Genetic disorder

Genetic disorder
Drill.jpg
A boy with Down syndrome, one of the most common genetic disorders
Classification and external resources
SpecialtyMedical genetics
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D030342

A genetic disorder is a genetic problem caused by one or more abnormalities in the genome. Most genetic disorders are quite rare and affect one person in every several thousands or millions.[citation needed]

Genetic disorders may be hereditary, meaning that they are passed down from the parents' genes. In other genetic disorders, defects may be caused by new mutations or changes to the DNA. In such cases, the defect will only be passed down if it occurs in the germline.

Some types of recessive gene disorders confer an advantage in certain environments when only one copy of the gene is present.[1]

Single-gene

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 (or monogenic) disorder is the result of a single mutated gene. Over 6000 human diseases are caused by single-gene defects.[4] 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.[5] When a couple where one partner or both are sufferers or carriers of a single-gene disorder wish to have a child, they can do so through in vitro fertilization, which enables preimplantation genetic diagnosis to occur to check whether the embryo has the genetic disorder.[6]

Most congenital metabolic disorders known as inborn errors of metabolism result from single-gene defects.

Autosomal dominant

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.[7] 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,[8] neurofibromatosis type 1, neurofibromatosis type 2, Marfan syndrome, hereditary nonpolyposis colorectal cancer, hereditary multiple exostoses (a highly penetrant autosomal dominant disorder), Tuberous sclerosis, Von Willebrand disease, and acute intermittent porphyria. Birth defects are also called congenital anomalies.

Autosomal recessive

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% risk with each pregnancy of having a child affected by the disorder. Examples of this type of disorder are Albinism, 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.[9][10]

Human chromosome diseases set en.svg

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 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

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

Y-linked disorders are caused by mutations on the Y chromosome. These conditions may only be transmitted from the heterogametic sex (e.g. male humans) to offspring of the same sex. More simply, this means that Y-linked disorders in humans can only be passed from men to their sons; females can never be affected because they do not possess Y-allosomes.

Y-linked disorders are exceedingly rare but the most well-known examples typically cause infertility. Reproduction in such conditions is only possible through the circumvention of infertility by medical intervention.

Mitochondrial

This type of inheritance, also known as maternal inheritance, applies to genes encoded by mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only mothers can pass on mitochondrial DNA conditions to their children. An example of this type of disorder is Leber's hereditary optic neuropathy. It is important to stress that the vast majority of mitochondrial disease (particularly when symptoms develop in early life) is actually caused by an underlying nuclear gene defect, and most often follows autosomal recessive inheritance.[citation needed]

Other Languages
العربية: اضطراب جيني
Deutsch: Erbkrankheit
한국어: 유전성 질환
Bahasa Indonesia: Penyakit genetik
עברית: פגם גנטי
lietuvių: Genetinė liga
Bahasa Melayu: Gangguan genetik
日本語: 遺伝子疾患
português: Anomalia genética
Simple English: Genetic disorder
Basa Sunda: Cacad génétik
українська: Генетичні хвороби
Tiếng Việt: Bệnh di truyền