Genomes and Genomics

Chapter 14: Genomes and Genomics

14.1 The Genomics Revolution

• Genomics is a rapidly evolving discipline driven by advances in technology.
• Major techniques include whole genome sequencing and genome-level expression profiling (e.g. RNAseq).

14.2 Obtaining the Sequence of a Genome

• The DNA sequence serves as a foundation for analyzing the genome’s structure, function, and evolution.
• Concepts:
  • Bioinformatics: Analysis of genomic data for meaningful insights.
  • Comparative Genomics: Comparing genomes of related species to glean evolutionary and functional information.
  • Functional Genomics: Techniques to understand gene functions within the genome.

14.3 Bioinformatics: Meaning from Genomic Sequence

• Involves annotating genomes and identifying open reading frames (ORFs).
• Tools like BLAST (Basic Local Alignment Search Tool) are crucial for alignment and annotation of sequences, leveraging genetic similarities across species.

14.4 The Structure of the Human Genome

• Roughly 45% of the human genome consists of repetitive sequences (transposable elements).
• Protein-coding genes (exons) account for less than 3% of the genome. Exons are generally small (~150 bp).
• Approximately 20,000-25,000 protein-coding genes exist in the human genome.

14.5 Comparative Genomics

• Focuses on orthologs, identifying similarities in genes from different species, based on common ancestry.
• Approximately 80% of human and mouse genes are identifiable orthologs, indicating a close evolutionary relationship.
  • Syntenic blocks display conserved gene order across species, revealing structural similarities and differences in genomic content.

14.6 Functional Genomics and Reverse Genetics

• Functional genomics studies global patterns of expression, including transcriptomes (gene transcripts) and proteomes (protein expression).
• Reverse Genetics methods disrupt specific genes to determine their functions, utilizing:
  1. Random mutagenesis.
  2. Targeted mutagenesis (e.g., homologous recombination).
  3. Phenocopying (temporary disruption without genetic change).

14.7 Whole Genome Shotgun (WGS) Sequencing

• WGS involves breaking the genome into short segments, sequencing them, and then reassembling overlaps.
  • Traditional vs. Next-Generation WGS:
  • Traditional WGS requires creating genomic libraries and amplifying clones.
  • Next-Generation WGS employs advanced technologies allowing for parallel sequencing without cloning.
• Addressing repetitive sequences is essential for accurate genome assembly, sometimes mitigated by paired-end reads, which span gaps in sequence data.

Challenges in Genomics

• The presence of repetitive sequences complicates the assembly of DNA during sequencing.
• High-throughput techniques, like those used in Next-Gen sequencing, significantly increase the amount of data that can be generated, speeding up research.

Conclusion

• Genomics encompasses vast areas of study, utilizing bioinformatics, comparative genomics, and functional genomics to advance our understanding of genetic materials and their implications in health and evolution. The commit to resolving the complexities of genomes continues to propel the field forward, with numerous applications including personalized medicine and evolutionary biology research.