Multifactorial Disorders
Researchers suspect many health conditions arise
as a result of an interplay between genetic and
environmental factors. Geneticists call such condi-
tions multifactorial disorders because it appears a
certain combination of events must take place for
disease to result; doctors may refer to them as
conditions of GENETIC PREDISPOSITION. These are the
conditions that tend to run in families; some fam-
ily members develop them and others do not.
Health conditions in which genetics, lifestyle, and
other variables participate in the development of
disease are numerous. Some of those that are
common include CORONARY ARTERY DISEASE(CAD),
HYPERTENSION(high BLOOD PRESSURE), CANCER, DIA-
BETES, GALLBLADDER DISEASE, and NEPHROLITHIASIS
(kidney stones), and numerous other conditions.
Mitochondrial Disorders
Mitochondria are self-replicating structures within
a cell (called organelles) that carry out the meta-
bolic functions of the cell. Mitochondria have
their own DNAthat directs their specific functions,
and have multiple copies; MITOCHONDRIAL DNA
(MTDNA) is different from the cell’s nuclear DNA.
MITOCHONDRIAL DISORDERS, which are the rarest of
the genetic disorders, occur when the genes that
encode mitochondrial activity contain mutations
or when there are defects in the mtDNA. Mito-
chondrial disorders tend to vary widely among
individuals, causing different symptoms because
they affect different, and usually multiple, organs
or structures. Doctors define the disorder as a
complex of symptoms. Some forms of
ENCEPHALOPATHY, MYOPATHY, and CARDIOMYOPATHYare
mitochondrial disorders.
See also CONGENITAL ANOMALY; INHERITANCE PAT-
TERNS; MOSAICISM.
genetic imprinting The inactivation of certain
genes, determined by whether the GENEis mater-
nal (comes from the mother) or paternal (comes
from the father). Genetic imprinting, also called
genomic imprinting, appears to be another
method of controlling genes by requiring one copy
of each of certain chromosomes from each parent.
INHERITANCE PATTERNS, which establish gene
expression through dominance, regulate most
gene expression and normally present paired
chromosomes that determine which traits are
expressed in the PHENOTYPE. However, it is possible
for mutations to occur that result in both sets of a
particular chromosome coming from the same
parent (uniparental disomy). Though such muta-
tions likely occur with no noticeable effect and
thus remain undetected, they can allow rare
recessive abnormalities to be expressed.
Though rare, the CHROMOSOMAL DISORDERS
Prader-Willi syndrome and Angelman syndrome
represent the most common pathology of genetic
imprinting. These syndromes reflect uniparental
disomy of CHROMOSOME15, one of the chromo-
somes known to incorporate genetic imprinting.
Chromosome 15 regulates numerous neurologic
and musculoskeletal structures and functions that
affect intelligence, cognition (the ability to think,
reason, and remember), behavior, emotion, physi-
cal appearance, MUSCLE tone, movement, and
METABOLISM as well as reproductive health and
capability.
Normal development requires one copy of
chromosome 15 from each parent. When both
copies of chromosome 15 are maternal (called
paternal deletion), genetic imprinting produces a
constellation of symptoms known as Prader-Willi
syndrome. When both copies of chromosome 15
are paternal (called maternal deletion), genetic
imprinting produces a constellation of symptoms
known as Angelman syndrome. Each syndrome
presents differing manifestations of neurologic
dysfunction, musculoskeletal and other physical
anomalies, and intellectual impairment.
Researchers believe genetic imprinting is a
mechanism intended to prevent damaging muta-
tions from propagating (extending themselves).
Genetic imprinting appears to affect only certain
chromosomes and, when it causes a disease state,
results in related though differing symptoms,
depending on the deletion.
See also CELL STRUCTURE AND FUNCTION.genetic predisposition The tendency to develop
a health condition as a consequence of the inter-
action between genetics and lifestyle factors. Doc-
tors believe genetic influences underlie many if
not all health conditions that develop over time,
such as HYPERTENSION(high BLOOD PRESSURE), ATHER-
OSCLEROSIS, OSTEOARTHRITIS, RENAL FAILURE, LIVERdis-genetic predisposition 129