For a non-technical introduction to the topic, see Introduction to genetics.
|
|
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2008) |
| Genetic disorder |
| Classification and external resources |
| MeSH |
D030342 |
A genetic disorder is an illness caused by one or more abnormalities in the genome, especially a condition that is present from birth (congenital). Most genetic disorders are quite rare and affect one person in every several thousands or millions.
Genetic disorders are heritable, and are passed down from the parents' genes. Other defects may be caused by new mutations or changes to the DNA. In such cases, the defect will only be heritable if it occurs in the germ line. The same disease, such as some forms of cancer, may be caused by an inherited genetic condition in some people, by new mutations in other people, and by nongenetic causes in still other people.
Some types of recessive gene disorders confer an advantage in certain environments when only one copy of the gene is present.[1]
Contents
- 1 Single gene disorder
- 1.1 Autosomal dominant
- 1.2 Autosomal recessive
- 1.3 X-linked dominant
- 1.4 X-linked recessive
- 1.5 Y-linked
- 1.6 Mitochondrial
- 2 Multifactorial and polygenic (complex) disorders
- 3 Prognosis and treatment of genetic disorders
- 4 See also
- 5 References
- 6 External links
Single gene disorder[edit source | edit]
Prevalence of some single gene disorders[citation needed]
| Disorder prevalence (approximate) |
| Autosomal dominant |
| Familial hypercholesterolemia |
1 in 500 |
| Polycystic kidney disease |
1 in 1250 |
| Neurofibromatosis type I |
1 in 2,500 |
| Hereditary spherocytosis |
1 in 5,000 |
| Marfan syndrome |
1 in 4,000 [2] |
| Huntington's disease |
1 in 15,000 [3] |
| Autosomal recessive |
| Sickle cell anaemia |
1 in 625 |
| Cystic fibrosis |
1 in 2,000 |
| Tay-Sachs disease |
1 in 3,000 |
| Phenylketonuria |
1 in 12,000 |
| Mucopolysaccharidoses |
1 in 25,000 |
| Lysosomal acid lipase deficiency |
1 in 40,000
|
| Glycogen storage diseases |
1 in 50,000 |
| Galactosemia |
1 in 57,000 |
| X-linked |
| Duchenne muscular dystrophy |
1 in 7,000 |
| Hemophilia |
1 in 10,000 |
| Values are for liveborn infants |
A single gene disorder is the result of a single mutated gene. Over 4000 human diseases are caused by single gene defects. Single gene disorders can be passed on to subsequent generations in several ways. Genomic imprinting and uniparental disomy, however, may affect inheritance patterns. The divisions between recessive and dominant types are not "hard and fast", although the divisions between autosomal and X-linked types are (since the latter types are distinguished purely based on the chromosomal location of the gene). For example, achondroplasia is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe skeletal disorder of which achondroplasics could be viewed as carriers. Sickle-cell anemia is also considered a recessive condition, but heterozygous carriers have increased resistance to malaria in early childhood, which could be described as a related dominant condition.[4] When a couple where one partner or both are sufferers or carriers of a single gene disorder and wish to have a child, they can do so through in vitro fertilization, which means they can then have a preimplantation genetic diagnosis to check whether the embryo has the genetic disorder.[5]
Autosomal dominant[edit source | edit]
Main article: Autosomal dominant#Autosomal dominant gene
Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent.[6] The chance a child will inherit the mutated gene is 50%. Autosomal dominant conditions sometimes have reduced penetrance, which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease. Examples of this type of disorder are Huntington's disease,[7] neurofibromatosis type 1, neurofibromatosis type 2, Marfan syndrome, hereditary nonpolyposis colorectal cancer, and hereditary multiple exostoses, which is a highly penetrant autosomal dominant disorder. Birth defects are also called congenital anomalies.
