focus was on yeast organelles called
vacuoles, which are cell membrane compartments that vary in size and shape in response to
various stimuli, and we develop a framework relating changes in cellular morphology to genetic
modification. The approach combines a convolutional neural network (CNN) with an
unsupervised learning pipeline and a segmentation, classification, and anomaly detection
algorithm that are all based on deep learning.
The shape and structure of cellular organelles, such as the nucleus, mitochondria, and vacuoles, which
are compartments designed specifically for carrying out biochemical operations, are related to the
biological processes they mediate. Therefore, being able to control and influence the outcome of
specific biochemical events would mean being able to design a specific organelle morphology.
Significant new theoretical paradigms for the computational design of cellular structures have
been developed through recent developments in computers. It's not very novel to connect cellular
shape in model organisms like yeast to mutations. However, because of the inherent biological
heterogeneity, it is clear that creating a sizable and thorough training set whether annotated or not
is a significant bottleneck. We provide a hybrid supervised-unsupervised learning strategy that
tries to accurately execute end-to-end mapping between existing morphologies and genetic
damage in budding yeast organelles in order to address this problem.
Methodology, which is composed of several steps can be summarized as follows: after the cellular
images are acquired, a segmentation step is performed using a U-Net CNN trained on a small
fraction of the dataset. The segmented images are then analysed and a set of features is extracted
from the masks. Images are partitioned in an unsupervised fashion with the number of classes
automatically inferred from the data, and the resulting clusters are used as the training set for
another CNN, which is ultimately used to classify the cells. Our results suggest that this
methodology can reveal the relationship between phenotype and genotype in an accurate and
unbiased way.
Even though the mechanistic design of cells and cellular structures is still a long-term research objective,
developing tools that may infer biological design principles is a crucial first step towards the
mechanistic realisation of biological systems for practical uses. An organelle that can function as
a biological reactor for the synthesis of chemicals is the yeast vacuole. We can link various

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vacuole shapes to genetic disturbances using our system. In order to accomplish this, we use a
mixed supervised-unsupervised learning methodology in an effort to lessen the load of annotation
and the inherent bias associated with the human annotation work. Our findings demonstrate that
the genotype-cellular phenotypic relationship may be determined with high accuracy and little
user involvement. We believe our investigation provides the necessary background for a more
comprehensive understanding of the engineering process, even though it has not examined more
difficult engineering tasks like creating desired cellular structures using a number of co-occurring
mutations or altering the cellular environment.
An essential goal of modern biotechnology is the examination of the link between genotype and
phenotype with the goal of defining design principles for the rational engineering of cells and
cellular structures. While it is crucial to obtain exact control over the design task, it is also crucial
to perfect the experimental realisation. New professional figures will emerge as more
computational methods are included into the bioengineering playbook, which will be
advantageous to society as a whole. From an ethical standpoint, the need to produce desired
results and consider a wider range of potential outcomes lessens the uncertainty surrounding the
effects of the synthetic engineering process. Any pipeline that intends to create living things
should have a more controlled design, even though this uncertainty cannot be totally eliminated
from the equation.

3.9 CHROMOSOMAL ABNORMALITIES AND SYNDROMES

Almost every cell in the human body includes 23 chromosomal pairs, a total of 46 chromosomes. Half
of our chromosomes are inherited from our mother, while the other half are inherited from our
father. The initial 22 pairs are known as autosomes. The 23rd pair comprises the X and Y
chromosomes, which are sex chromosomes. Females typically have two X chromosomes in each
cell, while males have one X and one Y chromosome.
Chromosomal abnormalities come in many forms, but they can be categorised as numerical or structural.
Whole chromosomes that are either extra or absent from their typical pair are considered
numerical anomalies. Structural issues arise when a chromosome has a section that is missing,
extra, moved to another chromosome, or inverted. Accidental chromosomal abnormalities can
arise during the development of the egg, sperm, or early stages of the foetus. There may be a
connection between the mother's age, the environment, and the frequency of genetic errors.
Through prenatal screening and testing, it is feasible to examine the foetus' chromosomes and
find some, but not all, types of chromosomal abnormalities.
3.9.1 Single gene disorders in humans
Chromosomes can be harmed or altered in number under particular conditions, such as those brought
on by radiation from the environment, dietary factors, or inherited genetic abnormalities.
Numerical chromosomal abnormalities refer to changes in the number, while structural
chromosomal abnormalities (or aberrations) refer to changes in structure. When one of a pair of
chromosomes is missing, the situation is referred to as monosomy (2n-1), for example,
monosomy of chromosome 1. Trisomy (2n+1), such as that of chromosome X, is the term used
to describe the presence of three copies of a chromosome. It's vital to note that aneuploidy, which

