Genetic

Genetics is a branch of natural science that deals with heredity due to the transmission of genes, gene regulation, and gene manipulation.

• Genetics is a connecting link between many disciplines like microbiology, biotechnology, medicine, and agriculture.
• Studies involving genes and chromosomes of living beings began quite late as it requires significant advances in the microscopy area.
• The influence of heredity and its application of cultivation and production improved organisms, however, had been recognized since ancient times.
• The study of genes and genetics began as a major concept after studies made by Mendel on pea plants. It was further strengthened and flourished by the works of Morgan.
• Eventually, genetics became a distinct area of study with the identification of genes and the study of genes at different levels, including their role in the cell, their regulation, and their expression.
• Initially, genetics was limited to understanding the concept and process of heredity via techniques like the formation of Punnet’s square. With the development of techniques like X-ray diffraction, the structure of DNA, and the presence of genetic code were established. This paved the way for modern genetics.
• Modern genetics focuses on the chemical composition of structures found in genes like the DNA that influences the chemical reactions taking place in the cell.
• Gene expression is influenced by two major factors; the genetic composition and the influence of the environment.
• The influence of the environment on gene expression can be distinctly observed in green plants where the gene responsible for the formation of chlorophyll is only expressed in the presence of sunlight.
•  Genes, through the proteins they encode, determine how efficiently foods and chemicals are metabolized, how effectively toxins are detoxified, and even how vigorously infections are targeted.
• Processes like mutations are now a significant cause of major genetic diseases. The mutations might arise due to a complex combination of genetic, behavioral, and environmental factors.

Genotype Etymology

• The word “genotype” is adapted from the German Genotypus based on the Greek word genea meaning “generation or race.” 
• Wilhelm Ludvig Johannsen developed the genotype-phenotype concept in 1909 to distinguish between hereditary and environmental variations.
• He stated that a person’s phenotype represents the observable structural and functional characteristics formed by the interaction between genotype and environment. In contrast, an individual’s genotype represents the totality of hereditary factors.
• This distinction resulted from Johannsen’s research on heritable plant variation, which also impacted his pure-line theory of heredity.

Genes, Alleles, and Genotype

• Genes typically come in pairs, or alleles, in eukaryotes.
• A variant of a particular gene is referred to as an allele.
• The paired alleles will be located at the same location on the chromosome.
• Each parent contributes one of the two alleles for a particular gene since most eukaryotes reproduce sexually.
• Because each parent comes from a different lineage of organisms, random replication errors and environmental interactions with the DNA have uniquely altered each parent’s genes.
• One of the alleles will be expressed while the other is suppressed if the trait inherits in a simple Mendelian pattern.
• The dominant allele is the one that expresses itself, whereas the recessive allele is the one that does not.
• Three distinct genotypes are possible if the dominant allele is “T” and the recessive allele is “t.”. They are “TT,” “tt,” and “Tt.”
• Because the alleles in the pair are identical, i.e., both dominant or both recessive, the term “homozygous” is used to describe the pairs and is represented by “TT” and “tt.” On the other hand, the allelic pair “tt” is referred to as “heterozygous.”
• Individuals having genotypes TT or Tt will display the dominant trait in their phenotypes, whereas those with genotype tt will display the recessive trait.
• Not all traits are determined by a single gene, many genes have multiple allelic variants, and not all gene pairs have a simple dominant/recessive relationship. 
• Non-Mendelian inheritance patterns include codominance, partial dominance, and polygenic inheritance.
• Many of the observable traits in humans are non-Mendelian.
• To fully write out an organismal genotype would require a set of characters representing the alleles for each of the 20,000 or so known genes in the human genome.

Punnett square and Genotype

• The Punnett square is an essential genetic tool to predict inheritance patterns and ratios. 
• It is a table that lists every potential result of a genetic cross between two individuals with known genotypes.
• It consists of a square divided into four quadrants. 
• Humans are diploid organisms.
• One genotype is provided at the top of each column and down the left side of the square for each conceivable genotype of the haploid female gametes.
• One genotype per row is presented for each conceivable genotype of the haploid male gametes.
• The table’s squares, which correspond to the cross’s possible outcomes, can then be filled up.
• The male gamete from the corresponding row and female gamete from the corresponding column combine at fertilization to form the diploid genotype in each square.

In a monohybrid cross TT x tt, where

1. TT – Pure tall plant
2. tt – Pure dwarf plant

monohybrid cross TT x tt

This gives us the 3:1 phenotypic ratio and 1:2:1 genotypic ratio, as described by Mendel.

