A
single-gene disorder (or
monogenic disorder) is the result of a single
mutated gene. 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, the common form of
dwarfism,
achondroplasia, is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe and usually lethal skeletal disorder, one that achondroplasics(ones affected with achondroplasia) could be considered carriers for.
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. When a couple where one partner or both are affected 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. Most congenital
metabolic disorders known as
inborn errors of metabolism result from single-gene defects. Many such single-gene defects can decrease the fitness of affected people and are therefore present in the population in lower frequencies compared to what would be expected based on simple probabilistic calculations.
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. 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,
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
genetic carriers. Each parent with a defective gene normally do not have symptoms. 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. Some autosomal recessive disorders are common because, in the past, carrying one of the faulty genes led to a
slight protection against an infectious disease or
toxin such as
tuberculosis or
malaria. Such disorders include cystic fibrosis, sickle cell disease,
phenylketonuria and
thalassaemia. File:Autosomal recessive inheritance for affected enzyme.png|Hereditary defects in
enzymes are generally inherited in an autosomal fashion because there are more non-X chromosomes than X-chromosomes, and a recessive fashion because the enzymes from the unaffected genes are generally sufficient to prevent symptoms in carriers. Autosomal dominant inheritance for structural protein.png|On the other hand, hereditary defects in structural proteins (such as
osteogenesis imperfecta,
Marfan's syndrome and many
Ehlers–Danlos syndromes) are generally autosomal dominant, because it is enough that some components are defective to make the whole structure dysfunctional. This is a
dominant-negative process, wherein a mutated gene product adversely affects the non-mutated gene product within the same cell.
X-linked dominant showing an overview of the
human genome. It shows annotated
bands and sub-bands as used in the
nomenclature of genetic disorders. It shows 22
homologous chromosomes, both the female (XX) and male (XY) versions of the
sex chromosome (bottom right), as well as the
mitochondrial genome (to scale at bottom left). 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 (44+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), but his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected foetus with each pregnancy, although in cases such as incontinentia pigmenti, only female offspring are generally viable.
X-linked recessive X-linked recessive conditions are also caused by mutations in genes on the X chromosome. Males are much more frequently affected than females, because they only have the one X chromosome necessary for the condition to present. 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 (since they receive their father's Y chromosome), but his daughters will be carriers of 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 are carriers of one copy of the mutated gene. 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, is the rarest and applies to the 13 genes encoded by
mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only mothers (who are affected) 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 diseases (particularly when symptoms develop in early life) are actually caused by a
nuclear gene defect, as the mitochondria are mostly developed by non-mitochondrial DNA. These diseases most often follow autosomal recessive inheritance. == Multifactorial disorder ==