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encompasses both monosomy and trisomy, is a general term. However, the phenomenon is known
as polyploidy when the full set of chromosomes is multiplied. Several polyploid plant varieties
that are frequently used in our cuisine have been created through artificially breeding plants. For
instance, tetraploid cabbages and mustards have four sets of chromosomes each, but bread wheat
contains six sets (hexaploidy). Likewise, strawberries and sugar cane are octoploids, while
bananas and apples both have three sets of chromosomes (8 sets of chromosomes). Significant
phenotypic circumstances might change as a result of structural or numerical changes,
manifesting as diseases or syndromes.
3.9.2 Structural chromosomal abnormalities
When a chromosome's structure or some components of it change, structural chromosomal
abnormalities result. Typically, there are 46 chromosomes in total in each cell. If a chromosome
has a portion that is missing, extra, or that has switched places with another portion, this is referred
to as a structural chromosome anomaly. In the end, this causes either an abundance or a shortage
of genetic material. This is a factor in several birth defects.
Structural chromosomal abnormalities may be of the following types:
1. Deletion— In deletion, a segment of a chromosome breaks away leading to the shortening of the
chromosome (Fig. 3.9a). Retinoblastoma and Cri-du-chat syndrome, as examples. A part of
chromosome 13 is deleted, which leads to retinoblastoma development.
2. Duplication— When a chromosome segment is duplicated, it lengthens the chromosome. This
process is known as duplication (Fig. 3.9b). This may result in diseases like Charcot-Marie-Tooth
disease, which is caused due to the duplication of certain genes on chromosome 17.
3. Inversion— An inversion occurs when a segment of a chromosome entirely separates, reverses, and
then re-joins the chromosome. Here, the chromosome's overall length is the same, but the genes'
orientation is 180 degrees backward (Fig. 3.9c). For instance, the inversion of a segment of
chromosome 17 results in RCAD syndrome.
4. Translocation—A gene can be translocated from one linkage group to another through this process.
Translocation occurs when a fragment of one chromosome separates and attaches itself to another
chromosome. Reciprocal translocation is the term for the exchange of segments between two
chromosomes. For instance, in Burkitt's lymphoma, the material is exchanged between
chromosomes 8 and 14. Without mutual exchange, attachment is referred to as Robertsonian
translocation. This can cause the cell's chromosome number to drop (Fig. 3.9d).

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Fig. 3. 9 (a) Deletion (b) Duplication (c) Inversion (e) Translocation

(Source: [Link]

