Linkage and Gene Mapping

Linkage and Gene Mapping

Objectives:

After completing this section, you should be able to..

1. Define linkage, loci, locus and crossover.

2. Contrast the inheritance of genes that are linked vs. those that are independent.

3. Define a map unit and calculate map distance.

4. Describe the relationship between map unit or linkage distance and physical distance between loci.

5. Assemble linkage maps from inheritance data in test cross and F2 families.

6. Predict the frequency of offspring with specific trait combinations or genotypes using mapping information.

7. Define a genetic marker, linkage group, and genome map.

8. Describe why DNA markers are valuable in gene mapping.

Key Terms:

Recombination frequency

Recombinant gamete

Parental gamete

2 point cross

3 point cross

Linkage map

Linkage group

Genome map

Locus

Loci

Crossover

Double crossover

DNA marker

Online Lessons:

Linkage Part I

Linkage Part II

(http://plantandsoil.unl.edu)

Linkage

Test Cross: Genetic test to detect linkage

Key questions: 1) What types of gametes are produced?

2) In what frequencies are the different kinds produced?

Answers: Classify gametes on the basis of phenotypes the zygotes produce.

Why? Each type of gamete produced by the heterozygote produces a unique phenotype if there is no epistasis.

AaBb ab

AaBb
Aabb
aaBb
aabb

Testcross example in corn: Are the genes for iojab and glossy linked?

I_ solid green leaf, dominant

ii iojap, recessive

G_ normal leaf surface, dominant

gg glossy leaf surface, recessive

cross two true breeding plants:

solid green, normal IIGG x iojap, glossy iigg

F1 solid green, normal IiGg

Testcross IiGg x iigg

Phenotype heterogamete observed expected if independent

solid, normal IG1 508 1/4 300

solid, glossy ig2 94 1/4 300

iojap, normal iG2 98 1/4 300

iojap, glossy ig1 500 1/4 300

The observed results vary from the 1:1:1:1 ratio expected if the genes were independently assorting, therefore linkage is suggested.

Linkage

What types of gametes are produced?

1. parental types – The same gene combinations that united to form the

heterozygotous parent.

2. recombinant types – Gene combinations that differ from those that united

to form the heterozygous parent.

In what frequencies are the different gametes produced?

Parentals Recombinants

IG 508 Ig 94

Ig 500 iG 98

1008 192

Convert each to % of total gametes:

Parental gametes 1008/1200 = 84%

Recombinant gametes 192/1200 = 12%

The deviation from equal frequencies indicates linkage. These two genes are on the same chromosome pair (#7).

Why aren’t all the gametes parental type, if the genes are on the same chromosome?

What would be the result of the test cross if the heterozygous F1 had been produced another way?

Parents: solid, glossy x iojap, normal

I g i G

Gametes: I g i G

F1 I g x i g

i G i g

Testcross results:

gametes from classification

heterozygote phenotype of gamete frequency

IG solid, normal recombinant 8

Ig solid, glossy parental 42

iG iojap, normal parental 42

ig iojap, glossy recombinant 8

Recombination Frequencies – same as the other experiment

Parental: Ig 42 84% recombinant IG 8 16%

iG 42 ig 8

Frequency of recombinant gamete production…

__A. Depends on which alleles are found at two linked loci (ie. Crossovers happen more between two dominate alleles)

__B. Depends on the distance between loci, not the alleles at two loci.

Linkage

Parentals -- The most frequent class of gametes

Recombinants -- Those that result from crossover

Features of Crossing Over:

*Reciprocal exchange of chromosome segments, break and rejoin

*Occurs during prophase I of meiosis

*Random event, probability increases with increasing distance between loci.

______

Parental gametes from a dihybrid can have either dominant genes, recessive genes, or both depending on the status of the initial parents.

Cis (coupling) – condition in a dihybrid in which 2 dominant liked genes came from one parent and their recessive alleles came from the other parent.

I G Cis heterozygote

i g

Trans (repulsion) – condition in a dihybrid in which a dominant gene and a linked recessive came one parent and their alleles came from the other parent.

Trans

i G heterozygote

I g

______

When parental type gametes are significantly more frequent than recombinant gametes we can suspect linkage.

Steps in Determining Linkage

1) Produce a dihybrid (AaBb)

2) Determine what gametes are produced by the heterozygote and the frequency of each.

Testcross: Direct method (why?)

F2: More complex results (why?)

F2 Segregation Data with Linkage

Coupling

I G x i g

Parents

I G i g

I G

i g

0.1764
IIGG / 0.0336
IIGg / 0.0336
IiGG / 0.1764
IiGg
0.0336
IIGg / 0.0064
IIgg / 0.0064
IiGg / 0.0336
Iigg
0.0336
IiGG / 0.0064
IiGg / 0.0064
iiGG / 0.0336
iiGg
0.1764
IiGg / 0.0336
Iigg / 0.0336
iiGg / 0.1764
iigg

F2 IG .42 Ig .08 iG .08 ig .42

.42 IG

.08 Ig

.08 iG

.42 ig

I_G_ I_gg iiG_ iigg

.1764 .0336 .0336 .1764

.0336 .0064 .0064

.0336 .0036 .0036

.1764 .0736 .0736

.0064

.1764

.0336

.6764

Repulsion

F2 IG .08 Ig .42 iG .42 ig .08

IIGG / IIGg / IiGG / IiGg
IIGg / IIgg / IiGg / Iigg
IiGG / IiGg / IiGG / iiGg
IiGg / Iigg / iiGg / iigg

.08 IG

.42 Ig

.42 iG

.08 ig

How would you calculate gamete frequency if you had collected

Phenotype data on the F2 offspring?

F2 Linkage problem

B_is normal eyes bb is blind

G_is grey gg is white

BBGG X bbgg ------give BG / bg

BG / bg X BG / bg give the F2

F2 phenotypes : grey, normal 622

grey, blind 128

white, normal 127

white, blind 123

F2 Linkage problem

BBgg X bbGG ------give Bg / bG

Bg / bG X Bg / bG give the F2

F2 phenotypes: grey, normal 523

grey, blind 227

white, normal 228

white, blind 22

BG / bg X bbgg: grey, normal 381

grey, blind 162

white, normal 168

white, blind 389

Lean Angus

Assume that in angus cattle… B (10 map units) F

B___ black F___ fatty

bb red ff lean

1) Red lean x Black fatty

F1 BbFf x red lean