You might be surprised to learn that only 1.5 percent of your DNA actually codes for proteins, leaving the remaining vast majority of your 3.1 billion base pairs with roles we are only beginning to understand.
Key Takeaways
- The human genome consists of approximately 3.1 billion base pairs of DNA
- There are about 20,000-25,000 protein-coding genes in the human genome
- Non-coding RNA genes make up around 10% of the human genome
- Whole genome sequencing cost was $2.7 billion for the Human Genome Project in 2003
- By 2023, the cost of human genome sequencing dropped to $562
- Illumina NovaSeq can sequence 20,000 genomes per year at 30x coverage
- The 1000 Genomes Project sequenced 2,504 individuals
- dbSNP database contains 1 billion+ variants as of 2023
- ENCODE project mapped functional elements in 1% then whole genome
- The average human heterozygosity is 0.1% or 1 in 1,000 bases
- Common SNPs (MAF>1%) number 84 million in 1000 Genomes
- Structural variants cover 25 Mb per human genome
- BRCA1/2 mutations confer 72% lifetime breast cancer risk
- CFTR deltaF508 mutation causes 70% of cystic fibrosis cases in Caucasians
- APC mutations underlie 80% of familial adenomatous polyposis
Human genome sequencing has become dramatically faster, cheaper, and more comprehensive, enabling breakthroughs in medicine and agriculture.
Applied Genomics
- Maize genome size is 2.3 Gb with 32,000 genes
- Rice genome sequenced at 430 Mb with 37,000 genes
- CRISPR improved wheat yield by 20% via gene editing
- GMO Bt corn reduces insecticide use by 37%
- Soybean genome has 1.1 billion bases and 46,000 genes
- Cattle genome project identified 22,000 genes
- Dog genome reveals 19,000 genes similar to human
- Arabidopsis thaliana genome is 135 Mb with 27,000 genes
- Golden rice with beta-carotene boosts vitamin A in rice
- Salmonella typhimurium genome 4.9 Mb used for vaccine development
- Yeast synthetic genome project rewrote 16 chromosomes
- Mosquito genome editing reduces malaria transmission 99% in labs
- Pig genome aids xenotransplantation with 25 edits
- Banana genome sequencing combats Panama disease
- CRISPR tomatoes with GABA boost flavor and shelf life
- E. coli minimal genome has 473 genes for synthetic biology
- Coronavirus genome 30 kb sequenced for vaccine design
- Cotton genome polyploidy decoded for fiber improvement
- Chicken genome has 1.05 Gb and aids avian flu research
- Genomic selection increases dairy cattle milk yield 100 kg/yr
- Virus-resistant papaya saved Hawaiian industry via transgene
- Atlantic salmon genome duplicated aids aquaculture
- Sugarcane genome 10 Gb sequenced for biofuel
- Genomic prediction accuracy 70% for pig growth traits
- Fungus-resistant wine grapes via CRISPR
Applied Genomics Interpretation
Despite the maize plant's genome being a sprawling 2.3 Gb estate with fewer genes than rice's compact 430 Mb studio apartment, it's clear we're no longer just reading life's blueprints but skillfully editing them to boost yields, fortify food, and outsmart diseases from malaria to Panama.
Disease Genomics
- BRCA1/2 mutations confer 72% lifetime breast cancer risk
- CFTR deltaF508 mutation causes 70% of cystic fibrosis cases in Caucasians
- APC mutations underlie 80% of familial adenomatous polyposis
- HTT CAG repeat >36 causes Huntington's disease
- FMR1 CGG repeat >200 leads to fragile X syndrome in 1/4,000 males
- TP53 mutations in 50% of all cancers
- KRAS mutations drive 30% of colorectal cancers
- EGFR mutations in 10-15% non-small cell lung cancers in Asians
- PCSK9 loss-of-function variants reduce LDL by 30%
- Factor V Leiden mutation increases VTE risk 5-fold
- GBA mutations increase Parkinson's risk 5-10 fold
- APP/PSEN1 mutations cause 5% early-onset Alzheimer's
- LDLR mutations cause 90% familial hypercholesterolemia cases
- SMN1 deletions cause 95% spinal muscular atrophy
- DMD deletions in 65% Duchenne muscular dystrophy
- Polygenic risk scores explain 20% schizophrenia heritability
- GWAS identified 100+ loci for type 2 diabetes
- Heritability of height is 80% from 12,000 loci
- Coronary artery disease PRS predicts 10% risk variance
- Somatic JAK2 V617F in 95% polycythemia vera
- CALR mutations in 25% essential thrombocythemia
- FLT3-ITD in 30% acute myeloid leukemia
- IDH1/2 mutations in 75% low-grade gliomas
- PTEN loss in 40-50% endometrial cancers
- MSI-high in 15% colorectal cancers responsive to immunotherapy
- TERT promoter mutations in 70% melanomas
- Genome-wide association studies link 500+ loci to breast cancer risk
- Alpha-1 antitrypsin deficiency from PI*Z allele in 1/2,500 Europeans
- Hemochromatosis HFE C282Y homozygotes 0.4% in Northern Europe
- Genome editing corrects 60% of DMD mutations in mice
Disease Genomics Interpretation
These statistics remind us that our genes are not always a friendly neighborhood, but rather a sometimes treacherous landscape where a single wrong turn can dictate destiny, yet they also map the precise coordinates for medical breakthroughs.