Autosomal recessive[edit source | edit]
Main article: Autosomal dominant#Autosomal recessive allele
Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder. Examples of this type of disorder are Medium-chain acyl-CoA dehydrogenase deficiency, cystic fibrosis, sickle-cell disease, Tay-Sachs disease, Niemann-Pick disease, spinal muscular atrophy, and Roberts syndrome. Certain other phenotypes, such as wet versus dry earwax, are also determined in an autosomal recessive fashion.[8][9]
X-linked dominant[edit source | edit]
Main article: X-linked dominant
X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance pattern, with a prime example being X-linked hypophosphatemic rickets. Males and females are both affected in these disorders, with males typically being more severely affected than females. Some X-linked dominant conditions, such as Rett syndrome, incontinentia pigmenti type 2 and Aicardi syndrome, are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females. Exceptions to this finding are extremely rare cases in which boys with Klinefelter syndrome (47,XXY) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of a female in terms of disease severity. The chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will all be unaffected (since they receive their father's Y chromosome), and his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected fetus with each pregnancy, although it should be noted that in cases such as incontinentia pigmenti, only female offspring are generally viable. In addition, although these conditions do not alter fertility per se, individuals with Rett syndrome or Aicardi syndrome rarely reproduce.[citation needed]
X-linked recessive[edit source | edit]
Main article: X-linked recessive
X-linked recessive conditions are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. A woman who is a carrier of an X-linked recessive disorder (XRXr) has a 50% chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the mutated gene and are therefore carriers. X-linked recessive conditions include the serious diseases hemophilia A, Duchenne muscular dystrophy, and Lesch-Nyhan syndrome, as well as common and less serious conditions such as male pattern baldness and red-green color blindness. X-linked recessive conditions can sometimes manifest in females due to skewed X-inactivation or monosomy X (Turner syndrome).
Y-linked[edit source | edit]
Main article: Y linkage
Y-linked disorders are caused by mutations on the Y chromosome. Because males inherit a Y chromosome from their fathers, every son of an affected father will be affected. Because females only inherit an X chromosome from their fathers, and never a Y chromosome, female offspring of affected fathers are never affected.
Since the Y chromosome is relatively small and contains very few genes, relatively few Y-linked disorders occur.[citation needed] Often, the symptoms include infertility, which may be circumvented with the help of some fertility treatments. Examples are male infertility.[citation needed]
Mitochondrial[edit source | edit]
Main article: Mitochondrial disease
This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only mothers can pass on mitochondrial conditions to their children. An example of this type of disorder is Leber's hereditary optic neuropathy.
Multifactorial and polygenic (complex) disorders[edit source | edit]
Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified.
On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e.g., blood pressure).
- asthma
- autoimmune diseases such as multiple sclerosis
- cancers
- ciliopathies
- cleft palate
- diabetes
- heart disease
- hypertension
- inflammatory bowel disease
- mental retardation
- mood disorder
- obesity
- refractive error
- infertility
Prognosis and treatment of genetic disorders[edit source | edit]
|
This section requires expansion. (August 2010) |
See also: Huntington's disease clinical research
Genetic disorders rarely have effective treatments, though gene therapy is being tested as a possible treatment for some genetic diseases, including some forms of retinitis pigmentosa[10]
Gauchers disease is a genetic disease affecting metabolism. It is more treatable than most other genetic diseases, and can be treated with enzyme replacement therapy, medication (miglustat and imiglucerase), and bone marrow transplantion.[11]
See also[edit source | edit]
- Genetic epidemiology
- Inborn errors of metabolism
- List of genetic disorders
- Medical genetics
- Population groups in biomedicine
References[edit source | edit]
- ^ WGBH Educational Foundation
- ^ Keane MG, Pyeritz RE (May 2008). "Medical management of Marfan syndrome". Circulation 117 (21): 2802–13. doi:10.1161/CIRCULATIONAHA.107.693523. PMID 18506019.
- ^ Walker FO (2007). "Huntington's disease". Lancet 369 (9557): 218–28 [221]. doi:10.1016/S0140-6736(07)60111-1. PMID 17240289.
- ^ Williams T. N., Obaro S. K. (2011). "Sickle cell disease and malaria morbidity: a tale with two tails". Trends in Parasitology 27 (7): 315–320.
