Genetic Disease- Categories, Inheritance, Patterns and Impact

genes interacting with environment

• balance of genetic and environmental factors

• e.g. stroke→ multifactorial with environment and polygenic factors

Cadasil

• single gene mutation causes predisposition to cerebrovascular disease

  • cerebral

  • autosomal

  • dominant

  • arteriopathy with

  • subcortical

  • infarcts and

  • leukoencephalopathy (Cadasil)

classification by genetic mechanism

• single gene→ mutation in a single gene

• somatic mutations→ postzygotic mutations occurring in a somatic cell

• chromosomal→ imbalance or rearrangement in chromosome number or structure

• multifactorial→ multiple genes interact w environmental factors

single gene modes of inheritance

• autosomal dominant

• autosomal recessive

• X-linked

• mitochondrial

autosomal dominant conditions

• Marfan Syndrome

• Huntington disease

• myotonic disease

penetrance

• frequency with which a specific genotype results in a phenotype, usually a percentage

expressivity

extent to which a heritable trait is manifested by an individual

anticipation

• symptoms of a genetic disorder become apparent at an earlier age as it is passed from one generation to the next

• may also be an increase in severity of symptoms

autosomal recessive conditions

• sickle cell disease (HBB)

• cystic fibrosis (CFTR)

• haemochromatosis (HFE)

• many of the metabolic disorders

  • often enzyme loss

X-linked inheritance

• cannot have male to male transmission

• if recessive:

  • only males affected

  • females unaffected carriers

• if dominant:

  • females affected→ mildly to fully affected

  • males often more sever than females

X-inactivation

• random inactivation of the X chromosomes in cells with more than one X chromosome

• compensates for presence of double X gene dosage

XL dominant conditions

• rare

• lethal in males, phenotype only in females

  • rett syndrome

  • orofaciodigital syndrome

• phenotype in females, silent in males

  • craniofrontonasal syndrome

mitochondrial inheritance

• 16-kb circular genome

• 27 genes

• inherited from mother

mosaicism

• new mutation occurring somatically

  • distribution of mutant cells unpredictable

signs used in family pedigree