TBL GEM 5 & 6

• Population


  A localized group of individuals belonging to same species
• Gene pool

  The total genes in a population
• Microevolution


  Evolution on the smallest scale that occurs when the relative frequency of alleles in a population changes over a succession of generations
• The frequencies of alleles in a population's gene pool remain constant over the generations unless acted on by agents other than sexual recombination
• The Hardy-Weinberg Principle

  • The frequency of an allele in a population will remain constant over time, provided that the following conditions are met:
  • The population is large and randomly breeding
  • There are no conditions acting on the population to change the allele frequency
• If two alleles, p & q, exist at one gene locus, the allele frequencies are:

  p + q = 1
• The frequency of the three possible genotypes AA, Aa, and aa results from the binomial distribution

  
• For Autosomal Recessive disorders 


  the incidence of disorder is $q^2$
• For cases in which the disease-causing allele "q" is much rarer than the normal allele "p"

  frequency of heterozygosity is about "2q"
• This example is the simplest case: 2 alleles in the population and one is dominant.

  • p = frequency of one allele
  • q = the frequency of the other allele
  • Then: p + q = 1
  • probability of AA genotype = p2
  • probability of aa genotype = q2
  • probability of Aa genotype = 2pq
  • Therefore: p2 + 2pq + q2 = 1
• Uses of Hardy-Weinberg Equation

  • You can calculate the frequency of a gene in a population if you know the frequency of the phenotypes
  • Important in genetic disease counseling
• Hardy-Weinburg relevance to Evolution

  • A population at genetic equilibrium does not evolve
  • Hardy-Weinberg tells us what to expect in non-evolving populations
  • Therefore, it is a baseline for comparing actual populations where gene pools may be changing.
  • Can determine if the population is evolving
• Hardy-Weinberg equilibrium is maintained only if the population meets all 5 of the following criteria:

  • Very large population size
  • Isolation from other populations
  • migration can affect the gene pool
  • No net mutations
  • Random mating
  • No natural selection
  • no difference in reproductive success
  • Describes an ideal conditions that rarely exists in nature
• For evolution to take place something must upset the genetic equilibrium of the population, Factors that change genetic equilibrium are:

  • Genetic drift
  • Migration (Gene flow)
  • Non-random mating (Isolation)
  • Mutation
  • Natural selection
• Genetic Change

  • Gene pool is the total number of alleles present in a population.
  • Genetic change is the change in frequency of alleles in the gene pool of a population.
  • The processes of mutation, natural selection, migration and genetic drift all affect the gene pool and change the frequency of the alleles in that gene pool.
  • Frequency of an allele = occurrence of allele/total number of alleles
• Evolution

  • Is the process by which new species of organisms develop from earlier forms.
  • Process normally occurs slowly.
  • Most often in response to a change in a species’ environment.
  • Is drived by changes in the frequency of the alleles in a population (some alleles ‘do better’ than others).
  • Evolution acts on populations (i.e. it is populations that evolve, not individuals).
• Natural Selection

  • The theory of natural selection was proposed by Charles Darwin over 150 years ago.
  • Populations typically produce more offspring than environmental resources can maintain – there is a competition for survival.
  • Individuals with the best adaptations survive and reproduce (this is what is meant by fitness) and pass their successful alleles onto their offspring.
  • The frequency of these successful alleles will then increase in the gene pool.
• Environmental factors (both biotic and abiotic) act as selecting agents of phenotypes
• When environmental factors change


  Different phenotypes will be selected for
• Phenotype is largely determined by genotype
• Successful genotype alleles

  Will increase in frequency in the gene pool
• Favourable alleles increase in frequency in a gene pool, while unfavourable alleles decrease.

  • If the frequency of alleles changes, evolution is occurring.
  • After a certain number of generations, the frequency of alleles and phenotypes might change so markedly that the population becomes reproductively isolated from others of that species.
  • It is now a new species.
• Genetic Drift

  • Changes in gene frequency of a very small population due to chance
  • Controlled by the laws of probability & chance
  • Bottleneck effect: Chance sampling error due to small population
  • Founder’s effect: a few individuals colonize a remote spot, causes drift
• Bottleneck Effect (genetic drift)


  Chance sampling error due to small population

  
• Gene Flow (Migration)

  • Movement of organisms into or out of a population
  • Takes their genes out of the gene pool
  • Most populations are not completely closed; gain & lose alleles
• Non-random Mating

  • More apt to mate with close neighbors
  • Promotes inbreeding
  • Assortative mating: seek mate like self (e.g., size, appearance)
  • Disassortative mating: individuals with diverse traits mate more frequently than would be expected in random mating
• Mutation

  • A change in a gene
  • An alteration of DNA
  • The original source of variation
  • Raw material on which natural selection works
• There are 3 types of natural selection

  *If one type produces more offspring than another, upsets the balance of the equilibrium.*

  1. Stabilizing Selection
  2. Directional Selection
  3. Disruptive or Diversifying Selection
• Stabilizing Selection

  
• Directional Selection

  
• Diversifying/Disruptive Selection

  
• What Do Medical Geneticists Do?

  • Diagnosis and treatment of genetic diseases
  • Pre-symptomatic testing for genetic diseases
  • Carrier testing, especially for high-risk people
  • Genetic counseling during pregnancy
• Genetic Counseling 


  An educational counseling process for individuals and families who have a genetic disease or who are at risk for such a disease.
• Genetic counseling: laboratory tests

  • Prenatal diagnosis: Cytogenetics, biochemistry, DNA, and/or other testing;
  • Neonatal screening
• Factors in genetic counseling

  • Genetic defects that occur frequently in certain populations
  • Either parent already has a child/children with birth defects or genetic disorders
  • Relatives (parents or siblings) having genetic disorders
• Additional Factors in Genetic Counseling

  • Delayed age of onset
  • Penetrance (the proportion of individuals with the mutation who exhibit clinical symptoms)
  • Expressivity (the proportion of individuals with a given genotype who also possess the associated phenotype: quantitative)
  • Phenocopy (Mimicking of a genetic phenotype caused by environmental conditions)
  • Pleiotropy (one gene influences multiple, seemingly unrelated phenotypic traits)
• Genetic counseling: Genetic heterogeneity

  • A similar phenotype being caused by more than one genetic mechanism. Most commonly used for a similar phenotype being caused by mutations in different genes.
  • Allelic heterogeneity refers to different mutations in the same gene.
• Genetic counseling: calculating and presenting the risk

  1. Genotype – Known: estimating the probability of recurrence risk by Mendelian principals. Examples:

  *AD: (Alzheimer’s disease). Affected genes: APP, PSEN1, or PSEN2

  *AR: (androgen insensitivity syndrome). Affected genes: AR, x-linked

  2. Genotype – Unknown: estimating the probability of recurrence risk (conditional probability or Bayes principal).
• Pre-implantation Screening/Diagnosis (PGS/PGD)

  • Carrier screening
  • Testing for lethal diseases/gender
• Prenatal Screening

  • MSAFP/Ultrasound
  • Amniocentesis/CVS