- ^ Kuliev A, Verlinsky Y (2005). "Preimplantation diagnosis: A realistic option for assisted reproduction and genetic practice". Curr. Opin. Obstet. Gynecol. 17 (2): 179–83. doi:10.1097/01.gco.0000162189.76349.c5. PMID 15758612. Retrieved 2009-04-01.
- ^ Griffiths, Anthony J.F.; Wessler, Susan R., Carroll, Sean B., Doebley, John (2012). "2". Introduction to Genetic Analysis (10 ed.). New York: W.H. Freeman and Company. p. 57. ISBN 978-1-4292-2943-8 .
- ^ Griffiths, Anthony J.F.; Wessler, Susan R., Carroll, Sean B., Doebley, John (2012). Introduction to Genetic Analysis (10 ed.). New York: W.H. Freeman and Company. p. 58. ISBN 978-1-4292-2943-8 .
- ^ Wade, Nicholas (January 29, 2006). "Japanese Scientists Identify Ear Wax Gene". New York Times.
- ^ Yoshiura K, Kinoshita A, Ishida T, et al. (March 2006). "A SNP in the ABCC11 gene is the determinant of human earwax type". Nat. Genet. 38 (3): 324–30. doi:10.1038/ng1733. PMID 16444273.
- ^ Retinitis Pigmentosa: Treatment & Medication~treatment at eMedicine
- ^ Gaucher's disease:Treatments and drugs, eMedicine WebMD, 2009-07-11, accessed 2010-03-31.
External links[edit source | edit]
- Public Health Genomics at CDC
- OMIM — Online Mendelian Inheritance in Man, a catalog of human genes and genetic disorders
- Genetic and Rare Diseases Information Center (GARD) Office of Rare Diseases (ORD), National Institutes of Health (NIH)
- CDC’s National Center on Birth Defects and Developmental Disabilities
- Genetic Disease Information from the Human Genome Project
- Global Genes Project, Genetic and Rare Diseases Organization
|
Personal genomics
|
|
| Data collection |
- Biobank
- Biological database
|
|
| Field concepts |
- Biological specimen
- De-identification
- Human genetic variation
- Genetic linkage
- Single-nucleotide polymorphisms
- Genetic disorder
|
|
| Applications |
- Personalized medicine
- Predictive medicine
- Genetic epidemiology
|
|
| Analysis techniques |
- Whole genome sequencing
- Genome-wide association study
- SNP array
|
|
| Major projects |
- Human Genome Project
- International HapMap Project
|
|
|
Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies
|
|
| (1) Basic domains |
1.2: Feingold syndrome · Saethre–Chotzen syndrome
1.3: Tietz syndrome
|
|
(2) Zinc finger
DNA-binding domains |
2.1 (Intracellular receptor): Thyroid hormone resistance · Androgen insensitivity syndrome (PAIS, MAIS, CAIS) · Kennedy's disease · PHA1AD pseudohypoaldosteronism · Estrogen insensitivity syndrome · X-linked adrenal hypoplasia congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis
2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome
2.3: Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome · MODY 7 · MRX 89 · Townes–Brocks syndrome · Acrocallosal syndrome · Myotonic dystrophy 2
2.5: Autoimmune polyendocrine syndrome type 1
|
|
| (3) Helix-turn-helix domains |
3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (MODY 4) · LMX1B (Nail–patella syndrome) · MSX1 (Tooth and nail syndrome, OFC5) · PITX2 (Axenfeld syndrome 1) · POU4F3 (DFNA15) · POU3F4 (DFNX2) · ZEB1 (Posterior polymorphous corneal dystrophy 3, Fuchs' dystrophy 3) · ZEB2 (Mowat–Wilson syndrome)
3.2: PAX2 (Papillorenal syndrome) · PAX3 (Waardenburg syndrome 1&3) · PAX4 (MODY 9) · PAX6 (Gillespie syndrome, Coloboma of optic nerve) · PAX8 (Congenital hypothyroidism 2) · PAX9 (STHAG3)
