Complex Disorders Intro


Chromosomal Abnormalities

Changes in visible alteration of chromosome or abnormality produced by chromosomal abnormalities e.g. reduction of chromosome number during meiosis

1. Numerical

  • Triploid/tetraploid - lethal and not compatible with animal life
  • Aneuploidy - extra copy of one or more chromosomes due to nondisjunction during meiosis and can be compatible with animal life e.g. trisomy 21 results in Down's Syndrome

2. Structural

  • deletion
  • duplication
  • translocation - one part of chromosome moves to another) e.g. philedelphia (chr 9-22)
  • inversion -part on chromosome is reversed, occurs when undergoes breakage and rearranges within itself. Can be paracentric or pericentric

If occurs in egg/sperm = constitutional abnormality = all cells

If occurs later in life = somatic abnormalities = some cells (mosaicism) 

Mendelian Disorders

  • Rare, monogenic (caused by single gene),
  • Mendelian inheritance - recessive, dominant or sex linked,
  • Doesn't include de novo mutations or mosaics 
  • High penetrance - prophylactic intervention
  • Environment effect weak but mutation effect can be modulated by common genetic variant and environmental factors e.g. diet

Gene mutation:

  • Point Mutation - e.g. sickle cell anaemia mutation in HBB. Silent, missense (changes amino acid), nonsense (change to stop codon)
  • Deletion - e.g. cystic fibrosis deletion in CFTR 
  • Insertion - e.g. Huntington's disease CAG repeated up to x120

1.Somatic (body) cells - not transmitted to progeny (acquired mutation) but can cause malignant transformation and congenital diseases 

2. Gamete cells (germ cells) - transmitted to progeny (inherited mutation) can give rise to inherited disease

Mendel's Laws

Not valid for multifactorial complex disease

Law of Segregation - during gamete formation, the 2 alleles for each gene (locus) segregate from each other so that each gamete carries only one allele for each gene (locus)

Law of Independent Assortment - Alleles for different traits separate independently during the formation of gametes

Law of Dominance - Some alleles…


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