BB2709 Genetics

• Population genetics

  The study of genetic variation within a group of individuals and the changes in that variation over time

  
• Population


  A group of individuals in a particular area who belong to the same species and can breed with one another
• Allele frequency


  Number of copies of a specific allele at a specific locus divided by the total number of all types of allele at a specific locus
• Genotype frequency


  Number of individuals with a specific genotype at a specific locus divided by the total number of individuals

  
• Hardy-Weinberg equilibrium (HWE)


  The idea that the allele frequencies at a particular genetic locus will remain the same from one generation to the next if that genetic locus is not affected by evolutionary pressure – subject to certain conditions

  
• Hardy-Weinberg equation


  p^2 + 2pq + q^2 = 1, where p is the frequency of allele 1, q is the frequency of allele 2, p^2 and q^2 are equal to the frequency of allele 1 and allele 2 homozygotes, respectively, and 2pq is the frequency of heterozygotes
• Usage of HWE


  • Estimating the prevalence of a recessive disorder
• Assumptions of HWE


  • No genetic drift
  • No migration
  • No natural selection
  • No nonrandom mating
• Genetic drift


  Where the allele frequencies in a population change randomly

  
• Bottleneck effect


  If the population size drops dramatically, then genetic drift is more likely to have a substantial effect on allele frequency

  
• Migration


  The movement of a group of individuals from one location to another
• Founder effect


  Same as bottleneck effect except that it involves migration
• Nonrandom mating


  Where individuals from a population reproduce with other individuals from that same population regardless of the genotype or phenotype of either individual
• Inbreeding


  When two individuals who share a common ancestor reproduce
• Inbreeding coefficient (f)


  A value closer to 1 means that a population is inbred
• Types of natural selection

  • Directional selection
  • Balancing selection
  • Disruptive selection
  • Stabilising selection
• Directional selection


  Where individuals with the more extreme phenotype are more likely to successfully reproduce
• Balancing selection


  Favours the presence of two alleles in a population, i.e. one allele is not consistently selected for over the other
• Heterozygote advantage


  Where individuals with a heterozygous genotype are more likely to reproduce than those with either of the two homozygous genotypes
• Negative frequency-dependent selection


  Where a genotype becomes less and less favourable the more common is gets in a population

  
• Disruptive selection


  Favours the presence of two or more distinct phenotypes
• Stabilising selection


  Favours the intermediate phenotype
• Remember p^2 + 2pq + q^2 = 1
• HWE is only true in the absence of natural selection, genetic drift, non-random mating, etc. because these things can alter allele and genotype frequencies

  
• Genetic Basis of Human Diseases

  Different patterns of inheritance of human diseases
• Autosomal Recessive


  • Tay-Sachs Disease (TSD)
  • Caused by mutation in gene encoding hexosaminidase A enzyme
  • Excessive accumulation of lipid in CNS cells causes neurodegenerative symptoms
  • Typically fatal by age 3-4
• Autosomal Dominant


  • Huntington Disease (HD)
  • Caused by mutation in huntingtin gene that adds polyglutamine tract
  • Leads to neuron degeneration, personality changes, dementia, early death
• 1. linked Recessive


  • Hemophilia
  • Caused by defect in Factor VIII or Factor IX clotting proteins
  • Affects males more severely, females can be carriers
• Detection of Disease Causing Alleles

  1. Haplotype Mapping

  2. Genome Wide Association Studies
• Genetic Screening


  Population-wide genetic testing
• Gene Therapy


  Use of genetic information to select personalized treatment
• Genetic insight is expected to bring about revolutionary changes in medical practices
• Currently, several hundred genetic tests are in clinical use
• DNA-sequencing technologies may progress to the point where sequencing a person's entire genome will be inexpensive enough to be done as a routine diagnostic procedure
• Thousands of genetic diseases afflict people, many directly caused by a mutation in one gene
• Genes also play roles in the development of diseases that have a complex pattern of inheritance, involving multiple genes
• When an individual exhibits a disease, the disorder is more likely to occur in genetic relatives than in the general population
• Identical twins share the disease more often than fraternal twins
• Concordance


  Degree to which a disorder is inherited
• The disease does not spread to individuals sharing similar environmental situations