Deciphering the mysteries of human genomes — Anna Přistoupilová

The human genome contains 3 billion letters (base pairs) with only 2% being coding DNA (genes), while the rest is non-coding DNA with regulatory functions

Rare diseases collectively affect up to 6% of the population, with over 6,000 different types identified:

• 72% are genetic in origin
• 70% start in childhood
• Only 5% have available treatments
• Can take 15-17 years for research findings to reach clinical practice

DNA sequencing technologies have evolved significantly:

• First human genome (2001): 13 years, $3 billion
• Current cost: ~$500 per genome
• Next-generation sequencing improved clinical diagnosis rates from 1% to 50%

Key sequencing approaches:

• Whole genome sequencing (entire DNA)
• Exome sequencing (2% coding regions only)
• Targeted sequencing (specific genes)
• Nanopore sequencing (long reads)

Bioinformatics workflow includes:

• Raw sequence data processing (FASTQ format)
• Quality control and filtering
• Mapping to reference genome
• Variant identification and annotation
• Data analysis using tools like Python, BioPython, and BioConda

Genetic variants can have different effects:

• Silent mutations (no effect)
• Missense mutations (amino acid change)
• Nonsense mutations (protein termination)
• Insertions/deletions (reading frame shifts)

When disease-causing variants are found:

• Validate findings
• Check family members
• Find other affected families
• Consider treatment options
• Provide genetic counseling
• Submit to databases
• Publish findings