1. TT (Pure tall)
2. Tt (Hybrid tall)
3. Tt (Hybrid tall)
4. tt (Pure dwarf)

Two of the four offsprings, one tall (TT) and one dwarf (tt), are homozygous, while the other two (Tt), both of which express the dominant tall trait, are heterozygous.

Genotyping

• Genotyping determines the DNA sequence or genotype at specific positions within an individual’s genome.
• In linkage and association studies, sequence variants can be employed as markers to find the genes responsible for particular traits or diseases.
• Genotyping is an experimental technique that identifies variations in DNA sequences between people or populations.
• Compared to a reference sequence generated from the general population or a specific subgroup, an individual genome is recognized as a different variant.
• There are many ways in which a variant sequence can diverge from the reference sequence.
• Single nucleotide variations (SNV), single nucleotide polymorphisms (SNPs), insertions and deletions (indels), and copy number variation (CNV) are different types of genetic variation.
• SNPs are the most common sequence variant investigated by researchers; they are typically defined as SNVs that occur at >1% in the population.
• Based on a haploid genome size of 3.1 x 109 bp and the number of SNPs listed in Build 151 of the SNP database, dbSNP, maintained by the National Center for Biotechnology Information (NCBI) (RefSNP count 660,773,127), the human genome should have an SNP around every 9.5 bases. 

The frequency of SNPs is also high in other popular model species.

Genotype Network

• In systems biology, genotype networks are used to investigate the “evolvability” or “innovability” of a group of genotypes sharing a single, broadly defined phenotype and to determine if a certain phenotype is resistant to mutations.
• They have been used to determine how much a metabolic network can be adjusted without losing the ability to survive utilizing a certain carbon source to research the evolvability of metabolic networks in simple organisms.
• They have also been applied to research how a metabolic network might “evolve” a new phenotype, such as the capacity to survive on a different carbon source.
• Genotype networks have also been used to explore the stability of RNA folds and protein structures to determine how many mutations can accumulate in a sequence without losing the secondary structure

Phenotypic Ratio

The phenotypic ratio depicts the ratio or probability of the resulting patterns and frequencies of inherited observable traits in the offspring of organisms.

Phenotype is the morphological characteristic of an organism that can be observed externally. It includes the characters such as sex, hair and skin color, shape, height, etc. In simple language, the phenotype is the resulting appearance of an individual depending upon the inherited genotype.

Phenotypic Ratio

An organism’s genes can be expressed (dominant) or unexpressed (recessive). The expressed genes result in the phenotypic characteristics of an organism

Calculation of Phenotypic Ratio

The calculation of the ratio of phenotypes for monohybrid, dihybrid, and trihybrid crosses is different. The basic steps of calculation are:

• Choosing the characters to be crossed or the characters under study.
• By applying Mendel’s Laws of Inheritance, cross them by forming a cross diagram or Punnett-square chart.
• Then calculate the number of phenotypes (not be confused with the genotype). TT and Tt can denote tallness, and they both are the same phenotypes.
• The type of phenotypic outcomes must be listed distinctly. The ratio can be finally determined by adjusting the characters and their specific numbers (as counted in the Punnett chart) respectively.

Phenotypic Ratio in Monohybrid Cross

Monohybrid Cross is the type of cross in which a single trait of an individual is taken and studied for its outcomes after the cross.

Let’s take, for example, height: a tall father (TT) who is crossed with a short mother (tt) where tallness is dominant over shortness, then the cross-ratio can be calculated as follows:

Phenotypic Ratio in Monohybrid Cross

The phenotypes in the second filial generation are tall (three: TT, Tt, Tt) and short (Only one: tt).

So the phenotypic ratio of short and tall will be 3:1, respectively. It simply indicates that if four offspring are born in the above case, then there is a higher probability of three of them being tall and one of them being short.

Phenotypic Ratio in Dihybrid Cross

Dihybrid Cross is the type of cross in which two characters or traits are considered, and the combined outcomes of both are calculated.

Let’s take, for example, height and color: a tall and white colored male (TTWW) who is crossed with a short and black female (ttww) (considering tallness and white skin are dominant over shortness and black skin), then the cross-ratio can be calculated as follows:

Phenotypic Ratio in Dihybrid Cross

The phenotypes in the second filial generation are tall and white (nine: TTWW, TTWw, TtWW, TtWw); tall and black (three: TTww, Ttww); short and white (three: ttWw, ttWW); short and black (only one: ttww).

