Bios220

TA Oce Hours
Fall 2016
Science Learning Center Darwin
M

TH

Xin

Yesha

10

ValenEna

11

Alexis
Kim

12

Sarah

Lorna

Rashida

John

Deanna

Jenny

Madu

Lec

Lec

Lec

Lec

Disc

Lecture 5.
Linkage and Recombination
Summary of Independent Assortment
Linked genes are inherited together:
modified Mendelian ratios

Linked genes are separated by crossing over

effect on gametes and on linkage
constant for one gene pair (0.001% to 50%)
Random incidence, a few per meiosis per chromosome
Linear map for each chromosome (linkage group)
Linkage map predicts linkage for all crosses

 Independent Assortment
Two genes are inherited independently
Each gene is located on a dierent chromosome
Alleles of the gene segregate during gamete
formaEon
Alignment of tetrads is random at MI

Frequency of F2 phenotypes can be obtained

by the product law of probabiliEes
Product rule states that the probability of
independent events BOTH occurring together is
the PRODUCT of their individual probabiliEes

 Independent Assortment

T ()
( ) ( ) 27/64 Y_R_T_

R
()
( ) 9/64 Y_R_b

t ()
Y
T () (
) ( ) 9/64 Y_rr T_


r

) 3/64 Y_rr b
t () ( ) (
23=8

T ( ) ( ) () 9/64 yy R_ T_
R

t ( ) ( ) ( ) 3/64 yy R_ b
y
T ( ) ( ) ( ) 3/64 yy rr T_

r
t ( ) (
) ( ) 1/64 yy rr b

Independent Assortment leads to

Extensive GeneEc VariaEon
Mendel studied 7 dierent traits (genes) with a simple
dominant/recessive pabern of inheritance with each trait
located on a dierent chromosome
If he made a heterozygote and crosses it to a homozygous
recessive individual
27 or 128 dierent phenotypes of pea would result in the
progeny of this testcross
In humans, we could calculate the possible geneEc variaEon
due to independent assortment
223 gamete combinaEons = 8 X 106
Each ospring (8 X 106)2 = (64 X 1012) potenEal geneEc
combinaEons

AA BB aa bb

For genes independently assorEng (on

dierent chromosomes, what is the
frequency of these gametes?

For genes independently assorEng (on

dierent chromosomes, what is the
frequency of these gametes?

Linkage
How many genes are present in the human
genome?
25,000 to 30,000 genes

How many chromosomes in humans?

23 homologous pairs

Conclusion- Many genes on each chromosome

Genes located on the same chromosome should not sort
independently
Genes located close together on the same chromosome
are called linked genes and belong to a linkage group

Inheritance of genes located on the

same chromosome
Linked genes do not strictly follow Mendels rules
of independent assortment, rather they tend to
be inherited together
This tendency to be inherited together requires a
new approach to understand their inheritance
and new approaches to predict the types of
ospring produced
A key to understanding the inheritance of linked
genes is to remember that genes are located on
chromosomes and the behavior of chromosomes
during gamete formaEon (meiosis).

Mendelian Inheritance
in Eight rules and deniEons
-ExcepEons to the rules

1.
2.
3.
4.
5.
6.
7.
8.
9.

Gene is necessary to produce trait (phenotype)

Two copies of each gene per cell
MulEple forms of genes: Alleles
Genes determine phenotype
Genes are transmibed intact
SegregaEon of gene pairs into gametes
Zygote: one allele from each parent
Independent Assortment of genes
Linked genes do not assort independently

Linked genes and Crossing Over

Genes closely linked together on the same
chromosome usually segregate as a unit
However, we know that crossing over between
homologous chromosomes occurs during meiosis
Crossing over results in recombinaEon of the
associaEon of linked genes
Linkage keeps genes together and crossing over mixes
them up
Concept of linked genes adds an addiEonal factor to
consider when interpreEng the results of a geneEc
cross
With an understanding of how linkage aects heredity,
predicEon of progeny produced from a cross is possible

NotaEon
Unlinked genes
A/a; B/b or Aa; Bb

Linked genes
AB/ab or Ab/aB

A B C A B C + + + Ab
a b c or a b c or a b c aB

Linkage relaEonship unknown
A/a B/b

Compare complete linkage versus

independent assortment

Genes on different chromosomes

assort independently
d d D D
ad

AD

P1: A/A;D/D X a/a; d/d

F1: Aa;Dd
What type of gametes are
produced?

OR
D D d d
aD

Ad

AD : Ad : aD : ad
1 : 1 : 1 : 1
P

Genes on the same chromosome do not

assort independently
d d D D
ab
d

AB
D

P1: AB/AB; D/D X ab/ab; d/d

F1: AB/ab; Dd
What type of gametes are
produced?

