Genetic disorder is a pathological condition caused by an absent/defective gene or by a chromosomal aberration.
Humans have 30,000 genes that can involve in changes to their structure, causing diseases.
Hereditary disorders are diseases derived from parents.
caused by genetic mutations or variations passed down from one parent to their children.
genetic mutations may affect a single or multiple genes
Familial disorders are diseases transmitted in gametes through generations.
refers to diseases that runs in families but may not necessarily be caused by genetic mutations.
can result from environmental or lifestyle factors among the family members.
Congenital disorders are diseases present at birth.
Genetic disorder → there is a mutation
It implies that there are permanent changes in DNA.
Mutations affects:
Germ cells – transmitted to progeny
Somatic cells – not transmitted but causes cancers or malformations.
Point mutations or missense mutations are substitution of a single nucleotide base resulting in replacement of single amino acid in protein molecule
An example of point mutation is Sickle-cell anemia, where there is a mutation resulting in substitution of valine for glutamic acid at position 6 of ß-globin protein
Frameshift mutation is the insertion/deletion of one or two base pairs; changes DNA reading frame.
An example of Frameshift mutation is Tay-sach's disease, which is caused by a frameshift mutation in the hexagene
Trinucleotide repeat mutations are mutations where there are amplification of 3 sequential nucleotides.
Mendelian disorder results from mutation in single genes; diseases are hereditary and familial.
includes many uncommon conditions such as:
storage diseases
inborn errors of metabolism
Complex disorders involves multiple genes as well as environmental influences or sometime called multifactorial diseases.
includes some of the most common disorders of mankind:
hypertension
diabetes
allergic & autoimmune diseases
Chromosomal abnormalities are changes in the number or structure of chromosomes.
several rare developmental abnormalities are attributable to chromosomes alterations.
Mendelian disorder are diseases caused by single-gene defects and it follows mendelian pattern of inheritance
Autosomal Dominant disorders manifests heterozygous states (not AA/BB→ occurs at AB); there is a mutation of one allele.
at least one parent is affected, males/females; both can transmit.
enzyme proteins not affected but receptors and structural protein are involved; onset late sometimes.
In autosomal dominant disorder, if an affected person marries an unaffected individual, every child has a 50% chance of inheriting the disorder
Marfan syndrome is inherited and affects connective tissue; it most commonly affects heart, eyes, blood vessels, and skeleton.
Achondroplasia syndrome is a disorder of bone growth that prevent the changing of cartilage; particularly in bone of arms and legs.
characterized by dwarfism
limited range of motion at elbows
Nervous system autosomal dominant disorders:
Huntington’s disease
Neurofibromatosis
Myotonic dystrophy
Tuberous sclerosis
Urinary system autosomal dominant disorder:
Polycystic kidney disease
Gastrointestinal system autosomal dominant disorder:
Familial polyposis coli
Hematopoietic system autosomal dominant disorders:
Hereditary spherocytosis
Von Willebrand disease
Skeletal system autosomal dominant disorders:
Marfan syndrome
Ehlers-Danlos syndrome
Osteogenesis imperfecta
Achondroplasia
Metabolic system autosomal dominant disorders:
Familial hypercholesterolemia
Acute intermittent porphyria
Autosomal Recessive disorders are the largest group; both copies (allele) are mutated
parents asymptomatic (trait), children shows disease
siblings → 1 in 4 chance of being affected (25% risk)
possibility more in consanguineous marriage
males and females equally affected; early onset
involves enzyme proteins
Metabolic system autosomal recessive disorders:
Cystic fibrosis
PKU
Galactosemia
Homocystinuria
Lysosomal storage diseases
A1 – Antitrypsin deficiency
Wilson disease
Hemochromatosis
Glycogen storage diseases
Hematopoietic system autosomal recessive disorders:
Sickle cell anemia
Thalassemia
Endocrine system autosomal recessive disorder:
Congenital adrenal hyperplasia
Skeletal system autosomal recessive disorders:
Ehlers-Danlos syndrome (some variants)
Alkaptonuria
Nervous system autosomal recessive disorders:
Neurogenic muscular atrophies
Friedrich ataxia
Spinal muscular atrophy
X-linked disorders are sex-linked disorders
most are recessive.
transmitted by heterozygous females to their sons.
affected males do not transmit to sons, but daughters become carriers.
Duchenne muscular dystrophy is one of the severe forms of inherited muscular dystrophy; most common hereditary neuromuscular disease that does not exhibit predilection in any race or ethnicity.
Mutation in dystrophin gene leads to muscle fiber degeneration weakness
Musculoskeletal system X-linked disorder:
Duchenne muscular atrophy
Blood system X-linked disorders:
Hemophilia A & B
Chronic granulomatous disease
G6PD deficiency
Immune system X-linked disorders:
Agammaglobulinemia
Wiskott-Aldrich syndrome
Metabolic system X-linked disorders:
Diabetes insipidus
Lesch-Nyhan syndrome
Nervous system X-liked disorder:
Fragile X syndrome
Chromosomal abnormalities are genetic disorders caused by changes in the number structure of chromosomes.
these changes can occur spontaneously during cell division or can be inherited from one or both parents.