Lecture 5. Linkage, Recombination and the Mapping
of Genes on Chromosomes
I. Importance
Reconciled exception of independent assortment with mendelian genetics
Establishing linkage of a trait with markers is the FIRST step in
the full genetic description of a gene
II History
Bateson and Punnett, deviation from 9331 ratios in sweet peas
F1 produced far more parental type of gametes than should have
been produced by independent assortment
X-chromosome linkage
Homologous chromosomes occasionally exchange parts in a process
called crossing-over
The new combinations are called crossover products
The crossover corresponds
to chiasmata
Used the chromosome theory of gene location to provide a physical
explanation of the genetic results
Linkage: when 2 loci are on the same chromosome
Meiotic recombination: any meiotic process that generates a
haploid product with a genotype that
differs
from both haploid genotypes that make-up the meiotic diploid cell. Recombination
occurs by
independent
assortment
Linkage Maps: Why does the amount of recombinant gamete types or
strength of linkage vary so much
from
locus to locus???
Sturtevant: The amount of recombination is proportional to the
distance on a genetic map and
roughly
corresponds to the distance between loci on a chromosome.
Recombination frequency (RF) can be used to mark distance apart
genes are from one another
1% RF = 1 centimorgan or 1 map unit (cM, m.u.)
Three-point cross
observed:
0.123 x 0.064 = 0.0079 =
0.79%
(13 + 9)/4197 = 0.0052 = 0.52%
Chromosomal interference- the occurrence of one crossover lowers
the chance of another crossover
occurring
nearby
Coefficient of coincidence = Frequency observed/Frequency expected;
0.52/0.79 = 0.66
Interference = 1 – Coeff. Coincidence = 0.34 and varies from 0-1
IV. Evidence for Recombination
V. Quantitative Tests for
VI. Tetrad Analysis
Fungal life cycles
Unordered Tetrad Analysis
When PD = NPD then loci are unlinked;
PD>NPD then loci are linked
Parental haploid cells:
arg3 ura2 x
F1 Diploid cell: arg3 ura2
/ Arg3 URA2
Meiosis
PD NPD
T
arg3
ura2 arg3 URA2 arg3 ura2
arg3
ura2 arg3 URA2 arg3 URA2
127 3 70
All spores in an NPD are recombinant; ½ spores in a
Tetratype are recombinant
RF = (NPD +1/2(T))/Total tetrads x 100
= (3 + 1/2x70)/200 x 100 = 19 m.u.
Same result if you examine each individual spore:
200 tetrads, of which each the 3 NPD’s have 4 recombinants and
each of the 70 T have 2 recombinants or
(12 + 140)/800 x 100 = 19 m.u.
Tetrad analysis confirms that recombination occurs at the 4-strand
stage
Only ¼ of all rarer double cross-overs = NPD
T >> NPD when there is linkage
Thus recombination occurs after the chromosomes have replicated,
when there are 4-chromatids for each pair
of
homologues.
Since recombination occurs after duplication then upper limit of
50% Recombination for genes on same
chromosome:
single x-over = 50%
½ double x-over
generate Non parental combinations and ½ parental combinations
Tetrad analysis reveals that recombination
is
USUALLY reciprocal
no
new alleles are formed?
both
classes of recombinants are found in equal frequency almost all of the time-
more later
Ordered Tetrad Analysis
Numerical example of Ordered-Tetrad Analysis
Tetrad
Group A B C D E F G
Seg. t a
t
a t a
t a+ t
a+ t a+ t a
Pattern t a
t+ a t
a+ t+ a t+
a t
a+ t+ a+
t+
a+ t+ a+ t+
a t+ a+ t+ a t+
a t+ a+
t+ a+ t
a+ t+ a+ t
a t a+ t+
a t a
Total 72 16
11 2
2
1 1
(105)
Centromere-t distance: (16 + 2 + 2 + 1)/105 x 100 = 10 mu
Centromere-a distance: (11 + 2 + 2 +1)/105 x 100 = 7.6 mu
Are t and a linked? PD (72 + 1) >>NPD (2+1)
RF = (NPD + 1/2T)/Total x 100
= (2 + 1 + ½(16 + 11 +
2))/105 x 100 = 16.7 m.u.
Because genes are on chromosomes they can be physically linked to
one another.
The amount of recombination between genes (loci) can be used to
quantify the distance between genes.
VIII. Terms/Concepts to know:
Recombination, homologous chromosome, recombination frequency,
centimorgans, map unit,
chromosomal interference, coefficient of
coincidence,interference, Chi-square,
ordered and unordered tetrad analysis, parental
ditype, nonparental ditype, tetratype,
HOW TO