Genetic Variation
- The average human heterozygosity is 0.1% or 1 in 1,000 bases
- Common SNPs (MAF>1%) number 84 million in 1000 Genomes
- Structural variants cover 25 Mb per human genome
- Inversions affect 1% of the human genome per individual
- Mobile element insertions number 100+ de novo per generation
- Tandem repeats vary in 10% of human disease loci
- African populations have 19% more genetic diversity than Europeans
- Neanderthal admixture contributes 1-2% DNA to non-Africans
- Denisovan DNA in Oceanians up to 5%
- Mutation rate is 1.2 x 10^-8 per base per generation
- De novo mutations average 60-70 per diploid genome
- Loss-of-function variants tolerated in 100 genes per person
- HLA alleles number 20,000+ in human population
- ABO blood group polymorphism affects 20% frequency variation globally
- Lactase persistence allele frequency 90% in Northern Europeans
- Sickle cell allele frequency 10-20% in malaria-endemic Africa
- CCR5-delta32 mutation frequency 10% in Europeans
- Copy number variants >1kb in 12% of genome per individual
- Microsatellite instability in 15% of colorectal cancers
- Haplotype blocks average 22 kb in Europeans
- Fst genetic differentiation between continents averages 0.11
- Mitochondrial haplogroups divide populations with 50% variance
- Y-chromosome haplogroups show 80% population structure
- Runs of homozygosity >1Mb in 10% of outbred individuals
- Segmental duplications cover 5% of human genome
- Karyotype abnormalities occur in 0.5-1% of newborns
- Trinucleotide repeats expand in 40+ disorders like Huntington's
- Somatic mutations accumulate 10^4 per cell per year post-puberty
- Driver mutations in cancer average 2-8 per tumor
Genetic Variation Interpretation
Hidden within our seemingly uniform human blueprint lies a riotous carnival of variation, where our common 0.1% differences orchestrate everything from disease resistance and ancestry tales to the chaotic mutational dice-roll of cancer.
Genome Structure
- The human genome consists of approximately 3.1 billion base pairs of DNA
- There are about 20,000-25,000 protein-coding genes in the human genome
- Non-coding RNA genes make up around 10% of the human genome
- The human genome has over 3 million single nucleotide polymorphisms (SNPs)
- Introns account for approximately 25% of the human genome
- The average gene density in the human genome is one gene per 100,000 base pairs
- Euchromatin regions comprise about 92% of the human genome
- The human genome contains around 1,800 ribosomal RNA genes
- Telomeres in humans consist of 5-15 kilobases of TTAGGG repeats
- Centromeres in human chromosomes average 1-4 Mb in size
- The Y chromosome is the smallest human chromosome with about 59 million base pairs
- Chromosome 1 is the largest human chromosome with 249 million base pairs
- Mitochondrial DNA in humans is 16,569 base pairs long
- The human genome has approximately 200,000 copy number variations (CNVs)
- Pseudogenes number around 14,000 in the human genome
- The haploid human genome size is 3,054,815,472 base pairs according to GRCh38
- Repeat elements constitute 50% of the human genome
- Alu elements number over 1 million in the human genome
- LINE-1 elements make up 17% of the human genome
- The human genome has 23 pairs of chromosomes
- Exons comprise only 1.5% of the human genome
- The p53 gene spans 20 kb with 11 exons
- BRCA1 gene is 81 kb long with 24 exons
- The HOX gene cluster spans 100 kb on chromosome 17
- Immunoglobulin heavy chain locus is 1.25 Mb on chromosome 14
- The major histocompatibility complex (MHC) spans 3.6 Mb on chromosome 6
- The alpha-globin gene cluster is 28 kb on chromosome 16
- Beta-globin locus control region is 10 kb upstream
- The dystrophin gene is the largest known human gene at 2.4 Mb
- Titin gene (TTN) has 363 exons and spans 282 kb
- The human genome has 19,000 lncRNA genes
Genome Structure Interpretation
While humanity's grand genetic library is composed of 3.1 billion letters, its most vital instructions—the protein-coding genes—are astonishingly sparse and scattered, comprising a mere fraction of the text, with the vast majority of our DNA serving as a complex, bustling regulatory apparatus, repetitive historical archive, and evolutionary playground that we are only just beginning to translate.