OR
D D d d
ab
D

AB
d

Overall result
for A, D:
AD 1 P
Ad 1 R
aD 1 R
ad 1 P

for A, B:
AB 2 P
Ab 0 R
aB 0 R
ab 2 P

P1: AB/AB x ab/Ab

F1 x F1: AB/ab x AB/ab

F1: AB/ab
AB

Ab
0.5

F1: AB/ab

AB
Ab

0.5
0

aB

ab

0.5

aB
0

ab

0.5

AB/AB AB/Ab AB/aB AB/ab

1/4

1/4

Ab/AB Ab/Ab Ab/aB Ab/ab

0

aB/AB aB/Ab aB/aB aB/ab

0

ab/AB ab/Ab ab/aB ab/ab

1/4

Non-Mendelian F2 ratios
for linked genes:

0
A_ B_
aa B_
A_ bb
aa bb

1/4

TesEng for Linkage using a testcross

directly reveals linkage
A testcross between a heterozygote to a
homozygous recessive
Heterozygote with linked genes produces two types of
gametes
A B or a b

Homozygote recessive produces only one type of

gamete
a b

Result of cross: yields parental ospring AB and ab

Result of cross: no recombinants in ospring
Ab or aB not observed

Testcross for linked genes directly reveals linkage

P1
AB/AB x ab/ab
F1
AB/ab
P2
F1 x tester ab/ab = AB/ab x ab/ab
F1: AB/ab

AB
1

Ab

aB

ab

ab AB/ab Ab/ab aB/ab ab/ab

1/2

1/2

1 : 1 AB/ab : ab/ab
not
1:1:1:1 AaBb:Aabb:aaBb:aabb.
Thus, F2 is 1:1 AB:ab
i.e., only parental gametes were made by F1

Linkage with crossovers versus

independent assortment

Non-sister chromaEds break and join reciprocally

at Meiosis prophase I, creaEng a crossover

Aver a crossover, a single meiosis yields both parental

and recombinant type gametes

Non-sister chromaEds break and join reciprocally

at Meiosis division I, creaEng a crossover

Aver a crossover, a single meiosis yields both parental

and recombinant type gametes

Linked genes segregate differently

after a crossover event

Linkage Analysis
How oven does crossing over occur?
Depends on how far apart the two genes are
Case 1: so close that they never cross over
Case 2: far enough that they oven cross over
Case 3: so far apart they always cross over

The % of recombinant chromosomes

is characterisEc of each gene pair
and mainly reects
gene-gene distance

A testcross gives % recombinaEon directly

Analysis of a cross
P Tall, Red X short, white
F1 All Tall, Red
What does this result tell us?
Tall is dominant to short
Red is dominant to white

F1 X short, white (testcross)

123 progeny

55 are Tall, Red

53 are short, white
8 are Tall, white
7 are short, Red

What does this result tell you?

If these were two independently assorEng genes what raEo would you
expect?
1:1:1:1
Do these results t that raEo?

CalculaEng RecombinaEon Frequency

The % of recombinant progeny produced in a
cross is the recombina@on frequency
RecombinaEon frequency is calculated as follows
recombinant = # of recombinant progeny X 100%
frequency Total # of progeny

Testcross of F1Tall, Red X short, white

8 + 7 X 100% = 15 X 100% = 12.2%
55 + 53 + 8 + 7 123

Testcross for linked genes with 20 % recombination

P1
F1
P2

AB/AB x ab/ab
AB/ab
F1 x tester ab/ab = AB/ab x ab/ab

F1: AB/ab

AB

Ab

aB

ab

ab

Testcross for linked genes with 20 % recombination

P1
F1
P2

AABB x aabb
AaBb (AB / ab )
F1 x tester aabb = AaBb x aabb

F1: AB/ab

AB
ab

Ab

aB

ab

Testcross for linked genes with 20 % recombination

P1
F1
P2

AABB x aabb
AaBb (AB / ab )
F1 x tester aabb = AaBb x aabb

F1: AB/ab

AB

Ab

aB

ab

ab AB/ab Ab/ab aB/ab ab/ab

P

RF (recombinaEon frequency)
= (R gametes)/(total P+R)

Linkage Map
From linkage analysis, we know that A and B
are on the same chromosome
There is 20% recombinaEon between A and B
From crossovers, we know they are 20 map
units apart
A

20 Map units

 Cause of recombinaEon
Ind. Assortment
Cross-overs

Complete Linkage (none)

Frequency of recombinaEon

0.5
0 < R < 0.5

0

A set of linked genes with R < 50% forms a linkage group.
Linkage groups can be arranged on linear geneEc maps, with
one map unit (cenEMorgan) = distance between two genes
with R =1%.
Number of linkage groups = Number of chromosomes