Fundamental Genetics

Lecture 8

Linkage and
Chromosome Mapping
in Eukaryotes
John Donnie A. Ramos, Ph.D.
Dept. of Biological Sciences
College of Science
University of Santo Tomas

Linked Genes
‰ Genes located in the same
chromosomes
‰ Initiated by Thomas Morgan and
Alfred Sturtevant
‰ Will not segregate independently
‰ Affected by crossing over

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Linkage vs Independent Assortment

Linked Genes in Drosophila

‰ Red eyes (bw+) dominant to
mutant brown eyes (bw)
‰ Thin wing veins (hv+) dominant to
mutant heavy wing veins (hv)

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X-Linked Genes in Drosophila
Cross A
‰ Gray body (y+) dominant
to mutant yellow body (y)
‰ Red eyes (w+) dominant to
mutant white eyes (w)

Cross B
‰ Red eyes (w+) dominant to
mutant white eyes (w)
‰ Normal wings (m+)
dominant to mutant
miniature wings (m)

‰ Due to linkage and

crossing over that occurred
during meiosis
‰ Distance between linked
genes is related degree of
crossing over

Chromosome Mapping
‰ Determining the distances between genes and the order
of sequence in a chromosome
‰ Uses the frequency of crossing
‰ The shorter the distance between linked genes, the lower the
frequency of crossing-over.
‰ The longer the distance, the higher the frequency of crossing over
to occur.
‰ Frequencies of crossing over:
1. Yellow, white 00.5 %
2. White, Miniature 34.0 %
3. Yellow, miniature 35.4 %

‰ 1% of crossing over = 1 map unit (centimorgan, cM)

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Distance Affects Crossover

Single Crossover

‰ 50% are recombinant gametes

‰ 50 % non-crossover gametes
‰ If distance between genes is more than 50 map units,
~100 % crossing over will occur.

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Multiple Crossover

‰ Occurrence of more than one crossovers between non-sister

chromatids.
‰ Produces double crossover (DCO) gametes
‰ If the probability of crossover between A and B is 20% (0.20)
and the probility of crossover between B and C is 30% (0.30),
the frequency of DCO is 6 % (0.06)
‰ Product Law: (0.2)(0.3)=0.06

Three-Point Mapping
‰ The percentage of crossing over could be used
to map genes in a chromosome
‰ Three criteria needed for successful mapping:
‰Genotypes of organisms producing the
crossover gametes must be heterozygous
for all gene loci
‰Cross must be constructed so that the
genotypes of gametes could be determined
based on the phenotypes of the offspring.
‰Large number of offspring must be
produced

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Traits considered:
1. Body color
Gray(y+)
dominant to
yellow (y)
2. Eye color
Red eyes (w+)
dominant to
white (w)
3. Eye shape
Normal (ec+)
dominant to
echinus (ec)

10,000

Determining Gene Sequence

Steps:
‰ Determine 3 possible orders
‰ w-y-ec (y at the middle)
‰ y-ec- w (ec at the middle)
‰ y-w-ec (w at the middle)
‰ Perform a theoretical double cross over
‰ Compare the theoretical DCO with actual DCO (least no.)
‰ Perform theoretical NCOI and NCOII and compare with data

White echinus eyes, gray body

Red normal eyes, yellow body

Yellow body, normal white eyes

Gray body, echinus red eyes

Yellow body, echinus red eyes

Gray body, white normal eyes

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Unknown Gene Sequence

Total=1109

Unknown Gene Sequence

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Not all crossovers can be detected

Degree of inaccuracy increases with

increasing distance between linked genes

Observed vs Expected DCO

‰ Observed DCO = double cross-over that actually

occurred
‰ Example: (44 + 42)/1109 = 0.078

‰ Expected DCO = theoretical double crossovers

‰ Product of all the SCOI and SCOII
‰ Example: (82+79+44+42) / 1109 = 0.223
(200+195+44+42) / 1109 = 0.434
DCO exp= (0.223)(0.434) = 0.097

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 Coefficient of Coincidence
and Interference
‰ Coefficient of Coincidence (C)
‰The measure of actual DCOs that occurred
‰C = Observed DCO / Expected DCO
= 0.078/0.097
= 0.804 or 80.4%

‰ Interference (I)
phenomenon when a crossover event in one region of a
chromosome inhibits a second event to occur in a nearby
region)
I = 1-C
= 1-0.804 = 0.196 or 19.6%

