linkage, recombiantion and deviation from mendelian ratios

• Sources of genetic variability in sexual life cycles

  • Mutation
  • Independent assortment of chromosomes during meiosis I
  • Crossing-over between homologous chromosomes during meiosis I
  • Random fertilization of ova by sperm
• The choice of which sperm fuses with which egg is random
• With 23 pairs of chromosomes, independent assortment means that the no. of possible combinations of chromosome types (paternal and maternal) is 2^23 or 8,388,608
• With 8,388,608 kinds of sperm and 8,388,608 kinds of eggs, the no. of possible chromosome combinations in the offspring from one couple is >70,000,000,000,000 (2^46)
• The process of crossing over adds even more variation
• Recombinant phenotype

  A phenotype where the combination of phenotypes differs from that found in either of the parents
• Crossing Over

  1. The process of genetic recombination that gives rise to new combinations of linked genes

  2. Occurs during the pachytene phase of prophase I

  3. Begins with synapsis - pairing of homologous chromosomes

  4. The synaptonemal complex is a protein 'zipper' that holds homologous chromosomes together in the tetrad

  5. Formation of the synaptonemal complex leads to crossing over between homologous chromosomes

  6. Result of crossing over - recombinant chromosomes with new combinations of linked genes
• Crossing over: its effect on allele combinations

  Creates new combinations of alleles
• Recombination frequency


  The percentage of the progeny that inherit a combination of alleles that differs from either parent
• Recombination frequencies are estimated by studying the results of a testcross i.e. a cross between a double (or triple) heterozygote and a double recessive line
• For genes on different chromosomes, the recombination frequency will be 50% (due to independent assortment)
• T.H.Morgan (1866-1945) was the first to observe gene linkage
• Gene nomenclature in Drosophila

  • Mutants are given a name that reflects their phenotype – usually abbreviated e.g. black (b) and vestigial (vg)
  • The normal allele (wild-type) is written with a superscript + sign
• Results of a testcross involving the linked genes black (b) and vestigial (vg)

  1. Coupling heterozygote: parentals = b+ vg+ and b vg, recombinants = b vg+ and b+ vg

  2. Repulstion heterozygote: parentals = b vg+ and b+ vg, recombinants = b+ vg+ and b vg

  3. In each case, the largest phenotypic classes in the progeny will be the parental classes
• In 1913, A.H. Sturtevant, a student of T.H. Morgan, realised this information could be used to draw chromosome maps
• He saw that the recombination freq. between two genes should be related to their distance apart on the chromosome
• Example of mapping based on Recombination Frequencies (RF) from three separate crosses


  1. b vg cn: 9.0 cM, 9.5 cM, 17 cM

  2. 1% recombination = 1 cM (centimorgan)

  3. Two-point crosses (double heterozygote crossed with double recessive)

  4. b+ b vg+ vg x bb vgvg: RF = 17%

  5. cn+ cn vg+ vg x cncn vgvg: RF = 9.5%

  6. b+ b cn+ cn x bb cncn: RF = 9.0%

  7. The map that can be deduced:
• Multiple crossovers lead to an underestimate of the distance between two loci
• Multiple crossovers mean that recombination frequencies >50% are not possible
• Genes far apart on the same chromosome appear to assort independently
• The Three-Point Cross - a shortcut to mapping three genes


  1. b+ b cn+ cn vg+ vg x bb cncn vgvg

  2. Note: The largest numbers always indicate the parental types – and the smallest numbers the result of a double crossover
• Using these data to map the three genes

  1. Calculate the individual recombination frequencies between each pair of genes:

  2. b-cn = (41 + 4 + 5 + 40)/1000 x 100 = 9.0%

  3. cn-vg = (42 + 4 + 5 + 44)/1000 x 100 = 9.5%

  4. b-vg = (41 + 42 + 44 + 40)/1000 x 100 = 17%
• Deviations from Mendelian ratios

  • Sex-linkage
  • Incomplete dominance
  • Co-dominance
  • Pleiotropy
  • Polygenic inheritance
  • Epistasis
• Sex Linkage

  • Humans and fruit flies have the same X-Y system of sex determination
  • Male: XY, Female: XX
  • Male gametes: X and Y, Female gametes: X
  • The X and Y chromosomes are the sex chromosomes (c.f. autosomes – the other chromosomes)
• Sex-linked inheritance was first observed in Drosophila
• Morgan's explanation - white is a sex-linked gene on the X chromosome

  • The Y chromosome lacks the white locus. The Eye colour locus is on the X chromosome.
  • This means that the male fly only needs one copy of the mutant Xw allele to have white eyes
• Sex-linked inheritance of eye colour

  1. Males always get their X c'some from their mother – in this case it is wild-type

  2. In this case the males all inherit a mutant X c'some – and one copy is sufficient for the mutant phenotype
• Incomplete dominance

  Where a dominant allele does not completely mask the effect of a recessive allele at the same locus
• Incomplete dominance

  • Flower colour in snapdragon: The F1 hybrid (Rr) has an intermediate phenotype (pink)
  • Familial Hypercholesterolaemia in humans
• Co-dominance

  Where each allele affects the phenotype in separate, distinguishable ways
• Co-dominance

  • The ABO blood group system in humans: The I gene encodes a protein (antigen) found on the surface of red blood cells. IA and IB alleles are said to be co-dominant
• Incomplete Dominance vs Co-dominance

  Incomplete Dominance: Blending of traits and a 'diluted' phenotype

  Co-dominance: No blending, traits appear together and remain distinct in the heterozygote
• Pleiotropy

  Where a single gene has multiple effects on the phenotype it is said to be pleiotropic
• Pleiotropy


  • In pea, the gene that determines flower colour also affects seed colour

  Many human diseases that are caused by single gene mutations have pleiotropic effects (e.g. cystic fibrosis or sickle cell anaemia)
• Polygenic Inheritance


  Where a single trait is determined by multiple genes

  A characteristic of polygenic inheritance is that the trait shows continuous variation in the population
• Polygenic Inheritance

  • Height, weight, skin pigmentation, hair colour, eye colour in humans
• Epistasis

  When one gene masks or modifies the expression of another gene it is said to be epistatic to that gene
• Epistasis for coat colour in mice

  • Black (B) dominant, Brown (b) recessive

  But a second locus (C) determines whether the colour is deposited in the hair

  If homozygous recessive (cc), then mouse is white

  Gene C is epistatic to Gene B i.e. it can mask the phenotype conferred by B
• If the mouse is homozygous recessive at the C locus, it doesn't matter which alleles are present at the B locus – the mouse will always be white.
• The ratio of phenotypes in the F2 is not the usual 9:3:3:1 - but 9:3:4 (a modified 9:3:3:1 ratio).