3.9.3 Monogenic Disorders

An error in a single gene is the root cause of monogenic illness. According to current estimates, nearly
10,000 human diseases that impact millions of people globally are thought to be monogenic. The
functions that the altered or faulty gene performs determine the type of disease, as well as its
signs and symptoms. Mendel's Laws state that certain illnesses are inherited. The mutation may
occur suddenly in some circumstances, in which case we won't know the preceding family
history. One gene may have a single mutation producing a specific disease, such as sickle cell
anaemia, or it may have several mutations producing the same disease, such as cystic fibrosis
(more than 200 different types of mutation can occur in one gene). According to the inheritance
pattern, single-gene or monogenic disorders can be divided into the following groups:
a) Autosomal recessive b) Autosomal dominant c) X-linked recessive d) X-linked dominant
a) Autosomal recessive disorder
Recessive means that two copies of the gene must be present for a trait or condition to exist in the case
of a mutated gene. One gene out of the two copies is inherited from the father and the other from
the mother. An individual will be the carrier and not get the disease if they have one normal
recessive gene and one deficient recessive gene. According to statistical projection, it is thought
that every human possesses at least five recessive genes that are defective and can lead to
hereditary diseases. A recessive disorder's disease phenotype results from the homozygosity of a
recessive allele, while the unaffected phenotype is caused by the matching dominant allele. This
can be described using the example of the autosomal recessive disease sickle cell anaemia. A
chromosome 11 haemoglobin gene mutation results in sickle cell disease. As a result, the
haemoglobin is damaged (Hb). These faulty Hb molecules group together after donating their
oxygen, forming rod-like formations.

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Sickle cell anaemia is determined by an allele which we can designate as s and the normal condition by
S. Affected individuals will have the genotype s/s, while unaffected individuals will either have
S/S or S/s. People with sub-Saharan African, South American, Cuban, Central American, Saudi
Arabian, Indian, and Mediterranean ancestry are particularly susceptible to sickle cell anaemia.
It is widespread among residents of the Deccan plateau in central India, with a lesser
concentration in Kerala and Tamil Nadu's northern regions.
Phenylketonuria, Tay Sach's disease, and cystic fibrosis are more examples of autosomal recessive
illnesses. People with cystic fibrosis produce abnormally thick, sticky mucus that can harm many
organs, particularly the lungs, leading to chronic infections. The absence of the hexosaminidase
A enzyme, which causes Tay-Sachs disease, causes fatty material accumulation in nerve cells,
with the brain being severely affected. It is a deadly condition that first appears in children. The
Tay-Sachs gene is carried by one in every 27 individuals of European Ashkenazi Jewish descent.
A phenylalanine hydroxylase gene mutation that results in an increase in blood phenylalanine is
the cause of phenylketonuria.
b) Autosomal dominant disorder
The normal allele is recessive and the abnormal allele is dominant in this kind of inheritance. An
uncommon autosomal dominant condition Achondroplasia is one condition that can cause a
specific form of dwarfism in those who are affected. In this condition, those with mild disease
have the genotype d/d, and those with severe disease have the genotype d/D, which is frequently
fatal. Thus, heterozygotes make up the majority of the remaining instances of achondroplasia.
Another rare autosomal dominant condition that affects the neurological system is Huntington's
disease.
c) X-linked recessive disorder
Only males (XY) are typically afflicted by the disorder in X-linked recessive inheritance in the mother
(XX), where the defective gene stays on one X chromosome. As a result, she becomes the carrier.
The Y chromosome is passed down to sons while the X chromosome is passed down to daughters
in the male progeny. A male who has the condition will thus not pass it on to his sons, but all of
his daughters will be carriers. Haemophilia and Duchenne muscular dystrophy are a few X-linked
recessive illnesses. Haemophilia is a bleeding disorder linked to mutations in the factor IX or VIII
coagulation genes (type A) (type B). Coagulation factors VIII or IX are produced in an abnormal
form or insufficiently as a result of mutations in the coagulation factor genes. Blood cannot
properly clot due to the changed or absent coagulation factor, which results in increased or
spontaneous bleeding tendencies. The dystrophin gene is mutated in Duchenne muscular
dystrophy (DMD), which results in decreased or absent dystrophin or the presence of abnormal
proteins. Muscles become more frail and weaker as a result of dystrophy or degeneration brought
on by dystrophin abnormalities or deficiency.

d) X-linked dominant disorder

In this type of inheritance, the affected males pass on the mutated dominant gene to all their daughters
but to none of their sons. In the case of affected females married to unaffected male, the condition
is passed on to half of their sons and daughters. Examples of these conditions include Alport
syndrome, which is linked to progressive hearing loss and renal disease, and hypophosphatemia,
a kind of vitamin D-resistant rickets.