Interpretation: 19.6% of expected DCO did not occur or only

80.4% of expected DCO was observed

Problem 1
A stock of corn homozygous for the recessive linked genes colorless (c), shrunken
(sh), and waxy (wx) was crossed to a stock of homozygous for the dominant wild
type alleles of the genes (+ + +). The F1 plants were then backcrossed to the
homozygous recessive stock. The F2 results were as follows:

Phenotype Number Phenotype Number

+++ 17,959 + + wx 4,455
c sh wx 17,699 c sh + 4,654
+ sh wx 509 + sh + 20
c++ 524 c + wx 12

a. Determine the distance between the c and sh

b. Determine the distance between the sh and wx
c. Determine the distance between c and wx
d. Give the coefficient of coincidence
e. Compute for the interference

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Problem 1: Solution
c sh wx + + +
c sh wx
x + + +

c sh wx c sh wx
+ + + x c sh wx

NCO + + + = 17,959
35,658 = 77.80 %
c sh wx = 17,699
SCOI + sh wx = 509
c + + = 524 1,033 = 02.25 %
SCOII + + wx = 4,455
c sh + = 4,654 9,109 = 19.87 %
DCO + sh + = 20
32 = 00.07 %
c + wx = 12
Total = 45,832

Problem 1: Solution

Distance between c and sh = (509 + 524 + 20 +12) / 45,832

= 0.0232 or 2.32 %

Distance between sh and wx = (4466 + 4654 + 20 + 12) / 45832

= 0.1994 or 19.94 %

Distance between c and wx = 2.32 + 19.94

= 22.26

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Problem 1: Solution

c sh wx

2.32 mu 19.94 mu
22.26 mu

C = (0.0007) / (0.0232)(0.1984)
= 0.1521 or 15.21%

I = 1-C
= 1-0.1521
= 0.8479 or 84.79 %

Problem 2
In a variety of tomato plant, the mutant genes o (oblate fruit), h (hairy fruit), and c
(compound inflorescence) are all located in chromosome 2. These genes are recessive
to their wild type alleles round fruit, hairless and single inflorescence, respectively. A
testcross mating of an F1 heterozygote for all three genes resulted in the following
phenotypes:

Phenotypes Number Phenotypes Number

+++ 73 ++c 348
+h+ 2 +hc 96
o++ 110 o+c 2
oh+ 306 ohc 63

a. Determine the sequence of the 3 genes in chromosome 2

b. Give genotypes of the homozygous parents (P1) used in making the F1 heterozygote.
c. Compute for the map distances between the genes
d. Give the coefficient of coincidence and interference

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Problem 2: Solution
+++ ohc
x
ohc ohc Inference from given data:
‰ Sequence of genes is not correct
NCO: o h + = 306
‰ One chromosome contains 2 wild
+ + c = 348 type alleles while the homolog
DCO: +h+ = 2 contains the 3rd wild type allele

o+c = 2
Three possible orders of the genes involved:
oh+
‰o h c Find a sequence Satisfies NCO but not DCO
++c
‰o c h that will satisfy +ch
both NCO and Satisfies DCO but not NCO
o++
‰h o c DCO
+oh Satisfies both NCO and DCO
c++

Problem 2: Solution
+oh ohc Try if the sequence can
x
c++ ohc satisfy the SCOs

NCO: oh+ (same as + o h) = 306 654 = 0.654 or 65.4%

++c (same as c + +) = 348
DCO: +h+ (same as + + h) = 2
4 = 0.004 or 0.4%
o+c (same as c o +) = 2
SCO I: +++ = 73 136 = 0.136 or 13.6%
o h c (same as c o h) = 63
SCOII: o + + (same as + o +) = 110
+ h c (same as c + h) = 96 206 = 0.206 or 20.6%
Total = 1,000

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Problem 1: Solution

Distance between c and o = (73 + 63 + 2 + 2) / 1,000

= 0.140 or 14 % / cM

Distance between o and h = (110 + 96 + 20 + 12) / 1000

= 0.210 or 21 % / cM

Distance between c and wx = 14 + 21

= 35 cM

Problem 1: Solution

c o h

14 cM 21.0 cM
35 cM

C = (0.004) / (0.14)(0.21)
= 0.1361 or 13.61%

I = 1-C
= 1-0.1361
= 0.8639 or 86.39 %

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