BIN300- W2 Linkage between markers

Phase of the parents with genotype M1M2N1N2

M1N1/M2N2 (50%), M1N2/M2N1 (50%)

→ Phase either recombinant or non-recombinant gametes

Gametes transmitted from parent to offspring

All possible gametes (recombinant/non recombinant)

probabilities (as a function of Ɵ)

Identify gametes in offspring

sometimes not possble from gentoype information → non-informative offspring

Estimate recombination fraction

phase of the parents with genotype M1M2N1N2

Gametes transmitted from parent to offspring

Identify gametes in offspring

Non-infomrative offspring

•All heterozygots:

  M1N1/M2N2     *  M1N1/M2N2

  M1M2N1N2

•Some homozygots:

  M1N1/M1N2   *  M1N1/M2N1

  any possible offspring

For heterozygots not sure which chromosome came from which, also for homozygots

maximum likelihood estimation of Ɵ

From M1N1/M2N2 * M1N1/M1N1

Plot of likelihood function

Also possible for family

plot of Lfam (Ɵ)

What happens if there are more families for the likelihood:

multiply L(Ɵ) of each family

D

Detection of linkage

H0 = Ɵ = 0.5: unlinked, different chroms

H1: Ɵ = Ɵ1<0.5 (linked, same chrom)

LODscore

Z(Ɵ)>3: linkage (10³ = 1000 times more likely)

Design of mapping experiment

1 sire + 1 prog: 2 genotypings: 1 meiousis

1 sire + 10 prog: 11 typings: 11 meiosis

1 sire + 10 dams + 10 prog (HS fam): 21 typings: 20 meiosis

1 sire + 1 dam + 10 prog (FS fam): 12 typings: 20 meiosis

Large FS fams → most information

Homozygous parents are non-informative

need highly polymorphic markers

Design of mapping experiment - needs

Homozygous parents are non informative, need highly polymorphic marrkers, fullsib fams better than halfsib fams, larger families, small Ɵtrue → dense markers

linkage between SNPs

detected by linkage analysis

• study inheritance of marker alleles from parent to offspring, how many recombinants/nonrecombinants

best desing: large full sib families, fish ideal species

uses maximum likelihood (ML)

• write likelihood of data as function of parameters (Ɵ)

• ask computer to maximise this function by varying Ɵ, gives best recombiantion rate Ɵ