Lesson 19: Genomics

🧬 Major Components of Genomics

Genomics is the study of entire genomes—including all genes, their nucleotide sequences, organization, and interactions.
Combines classical genetics with modern molecular biology and bioinformatics.
Major components:
- Structural Genomics – studying DNA sequences and genome structure.
- Functional Genomics – studying gene functions and expression.
- Comparative Genomics – comparing genomes between species.
- Proteomics – studying all proteins made by an organism.

Example: The Human Genome Project mapped all human genes, providing insights into disease-related genes.

Feature	Genetic Map	Physical Map
Definition	Shows relative positions of genes based on recombination frequency	Shows actual physical distance between DNA sequences (in base pairs)
Basis	Linkage analysis (crossing over)	DNA sequence data or molecular markers
Units	Centimorgans (cM)	Base pairs (bp or kb)
Example	Flower color and pollen shape genes in peas inherited together	Sequence-tagged site (STS) or restriction site maps

Analogy: Genetic map = interstate map (broad overview); Physical map = street map (detailed).

Sanger (Dideoxy) Sequencing:
- Uses dideoxynucleotides (ddNTPs) that terminate DNA synthesis.
- Each ddNTP labeled with a fluorescent dye (A, T, G, C).
- Automated machines detect the sequence by reading fluorescence.
- Example: Used in early human genome sequencing.
Next-Generation Sequencing (NGS):
- Faster, cheaper, high-throughput.
- DNA fragments attached to a solid surface; sequenced in parallel.
- Allows sequencing of millions of fragments simultaneously.
- Example: Used for rapid COVID-19 variant tracking.

Approach	Clone-Contig	Shotgun
Method	Genome divided into overlapping clones (BACs or YACs) that are sequenced in order	Genome randomly broken into fragments; computer reassembles overlapping sequences
Speed	Slower	Faster
Accuracy	High	Requires computational correction
Used by	Human Genome Project (initially)	Craig Venter’s Celera Genomics

Example: Shotgun sequencing is now standard for bacterial genomes and NGS projects.

Converts raw DNA sequences into meaningful information.
Identifies genes, coding regions, promoters, start/stop codons, etc.
Uses tools like BLAST to compare unknown sequences to known genes.
Importance: Turns sequence data into biological understanding—like translating a “book of letters” into readable text.
Example: Annotation helped identify the BRCA1 gene related to breast cancer.

Makes up most of the human genome (over 98%).
Roles:
- Regulate gene expression (enhancers, silencers).
- Code for non-coding RNAs (tRNA, rRNA, miRNA).
- Maintain chromosome structure (centromeres, telomeres).
Example: The ENCODE Project found that many non-coding regions are biochemically active even if not coding for proteins.

Type	Focus	Example/Application
Comparative Genomics	Compares genomes between species to find similarities (synteny)	Comparing human and chimpanzee DNA to trace evolution
Functional Genomics	Studies gene expression and interaction (genotype → phenotype)	DNA microarrays or RNA-seq to see which genes are “on” or “off”
Proteomics	Studies all proteins made by a cell or organism	Using mass spectrometry to detect cancer-related protein changes

Medicine: Identify disease-causing genes, design personalized treatments (pharmacogenomics).
- Example: Using genomic testing to determine the best cancer therapy.
Forensics: Identify individuals or pathogens from DNA samples.
- Example: Anthrax case solved using microbial genomics.
Agriculture: Engineer disease-resistant or higher-yield crops.
- Example: Bt corn produces its own natural insecticide.
Environmental Science: Metagenomics studies microbial communities for pollution cleanup.
- Example: Oil spill bacteria identified using environmental DNA sequencing.
Evolutionary Biology: Mitochondrial DNA tracing reveals human migration patterns.