Linkage and mapping

• Reciprocal cross = crossing a pair of parents with the sexes reversed

  Used to test for sex linkage
• Sex linkage = gene carried on the X chromosome

  Alleles are carried through females but only expressed in males

  E.g. haemophilia (blood cannot clot); Lesch-Nyhan (error in purine metabolism)
• X chromosome inactivation (XCI) - equalises the dose of X linked alleles in males and females (as females would produce twice the amount of proteins as males)

  E.g. tortoiseshell cat - patches of black and orange fur, in females half the cells have the orange gene switched on and the other half have the black gene switched on
• Two-point mapping = inheritance of two loci together on the same chromosome
• Backcross = cross with a parental genotype

  Testcross = cross with a double mutant (used to determine an unknown genotype)
• Morgan's coupling experiment:

  P1: purple vestigal (double mutant) x red normal (double normal)

  F1: all red normal (double heterozygous)

  F2: red normal female F1 x purple vestigal male
• Parental class = same combination of phenotypes seen in P1 individual

  Recombinant class = new combinations not seen in P1
• Morgan's repulsion experiment:

  P1: red vestigal x purple normal (2 mutants & 2 wild type in each parent)

  F1: all red normal (double heterozygous)

  F2: red normal female F1 x purple vestigal male
• The further apart two loci are, the greater the probability of chiasma formation between the loci and the greater the frequency of recombinant phenotypes
• Recombination frequency = recombinants / total
• Crossover interference:

  Coefficient of interference = 1 - coefficient of coincidence

  Coefficient of coincidence = observed DR frequency / expected DR frequency

  Expected DR frequency = product of the observed frequencies (multiplied by total)
• To establish the order in any cross, take the two rarest recombinant classes and arrange them next to each other. Which one would move to become the parental class?

  a + c

  + b +

  Therefore, B is in the middle
• To work out whether inheritance is sex-linked, look at reciprocal crosses

  To work out whether inheritance is recessive, see if it skips generations
• Holandric = genes appearing on the Y-chromosome and only appearing in males

  Transmitted from male to male without skipping generations
• Chromosome theory - chromosomes are the carriers for Mendel's factors (genes)
• Recombinant gamete formed if a chiasmata forms between the two linked loci

  Parental genotype formed if a chiasmata forms outside the two loci
• Synapsis - maternal and paternal chromosomes 'zip up'

  Chiasmata - the chromosomes exchange DNA
• Map distance = the probability of getting a crossing over event between any pair or set of loci

  e.g. 25 m.u means recombinants must be 25% of the total
• Metacentric = centromere in the middle of the chromosome

  Acrocentric = off centre, one chromosomal arm is longer

  Submetacentric = less off centre than acrocentric

  Halocentric = entire length of the chromosome acts as the centromere
• Maximum recombination rate is 50%
• Haplotype = a group of alleles in an organism that are inherited together from a single parent, discussed in the context of single nucleotide polymorphisms (SNPs)
• Closely linked SNPs will be passed on together
• Genome wide association studies (GWAS) - studies different genomes from 2 groups of individuals. if a particular locus is associated with the phenotype of interest, individuals who share the trait will share the same genetic variant (testing the association of SNPs)
• Sickle cell haplotypes:

  5 different haplotypes from different origins, mutations arose due to natural selection as it gave resistance to malaria with the 5 haplotypes evolving independently

  Portuguese has many haplotypes in its population, showing the significance of migration on allele frequencies
• Human skin colour haplotypes:

  Dark skinned near the equator due to protection from UV radiation and skin cancers.

  Dark skin associated with vitamin D deficiency (rickets as it is produced when the skin absorbs UV)

  Light skin associated with spina bifida (lack of folic acid which absorbs UV)