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3.10 CONCEPT OF COMPLEMENTATION USING GENETICS

Complementation refers to a relationship between two different strains of an organism that both have
homozygous recessive mutations that produce the same phenotype (for example, a change in wing
structure in flies Fig. 3.10) but which do not reside on the same (homologous) gene. These strains
have undergone true mutational breeding. When these strains are crossed, it is said that there has
been "genetic complementation" if some of the offspring recover the wild-type phenotype. This
results in heterozygous mutations in every linked gene in the progeny because each strain's
haploid provides a wild-type allele to "complement" the mutant allele of the other strain's haploid.
Due to the recessive nature of the mutations, the offspring will exhibit the wild-type phenotype.
A complementation test (sometimes called a “cis-trans” test) refers to this experiment, developed by
American geneticist Edward B. Lewis. It responds to the query: "Does a wild-type copy of gene
X rescue the function of the mutant allele thought to define gene X?" One can inquire as to
whether the function that was lost as a result of the recessive allele can be replaced by another
mutant genotype if there is an allele with an observable phenotype that can be provided by a wild-
type genotype (i.e., the allele is recessive). If not, the same gene must have two defective alleles.
The beauty of this test is that, even without understanding what the gene is doing at the molecular
level, the trait may be used as a read-out of gene function.
Complementation develops because the same phenotype might result from the loss of function in genes
responsible for various steps in the same metabolic pathway. When strains are crossed, the
progeny receives either of the parent's wild-type copies of each gene. The recessive nature of the
mutations causes a recovery of function in that pathway, which allows offspring to regain the
wild-type phenotype. Consequently, the test is used to determine whether two independently
derived recessive mutant phenotypes are brought on by mutations in one gene or two. If the same
gene mutated in both parent strains, no normal copies of the gene are passed down to the
offspring, who exhibit the same mutant phenotype, indicating that complementation has not taken
place.
Fig 3.10 states that Due to two distinct autosomal recessive mutations that affect various steps in a single
biochemical process that produces pigment, two strains of flies have white eyes. Since the
progeny of their cross can complete the entire metabolic pathway and have red eyes as a result,
flies from Strain 1 have complimentary mutations to flies from Strain. In other words, there are
three possibilities if the fusion of two haploid genomes with various recessive mutations results
in a mutant phenotype: Similar genes experience mutations; The expression of one mutation is
impacted by the other's; A single mutation could produce an inhibiting substance. If two haploid
genomes with different recessive mutations combine to produce the wild-type phenotype, the
mutations must be in different genes.

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Fig. 3. 10 : Complementation Test: An illustration of a complementation test

(Source: [Link] (Creative commons licenses)

In conclusion, genetics has always been concerned with how the hereditary information in DNA
regulates the appearance and function of an organism. Historically, this consisted of using genetic
variants (mutants) to disrupt the biological function of cells or animals and then deducing how
cells and organisms functioned based on the effect of these mutations. At the molecular end of
the subject, the availability of sequence information and genomic analysis, as well as
sophisticated techniques for gene replacement and analysis of gene expression patterns
(microarray technology), provides us with significantly more potent tools for examining how
genes function to make us who we are. At the opposite end of the spectrum, genetic knowledge
is essential to comprehending how organisms, populations, and species evolve. Through the
application of the new molecular systematics to the challenges of development, evolution, and
speciation, one of the most fascinating developments in the field over the past few years has been
the approach of these two extremes.
Geneticists think that the tools and techniques of genetics are applicable across the entire spectrum of
biological activity, and are as appropriate to molecular biology and population studies as they are
to population genetics. Some of the fundamental tools of contemporary biology (analysis of
genomic sequences and bioinformatics) are utilised most intelligently in the understanding of the
genetic principles underlying the design and use of the software. On the opposite end of the
spectrum, genetic knowledge is essential for comprehending the evolution of populations and
species. The breakthroughs in sequencing genomes and microarray technology, which are now
utilised by the vast majority of biologists, do not negate the fact that genetics offers a perspective
and a variety of experimental methods applicable to numerous fields of biological investigation.
To date, public health practice has focused on environmental or socioeconomic determinants of
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health and disease and has given genetic variability within the population limited consideration.
The progress made in genomics is altering these perceptions. Long-term, this information will
allow health promotion and disease prevention programmes to be focused particularly on
susceptible individuals and families, or subsets of the community, depending on their genomic
risk profile.