Genomic Databases
- The 1000 Genomes Project sequenced 2,504 individuals
- dbSNP database contains 1 billion+ variants as of 2023
- ENCODE project mapped functional elements in 1% then whole genome
- GENCODE annotates 59,000+ human genes
- ClinVar has 2 million+ variant pathogenicity assertions
- gnomAD aggregates variants from 807,162 exomes and 1.3 million genomes
- UCSC Genome Browser hosts 50+ assemblies
- Ensembl database covers 500+ species
- RefSeq has 300,000+ reference sequences
- GTEx portal analyzes eQTLs from 49 tissues in 948 donors
- Roadmap Epigenomics profiled 111 reference epigenomes
- 100,000 Genomes Project sequenced 85,000 cancer and rare disease genomes
- UK Biobank genotyped 500,000 participants
- All of Us Research Program aims for 1 million diverse genomes
- TCGA analyzed 11,000+ tumor samples across 33 cancers
- ICGC sequenced 2,500 cancer genomes initially
- GEO database has 5 million+ samples
- SRA stores 40 petabases of sequencing data
- COSMIC catalogs 37 million coding mutations in cancer
- OMIM documents 8,000+ Mendelian disorders
- GWAS Catalog lists 6,000+ studies with 250,000+ associations
- STRING database has 2.4 billion interactions for 12,000 species
- Reactome pathways number 2,800 for human
- KEGG has 18,000 pathways across organisms
- Pfam database classifies 19,000 families
- UniProt has 570,000 reviewed protein entries
- PDB structures 200,000+ macromolecular structures
- AlphaFold predicted structures for all 20,000 human proteins
- Human Protein Atlas maps 20,000 proteins in 47 tissues
- DepMap CRISPR screens 1,000+ cancer cell lines
- CCLE profiles genomics of 1,400 cancer cell lines
Genomic Databases Interpretation
In the breathtakingly complex library of human biology, we have now moved from carefully reading a few chosen sentences to attempting, with a mix of hope and hubris, to scan every footnote, cross-reference, and coffee stain across millions of volumes, all while trying to translate the text into something that might actually help someone.
Sequencing Technology
- Whole genome sequencing cost was $2.7 billion for the Human Genome Project in 2003
- By 2023, the cost of human genome sequencing dropped to $562
- Illumina NovaSeq can sequence 20,000 genomes per year at 30x coverage
- Oxford Nanopore MinION reads up to 2.8 Gb per flow cell in 72 hours
- PacBio HiFi reads achieve 99.9% accuracy for 15-20 kb reads
- CRISPR-Cas9 editing efficiency reaches 80% in human cells
- Single-cell RNA-seq profiles 10,000+ cells per run with 10x Genomics
- Long-read sequencing assembles 99% of human genome including centromeres
- Third-generation sequencing error rate improved to <1% in 2022
- BGISEQ-500 sequences 75 Gb per run
- Ion Torrent S5 sequences 15 Gb in 7 hours
- Hi-C chromatin mapping captures 1 billion contacts per diploid genome
- Optical genome mapping detects 90% of SVs missed by short-reads
- Spatial transcriptomics resolves 1 μm resolution with Visium
- ATAC-seq identifies 100,000+ open chromatin regions per cell type
- ChIP-seq peaks average 500-1000 bp for histone marks
- RNA-seq detects 150,000 transcripts in human cells
- Whole exome sequencing covers 98% of coding regions at 20x depth
- Nanopore direct RNA sequencing reads full-length transcripts without fragmentation
- Linked-read sequencing phases 90% of human haplotypes
- Ultra-long reads >100 kb enable telomere-to-telomere assemblies
- Base editing efficiency >50% for C-to-T transitions
- Prime editing corrects 89% of mutations without DSBs
- Illumina iSeq 100 sequences 1.5 million reads per run
- Element Biosciences AVITI achieves Q40 accuracy
- MGI Tech DNBSEQ-T7 produces 12 Tb per run
Sequencing Technology Interpretation
The cost of reading the book of life has plummeted from a king's ransom to a paltry sum, while our tools now edit its pages with startling precision and assemble its most enigmatic chapters, proving that in genomics, the only thing shrinking faster than sequencing costs is the list of things we cannot do.
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