3.3: FOXC1 (Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type) · FOXC2 (Lymphedema–distichiasis syndrome) · FOXE1 (Bamforth–Lazarus syndrome) · FOXE3 (Anterior segment mesenchymal dysgenesis) · FOXF1 (ACD/MPV) · FOXI1 (Enlarged vestibular aqueduct) · FOXL2 (Premature ovarian failure 3) · FOXP3 (IPEX)
3.5: IRF6 (Van der Woude syndrome, Popliteal pterygium syndrome)
|
|
(4) β-Scaffold factors
with minor groove contacts |
4.2: Hyperimmunoglobulin E syndrome
4.3: Holt–Oram syndrome · Li–Fraumeni syndrome · Ulnar–mammary syndrome
4.7: Campomelic dysplasia · MODY 3 · MODY 5 · SF1 (SRY XY gonadal dysgenesis, Premature ovarian failure 7) · SOX10 (Waardenburg syndrome 4c, Yemenite deaf-blind hypopigmentation syndrome)
4.11: Cleidocranial dysostosis
|
|
| (0) Other transcription factors |
0.6: Kabuki syndrome
|
|
| Ungrouped |
TCF4 (Pitt–Hopkins syndrome) · ZFP57 (TNDM1) · TP63 (Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8)
|
|
| Transcription coregulators |
coactivator: CREBBP (Rubinstein–Taybi syndrome)
corepressor: HR (Atrichia with papular lesions)
|
|
see also transcription factors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, membrane: Solute carrier disorders
|
|
| 1-10 |
SLC1A3 (Episodic ataxia 6) · SLC2A1 (De Vivo disease) · SLC2A5 (Fructose malabsorption) · SLC2A10 (Arterial tortuosity syndrome) · SLC3A1 (Cystinuria) · SLC4A1 (Hereditary spherocytosis 4/Hereditary elliptocytosis 4) · SLC4A11 (Congenital endothelial dystrophy type 2, Fuchs' dystrophy 4) · SLC5A1 (Glucose-galactose malabsorption) · SLC5A2 (Renal glycosuria) · SLC5A5 (Thyroid dyshormonogenesis type 1) · SLC6A19 (Hartnup disease) · SLC7A7 (Lysinuric protein intolerance) · SLC7A9 (Cystinuria)
|
|
| 11-20 |
SLC11A1 (Crohn's disease) · SLC12A3 (Gitelman syndrome) · SLC16A1 (HHF7) · SLC16A2 (Allan–Herndon–Dudley syndrome) · SLC17A5 (Salla disease) · SLC17A8 (DFNA25)
|
|
| 21-40 |
SLC26A2 (Multiple epiphyseal dysplasia 4, Achondrogenesis type 1B, Recessive multiple epiphyseal dysplasia, Atelosteogenesis, type II, Diastrophic dysplasia) · SLC26A4 (Pendred syndrome) · SLC35C1 (CDOG 2C) · SLC39A4 (Acrodermatitis enteropathica) · SLC40A1 (African iron overload)
|
|
see also solute carrier family
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, membrane: cell surface receptor deficiencies
|
|
G protein-coupled receptor
(including hormone) |
| Class A |
- TSHR (Congenital hypothyroidism 1)
- LHCGR (Male-limited precocious puberty)
- FSHR (XX gonadal dysgenesis)
- EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
- AVPR2 (Nephrogenic diabetes insipidus 1)
- PTGER2 (Aspirin-induced asthma)
|
|
| Class B |
- PTH1R (Jansen's metaphyseal chondrodysplasia)
|
|
| Class C |
- CASR (Familial hypocalciuric hypercalcemia)
|
|
| Class F |
- FZD4 (Familial exudative vitreoretinopathy 1)
|
|
|
Enzyme-linked receptor
(including
growth factor) |
| RTK |
- ROR2 (Robinow syndrome)
- FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
- FGFR2 (Apert syndrome, Antley-Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson-Weiss syndrome)
- FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
- INSR (Donohue syndrome
- Rabson–Mendenhall syndrome)
- NTRK1 (Congenital insensitivity to pain with anhidrosis)
- KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
|
|
| STPK |
- AMHR2 (Persistent Mullerian duct syndrome II)
- TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
