Linked genes
Genes on the same chromosome
Linkage group
Group of genes located on the same chromosome
- It corresponds to the haploid number of chromosomes
To provide a simplified (hopefully) overview of the major theme of this chapter, we will discuss the types and relative proportions of gametes produced by an individual that is heterozygous for two genes, A and B.
1. Genes A and B are on two different chromosomes
2. Genes A and B are on the same chromosome and very very close to each other
3. Genes A and B are on the same chromosome and not so close to each other
4. Genes A and B are on the same chromosome and very very far from each other
1. Genes A and B are on two different chromosomes
- The gametes in this case are produced in equal proportions
2. Genes A and B are on the same chromosome and very very close to each other
- This is termed complete linkage
- The gametes in this case are produced in equal proportions
3. Genes A and B are on the same chromosome and not so close to each other
- This is termed incomplete linkage
- The gametes in this case are produced in unequal proportions
4. Genes A and B are on the same chromosome and very very far from each other
- This is termed complete incomplete linkage
- The gametes in this case are produced in equal proportions
Alleles and Genetic Symbolism
� Alleles are alternative forms of same gene
Wild Type allele
- Occurs most frequently in the natural population
- Arbitrarily designated as normal
- Responsible for the normal function and the wild-type phenotype
- When mutated gives new alleles
- New alleles often change the activity of the cellular product of the gene
=> a change in the phenotype
Alleles for simple Mendelian traits are symbolized with lowercase letters for recessive alleles and uppercase letters for dominant alleles
� Note: The names of genes are usually written in italics
Alleles for another useful system was developed in Drosophila
- The symbol for a gene comes from the first mutant strain found
- The mutant allele is denoted by the initial letter, or a combination of two or three letters
- The wildtype allele is denoted by the same letter(s) but with a + superscript, or simply by the + symbol
- If the mutant trait is recessive, the lowercase form is used
- If the mutant trait is dominant, the uppercase form is used
1. Ebony is a recessive body color mutation
e = ebony e+ = gray
e+e+ Gray homozygote
e+e Gray heterozygote
e e Ebony homozygote
2. Wrinkled is a dominant wing-shape mutation
Wr= Wrinkled Wr + = Normal
Wr +Wr + Normal Wing Shape
Wr +Wr Wrinkled Wing Shape
Wr Wr Wrinkled Wing Shape
Cross A
y = yellow body y+ = gray body
w = white eyes w+ = red eyes
P yellow body, white eyes X gray body, red eyes
Cross B
m = miniature wing m+ = wild-type wing
w = white eyes w+ = red eyes
P miniature wing, white eyes X wild-type wings, red eyes
Questions
1. What was the source of recombinant offspring?
2. Why is the frequency variable?
Based on these experiments
Morgan hypothesized that genes occurred in a linear array on a chromosome, and that the linkage could only be modified by crossing over
Concluded from Morgan's two aforementioned experiments that
Y is closer to w than it is to m
AND, with one more cross, the relationship between y and m can be established
- There are two choices:
Y W M
W Y M
- If first choice ==> RF of y - m > RF of w - m
- If second choice ==> RF of y - m < RF of w - m
Sturtevant considered two other X-linked genes and constructed the first chromosomal map
- He proposed that the percentage of recombinants be used as a quantitative measure of the
distance between two gene pairs of a genetic map
- Recombination Frequency = # of recombinant offspring/total # of offspring
Genotypic Notations
� Different notations are used to present genotypes:
yy ww Linkage arrangement of the loci is unknown
yw / yw Loci are on the same chromosome
y/y w/w Loci are on different chromosomes
...
