Topic 9: Genomics and Bioinformatics

Genomics

The study of all genes in a genome simultaneously to understand the "big picture" of an organism's content, organisation, and evolution.

Bioinformatics

A multidisciplinary field combining biology, computer science, mathematics, and statistics to manage, analyse, and interpret massive biological datasets.

Transcriptomics

The study of the entire transcript (all mRNA) of an organism; it explains why cells with the same 46 chromosomes (like retinal vs. renal cells) are structurally and functionally different.vs

Proteomics

Identifying and studying all proteins expressed by a cell, including their structures, functions, and complex interactions.

Metagenomics

The study of DNA sequences recovered directly from environmental samples (like soil or slaughterhouses) where many organisms cannot be cultured.

Metabolomics

Study of all metabolites in a cell and how they change in response to conditions.

Pharmacogenomics

Studying how an individual’s genotype affects their response to medications to create "Personalised Medicine."

Cytological Map

A visual representation of chromosomes (karyotypes) where genes are positioned based on staining (banding) or FISH to detect macroscopic abnormalities. Lowest resolution.

Genetic (Linkage) Map

A map relating distances between markers based on recombination frequency, measured in CentiMorgans (cM).

Physical Map

The highest resolution map providing the complete and precise order of nucleotides, measured in the number of base pairs (bp).

Clone-by-clone approach

A sequencing method where the genome is broken into large random fragments, cloned into a library, ordered by overlaps, and then sequenced.

1. DNA Shearing - DNA broken into fragments

2. Cloning: these fragments are individually inserted into vectors to create a library of clones, each containing a specific DNA segment

3. Clone Ordering: identify overlaps between cloned fragments, & establish the order in which these fragments appear within the chromosome

4. Sequencing and Assembly: The DNA sequence of each individual clone is determined, and the complete sequence is assembled

Shotgun Approach

A method where the entire genome is randomly broken into short fragments that are directly sequenced and then pieced together using computational tools.

DNA Fragmentation: The entire genome is randomly broken down into smaller fragments.

• Sequencing: fragments are sequenced without prior cloning.

• Assembly Challenge: tools are used to piece together the short sequences based on overlapping regions, reconstructing the original larger sequence.

• Gap Filling: smaller fragments = some gaps might remain in the assembly.
These gaps may require additional techniques for closure.

Contig (Contiguous Sequence)

A continuous stretch of nucleotides assembled from overlapping shorter DNA fragments; these are the "building blocks" of genome maps.

ESTs (Expressed Sequence Tags)

Partial cDNA sequences that serve as landmarks on chromosomes to identify the positions of genes.

Haploid Genome Size

Approximately 3×109 base pairs.

Human Gene Count

The completed sequence revealed roughly 20,000–30,000 genes, significantly lower than the original prediction of 80,000–100,000.

Coding vs. Repetitive Sequences

Only 1.5% of the human genome is coding sequence; 50% consists of repetitive sequences used for chromosome stability.

Nucleotide Identity

Any two human beings are 99.9% identical at the nucleotide level.

Comparative Genomics

Focused on comparing genomes of different species; if the order of genes is preserved (synteny), it indicates a common ancestor.

2-D Gel Electrophoresis

A technique used in proteomics to separate proteins based on their Isoelectric Point (IEF) (the pH where net charge is zero) and their mass (SDS-PAGE).

Systems Biology

An approach that focuses on the complex interactions within whole systems of genes, proteins, and metabolites rather than studying them in isolation.

Eugenics

The scientifically invalid and morally condemned belief in "improving" human genetic quality through selective reproduction.

Ethical Implications of Genomics

Concerns regarding privacy and who (employers, insurers, government) should have access to an individual's genomic data.

NCBI (National Centre for Biotechnology Information

A major public database that stores and provides access to biological information online, including DNA and protein sequences and genome data. Big umbrella organisation.

GenBank

The public DNA and protein sequence database maintained by NCBI, containing submitted nucleotide and gene sequences from many organisms. Actual storage database.

ENTREZ

NCBI's search and retrieval system used to access biological databases for gene sequences, proteins, and scientific papers. Search engine for NCBI like Google.

BLAST (Basic Local Alignment Search Tool)

A bioinformatics tool used to compare a DNA or protein sequence against databases to identify similar sequences and detect evolutionary relationships. Compares sequences to find similarities.

Genetics

Studying single genes / traits - one at a time (snapshot).