The short version
Short, plain definitions for the terms used in the GEN series. If a term is missing, it should be added here with a one-line definition and linked from the article that uses it.
Terms
| Term | Plain-English meaning |
|---|---|
| AADC (aromatic L-amino acid decarboxylase; gene DDC) | The enzyme that turns L-DOPA into dopamine |
| Allele | One version of a gene or DNA variant. You have two copies of most genes, one from each parent |
| Autosomal dominant | One changed copy is enough to cause the condition |
| Autosomal recessive | Two changed copies are needed; parents are usually unaffected carriers |
| Basal ganglia | Deep brain structures involved in movement and habit, and heavily dependent on dopamine |
| BH4 (tetrahydrobiopterin) | A helper molecule that tyrosine hydroxylase needs to make L-DOPA. The enzyme GCH1 controls the rate-limiting step of making it |
| Candidate gene | A gene chosen in advance because it seemed plausible. Studies of candidate genes are older and less reliable than genome-wide ones |
| Carrier | Someone who has a changed copy of a gene |
| CNV (copy-number variant) | A stretch of DNA that is missing or repeated |
| De novo | New in a person, not inherited from either parent |
| DAT (dopamine transporter; gene SLC6A3, old name DAT1) | The protein that pulls dopamine back into the cell after release |
| Differential diagnosis | The list of conditions a clinician is weighing and needs to rule in or out |
| Dystonia | Sustained or repeated muscle contractions that cause twisting movements or abnormal postures |
| Dopa-responsive dystonia (DRD) | A group of conditions, often involving the GCH1 or TH genes, in which symptoms improve markedly with low-dose levodopa |
| Effector gene | The gene in a risk region that is thought to actually drive the effect. Proposed by computer methods and needs confirmation |
| Exome | The protein-coding parts of the genome |
| Expressivity | How strongly or in what way a variant shows up in a person |
| GWAS (genome-wide association study) | A study that scans the whole genome in many people to find common DNA differences linked to a trait |
| Heritability | The proportion of differences in a trait across a population that is explained by genetic differences. It is not the proportion of any one person's condition |
| Heterozygous | Having one changed copy and one typical copy of a gene |
| Homozygous | Having two identical copies of a variant |
| HSP (hereditary spastic paraplegia) | A group of inherited conditions causing progressive stiffness and weakness in the legs |
| Liability | An underlying tendency toward a condition, spread across a population. Diagnosis is thought of as the point where liability passes a threshold |
| Levodopa (L-DOPA) | The precursor that the body converts to dopamine. Used as a medicine and as a diagnostic clue |
| Locus (plural loci) | A region of DNA |
| MAO / COMT | Enzymes that break down dopamine and related chemicals |
| Penetrance | The share of carriers who develop the condition. "Reduced penetrance" means some carriers never do |
| Pharmacogenomics | The study of how genes change the way the body handles a drug |
| Polygenic | Influenced by many genes, each with a small effect |
| Polygenic score (PGS) | A number that adds up many small DNA effects into one risk estimate for a person |
| Proband | The first person in a family to be identified with a condition |
| Rate-limiting step | The slowest step in a chain, which sets the pace of the whole pathway |
| SNP (single-nucleotide polymorphism) | A change in a single DNA letter that is common in the population |
| SNP heritability | The share of heritability explained by common variants |
| Spasticity | Muscle stiffness caused by a fault in the nervous-system control of muscle tone, often with exaggerated reflexes |
| TH (tyrosine hydroxylase) | The rate-limiting enzyme in dopamine production |
| Trio | A child and both parents sequenced together, to find new (de novo) variants |
| Twin study | Comparing identical with non-identical twins to estimate how much of a trait is genetic |
| V-ATPase | A pump that uses ATP to build a proton gradient across a vesicle's membrane. VMAT2 uses that gradient to pack dopamine into the vesicle |
| Variant | A difference in DNA from the typical sequence |
| VMAT2 (vesicular monoamine transporter 2; gene SLC18A2) | The protein that loads dopamine, serotonin and noradrenaline into storage vesicles |
| VNTR | A stretch of DNA made of a repeating unit. The number of repeats varies between people. DAT1 and DRD4 have well-known ones |
| VUS (variant of uncertain significance) | A DNA change where there is not enough evidence to call it harmful or harmless. Not a diagnosis |
| Vesicle | A tiny bubble inside a nerve cell that stores chemical messengers ready for release |
Limits
Definitions are simplified for readability. Where a term has a precise technical definition, the source article gives it.
Sources
Definitions are standard genetics and pharmacology terms. Where a definition depends on a specific paper, see the article that uses it (GEN-01 to GEN-10).