Genomics

THE HUMAN BODY consists of trillions of cells. Almost all contain an entire genome-the complete set of inherited genetic information encoded in our DNA. When humans reproduce, the parents' sperm and egg DNA combine to contribute a genome's worth of genetic information to the fertilized embryo. That same information is in each of the cells that eventually make up an organism.

Some segments of DNA, called genes or "coding" DNA, contain the chemical recipe that determines particular traits; genetics is the study of the inheritance and function of these genes. Scientists now estimate that humans have about 30,000 genes, located along threadlike, tightly coiled strands of DNA called chromosomes. Genes, however, are only about three percent of human DNA; the rest is "noncoding" DNA. Within these noncoding regions of the genome is the information that determines when and where genes are active-for example, in which cell types and at what stages in the life of an organism. Genomics is the study of the entire set of DNA sequences-both coding and noncoding DNA.

Over the past decade, the decoding of the genomes of human beings and other important organisms has sparked an extraordinary biological revolution. The information and technology of genomics is transforming our understanding of human evolution, the mechanisms of disease, the relationship between heredity and environment, and our ancient connection with all forms of life. In the next few years we will see many exciting discoveries leading to a better understanding of the complexity of life, as well as new drugs, vaccines, and diagnostics and less expensive, more efficient, and safer ways to restore the environment.

The human genome....by the numbers:

75-100 trillion . . . Cells in the human body
3.1 billion . . . Base pairs in each cell
2.4 million . . . Base pairs in the largest human gene (dystrophin)
28,000-35,000 . . . Genes in the human genome
46 . . . Chromosomes in each cell


Types of genomic studies:


(1) structural genomics
(2) functional genomics

Structural Genomics:

Structural genomics consists in the determination of the three dimensional structure of all proteins of a given organism, by experimental methods such as X-ray crystallography, NMR spectroscopy or computational approaches such as homology modelling.

As opposed to traditional structural biology, the determination of a protein structure through a structural genomics effort often (but not always) comes before anything is known regarding the protein function. This raises new challenges in structural bioinformatics, i.e. determining protein function from its 3D structure.

One of the important aspects of structural genomics is the emphasis on high throughput determination of protein structures. This is performed in dedicated centers of structural genomics.

 While most structural biologists pursue structures of individual proteins or protein groups, specialists in structural genomics pursue structures of proteins on a genome wide scale. This implies large scale cloning, expression and purification. 

Functional Genomics:

Functional genomics is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects (such as Genome Sequencing Projects) to describe gene (and protein) functions and interactions. Unlike genomics and proteomics, functional genomics focuses on the dynamic aspects such as gene transcription, translation, and protein-protein interactions, as opposed to the static aspects of the genomic information such as DNA sequence or structures.

Functional genomics includes function-related aspects of the genome itself such as mutation and polymorphism (such as SNP) analysis, as well as measurement of molecular activities. The latter comprise a number of "-omics" such as transcriptomics (gene expression), proteomics (protein expression), phosphoproteomics and metabolomics. Together this measurement modality quantifies the various biological processes and powers the understanding of gene and protein functions and interactions.

Functional genomics uses mostly high-throughput techniques to characterize the abundance gene products such as mRNA and proteins. Some typical technology platforms are:

• DNA microarrays and SAGE for mRNA.
• two-dimensional gel electrophoresis and mass spectrometry for protein.

Because of the large quantity of data produced by these techniques and the desire to find biologically meaningful patterns, bioinformatics is crucial to this type of analysis. Examples of techniques in this class are data clustering or principal component analysis for unsupervised machine learning (class detection) as well as artificial neural networks or support vector machines for supervised machine learning (class prediction, classification).