Mutations (L2)

• What are recessive mutations generally characterized by?


  A loss of function, resulting in less or no functional gene product
• How do recessive mutations alter the phenotype?


  By producing less or no functional gene product
• What are four biochemically related conditions caused by recessive mutations?

  • Albinism
  • Alkaptonuria
  • Cretinism
  • Phenylketonuria
• What causes Albinism?


  Mutations in the tyrosinase enzyme pathway
• What is the effect of Albinism on melanin production?

  It leads to light skin and increased risk of skin cancer
• How does the mutation in Albinism affect tyrosine and melanin levels?

  It leads to too much tyrosine being produced without enough melanin
• What condition results from mutations in the phenylalanine hydroxylase gene?

  Phenylketonuria (PKU)
• What is the consequence of the mutation in Phenylketonuria?

  A build-up of phenylpyruvic acid, resulting in progressive brain function issues
• What are the treatments for Phenylketonuria?

  Phenylpyruvic acid birth test and a low phenylalanine diet
• What is a commonality among recessive mutations?

  • Less or no activity of enzyme (gene product)
  • Distinct phenotypic outcomes
  • Examples:
  • Cretinism = Brain retardation
  • Alkaptonuria = Black urine
• How is dominance/recessivity determined in genetics?

  By how the pool of product encoded by the two alleles functions in a heterozygote
• What are dominant mutations generally characterized by?

  A gain of function
• What are the two types of dominance that can manifest in dominant mutations?

  Complete dominance and incomplete dominance
• What is the difference between a gain of 'normal' function and a gain of 'new' function in dominant mutations?

  A gain of 'normal' function is more active enzyme production, while a gain of 'new' function is unrelated to the gene's normal activity
• What is Achondroplasia?


  The most common form of dwarfism caused by a gain of 'normal' function
• What is the genetic basis of Achondroplasia?

  Mutations in the FGFR3 gene that inhibit bone growth
• What percentage of individuals with Achondroplasia have parents with the mutation?

  20%
• What causes Huntington's disease?

  Expanded CAG repeat in the HTT gene
• What is the consequence of the expanded CAG repeat in Huntington's disease?

  Toxic effects due to increased polyglutamine repeat length in the Huntington protein
• What are the symptoms of Huntington's disease?

  Loss of limb control and death within 10-15 years of first symptoms
• What are the treatment strategies for recessive and dominant mutations?

  • Recessive mutations:
  • Gene therapy to provide a ‘wild-type’ allele
  • Disrupt expression of a mutant gene
  • Dominant mutations:
  • Pharmacological approaches to develop inhibitors
• What are somatic mutations?

  Mutations that occur in non-reproductive cells and are not passed on to offspring
• How can somatic mutations contribute to health issues?

  They can contribute to cancers
• What are germline mutations?

  Mutations that occur in reproductive cells and can be inherited by offspring
• What is the effect of germline mutations on the next generation?

  They affect every cell in the body of the next generation