Genetic Variation

• Gene

  Segment of DNA that codes for a specific phenotypic trait
• Allele

  Different versions of a gene
• Genotype

  Set of genes in the DNA which is responsible for a particular phenotypic trait
• Phenotype

  • Physical expression of an trait
  • Can be expressed as a protein or physically observable characteristic
• Meiosis

  • Results in four genetically unique daughter cells (gametes)
  • Each with half the number of chromosomes of the parent cell
• Crossing Over

  • Alleles are exchanged between non-sister chromatids of homologous chromosomes
  • Results in new combinations of alleles on a chromosome
  • Produces variation of genotypes upon fertilisation
• Independent Assortment

  • Genes and alleles of one trait are inherited independently of another trait
  • Produces new variation of genotypes at loci across chromosomes
• Random Segregation

  • Alleles of the same gene separate randomly and equally into daughter cells
  • Produces new variation of genotypes at loci across chromosomes
• Genetic Variation from Fertilisation

  • Human male ejaculates approx. 300 million sperm
  • Each of the sperm is genetically unique due to crossing over, independent assortment and random segregation
  • Only one fertilises the egg (determined by chance)
  • Results in billions of possible genotype combinations that can be expressed in the phenotype of the offspring
• Mutation

  • Permanent change in the nucleotide sequence of the DNA
  • Can be harmful, beneficial or neutral
  • Essential for evolution (genetic traits were originally the result of a mutation)
• Somatic Mutation

  Occurs in a body cell and is not passed onto offspring
• Gametic Mutation

  • Occurs in a sex cell and is heritable (can be inherited by offspring)
  • Leads to the formation of new alleles
• Substitution Mutation (Nonsense)


  • Change in one DNA base pair
  • Instead of substituting one amino acid for another the altered DNA sequence signals the cell to stop building a protein
  • Likely to lead to large-scale changes in the amino acid sequence and polypeptide length resulting in a nonfunctional protein
• Substitution Mutation (Missense)


  • Change in one DNA base pair that results in the substitution of one amino acid for another in the resulting polypeptide
  • Can have a range of phenotypic effects
• Frameshift Mutation (Insertion)


  • Insertion of a nucleotide that shifts the sequence
  • Likely to lead to large-scale changes in amino acid sequence and polypeptide length resulting in a nonfunctional protein
• Frameshift Mutation (Deletion)


  • Deletion of a nucleotide that shifts the sequence
  • Likely to lead to large-scale changes in amino acid sequence and polypeptide length resulting in a nonfunctional protein
• Homozygous

  Both alleles are the same for a particular characteristic/trait (eg. TT or tt)
• Heterozygous

  Alleles are different for a particular trait (eg. Tt)
• Dominant Allele

  • Always expressed in the phenotype.
  • Homozygous (TT) dominant individual will have the same phenotype as a heterozygous (Tt) individual
• Recessive Allele

  Can only be expressed in the phenotype when the genotype is homozygous (tt)
• Gregor Mendel

  • Austrian monk and botanist
  • Often referred to as the ‘father of modern genetics’ for his inheritance studies of pea plants
  • Worked with pure breeding plants (TT or tt) and then hybrids (Tt), studying the inheritance of one particular trait at a time through monohybrid crosses
  • Demonstrated that characteristics were inherited in a specific pattern
• Gregor Mendel's Results

  • Inheritance is not a blending of characteristics
  • Inheritance is controlled by a pair of factors; one from each parent (which we now know are genes/alleles)
  • These two factors segregate from one another when sex cells are formed
  • Characteristics are either dominant or recessive
  • Ratios of various types of offspring from two parents were able to be predicted using mathematical calculations.
• Autosomal

  Specific gene is located on numbered, or non-sex chromosomes
• Monohybrid Cross

  • Study of inheritance of a single trait (characteristic)
  • Monohybrid crosses only have two possible outcomes
  • All of Mendel’s monohybrid crosses displayed the dominant characteristic in the phenotype of the F1 generation
  • Crossing between the F1 offspring always yields a characteristic 3:1 ratio of dominant:recessive phenotypes in the following F2 generation
• Pedigrees

