Growing up, growing old and passing on your genes

Variation in the next generation

Discontinuous variation

• IMG 5-14-2
• Limited number of distinct phenotypes / categories (eg ABO blood groups)
• Strong genetic factor controlled by alleles on one gene
• Frequency histogram has separate bars
• Unaffected by the environment

Continuous variation

• Continuous range of values / class intervals (eg human height)
• Alleles on many genes located on different chromosomes / polygenic inheritance
• Frequency histogram is a smooth (normal distribution) curve
• Phenotype is affected by environmental factors
  • Lower skin temperature activates a gene for pigment production
  • Diet affects individual's size and health. Malnourishment results in shorter height
  • Thus, genes + environment → phenotype (continuous variation)

Normal distribution about the mean

• Mode (most frequent) = median (mid) = mean (average value)
• Bell-shaped/ even distributions of values above and below mean
• Standard error (SE)
  • True mean of SE is ±1.96
  • In a number of samples each sample will have its own mean
  • Standard error measures how much the value of a sample mean is likely to vary
  • The greater the standard error, the greater the variation of the mean
• Standard deviation (σ)
  • Measure of the spread of results about the mean of a normal distribution curve
  • Thinner bell-shape / smaller standard deviation / less variation
  • Same pattern with bigger bell-shape

Where variation comes from

Gene mutation

• Produces new alleles
• Addition: at least one base is added during DNA replication
• Deletion: at least one base is not copied (frameshift)
• Substitution: at least one base is copied wrongly
• Interferes with normal base pairing (A-T;C-G)
• Degenerate code: different triplets can code for same amino acids

Meiosis

• Causes new combination of alleles
• Crossing over
  • During prophase I
  • At synapsis, non-sister chromatids of homologous pairs cross over at chiasmata
  • Homologous chromatids (corresponding pieces of genetic material) break and exchange equivalent segments between maternal and paternal chromatids
• Independent assortment
  • From the equator
    • Homologous chromosomes pulled to opposite poles at random (anaphase I)
    • Chromatids pulled to opposite poles at random (anaphase II)
  • 2²³ different combinations possible in 4 haploid cells where 23 is the number of chromosomes
• Fertilization
  • Random fusion of gametes
  • Genetic difference amongst the zygote
  • New combinations of alleles

Twin Studies

• Phenotype depends on genes and environment
• Twins are
  • Monozygotic (identical) → one zygote develops into 2 embryos
    • Very high concordance
    • Have identical DNA but phenotype is not exactly the same
    • Different environment in womb and in later life
    • Causes different genes to switch on and off
  • Dizygotic (non-identical) → two zygotes
    • High concordance as they are related (many genes similar)
• Concordance and discordance
  • Helps to find out whether a disease has a genetic cause
  • Useful to compare identical and non-identical twins
  • High concordance
    • Identical twins only → not influenced by environment (eg blood group)
    • Identical and non-identical twins → environmental factor likely (eg virus)
  • Low concordance
    • Requires strong environmental factor
  • Best results with
    • Identical twins living together → same environment
    • Non-identical twins with same sex → sex affects height and body mass

Epigenetic Imprinting

• Expression of certain genes by one allele depending on which parent it comes from
• DNA methylation
  • Occurs during gametogenesis
  • Methyl groups are added to cytosine bases of certain genes (imprinting)
  • Modifies DNA structure rather than base sequence (epigenetic)
  • Methyl groups inhibit transcription (genes are switched off)
• Methylation is reversible
  • Old imprints are removed and re-formed during gametogenesis
  • New sperm → imprinted gene is re-tagged as paternal
  • New oocyte → imprinted gene is re-tagged as maternal
  • Therefore, father passes on chromosome imprinted as "paternal" → his daughter passes on same chromosome imprinted as "maternal"
• There are <1% of imprinted genes on autosomal chromosomes

Prader-Willi Syndrome (PWS)

• Characteristics
  • Obesity
  • Short stature
  • Learning difficulties
  • Small testes
• Caused by the deletion of imprinted genes on chromosome 15
  • Imprinting prevents expression of maternal genes
  • Maternal allele for the gene is methylated
  • This inhibits transcription of the defective gene and PWS cannot develop
  • Therefore, defective gene only causes PWS when inherited from the father