Note sull'episodio
A genome is the complete genetic blueprint of an organism, and genomics is the study of the structure, function, organization, and evolution of entire genomes. In cellular organisms, the genome consists of deoxyribonucleic acid (DNA), whereas some viruses use ribonucleic acid (RNA) as their genetic material. Although the terms genome and are often used interchangeably, they represent distinct concepts. The genome encompasses all the hereditary information required to build, maintain, and reproduce an organism, whereas the genome sequence is simply the linear arrangement of nucleotide bases that encodes this information.
Like words and sentences in a language, DNA and RNA sequences consist of ordered strings of discrete nucleotide units. These nucleotide sequences form the fundamental genomic elements that collectively determine the structure, regulation, and function of living organisms.
The classical central dogma of molecular biology—DNA → RNA → Protein—was formulated largely from studies in bacteria and provides a partial description of the genetic program of complex eukaryotes. Subsequent large-scale investigations, including the exhaustive analysis of approximately 1% of the human genome by the ENCODE pilot project, revealed an unexpectedly rich landscape of functional genomic elements1. Although only about 1.5% of the human genome is translated to encodes proteins, genome-wide studies using technologies such as EST sequencing, tiling microarrays and RNA sequencing have demonstrated that a substantial fraction of the genome is transcribed. Many of these transcribed sequences function as regulatory RNAs that influence gene expression, chromatin organization, development, and disease.
For many years, non-protein-coding regions were dismissed as "junk DNA" or referred to as genomic "dark matter" because their biological functions were poorly understood. It is now evident that many of these regions contain functional elements, including promoters, enhancers, non-coding RNAs, cis-regulatory elements, and structural features that play essential roles in regulating gene expression and cellular function.
The ability to identify sequence variation within these genomic elements has transformed biology and medicine. Once variants associated with specific biological traits or diseases are identified, they can be exploited for diagnostics, therapeutics, crop improvement, and vector control. Furthermore, genome-editing technologies such as CRISPR-Cas systems now allow many of these elements to be modified directly, creating unprecedented opportunities for functional studies and precision genetic engineering.
This chapter introduces the major classes of genomic and epigenomic elements currently investigated using high-throughput technologies, including genes and transcripts, promoters, enhancers, non-coding RNAs, small interfering RNAs (siRNAs), cis-regulatory elements, single nucleotide polymorphisms (SNPs), structural variants, and epigenetic modifications to find causative genotype under a phenotype of interest.