Co-segregation and linkage analysis in humans

1
Co-segregation and linkage analysis in humans

• Genetic map metric cM percent recombination
• Recombination a new combination of alleles
• Independent assortment is 50 recombination
• so yes! unlinked genes recombine!

2
Genes on the same chromosome

• Are syntenic (on the same thread)
• Are physically linked
• May or may not be genetically linked
• if close together, the frequency () of
  recombination will be low and they will be
  genetically linked
• if far apart, a crossover will occur in every (or
  nearly every) meiosis and they will exhibit 50
  recombination - unlinked

3
The phase problem - key to assessing
recombination

• Remember co-segregation traveling together
  through the generations (through meioses)
• must determine what comes in and what goes
  out from an individual
• The evaluation of whether a gene allele
  combination is recombinant or not is founded on
  knowledge of the linkage phase

4
Linkage phase - essential for determination of
recombination

• Generally, need information across 3 generations
  (grandparents, parents, offspring)
• Haplotype linear array of alleles
• An informative meiosis is one where we can
  identify the gamete haplotype and whether or not
  it is recombinant

5
Special problems for human recombination analysis

• Small families (small sibships), not all matings
  are informative
• Therefore, must combine data across unrelated
  families and estimate lod score
• relative likelihood (odds) of obtaining the
  observed data when 2 loci are linked at a set
  recombination fraction (theta) compared to being
  unlinked
• test data at various theta values