INTRODUCTION TO GENOMICS

What is Genomics?

1.  Genomics is an area within genetics that  concerns the sequencing and analysis of an  organism’s genome.

2.  It involves the study of all genes at the DNA,  mRNA, and proteome level as well as the cellular  or tissue level.

·        The term genomics was first coined in 1986 by  Tom Roderick, a geneticist at the Jackson  Laboratory in Maine, during a meeting about the  mapping of the human genome.

·        Genomics is the study of all genes present in an  organism.

·        By definition, it can be defined as “A discipline in  genetics that applies recombinant DNA,DNA  sequencing methods and bioinformatics to  sequence, assemble and analyze the structure  and function of genomes.”

·        It includes studies of intragenomic phenomena  such as heterosis, epistasis, pleiotropy and other  interactions between loci and alleles within the  genomes.

 

History:

·        Genomics is the study of all genes present in an  organism.

·        By definition, it can be defined as “A discipline in  genetics that applies recombinant DNA,DNA  sequencing methods and bioinformatics to  sequence, assemble and analyze the structure  and function of genomes.”

·        It includes studies of intragenomic phenomena  such as heterosis, epistasis, pleiotropy and other  interactions between loci and alleles within the  genomes. 

 

Genetics Vs Genomics:

•      GENETICS:

·        Genetics is the study of  heredity.

·        “Gene" refers to a specific  sequence of DNA on a  single chromosome.

Genetics involves the  study of functions and  composition of the single  gene.

 

•      GENOMICS:

·        Genomics is the study of  the entirety of an  organism’s genes.

·        “Genome” refers to an  organism's entire genetic  makeup.

Genomics addresses all  genes and their inter  relationships.

 

Subfields of genomics:

The different research areas of genomics can be

as follows :

1.     Structural Genomics

2.     Functional Genomics

3.     Comparative Genomics

 

STRUCTURAL GENOMICS:

                       

•      Structural genomics helps to describe the 3-D dimensional structure of every protein encoded by a particular genome.

•      The principal difference between structural genomics and traditional structural prediction is that structural genomics attempts to determine the structure of every protein encoded by the genome, rather than focusing on one particular protein.

•      It involves taking a large number of approach to structure determination, including

•      Experimental methods using genomic sequence or

•      Modelling based approaches…..

•      Based on sequence or structural homology of a protein of known structure or

•      Based on chemical and physical principles for a protein based with no homology to any known structure.

 

GOALS:

 

·        Structural genomics has role in determining of function of protein.

·        Used in drug discovery

·        In protein engineering on large scale

·        Interpretation of protein structure

·        The gene sequence of the target protein can also be compared to a known sequence and structural information can then be inferred from the known protein structure.

 

FUNCTIONAL GENOMICS:

§  Branch of genomics that determines the biological functions of genes and their products.

Functional genomics (transcriptomics and proteomics ) is a global, systematic and comprehensive approach foe identification and description of the process and pathways involved in the normal and abnormal state of genes

Why we need to study?

It is estimated that approximately 30% of the open reading frames in a fully sequenced organism have unknown function at the biochemical level and are unrelated to any known gene. This is why recently the interest of research has shifted from genome mapping and sequencing to determination of genome function by using the functional genomics approach

 

COMPARATIVE GENOMICS:

•      Field of biological research in which the genomics features of different organisms are compared the genomic features may include the DNA sequence genes gene order regulatory sequences.

PURPOSE;

·      In this branch of genomics, whole or large parts of genomes resulting from genome projects are compared to study basic biological similarities differences evolutionary relationships between organisms. The major principle of comparative genomics is that common features of two organisms will often be encoded within the  DNA that is evolutionarily conserved between them.

·        By comparing the sequences of genomes of different organisms, researchers can understand what, at the molecular level, distinguishes different life forms from each other.

·        Comparitive genomics also provides a powerful tool for,

·        Studying evolutionary changes

·        Helping to identify genesthat are conserved or common among species

·        Genes that give each organism its unique characteristics

 

Goals;

The main goal of genomics is to :

·        Sequence the entire genome by cutting it  into small, manageable pieces (fragments).

·        Assemble the entire genome from the  pieces (fragments).

·        Understand how gene expression  place.

 

Why to sequence Genomic?