UNIT SUMMARY
● The three laws of inheritance proposed by Mendel include:
▪ Law of Dominance - Hybrid offspring shows Dominant characters frequently and Recessive
characters rarely.
▪ Law of Segregation - 2 alleles of a gene always segregate during gamete formation
▪ Law of Independent Assortment - The alleles segregate independently of each other during
gamete formation
● Monohybrid cross - Observing the inheritance pattern with only one gene into consideration.
The Monohybrid ratio is 3:1
● Dihybrid cross - Observing the inheritance of 2 different characters at a time. Ratio is 9:3:3:1
● Mutation: Any heritable change of the base-pair sequence of genetic material
● Allele - Each gene exists in two alternate forms called alleles (e.g; Height gene’s allele - Tall
& Short)
● Loci – The location of the gene on a chromosome is called a locus (Plural: loci). Always
alleles of genes occupy the same loci
● Gene mapping - The linkage of the genes in a chromosome can be represented in the form of
a genetic map
▪ In the gene map, the distance is measured in terms of recombination frequency
▪ Molecular markers enable us to identify the gen location and its linkage pattern
● Gene interaction - when two or more nonallelic genes influence the outcome of a single trait,
this is known as Gene interaction
● Epistasis - is the interaction between different genes (i.e. non-alleles) whereas dominance is
the interaction between different alleles of the same gene (i.e. intra-allelic)
● Mitosis is the type of cell division that results in the formation of two daughter cells each
with the same number and kind of chromosomes as the parent cell. (e.g; skin cells)
● Meiosis is a type of cell division that results in the formation of four daughter cells each with
half the number of chromosomes as the parent cell. (e.g; gametes)
● Any change in an organism's DNA (Chromosome) that is unique and heritable is termed
‘Mutation’. Mutations are the sole reason for evolution and will remain the most important
part of life
● Chromosomal abnormalities & Disorders: alteration can be structural or numerical
▪ Deletion of a segment of a chromosome - Retinoblastoma
▪ Duplication refers to when a segment of the chromosome gets repeated - Charcot Marie
tooth disorder
▪ In an inversion, a segment of the chromosome breaks away, completely reverses itself and
reattaches with the chromosome

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▪ In translocation, a segment of a chromosome breaks away and attaches itself with another
chromosome
▪ Monogenic Disorders - caused by an error in a single gene
▪ Autosomal recessive disorder - Both allele copies of gene defected mutated causes this
disorder - Sickle cell anaemia
▪ Autosomal dominant disorder – an inheritance of the normal allele is recessive and the
abnormal allele is dominant - Huntington’s disease
▪ X-linked recessive disorder - From mother, the affected gene remains on one X
chromosome, as a result, she becomes the carrier and usually only males (XY) are affected
- Haemophilia
▪ X-linked dominant disorder - In this type of inheritance the affected males pass on the
mutated dominant gene to all their daughters but to none of their sons - Alport syndrome
 Complementation - a relationship between two different strains of an organism that both have
homozygous recessive mutations that produce the same phenotype
 A complementation test allows us to determine whether two independently isolated mutants
with the same phenotype have mutations in the same or different gene.

