Genomics

Characteristics of the human genome

To date, the structure and properties of the human genetic apparatus have been studied in detail. It has been established that the genome is represented by double-stranded discontinuous DNA. Normally, the genetic material is distributed across 24 chromosome types: it includes 22 autosomes and 2 sex chromosomes.

The total size of the genome reaches a colossal 3 billion base pairs. Meanwhile, the total number of genes is estimated at 20–25 thousand. A surprising fact is that exons (coding regions) make up only 1% of the total volume of genetic information.

Individual differences between people are minimal and affect only 0.1% of genomes. The genomes of two different people overlap in approximately half of single nucleotide polymorphisms. However, this tiny fraction is of immense clinical significance: it explains phenotypic differences, susceptibility to diseases, and the body's response to medications or environmental factors.

Genetic variability includes:

• Single nucleotide polymorphisms (SNPs): 2.5 to 4 million.
• Repeats (copy number variability): hundreds or thousands per genome.
• Insertions and deletions: hundreds of thousands.

Knowledge of these parameters is critically important for medicine. Genes whose mutations cause over 350 different diseases have already been identified. Such pathologies include certain types of cancer, Alzheimer's disease, Parkinson's disease, hyperlipidemia (elevated serum lipid levels), and porphyrias.

A brief history of sequencing

The development of genomics is inextricably linked with the improvement of DNA study technologies. Key milestones in the history of genome research:

• 1973 — the first cloning of eukaryotic genes into bacterial plasmids was carried out.
• 1980 — W. Gilbert, P. Berg, and F. Sanger were awarded the Nobel Prize in Chemistry for developing DNA sequencing methods.
• 1984 — The US Congress funded the launch of the large-scale Human Genome Project, allocating 3 billion dollars for complete sequencing.
• 1989 — a scientific council for the "Human Genome" program was established in Russia.
• 2000 — the "first draft" of the human genome was completed.
• 2006 — complete decoding of the genome took place (the first and largest chromosome was successfully sequenced).
• 2012 — the cost of a full genome analysis dropped to $1,500.

Modern third-generation sequencing technologies open up incredible prospects, making it possible to decode the genome in just a few minutes.

Comparative genomics

In addition to humans, scientists have completely decoded the genomes of important model organisms such as the nematode Caenorhabditis elegans and the classical fruit fly Drosophila. The genomes of key agricultural plants, namely rice and corn, have also been sequenced.

Of particular interest is the comparison of human DNA with other species:

• Neanderthal: identity reaches 99.7%. At the same time, modern humans were found to have 5 unique genes that Neanderthals lack. These genes are associated with skin functions, energy metabolism, and cognitive activity.
• Chimpanzee: identity is 98.8%.
• Mouse: genetic material matches by approximately 80%.

Medical applications and new directions

A deep understanding of genome structure has opened up entirely new prospects in clinical practice. The main areas for the practical application of genetic knowledge include:

1. Diagnostics: searching for genes responsible for hereditary pathologies, as well as performing early and prenatal diagnostics.
2. Therapy: development and implementation of gene therapy methods.
3. Pharmacogenomics: creation of strictly personalized medications tailored to the patient's DNA characteristics.
4. Prevention: monitoring and influencing the transmission mechanisms of hereditary diseases in future generations.
5. Identification: conducting precise personal identification using "genomic fingerprinting".

The integration of fundamental genetics into clinical biology and medicine has facilitated the formation of cutting-edge specialized disciplines: immunogenetics, pharmacogenetics, and pharmacogenomics.

Class and exam questions

What else to study on this topic

• Types of genetic variability: SNPs, insertions, deletions, and repeats
• Human Genome Project: stages and results
• Differences between sequencing technologies of different generations
• Application of pharmacogenomics in the creation of personalized drugs
• Genes associated with Alzheimer's disease and porphyrias

Other topics in the "Medical Genetics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.