Introduction:

The study of an organism’s genome with a focus on its structure, function, mapping, and analysis is known as genomics.¹
The genome is a blueprint of the inherited genetic information encoded in an organism’s DNA (or, for some viruses, RNA).
In 1986, Thomas Roderick (Coined genomics) used the term Genomics for “mapping, sequencing and characterizing genomes”
Later, Frederick Sanger (Father of genomics) started techniques for genome sequencing, mapping, biological database, and bioinformatic analyses (1970s – 1980s) and initiated the human and other biological species genome projects in the 1990s. ²

Contents

GENOMICS: AN OVERVIEW

Introduction

Types of Genomics

Structural Genomics

Functional genomics

Comparative genomics:

Methods in genomics

Genome Sequence Assembly

Genome Annotation

Gene Ontology

Whole genome alignment

Microarray-based approach

Application of genomics

Ethical issues raised by genomics (ELSI) (Ethical legal, societal implications)

Future of Genome sequencing (Post genome era)

References

Types of Genomics

Genomics study is moreover divided into structural genomics and functional genomics.^2,3 ⁴However, it can be further classified as:

Comparative Genomics
Epigenomics
Metagenomics
Pharmacogenomics
Mutation Genomics

Structural Genomics:

It is the foremost phase of genome analysis that constructs genetic & physical maps of a genome.
It helps to identify the gene, annotate the gene features & compare their genome structures.
It is used to describe the three-dimensional structure of all the proteins encoded in a genome.

Functional genomics:

It describes the functions and interactions of genes and proteins with known data.
Mainly gene transcription, translation, regulation of gene expression, and also that of protein–protein interaction.

Comparative genomics:

To study evolutionary changes of the organisms based on genomic features like DNA sequence, and gene (order, number, content), various genomic components are compared to conserved or common species.
To compare between a new species genome and molecular evolution that has occurred to evolve a phenotypically different species.

Epigenomics:

It is the study of epigenetic modifications (DNA methylation, chromatin architecture, histone modification, and non-coding RNA) on the genetic structure of the cell.
These modifications do not alter genomic sequence however can be inherited to the final phenotypes.

Meta Genomics:

It is the study of genetic material directly from environmental samples.
Information on the composition and functional traits of an ecosystem.

Pharmacogenomics:

It studies the variation in the human population correlates with drug response patterns.
Prescreening and effective drugs can be provided based on individual genomic information.⁵

Mutational Genomics:

The study of the genome in terms of mutations that occur in individual DNA or Genome.
The main aim is to determine the function of an unknown gene sequence.

Methods in genomics

The structure of genomes and their functions are sequenced, assembled, and analyzed in genomics using a combination of different methods such as recombinant DNA technology, DNA sequencing techniques, and bioinformatics.⁶

Genome Mapping:

Genome mapping identifies and records the particular location of specific genes and their relative distances between genes on the chromosome. ⁷

Maps type:

1. Linkage maps

It displays the gene arrangement and its genetic markers also, the chromosomes and their inherited frequency during recombination or crossing over.

2. Physical maps

It provides physical distances between chromosomes in terms of nucleotide bases.

Genome Sequencing

Genome sequencing is to determine the exact order of DNA nucleotides, or bases, of a genome in the order of A, C, G, and T, in a strand of DNA.
The idea of genome sequencing is to break your genome into numerous tiny fragments, and then clone each with a cloning vector, isolate many copies, and sequence each copy.
Modern DNA sequencing consists of high-throughput methods that rapidly sequence the DNA of different species, including humans, animals, plants, and microorganisms.