·        Sequencing genomes helps understand how the  genome as a whole and how the genes work  together to direct the growth, development and  maintenance of an entire organism.

·        The genome sequence will represent a valuable  shortcut, thus helping to find genes much more  easily and quickly.

 

Technical foundation

 

The technical foundation of genomics involves :

1. Construction of Genomic and cDNA libraries

     2. DNA Hybridization

3. Restriction-enzyme mapping

    4. DNA sequencing

5. PCR amplification

 

Steps in Genomic sequence

1. Break genome into smaller fragments

 2.Sequence those smaller pieces

3. Piece the sequences of the short fragments  together

 

GENOME SEQUENCING  APPROACHES

.    

1   Hierarchical shotgun sequencing

        Useful  for     sequencing  genomes      of      higher

             vertebrates that contain repetitive sequen

2. Whole genome Shotgun Sequencing

Useful for smaller genomes.

Human genome project

1. The Human Genome Project (HGP) is an  international scientific research project with the  goal of determining the sequence of chemical  base pairs which make up human DNA, and of  identifying and mapping all of the genes of

            the human genome from both a physical and  functional standpoint.

2. HGP was formally founded in 1990 by the US  Department of Energy and the National Institute  of Health and was declared completed on 14^th  April,2003.

 

The basic goals of HGP were :

1. To indentify all the genes and their functions in a  human DNA.

2. To determine the sequences of 3 million base  pairs the makeup the human DNA.

3.     To develop tools for data analysis.

4.     To obtain physical map of human genome.

5.     To store the information in public databases.

 

 

Benefits and Application

Genomics can be useful in following ways :

1.     It can be used in the field of medicine for early  detection of genetic diseases and its diagnosis  and treatment.

    2.  It is also useful in the field of agriculture.

3. To study evolution through mutation lineages

4. In forensic science.

 

 

PLANT GENOME PROJECT

 

1. A plant genome project aims to discover all genes and their function in   a particular plant species.

2.  Initially Plant genome projects focused on a few model organisms

 Characterized by  ;

3. Small genomes or their amenability to genetic studies. q In 1990, NSF led a multi-agency, multinational project to identify all the genes in Arabidopsis thaliana by the end of 2000.

4. Arabidopsis thaliana was the first plant to be completely sequenced.

5. The flowering plant Arabidopsis thaliana is an important model system for identifying genes and determining their functions.

6.  Recent advances in DNA sequencing technologies have dramatically reduced the cost and time needed to sequence an organism's entire genome.

7.  Large-scale sequencing projects have been undertaken to take advantage of the speed and efficiency of next generation DNA sequencing.

8. In 2008, the 1001 Genomes Project was launched.

9. The project aimed to obtain the complete genome of 1001 strains of Arabidopsis from different geographical regions.

 10. Eleven institutes participated in this project worldwide.

 

INTRODUCTION TO ARABIDOPSIS THALIANA

 

Arabidopsis thaliana also called the Thale cress, mouse-ear cress or Arabidopsis.

• Arabidopsis thaliana is an annual (rarely biennial) plant.

• Small flowering plant native to Eurasia (Europe & Asia)

 • A. thaliana is considered a weed. 

• It is found by roadsides and in disturbed land.

• It belongs to mustard family but have white flower.

 

ARABIDOPSIS – A MODEL PLANT

 

Arabidopsis thaliana has basic similarities to most plants. 

• Short-generation time; 8 weeks from seed to seed.

 • Small plant (20 cm tall), easily grown at high density in glasshouse or culture room.

 • Self fertilizes. A single plant produces hundreds or thousands of seeds.

• Small genome size (125 Mb, 5 chromosomes). • Simple organization of genome.

 

ARABIDOPSIS THALIANA GENOME PROJECT

 

1. In 1990, NSF led a multi-agency, multinational project to identify all the genes in Arabidopsis thaliana.

• This included; saturating the genome with mutations, identifying every essential gene, and sequencing the entire genome by the end of the decade. 

• The Arabidopsis stock centers were established in 1991 to preserve and distribute biological materials

• There are two such centers—the Arabidopsis Biological Resource Center (ABRC) at Ohio State University in Columbus, and the Nottingham Arabidopsis Stock Centre (NASC) at the University of Nottingham, United Kingdom.