Allelic and X-linked inheritance

• Codominance


  Joint expression of two alleles of a gene in a heterozygote results in phenotypic detection of both gene products
• Multiple Alleles


  The ABO blood groups are an example of multiple alleles
• ABO blood group genotypes and phenotypes


  • IA IA - A
  • IA IO - A
  • IB IB - B
  • IB IO - B
  • IA IB - AB
  • IO IO - O
• IA allele


  Responsible for an enzyme that can add the terminal sugar N-acetylgalactosamine (AcGalNH) to the H substance
• IB allele


  Responsible for a modified enzyme that cannot add N-acetylgalactosamine but instead can add a terminal galactose
• O phenotype


  Results from an absence of either terminal sugar
• Epistasis


  When one gene masks the effect of another gene, or two gene pairs complement each other such that one dominant allele is required at each locus to express a certain phenotype
• Pleiotropy


  When expression of a single gene has multiple phenotypic effects
• Marfan syndrome


  • Tall - thin - long arms/legs -thin fingers
  • Near-sightedness
  • Weak connective tissue - esp in aorta - stress can lead to aortic rupture
  • Chromosome 15q21 - gene (FBNI) makes fibrillin I
  • Microfibrils integral for elastic fibres
  • 1:5000 prevalence
• Many traits characterized by a distinct phenotype affected by more than one gene
• Gene interaction


  Cellular function of numerous gene products contributes to development of a common phenotype
• X Linkage


  Genes on X chromosome exhibit unique patterns of inheritance as males have only one
• Lethal X-linked recessive disorders


  Only in males, females can only be heterozygous carriers that do not develop the disorders
• X linked dominant disorders


  • Very few, examples include hereditary enamel hypoplasia, faulty tooth enamel and dental discolouration, webbing to tips of toes, hypophosphataemia, causes bow leggedness - associated with bone disease and spine degeneration
  • More females than males affected
• Sex-limited and sex-influenced inheritance


  Expression of autosomal genes responsible for a certain phenotype depends on the hormone levels/expression, thus one phenotype may be expressed in males and another in females
• Environmental phenotype


  Phenotypic expression of a trait may be influenced by environment as well as by genotype
• X linked recessive traits


  • Colour blindness
  • Fabrys disease
  • G-6-PD deficiency
  • Hemophilia A
  • Hemophilia B
  • Hunters syndrome
  • Ichthyosis
  • Lesch-Nyhan syndrome
  • Muscular dystrophy
• X linked dominant traits


  • Hereditary enamel hypoplasia
  • Hypophosphataemia (causes bow leggedness)
  • Webbed toes
• Autosomal dominant traits


  • Camptodactyly (stiff permanently bent little fingers)
  • Ehlers-Danlos syndrome (connective tissue disorder)
  • Hypercalcaemia
  • Marfan Syndrome
  • Familial hypercholesterolaemia
  • Achondroplasia (dwarfism)
  • Huntington's disease (degeneration of nervous system)
  • Adult polycystic kidney disease
  • Brachydactyly (shortened fingers)
• Autosomal recessive traits


  • Albanism
  • Cystic fibrosis
  • Galactosaemia
  • Phenylketonuria
  • Tay-Sachs disease
  • Fanconi anaemia
  • Sickle cell anaemia
  • Thalassaemia
  • Xeroderma pigmentosum
  • Haemochromatosis
• Turner syndrome


  One X chromosome, no Y chromosome, female genitalia
• Klinefelter syndrome


  • Male genitalia, sterile, tall & long arms, legs
  • More than one X chromosome (usually a 47,XXY or 48, XXXY)