- TGFBR1/TGFBR2 (Loeys-Dietz syndrome)
|
|
| GC |
- GUCY2D (Leber's congenital amaurosis 1)
|
|
|
| JAK-STAT |
- Type I cytokine receptor: GH (Laron syndrome)
- CSF2RA (Surfactant metabolism dysfunction 4)
- MPL (Congenital amegakaryocytic thrombocytopenia)
|
|
| TNF receptor |
- TNFRSF1A (TNF receptor associated periodic syndrome)
- TNFRSF13B (Selective immunoglobulin A deficiency 2)
- TNFRSF5 (Hyper-IgM syndrome type 3)
- TNFRSF13C (CVID4)
- TNFRSF13B (CVID2)
- TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
|
|
| Lipid receptor |
- LRP: LRP2 (Donnai-Barrow syndrome)
- LRP4 (Cenani Lenz syndactylism)
- LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
- LDLR (LDLR Familial hypercholesterolemia)
|
|
| Other/ungrouped |
- Immunoglobulin superfamily: AGM3, 6
- Integrin: LAD1
- Glanzmann's thrombasthenia
- Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR Hypohidrotic ectodermal dysplasia)
- PTCH1 (Nevoid basal cell carcinoma syndrome)
- BMPR1A (BMPR1A Juvenile polyposis syndrome)
- IL2RG (X-linked severe combined immunodeficiency)
|
|
- See also
- cell surface receptors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders (E80.3, 277.86)
|
|
| Peroxisome biogenesis disorder |
- Zellweger syndrome
- Neonatal adrenoleukodystrophy
- Infantile Refsum disease
- Adult Refsum disease-2
- RCP 1
|
|
| Enzyme-related |
- Acatalasia
- RCP 2&3
- Mevalonate kinase deficiency
- D-bifunctional protein deficiency
- Adult Refsum disease-1
|
|
| Transporter-related |
- X-linked adrenoleukodystrophy
|
|
| Lysosomal |
|
|
See also: proteins, intermediates
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, organelle: Ciliopathy
|
|
| Structural |
- receptor: Polycystic kidney disease
- cargo: Asphyxiating thoracic dysplasia
- basal body: Bardet–Biedl syndrome
- mitotic spindle: Meckel syndrome
- centrosome: Joubert syndrome
|
|
| Signaling |
|
|
| Other/ungrouped |
- Alström syndrome
- Primary ciliary dyskinesia
- Senior–Løken syndrome
- Orofaciodigital syndrome 1
- McKusick–Kaufman syndrome
- Autosomal recessive polycystic kidney
|
|
See also: ciliary proteins
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, extracellular: scleroprotein disease (excluding laminin and keratin)
|
|
| Collagen disease |
COL1: Osteogenesis imperfecta · Ehlers–Danlos syndrome, types 1, 2, 7
COL2: Hypochondrogenesis · Achondrogenesis type 2 · Stickler syndrome · Marshall syndrome · Spondyloepiphyseal dysplasia congenita · Spondyloepimetaphyseal dysplasia, Strudwick type · Kniest dysplasia (see also C2/11)
COL3: Ehlers–Danlos syndrome, types 3 & 4 (Sack–Barabas syndrome)
COL4: Alport syndrome
COL5: Ehlers–Danlos syndrome, types 1 & 2
COL6: Bethlem myopathy · Ullrich congenital muscular dystrophy
COL7: Epidermolysis bullosa dystrophica · Recessive dystrophic epidermolysis bullosa · Bart syndrome · Transient bullous dermolysis of the newborn
COL8: Fuchs' dystrophy 1
COL9: Multiple epiphyseal dysplasia 2, 3, 6
COL10: Schmid metaphyseal chondrodysplasia
COL11: Weissenbacher–Zweymüller syndrome · Otospondylomegaepiphyseal dysplasia (see also C2/11)
COL17: Bullous pemphigoid
|
|
| Laminin |
Junctional epidermolysis bullosa · Laryngoonychocutaneous syndrome
|
|
| Other |
Congenital stromal corneal dystrophy · Raine syndrome · Urbach–Wiethe disease · TECTA (DFNA8/12, DFNB21)
|
|
see also fibrous proteins
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
