INHERITED v ACQUIRED
Genetic disorders are usually inherited. However, if somebody has relatives with
the same medical disorder it does not mean that it has been inherited. People
within the same family can share the same medical disorder because they have
similar environmental factors. Genetic disorders can also be acquired in people
that have no relatives with that genetic disorder. So the fact that somebody
does or does not have relatives with the same medical disorder is no guide to
whether their medical disorder is genetic. Nobody really knows whether or not
their medical disorder is genetic until it is specifically tested.
Genetic disorders usually have effect due to the the faulty formation of
proteins. Proteins are essential for the body to carry out virtually all
biological functions in the body. Enzymes are one type of protein that
facilitate biochemical reactions in the body. Some hormones are proteins that
stimulate or reduce biochemical functions.
Proteins are a chain of amino acids just like pearl necklaces are a chain of
pearls, such as in the following example : Tyr-Ser-Phe-Pro-Cys-Thr
When there is a genetic disorder, instead of producing the above example, the
following faulty version may be produced instead :Tyr-Ser-Phe-Glu-Cys-Thr
One amino acid, in this case Proline (Pro), is replaced by another amino
instead, in this case Glutamic Acid (Glu).
EFFECTS OF GENETIC DISORDERS
Although there is often not much difference in the faulty protein that is
formed, this can be enough to bring a biochemical function to a complete halt.
Some genetic disorders can cease a biochemical function completely, from birth
until death. Soome genetic disorders will make a medical disorder more likely
but not inevitable. Some genetic disorders will cause no problem at all.
Judging from the faults caused by genetic Parkinson's Disease, it appears likely
that somebody will either be more inclined to develop Parkinson's Disease, or
for Parkinson's Disease to have more effect when it is developed. In theory at
least it does not appear as if causes Parkinson's Disease inevitably or
Those fault genes know to affect Parkinson's Disease are : PARK 2 (Parkin), PARK
6 (PINK 1), PARK 7 (DJ-1), SNCA, LRRK2, UCHL1, SNCAIP, GBA, NR4A2, CYP2D6, PARK
3; PARK 4, PARK 8, PARK 10 and PARK 11.
PARK1 (OMIM #168601), caused by mutations in the SNCA gene, which codes for the
protein alpha-synuclein. PARK1 causes autosomal dominant Parkinson disease.
So-called PARK4 is probably caused by triplication of SNCA.
PARK2 (OMIM #602544), caused by mutations in protein parkin. Parkin mutations
may be one of the most common known genetic causes of early-onset Parkinson
disease. In one study, of patients with onset of Parkinson disease prior to age
40 (10% of all PD patients), 18% had parkin mutations, with 5% homozygous
mutations. Patients with an autosomal recessive family history of
parkinsonism are much more likely to carry parkin mutations if age at onset is
less than 20 (80% vs. 28% with onset over age 40). Patients with parkin
mutations (PARK2) do not have Lewy bodies. Such patients develop a syndrome that
closely resembles the sporadic form of PD; however, they tend to develop
symptoms at a much younger age.
PARK3 (OMIM #602404), mapped to 2p, autosomal dominant, only described in a few
PARK5, caused by mutations in the UCHL1 gene (OMIM #191342) which codes for the
protein ubiquitin carboxy-terminal hydrolase L1
PARK6 (OMIM #605909), caused by mutations in PINK1 (OMIM #608309) which codes
for the protein PTEN-induced putative kinase 1.
PARK7 (OMIM #606324), caused by mutations in DJ-1 (OMIM #602533)
PARK8 (OMIM #607060), caused by mutations in LRRK2 which codes for the protein
dardarin. In vitro, mutant LRRK2 causes protein aggregation and cell death,
possibly through an interaction with parkin. LRRK2 mutations, of which the
most common is G2019S, cause autosomal dominant Parkinson disease, with a
penetrance of nearly 100% by age 80. G2019S is the most common known genetic
cause of Parkinson disease, found in 1-6% of U.S. and European PD patients.
It is especially common in Ashkenazi Jewish patients, with a prevalence of 29.7%
in familial cases and 13.3% in sporadic.
PARK12 (OMIM #300557), maps to the X chromosome