EXERCISES
Multiple Choice Questions
1) In a cross between a male and female, both heterozygous for the Sickle cell anaemia gene, what
percentage of the progeny will be diseased?
A. 25%
B. 100%
C. 0%
D. 75%

2) Select the correct match

A. Phenylketonuria - Autosomal dominant trait
B. Sickle cell anaemia - Autosomal recessive trait
C. Hypophosphatemia - X linked
D. Haemophilia - Y linked

3) How many true-breeding pea plant varieties did Mendel select as pair that were similar except
one character with contrasting traits?
A. 2
B. 14
C. 6
D. 4

4) The mechanism that causes a gene to move from one linkage group to another is called ______
A. Translocation
B. Crossing over

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C. Duplication
D. None of the above

5) The incorrect statement with regard to haemophilia is ____

A. It is a recessive disease
B. A single protein involved in the clotting of blood is affected
C. It is a dominant disease
D. None of the above

6) Genotype of dominant plant can be determined by_____

A. Pedigree analysis
B. Back cross
C. Test cross
D. Dihybrid cross

7) The Phenomenon of two or more than two genes affecting the expression of each other is called
_______
A. Crossing over
B. Pairing
C. Linkage
D. Gene interaction

8) _________ is a form of cell division which results in the creation of gametes or sex cells.
A. Mitosis
B. Meiosis
C. Miosis
D. None of the above

9) Continuous variations are due to ______

A. Mutation
B. Crossing over
C. Polyploidy
D. Chromosomal aberrations

10) "Cri‐du‐chat" syndrome is caused by change in a chromosome structure involving _____

A. Deletion
B. Duplication
C. Inversion
D. Translocation

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11) The "cis‐trans" test developed by American geneticist _____

A. Thomas Morgan
B. William Gosset
C. Karl Pearson
D. Edward Lewis

12) Which of the following is a result of reciprocal translocation?

A. Trichothiodystrophy
B. Burkitt's lymphoma
C. Cockyne's syndrome
D.
E. Thalassemia

13) RCAD syndrome caused due mutation in Gene HNF1B by inversion located on chromosome
____
A. 11
B. 15
C. 7
D. 17

14) The tendency of an offspring to resemble its parent is known as _____

A. Heredity
B. Variation
C. Resemblance
D. Inheritance
15) The geometrical test that helps predict the outcome of monohybrid or dihybrid crosses _______
A. Chi-square
B. Student T-test
C. Punnett square
D. ANOVA

16) When a recessive allele masks the expression of both dominant and recessive alleles, alleles
referred to as what type of epistasis?
A. Dominant
B. Recessive
C. Duplicate-dominant
D. Duplicate recessive

17) Which of the following is NOT a type of epistasis?

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A. Duplicate gene interaction

B. Complementary gene interaction
C. Polymeric gene interaction
D. Sex-linked

18) With four alleles, how many different combinations of alleles can there be?
A. 4
B. 8
C. 12
D. 16

Answers: 1) A; 2) B; 3) B; 4) A; 5) C; 6) C; 7) D; 8) B; 9) A; 10) A; 11) D; 12) D; 13) D; 14) A; 15)

C; 16) A; 17) B; 18) C

Short Answer Type Questions

1. What do we inherit from our parents? Genotype or Phenotype?
2. What do you think, do we find Mendelian inheritance in Human beings too?
3. What do you think, parents, donate genes to offspring in equal numbers?
4. Chromosomal mutation and gene more lethal gene mutation chromosome number increases
mutation rate increase, is the statement true?

NUMERICAL PROBLEM
A. If gene A and B genes are linked by a 10 cm distance. What might be the probability of obtaining
the homozygous gametes for genes A and B?

KNOW MORE
● Paweletz, N. (2001), Walther Flemming: Pioneer of mitosis research. Nature Reviews Molecular
Cell Biology 2, 72–75 doi:10.1038/35048077
● Bateson, W. (1909). Mendel’s Principles of Heredity: Cambridge University Press. März 1909;
2nd Impr, 3, 1913.
● [Link]
● [Link]
460/
● [Link]

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REFERENCES AND SUGGESTED READINGS

● [Link]
● [Link]
ofinheritance/
● [Link]
Worksheet-1811886
● [Link]
● [Link]
environment-and-behavior
● [Link]
● [Link]
● [Link]
● [Link]
3A_Microbial_Genetics/7.11%3A_Genetic_Transfer_in_Prokaryotes/7.11E%3A_Complement
ation
Dynamic QR Code for Further Reading

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