6 Etiology of Diseases

• 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.