A guide to DNA
What DNA is, how it is inherited, what a SNP means in a person, and how to look up a variant without uploading a genome.
DNA itself
What is DNA?
DNA is a four-letter molecule cells copy. A pairs with T, C with G. Most of it is not a gene.
What is a gene?
A gene is a usable stretch of DNA. Humans have about 20,000 protein-coding genes.
What is a genome?
A genome is the full genetic library: nuclear DNA plus a small mitochondrial circle.
Human chromosomes
Human chromosomes pack DNA into 23 pairs. Autosomes 1 to 22, plus X and Y.
How genetic inheritance works
You inherit two copies of most genes. Mendel helps. Most traits still are not Mendelian.
Genotype vs phenotype
Genotype is the DNA you carry. Phenotype is the trait a body actually shows.
What is a SNP?
A SNP is a one-letter DNA difference with a public name. A chip samples it. That is not a diagnosis.
Mutation vs variant
Mutation vs variant: NIH and ClinVar prefer variant. Pathogenic is a submitted label, not a sentence about you.
Types of DNA tests
Types of DNA tests, from ancestry chips to whole genomes. A 23andMe file is not a BRCA test.
Ancestry DNA vs health DNA
Ancestry DNA vs health DNA: one kit, two questions. Ethnicity is a model. Health reports are not clinical care.
Mitochondrial DNA
Mitochondrial DNA is a 16.5 kb maternal genome with 37 genes. A haplogroup is not your whole ancestry.
How to read your DNA
How to read your DNA: rsID, two letters, homozygous vs heterozygous, and public lookup without uploading the file.
Look up identifiers
How to look up an rsID
Query dbSNP, ClinVar, and gnomAD for an rsID without uploading a genome.
Query ClinVar command line
Query ClinVar from the terminal with a local index instead of a web scrape.
gnomAD allele frequency lookup
Look up gnomAD allele frequency by rsID on the CLI or the open REST API.
Genetic variant REST API
Open REST API for rsIDs, genes, and coordinates. No key. No VCF upload.
What is an rsID?
An rsID is dbSNP’s cluster id for a variant site, not the letters you carry.
Files on this machine
Annotate a VCF locally
Annotate a VCF locally through ClinVar and gnomAD, with no cloud upload.
What is a VCF file?
VCF is the standard variant table: one row per site, genotypes in sample columns.
Interpret 23andMe raw data locally
Look up 23andMe rsIDs in ClinVar on disk. The export never has to leave the tab.
DNA analysis without upload
Analyze a VCF or 23andMe file on disk. Public rsID lookup stays separate.
Read the annotations
ClinVar clinical significance, explained
Read ClinVar clinical significance with review status, not only Pathogenic.
ClinVar vs gnomAD
ClinVar vs gnomAD: submitted significance versus population allele frequency.
HGVS notation explained
HGVS notation explained: c. and p. expressions, transcripts, and genome.sh queries.
AlphaMissense pathogenicity scores
AlphaMissense pathogenicity scores next to ClinVar and gnomAD, not instead of them.
PharmGKB pharmacogenomics lookup
PharmGKB pharmacogenomics lookup for rsIDs. Annotation, not a dosing engine.
Known variants
BRCA1 variant lookup
BRCA1 variant lookup in ClinVar: gene catalog versus rsID. Not a clinical BRCA test.
HFE rs1800562 rs1799945
Look up HFE rs1800562 (C282Y) and rs1799945 (H63D). Not a hemochromatosis diagnosis.
APOE rs429358
Look up APOE rs429358 and rs7412. Haplotypes, frequency, privacy. Not a diagnosis.
rs334 sickle cell
Look up rs334 sickle cell (HBB Glu6Val) in ClinVar. Worked CLI example, not a diagnosis.
Compared with other tools
Install and pipe
genome.sh reports public annotations. It is informational software, not a medical device or a substitute for clinical care.