Genome Sequence Assembly

Genome assembly is the process of arranging nucleotide sequences into the correct order.
A genome sequence assembly can be performed in two ways: mapping and assembly, or de novo assembly.
In mapping and assembly, there is an existing genome sequence, so the newly acquired resequencing reads are first mapped to the reference genome through alignment and then assembled in the correct order.
In de novo assembly, there is no reference genome sequence. It occurs in the stepwise process beginning from the sequence reads (500 bases) assembly into contigs (5,000 to 10,000 bases), assembly of the contigs into scaffolds called super-contigs (30,000–to 50,000 bases), and the final assembly of the scaffolds into chromosomes.⁸

Genome Annotation

Genome annotation, done through gene prediction and functional assignment, identifies the biological function of the assembled sequence in a database. Three fundamental categories can be used to divide it.
Nucleotide-level annotation is the first, which describes the precise locations of genes, RNAs, and repetitive elements.
The second method is protein-level annotation, which aims to identify potential uses for genes found in a particular organism.⁹
The third type of annotation, known as a process-level annotation, identifies the different pathways and their processes in which various genes are involved in functional annotation.

Gene Ontology

A Gene Ontology description of a protein function includes three types of information: biological process, cellular component, and molecular function, each using a unique set of nonoverlapping vocabularies.
Similar terminology used in different organisms may refer to different genes or proteins which is often ambiguous and imprecise.
Gene Ontology standardizes and maintains consistency of the names, functions, and associated pathways in describing overall protein functions and grouping those related function proteins.
A database search using gene ontology (GO) for a particular protein can easily bring up other proteins of related functions in much the same way as using a thesaurus.
A genome annotator can assign the functional characteristics of gene products using GO.

Whole genome alignment

Whole-genome alignment (WGA) is the process of predicting, at the nucleotide level, the evolutionary relationships between two or more genomes.
With the rapid growth of the genome sequences database, it is important to identify the conserved functional elements in the genome sequences.
For WGA, direct genome comparisons or genome alignment can be performed and it is similar to that of basic alignment of the sequences.¹⁰

Microarray-based approach

In genomics, a DNA microarray-based approach is used to profile gene expression.
A high-density array of immobilized DNA oligomers (and occasionally cDNAs) representing the entire genome is attached to a slide as a microarray (or gene chip).
The cDNA labeled with fluorescent dyes or radioisotopes is allowed to hybridize with the oligo probes on the chip. It serves as a probe for binding to a specific or complementary cDNA.
In each spot position, the quantity of fluorescent or radioactive labels corresponds to the quantity of the corresponding mRNA in the cell.
This analysis can be used to look at the patterns of gene expression in a cell. It may be possible to identify gene sets that function in related regulatory or metabolic pathways.

Application of genomics:

Medicine

To detect genes responsible for disease susceptibility and risk factors
Improved prognostics or diagnostics.
Personalized prevention and drug therapies treatment of disease based on an individual’s genomic sequence, or pharmacogenomics.

Agriculture

Genome sequencing for the database of plant model organisms.
Use genomic data to pinpoint desirable traits, then transfer those traits to produce hybrids with the most desirable characteristics (crop breeding). For example, a crop that is sensitive to drought, more tolerant to dry season and high salinity.
Increases in crop yields and improvements in agricultural practices involve an increase in fruit and vegetable shelf-life and an improvement in nutritional quality such as protein and carbohydrate contents especially fat.

Livestock Breeding

Genetic improvement in animal husbandry is based on the selection of superior organisms for a trait of interest
To improve the quality of animal products (dairy products and beef) for human consumption.

Microbial Genomics

The ideal way to study microorganisms is not always pure culture conditions, but more preferable in microbial communities called biofilms.
Metagenomics studies the collective genomes of various species that develop and interact in a particular environmental niche.
Microbial genomics made it possible to improve vaccines, design novel disease therapies, and develop cutting-edge environmental cleanup technology.

Bioprocessing

Improved methods for harvesting biofuels from algae and cyanobacteria.
Antibiotics, useful new enzymes, and other anti-microbial products are manufactured.

Bioterrorism

Real-time diagnostics of biothreats.
Genomic analysis helps to determine whether the pathogen’s release was intentional or natural by analyzing sequence, annotating data, and observing cloned vectors at the restriction site of the causative agent.