  • Visual charts that show familial lineages and relationships
  • Used to track inherited traits and genetic disorders
  • Can be used to predict the likelihood of offspring having inherited traits or genetic disorders
• Sex-linkage

  • Refers to genes that are located on the sex chromosomes
  • XX in females and XY in males
  • Most sex-linked characteristics are found on the X chromosome and recessive
  • Normal 3:1 Mendelian ratio is not observed
• Thomas Hunt Morgan

  • Discovered sex-linkage in 1910
  • Attempted to repeat Mendel’s work in an animal model; eye colour in Drosophilia melanogaster (fruit flies). Red eye allele was dominant over white allele (which he developed as a mutation)
  • Anticipated that the 3:1 ratio in F2 generation would appear after initial truebreeding crosses
  • Observed a disproportionate number of white-eyed males, and concluded the trait must be linked to the sex chromosomes
• Sex-linked Genotypes (Female)


  • Normal – XTXT
  • Carrier - XTXt
  • Female with trait – XtXt
• Sex-linked Genotypes (Male)


  • Normal – XTY
  • Male with trait – XtY
• Co-dominance

  • Occurs when alleles of a gene pair in a heterozygote are both fully expressed in the phenotype
  • Neither allele is dominant or recessive
  • Each allele is represented by a capital letter
  • Normal 3:1 Mendelian ratio is not observed
• Incomplete Dominance

  • Occurs when one allele for a specific trait is not completely expressed over its paired allele. This results in a third phenotype in which there is a blending of the alleles in the phenotypes
  • Each allele is represented by a capital letter
  • Normal 3:1 Mendelian ratio is not observed
• Multiple Allele Inheritance

  • Occurs when there are three or more possible alleles for a gene
  • While the genotype of an individual will only ever have two alleles at a locus, there is a higher number of possible genotypes (and hence phenotypes) at the locus
• Polygenetic Inheritance

  • Determined by more than one gene, often found on different chromosomes
  • Contributing genes equally influence the phenotype
  • Results in individuals expressing varying degrees of a dominant, recessive or intermediate phenotype
• Allele Frequency

  Describes the fraction of allele copies for a particular gene in a population
• Single Nucleotide Polymorphism (SNP)

  • Point mutation (single base - G,C,A or T) in a segment of DNA that occurs in more than 1% of a population
  • Most SNPs are found in the introns (DNA between genes) and have little effect on cellular function
  • Exon (gene) SNPs have a more significant impact including the development of diseases and disorders
• Components of a Gene (DNA)

  • Exons: Protein-coding regions (1% of DNA)
  • Intergenic Space: Most non-coding DNA is located (99% of DNA)
  • Introns: Non-coding regions that are situated between the exons of each gene (99% of DNA)
  • Each gene consists on average of approx. 9 exons and 8 introns
• Function of SNPs

  • Most common type of genetic variation between individuals occuring every 500-1000 nucleotides (constitutes of 90% genetic variation between humans)
  • SNPs act as chromosomal tags to specific regions of DNA, and these regions can be scanned for variations that may be linked to diseases or disorder
• Uses of SNPs in Genome-Wide Association Studies (Pt.1)

  • Genome-wide association studies (GWAS) rapidly scan for SNP markers across the genomes of individuals with a known disease or disorder and compare them to ‘control’ individuals
  • Significant differences in allele frequency caused by SNPs are the first step in identifying cause and effect relationship between a SNP and a disease
• Uses of SNPs in Genome-Wide Association Studies (Pt.2)

  • Once a link is made, scientists look to develop better treatments and diagnostic and prevention strategies
  • GWAS have identified SNPs related to conditions including cancer, diabetes, heart disease, mental illness, Parkinson’s disease, Crohn’s disease and Alzheimer’s disease