Review of L22-GENOMICS

Genomics employs various strategies to analyze entire genomes.
Genetic Maps:
- Assign genetic landmarks (markers) to genome positions.
- Provide relative distances between markers.
- Linkage Mapping: Determines relative positions using genetic recombination.
Physical Maps:
- Provide absolute distances between markers.
- Include restriction maps, chromosome maps, and STS maps.
- Can correlate with genetic maps.
- Cloned genes can be placed on both map types.

Dideoxy Terminator Sequencing:
- Essential method in genome sequencing.
- Utilizes altered nucleotide chemistry to terminate DNA synthesis with fluorescent nucleotides.
Next-Generation Sequencing (NGS):
- Employs massively parallel technologies for increased throughput.
- Cost and time for sequencing reduced about 10,000-fold since the Human Genome Project.
- Analyzes isolated DNA through thousands of simultaneous reactions to produce extensive data.
Sequenced fragments are reconstructed into complete sequences using:
- Shotgun Sequencing: Assembles genomes from short overlapping DNA pieces.
- Clone-Contig Sequencing: Uses larger pieces and a tiling approach for genome assembly.

Human Genome Project:
- Mapped most of the human genome and sequenced it.
- Competitive race spurred rapid technological advances for early completion.
- Found significantly fewer genes than initially predicted.
Wheat Genome Project:
- Demonstrates improvements in genome assembly over four iterations.
- Recent versions utilize longer reads combined with shorter, error-prone reads.
1000 Genomes Project:
- Addresses genetic diversity by sequencing over a thousand individuals.
- Identified 80 million variants; average genome varies from reference at 4–5 million sites.
- Up to 200 genes can be deleted without any phenotype effects.

Genome Annotation:
- Assigns functions to DNA sequences in genomes.
- Identifies protein-coding genes via open reading frames.
Genes Comparison:
- Infers gene function by comparing unknown genes to known genes.
Types of DNA Sequences Found in Human Genome:
- Protein-Encoding Genes: About 20,000 genes scattered throughout chromosomes.
- Introns: Predominantly noncoding DNA in each gene.
- Segmental Duplications: Duplicated regions within the genome.
- Pseudogenes: Inactive genes with gene-like characteristics.
- Structural DNA: Constitutive heterochromatin near centromeres and telomeres.
- Simple Sequence Repeats: Repeated short nucleotide sequences.
- Transposable Elements:
  - 21% LINEs (active transposons).
  - 13% SINEs (active transposons).
  - 8% Retrotransposons (with LTRs at both ends).
  - 3% DNA transposon fossils.
- Noncoding RNA: Regulatory RNA with many unknown functions.

Comparative Genomics:
- Reveals conserved regions across genomes.
- More than half of Drosophila genes have human counterparts.
- Cereal genomes show large regions of synteny.
Functional Genomics:
- Analyzes gene function and gene products at genome level.
- High-Throughput Approaches:
  - DNA microarrays can monitor gene expression in cells.
  - SAGE and RNA-seq analyze the transcriptome directly.
  - Proteomics: Catalogs all proteins from the genome and characterizes them;
    - Complicated by posttranslational modifications and alternative splicing.

Genomic data enabled the creation of the first synthetic cell.
- Genome designed computationally and synthesized, assembled in yeast, added to a bacterium to form a new cell.
Genomics assists in disease identification and treatment:
- Expands the range of diseases linked to genetics, promoting personalized medicine.
Raises social and ethical issues:
- Concerns regarding synthetic cells and dangerous virus reconstruction.
- Individual genes cannot be patented, but synthetic products (e.g., cDNA) related to the gene can be.