Genetics 2 - Inheritance Patterns

• Gregor mendel:

  • Studied pea plant genetics in the 1800s
  • identified inheritance of traits - dominant & recessive
• What is a gene?

  Discrete factor of inheritance
• Allele - different forms of a gene
• Homozygote - Having the same allele of a gene
• Heterozygote - having 2 different alleles of a gene
• genotype - combination of alleles
• phenotype - appearance of a trait
• Dominant - Phenotype that suppresses another trait
• Recessive - Phenotype that is suppressed by a dominant phenotype
• Mendel's first law - Segregation

  • Each inherited trait is defined by a gene pair
  • later identified as chromosomal pairs, one allele from each parent
• Mendel’s second law - Independent assortment

  • Genes for different traits are sorted separately so inheritance of one trait is not dependent on another
• Mendel’s third law - Dominance

  • Organisms with alternate forms of a gene present only the dominant phenotype
  • e.g. dark hair, curly hair
• Pedigree symbols

  A) unaffected male

  B) unaffected female

  C) sex unspecified

  D) affected male

  E) affected male

  F) deceased

  G) carrier of condition

  H) partial affected carrier

  I) propositus

  
• Pedigree diagram symbols

  A) mating

  B) siblings

  C) identical twins

  D) consanguineous mating

  E) non-identical twins

  
• Autosomal Dominant

  • Affected person has a parent who is affected
  • 50% offspring affected
  • Affects males and females equally
  • e.g. Huntington disease & Marfan syndrome

  
• X-linked Dominant

  • Affected mother -> 50% offspring affected
  • Affected father -> No male offspring affected & All female offspring affected
  • e.g. fragile X syndrome

  
• Autosomal recessive

  • Both parents need to be carriers
  • 50% of offspring affected
  • e.g. cystic fibrosis, sickle cell anaemia, Tay-sachs disease

  
• X-linked recessive

  • Mother is a carrier -> 50% of offspring affected
  • For male to be affected only mother needs to be affected
  • For affected female -> both parents must be affected
  • can skip generations
  • e.g. Hemophilia, Fabry disease

  
• Y - linked

  • Y chromsome is affected
  • only males are affected
  • affected father -> 100 % of male offspring affected
• Exceptions to inheritance rules

  • Multiple mutations -> same condition
  • environmental triggers
  • changes in chromosome number/structure
  • e.g. type 2 diabetes, schizophrenia and certain types of cancer
• Obligate carriers

  • Known (from pedigree analysis) to possess a disease-causing gene
  • May not be affected with the disease phenotype
• Incomplete penetrance

  • Some disease gene carriers not exhibiting the phenotype due to variable expressivity, calculated by looking at family history
  • Age-Dependent Penetrance - phenotype expresses in older age and there is an increased frequency in population e.g. Huntington's
• Mitochondrial

  • Inherited from the mother (via egg)
  • Affected mother’s children are all affected
  • Many different diseases
  • e.g. Leber hereditary optic neuropathy (LHON) & Neuropathy, ataxia & retinitis pigmentosa (NARP)
  • Mitochondria can be replaced via transplant of DNA/Nucleus into a healthy egg
• Consanguinity

  • Mattings between relatives
  • Often produce offspring with genetic diseases (autosomal recessive disorders
  • Estimated that every person has 1-5 recessive mutations that would be lethal to offspring if matched with another copy of the mutation
• The rarer the recessive disease, the more likely the parents are consanguineous
• Pseudodominance

  • Homozygous for an autosomal recessive disorder (rr), Mating with a Heterozygous carrier the same disease (Rr)
  • Recessive disorder inherited like a dominant disease
  • 50% chance of affected offspring
  • 50% carrier
  • All offspring carry the disease gene
• Complementation

  • Different mutations that produce the same trait

  Example: Parents homozygous for different mutations display same phenotype

  • All children unaffected
  • All carriers for both mutations
• Mosaicism

  More than one genetically distinct cell line in the body

  • Mutation occurs in a cell
  • Passes mutation on to daughter cells
• Germline Mutation

  • Mutation in sperm and egg
  • Used to carry on to later generations
  • can result in an affected couple having multiple unaffected offspring.
• Somatic Mutation

  • Mutations in other cells
  • Organs/tissues
• Uniparental disomy

  • Inherited both genes from one parent (rare)
  • Error in the formation of sperm or ovum
  • Elimination of extra chromosome