BIOCELL GEN lecture 3.1 genetics

• Inherited Genetic disorders


  Recessive / Dominant
• Cystic fibrosis


  • Faulty chloride transport between cells
  • 4% of Caucasians of European descent in US are carriers
• Tay-Sachs disease


  • Faulty metabolic enzyme
  • High incidence among Ashkenazic Jews
• Sickle-cell disease


  • Faulty haemoglobin protein
  • One of 10 African-Americans is a carrier
  • Very high incidence rate, but carriers have an advantage
• Achondroplasia


  • Heterozygotes have the dwarf phenotype
  • 1 in 25,000
• Huntington's Disease


  • Lethal dominant allele which causes a fatal deterioration of the nervous system
  • Known to be located on the tip of chromosome 4
• How can such a disorder be passed among generations?
• cfDNA non invasive genetic testing


  e.g. Harmony Test
• Most genetic diseases are actually multifactorial: cancers, heart disease, diabetes, alcoholism, manic-depression, among many.
• Exercise, eat healthy, do not smoke.
• Most people with "Mendelian" genetic disorders have two heterozygous parents, as often the homozygous recessive are sterile or die before reproduction.
• Inbreeding has consequences, such as in endangered species conservation programs.
• Objectives of Genetics Section


  • Meiosis, mitosis and inheritance
  • Mendel's influence on genetic research
  • The chromosomal basis of inheritance
  • DNA structure, replication and repair
  • RNA transcription
  • The translation of proteins
• Sex determination varies with type of organism


  • Sex linked genes have unique patterns of inheritance
  • Chromosome related genetic disorders
  • Extranuclear genes exhibit non-Mendelian inheritance
• Chromosomal mapping of a gene locus by Lichter et al. 1990. Science 247: 64-67.
• Mendelian genes have a specific loci on chromosomes, and it is the chromosomes that undergo segregation and independent assortment.
• Drosophila melanogaster


  • 4 pairs of chromosomes, many offspring, generation every two weeks, and cheap!
  • Wild-type (Normal)
  • White-eye mutant (alternate types)
• Sex-linked genes


  Genes on a sex chromosome
• Linked genes


  Genes located on the same chromosome will tend to be inherited together
• Sex-linked gene


  The location of the gene on the sex chromosomes, and not their linkage to other genes
• Genetic symbols


  The first mutant character receives a symbol (such as w), then the wild-type receives a + symbol (such as w+)
• Linkage and inheritance


  1. b=black body, b+ is grey

  2. vg=vestigial wings, vg+ normal wings
• Genetic recombination results in offspring with new combinations of traits than parents.
• Parental types


  F1 or F2 with the same combination of traits as parents or P generation
• Recombinants


  Offspring with new combinations of traits than parents
• What ratio would exist if genes were completely linked?
• Crossing over


  Recombination frequencies used to map chromosomal distance in map units (centimorgans = 1% recombination frequency)
• Mendel- 7 characters, 7 chromosomes on peas, but… seed & flower colour…
• More than one gene can affect a phenotypic character even on a single chromosome.
• Cytological maps are based on gene position relative to chromosomal features.
• Secrets of the Bat Clade
• Sex determination varies with type of organism


  • Typical of mammals, many other groups. Sperm carry the sex determinant.
  • Some insects. No male sex chromosome. Typical of Hymenoptera. No sex chromosomes.
  • Typical of birds, some fishes. Ova carry the sex determinant
• Sex-linked disorders in humans


  • Colour-blindness
  • Duchenne muscular dystrophy
  • Hemophilia
• X inactivation in female mammals
• Barr-body


  One of the x chromosomes condenses into a compact object
• Aneuploidy


  • Trisomic (2n + 1)
  • Monosomic (2n - 1)
• Down syndrome


  • One per 700 births in US
  • Incidence of occurrence correlates with age of the mother
• Sex-chromosome aneuploidy


  • XYY- male or female?
  • XXX- Indistinguishable from normal females except by karyotype
  • One occurrence per 1000 females
• Klinefelter syndrome

  • XXY, or XXXXY
  • Once per 2000 live births
  • Male, but sterile, sometimes with feminine body characteristics

  
• Turner syndrome


  • XO
  • 1 per 5000 births
  • Female, but sterile