DNA Fingerprinting

In forensics, samples found at crime scenes use genomic data and tools for their analysis.
Based on massively parallel sequencing (MPS) genomic innovation has improved the ability to analyze even low-quality DNA.

Ethical issues raised by genomics (ELSI) (Ethical legal, societal implications)

When the Human Genome Project was proposed in the late 1980s, the Project’s first director, Dr. James Watson, suggested that 5% of the funding be set aside to study the ethical, social, and legal implications (ELSI) of human genetics. ¹¹

Four major issues related to identity that are raised by genomics are (forensic, personal, family, and ethnic) identity.

Prenatal Selection to Avoid Disease or Genetic Enhancement: He Jiankui, a Chinese researcher (2018) uses the genome editing tool (CRISPR/Cas9) to create HIV-free babies.
Uncovering the Past: DNA can reveal aspects of the past as well as of the present, so can raise issues of privacy.
Ownership and Control: The question of presumed consent and informed consent. The typical Iceland governmental medical data collection for public health purposes serves the interests of deCODE (private firm) more than the public and its proprietary use was ethical.
Patent issues: In the U.S. Supreme Court, Diamond v. Chakrabarty (1980), approved a patent on a genetically altered bacterium, stating humanly modified genomic sequences, such as ‘complementary DNA,’ could be patented.
Culture’s conflict between nature and nurture: “We used to believe that destiny was written in the stars”. DNA may appear to be evidence of a centuries-old debate over how people are shaped.

Future of Genome sequencing (Post genome era)

Sequencing costs have dropped each year and could reach $1,000/genome.
Introduce the possibility of sequencing genomes of individuals for personalized medicine.¹²
Greatly facilitates technologies for comparative genomics.
Creating the possibility for Synthetic Biology.
Biological data mining.
De-extinction of species (Woolly mammoth project).

References:

1. A Brief Guide to Genomics. Genome.gov. https://www.genome.gov/about-genomics/fact-sheets/A-Brief-Guide-to-Genomics. Accessed December 26, 2023.

2. Lesk AM. Introduction to Genomics. 2nd ed. Oxford ; New York: Oxford University Press; 2012.

3. Bainaboina G. Brief Note on Genomics and It Types. J Appl Bioinforma Comput Biol. 2020;2020. doi:10.37532/2329-9533.2020.9(3).172

4. EMBL-EBI. What is genomics? | Functional genomics I. https://www.ebi.ac.uk/training/online/courses/functional-genomics-i-introduction-and-design/what-is-genomics/. Accessed December 26, 2023.

5. Lecture 23: Genomics, Proteomics, and Metabolomics. Biology LibreTexts. https://bio.libretexts.org/Courses/University_of_California_Davis/BIS_2A_(2018)%3A_Introductory_Biology_(Singer)/Bis2A_Winter_2019/Lecture_23%3A_Genomics_Proteomics_and_Metabolomics. Published February 19, 2019. Accessed December 26, 2023.

6. Xiong J. Essential Bioinformatics. Cambridge: Cambridge University Press; 2006. doi:10.1017/CBO9780511806087

7. Genome Mapping. https://www.ncbi.nlm.nih.gov/probe/docs/applmapping/. Accessed December 30, 2023.

8. Genome Assembly – an overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/genome-assembly. Accessed December 26, 2023.

9. Genome Annotation – an overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/genome-annotation. Accessed December 26, 2023.

10. Dewey CN. Whole-Genome Alignment. In: Anisimova M, ed. Evolutionary Genomics: Statistical and Computational Methods. Methods in Molecular Biology. New York, NY: Springer; 2019:121-147. doi:10.1007/978-1-4939-9074-0_4

11. School SL. Ethical Issues in Genomics. Stanford Law School. https://law.stanford.edu/publications/ethical-issues-in-genomics/. Accessed December 26, 2023.

12. Hocquette JF. Where are we in genomics? J Physiol Pharmacol Off J Pol Physiol Soc. 2005;56 Suppl 3:37-70.