single gene disorders

• single gene disorders are caused by

  point mutations in a single gene
• autosomes are all chromosomes apart from the 


  X and Y
• autosomal modes of inheritance

  recessive (phenotype only in homozygous for disease allele)

  dominant (phenotype in heterozygotes)
• recessive inheritance characteristics

  • heterozygotes are unaffected - carriers
  • complete loss of gene function leads to phenotype
  • consanguinity increases frequency of affected children (sexual relationship with blood relative)
• dominant inheritance characteristics

  • partial loss of gene function -haploinsufficiency- leads to phenotype
  • toxic protein interferes with cell function
• autosomal recessive carriers have 25% chance of having an affected child
• males and females can be affected by autosomal recessive pedigree
• autosomal recessive examples


  cystic fibrosis, sickle cell anaemia
• cystic fibrosis is the most common life-shortening genetic disorder affecting _ population

  Northern European Caucasian
• 1 in 25 are carriers of CF
• there are 1 in 2500 CF births
• untreated CF, sufferers die before 5th birthday
• CF symptoms

  • accumulation of mucus in the lungs, pancreas, digestive tract and other organs
  • chronic bronchitis
  • recurrent bacterial infections
• CF gene codes for a chloride channel
• CFTR stands for


  cystic fibrosis transmembrane conductance regulator
• CFTR regulates the flow of chloride ions across the membrane
• deletion of 3 base pairs results in the loss of a Phe residue at position 508, means protein doesn't fold normally and is more quickly degraded
• more than 800 mutations of CFTR that can cause 


  CF
• defect in CFTR causes CF by

  • defect in Cl- transport
  • causing extracellular mucus to become thicker and sticker
• treatment of CF


  antibiotics and daily massage to clear mucus from airways
• precision medicines are used by

  sequencing of chloride channel gene in patient, able to offer precise treatment
• drugs can be given as precision medicine to improve function of mutated ion channel in CF
• gating mutation can be treated with

  drugs to help open gate
• mutations can be treated with combination therapies, to bring more of chloride channels to surface and help them to operate more effectively
• gene therapy treatment for CF

  • provide patients with copy of correct chloride channel
  • clinical trials for integrating and non-integrating gene therapies
• sickle cell anaemia affects 1 in 625 Afro-Caribbean/ Afro-American births
• symptoms of sickle cell anaemia

  • anaemia
  • joint pain
  • swollen spleen
  • frequent severe infections
• treatment of sickle cell anaemia

  regular blood transfusions
• sickle cell anaemia could be cured by

  bone marrow transplant
• molecular cause for SCA

  • mutation in gene for beta chain of haemoglobin, leads to incorrect folding
  • defective haemoglobin forms long chains of rigid polymers (deform RBCs)
• heterozygotes also have phenotype in low oxygen conditiond
• having sickle cell trait confers resistance to malaria (heterozygote advantage)
• autosomal dominant characteristics

  • males and females affected
  • affected individuals have affected parent
  • 50% chance of affected parent having affected child
• autosomal dominant examples


  Huntington's disease, familial hypercholesterolaemia
• symptoms of Huntington's disease

  • jerky movements
  • personality changes
  • deterioration of walking, speaking and swollowing abilities
• HD is a late-onset disease
• molecular cause of Huntington's

  • HD gene contains CAG repeats
  • 11-34 repeats is normal
  • 36-125 repeats is HD
  • defect is on chromosome 4
• familial hypercholesterolaemia symptoms

  • high levels of cholesterol in blood from early age
  • cholesterol deposits build up in joints
  • cardiovascular disease
• treatment of familial hypercholesterolaemia

  • cholesterol lowering drug such as statins
  • low cholesterol diet
• molecular cause of familial hypercholesterolaemia

  • lack of low density lipoprotein receptor