So the phenotypic will be 9:3:3:1, respectively, considering the above data and assumptions. It simply indicates that if 16 offspring are born in the above case, then there is a higher probability of nine of them being tall and white, considering the tall and white skin to be dominant and so on.

Phenotypic Ratio in Trihybrid Cross

Trihybrid Cross is the cross in which three characters are taken and studied for their combined outcomes in future generations. Let’s take, for example, height, eye, and hair color.

A tall, brown-eyed male with black hair (indicated by TTBBWW respectively) who is crossed with a short and blue-eyed female with white hair (ttbbww) (considering tallness (T), brown eye (B), and black hair (W) color are dominant over shortness (t), blue eye (b), and white hair color (w)), then the phenotypic-ratio can be calculated as follows:

Phenotypic Ratio in Trihybrid Cross

The phenotypes in the second filial generation are:

• 27 with tall height, brown eyes, and black hair (TTBBWW, TTBBWw, TTBbWw, TtBbWw, TtBbWW, TtBBWW)
• 9 with tallness, brown eyes, and white hair (TTBBww, TTBbww, TtBBww, TtBbww)
• 9 with short height, brown eyes, and black hair (ttBBWW, ttBbWw, ttBBWw, ttBbWW)
• 9 with tall height, blue eyes, and black hair (TTbbWW, TtbbWw, TtbbWW, TTbbWw)
• 3 with tall height, blue eyes, and white hair (TTbbww, Ttbbww)
• 3 with short height, blue eyes, and black hair (ttbbWW, ttbbWw)
• 3 with short height, brown eyes, and white hair (ttBBww, ttBbww)
• 1 with short height, blue eyes, and white hair (ttbbww)

So the phenotypic ratio of short and tall will be 27:9:9:9:3:3:3:1 respectively. It simply indicates that the probability of offspring with all the dominant characters i.e. tallness, brown eyes, and black hair is highest and mathematically 27/64, and lowest for offspring with all recessive characters i.e. shortness, blue eyes, and white hair, in this case, that is mathematically 1/64.

Phenotypic Ratio Significances

• Calculating the phenotypic ratio helps us predict the likelihood of expressing particular parental traits in the progeny.
• It helps predict gene expressions in future generations of an organism.
• These calculations aid in producing genetically engineered crops and animals with the required external features.

Some Important Terms

Filial generation

The offspring or progenies obtained after the cross between parents are called filial generation or first filial generation (F1 generation). When those progenies self-fertilize and result in another generation of progenies, then they are the second filial generation (F2 generation).

Punnett square

It illustrates all the possible combinations of phenotypes in the offspring after crossing the specific traits of parents. It is represented in the form of a square-shaped table. R.C. Punnett invented it in the year 1906. In this table, all the possible gametes from the male are arranged in the top horizontal boxes, and all the gametes from the female are arranged in the left vertical boxes.

Note: All the above given phenotypic ratios are based on Mendel’s laws of inheritance where the mutation is not considered. All the characters in parents are based on homozygous alleles. The dominant allele is written in capital and at first whereas the recessive one is written in small.

Phenotypic Ratio vs. Genotypic Ratio

Phenotypic Ratio	Genotypic Ratio
It is the ratio of external observable characters in the progenies of an organism.	It is the ratio of genes’ composition in an organism’s progenies.
It is influenced by the pattern of inheritance pattern of expressing genes, age, and environmental factors as well.	The pattern of inheritance of genes from parents influences the genotypic ratio.
If the individuals have a similar phenotype, it doesn’t necessarily mean they have similar genotypes. For eg., if two boys in the same family and generation are tall, then also they might have different allele compositions such as TT and Tt both result in tallness.	If the individuals possess similar genotypes, they mostly have similar phenotypes.
In the case of a monohybrid cross for a particular trait, the phenotype ratio is 3:1 in the second filial generation.	While in the same case of a monohybrid cross, the genotype ratio is 1:2:1 in the second filial generation.
It can be determined easily by the external appearance of an individual.	It is hard to determine as genetic arrangements also need to be studied.

References

• Knapp S. (2020) Phenotypic Ratio. Accessed from: https://biologydictionary.net/phenotypic-ratio/ Accessed on: 11/28/2022
• Keshari A.K. and Ghimire K.R. (2010) Mendel’s Laws of Inheritance. Vidyarthi Pustak Bhandar. 4th ed. pg. 618-640.
• Ahluwalia, K.B. (2009) Genetics. 2nd ed. New Delhi. New Age International.Klug W.S. (2015). Concepts of Genetics. 11th ed. Boston