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Dominance and Recessivity

  1. Andrew OM Wilkie

Published Online: 27 JAN 2006

DOI: 10.1038/npg.els.0005475

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Wilkie, A. O. 2006. Dominance and Recessivity. eLS. .

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  1. University of Oxford, Oxford, UK

Publication History

  1. Published Online: 27 JAN 2006
Table 1. Classification of cellular mechanisms of dominance in human disorders (where possible, the examples are selected from the text or Tables 2 and 3)
Category of mutationMechanismAffected gene/proteinSelected disorder
Full names of gene and links to further information can be found on the Genew: Human Gene Nomenclature Database Search Engine (see Web links).
Loss of function   
HaploinsufficiencyMetabolic rate determining stepLDL receptorFamilial hypercholesterolemia
 Developmental regulatorTranscription factorsWaardenburg syndrome (PAX3), many developmental disorders
Gain of function: dominant negative   
Substrate sequestrationBinding by inactive monomerLigands, transcription factorsShort stature (GH1, POU1F1)
Dimer sequestrationFormation of inactive dimersReceptorsPiebaldism (KIT), insulin resistance (INSR)
Disruption of structureMissense substitutionCollagensOsteogenesis imperfecta, Stickler syndrome
Gain of function: dominant positive   
Increased gene dosageDuplicationPMP22Charcot–Marie–Tooth disease
 AmplificationOncogene productsMany tumors (MYC, RAS)
Altered mRNA expressionIncreased gene expressionγ HemoglobinHereditary persistence of fetal hemoglobin
 Alternative splicingWT1Frasier syndrome
 Toxic RNA inclusionsDMPKMyotonic dystrophy
Altered protein activityConstitutive activityIon channels, receptorsMyotonia congenita (CLCN1), McCune–Albright syndrome (GNAS)
 Increased binding affinityHemoglobinMethemoglobinemia
 Formation of toxic proteinsDiverseAmyloidosis (TTR, FGA), polyglutamine disorders (HD)
Novel protein activityAltered substrate specificityα1 AntitrypsinPittsburgh mutation (antithrombin activity)
 Chimeric protein (translocation)Transcription factorsAlveolar rhabdomyosarcoma (PAX3/FOXO1A)
Table 2. Cases of molecularly proven homozygosity for mutations showing dominant inheritance
GeneaOMIM NobDisorderHomozygous mutant phenotype more severe than heterozygote?
  1. a

    Full names of gene and links to further information can be found on the Genew: Human Gene Nomenclature Database Search Engine (see Web links).

  2. b

    See Online Mendelian Inheritance in Man (Web links).

BRCA1120160Familial breast cancerNo
HD143100Huntington diseaseNo
KRT5148040Epidermolysis bullosa simplexNo
MEN1131100Multiple endocrine neoplasia, type 1No
PRNP123400Familial Creutzfeldt–Jakob diseaseNo
TTR176300Familial amyloidotic polyneuropathyNo
CACNA1A601011Spinocerebellar ataxia type 6Yes
CASR601199Hypocalciuric hypercalcemiaYes
COL1A2120160Osteogenesis imperfectaYes
CRX602225Leber congenital amaurosis, cone rod dystrophy 2Yes
DRPLA125370Dentatorubralpallidoluysian atrophyYes
DMPK605377Myotonic dystrophyYes
EFEMP1601548Honeycomb retinal dystrophyYes
FBN1134797Marfan syndromeYes
FGFR3100800AchondroplasiaYes
GDF5601146Brachydactyly type C (AD), Grebe syndrome (AR)Yes
HOXD13186000SynpolydactylyYes
KRT14148066Epidermolysis bullosa simplexYes
LDLR143890Familial hypercholesterolemiaYes
MJD109150Machado–Joseph diseaseYes
PABPN1602279Oculopharyngeal muscular dystrophyYes
PAX3193500Waardenburg syndromeYes
PAX6106210AniridiaYes
PMP22601097Charcot–Marie–Tooth diseaseYes
ROR2602337Brachydactyly type B (AD), Robinow syndrome (AR)Yes
TRPS1604386Trichorhinophalangeal syndrome IYes
Table 3. Genes additional to those in Table 2 for which both heterozygous and homozygous mutations have been identified
GeneaOMIM NobDisease
  1. a

    Full names of gene and links to further information can be found on the Genew: Human Gene Nomenclature Database Search Engine (see Web links).

  2. b

    See Online Mendelian Inheritance in Man (Web links).

AD: autosomal dominant; AR: autosomal recessive.
ABCC6603234AD and AR pseudoxanthoma elasticum
ACTA1102610AD and AR nemaline myopathy
ALPL171760AD and AR hypophosphatasia
ANK1182900AD and AR hereditary spherocytosis
APOE107741AD and AR hyperlipoproteinemia
AQP2107777AD and AR diabetes insipidus
AVP192340AD and AR familial central diabetes insipidus
CLCN1118425AD and AR myotonia congenita
CHRNE100725AD and AR myasthenic syndromes
COL4A4120131Benign familial hematuria (AD), Alport syndrome (AR)
COL7A1120120AD and AR epidermolysis bullosa
COL11A2601868Stickler syndrome type III (AD), deafness (AD), otospondylomegaepimetaphyseal dysplasia (AR)
DES125660AD and AR desmin-related myopathy
EDAR604095AD and AR hypohidrotic ectodermal dysplasia
EVC604831Ellis–van Creveld syndrome (AR), Weyers acrodental dysostosis (AD)
FECH177000AD and AR erythropoietic protoporphyria
FGA134820Amyloidosis (AD), congenital afibrinogenemia (AR)
GCH1600225Progressive dystonia (AD), hyperphenylalaninemia (AR)
GH1139250AD and AR growth hormone deficiency
GJB2121011AD and AR deafness, Vohwinkel syndrome
GJB3603224AD and AR deafness, erythrokeratoderma variabilis
GLRA1138491AD and AR familial hyperekplexia
HBB141900AD and AR beta thalassemia
HF1134370AD and AR hemolytic uremic syndrome
INSR147670AD and AR insulin resistance, leprechaunism (AR)
KCNQ1192500Long QT syndrome (AD), Jervell and Lange–Nielsen syndrome (AR)
LHCGR152790Leydig cell hypoplasia with male pseudohermaphroditism (AD), male limited precocious puberty (AR)
LMNA150330AD and AR Emery–Dreifuss muscular dystrophy, dilated cardiomyopathy, familial partial lipodystrophy
MAT1A250850AD and AR methionine adenosyltransferase deficiency
MC4R155541AD and AR obesity
MYO7A276903AD nonsyndromic deafness, Usher syndrome type 1B (AR)
PMP22601097AD and AR Charcot–Marie–Tooth disease
POU1F1173110AD and AR combined pituitary hormone deficiency
PROC176860AD and AR thrombophilia
PTH168450AD and AR hypoparathyroidism
RGR600342AD and AR retinitis pigmentosa
RHO180380AD and AR retinitis pigmentosa
SERPING1106100AD and AR hereditary angioneurotic edema
SLC4A1109270Hereditary spherocytosis, renal tubular acidosis
SOD1147450AD and AR amyotrophic lateral sclerosis
TECTA602574AD and AR deafness
TG188450AD and AR congenital goiter
THRB190160AD and AR thyroid hormone resistance
TNFRSF6134637AD and AR lymphoproliferative syndrome
UROD176100AD porphyria cutanea tarda, AR hepatoerythropoietic, porphyria
VWF193400AD and AR von Willebrand disease