Two possible configurations exist for a genotype that is heterozygous for two linked genes: (Fig. 5.2)
1. Cis or Coupling m+ w+
m w
2. Trans or repulsion m w+
m+ w
Crossing Over
� The physical exchange between non-sister chromatids of homologous chromosomes
� Crossing-over has the following features:
- It occurs in prophase I of meiosis, when the four chromatids are closely synapsed
- It occurs more or less randomly along the length of a chromosome pair
- It involves a reciprocal exchange of equal and corresponding segments
Crossing Over is Not detectable if it occurs:
-outside the region between the two marker genes
- An even number of times between the two marker genes
� In a single tetrad, multiple crossing-overs are possible
Genetic mapping in plants and animals
Genetic mapping is also known as gene mapping or chromosome mapping
� Its purpose is to determine the linear order of linked genes along the same chromosome
� Figure 6.8 illustrates a simplified genetic linkage map of Drosophila melanogaster
� Genetic maps allow us to estimate the relative distances between linked genes, based on the likelihood that a crossover will occur between them
� Experimentally, the percentage of recombinant offspring is correlated with the distance between the two genes
- If the genes are far apart many recombinant offspring
- If the genes are close very few recombinant offspring
Map distance = Number of recombinant offspring/total number of offspring x 100
�The units of distance are called map units (mu)
- They are also referred to as centiMorgans (cM)
- One map unit is equivalent to 1% recombination frequency
Genetic distance between two loci may be represented as a
1. Frequency of recombination
2. Percent recombination
3. Map distance in map units
4. Map distance in centriMorgans
Genetic mapping experiments are typically accomplished by carrying out a testcross
- A mating between an individual that is heterozygous for two or more genes and one that is homozygous recessive for the same genes
� Figure 6.9 provides an example of a testcross
- This cross concerns two linked genes affecting bristle length and body color in fruit flies
Morgan's Trihybrid Cross
Morgan actually did a trihybrid cross involving all three X-linked traits we discussed earlier
- Body color
- Eye color
- Wing length
� Refer to Figure 6.3
Morgan observed a much higher proportion of the combinations of traits found in the parental generation
- His explanation:
- All three genes are located on the X chromosome
- Thus, they tend to be transmitted together as a unit
Three Point Test Cross
Involves the analysis of three loci, each segregating two alleles
� Three criteria must be met for a successful mapping cross:
1. Genotype of organism producing recombinant gametes must be heterozygous at all loci in question
2. Cross must be constructed so that genotypes can be deduced from phenotype
3. A large number of offspring must be produced
If the 3 loci are unlinked ==> the trihybrid produces 8 types of gametes
0
If the 3 loci are completely linked ==> the trihybrid produces 2 types of gametes
0
If the 3 loci are incompletely linked ==> the trihybrid produces 8 types of gametes
0
Steps to follow:
1. Arrange data in reciprocal classes
F2
y w ec 4685
y+ w+ ec+ 4759
y w+ ec+ 80
y+ w ec 70
y w ec+ 193
y+ w+ ec 207
y w+ ec 3
y+ w ec+ 3
2. Identify the parental classes as the most frequent phenotypes in the progeny
3. Identify the double recombinants as the least frequent phenotypes in the progeny
4. Determine the gene order in the following manner
- Compare P to DCO classes
- The gene that is interchanged represents the inside locus
5. Assign single cross-overs to the region involved
6. Calculate the frequencies of recombination
7. Draw the genetic map
RF (y-w)=
(80+70+3+3)/10,000
156/10000
0.0156
1.56%
RF (w - ec) =
(193+207+3+3)/10,000
406/10,000
0.0406
4.06
Therefore, MAP is
Y w ec
1.56 4.06
Map distances computed this way are Additive ==> distance between y & ec =
1.56+4.06=
5.62 map units
This estimate can be verified by directly calculating the average # of recombinants between the "y" and "ec" loci
- RF (y - ec) =
(80+70+193=207+(3+3)2/10,000
0.0562
5.62 m. u.
- Note: DCO are counted twice because each represents a double recombinant class
Interference
Are cross-overs in adjacent regions of a chromosome independent of one another or do they affect each
other in some way?
� In reality, once one CO event has occurred, the likelihood of a second CO in the same region can be altered
Let us use the last example
- y is 1.56 map units from w ==> the probability of a CO between y and w is 0.0156
- w is 4.06 map units from ec ==> the probability of a CO between w and ec is 0.0406
- Thus the probability that there will be a CO between y & w and between w & ec is 0.0156x0.0406= 0.000634
- The observed number of offspring = 10,000
==> Expected number of DCO recombinants out of 10,000 offspring is 0.000634x10,000=6.4=34
- SO we see a reduction in DCO from the expected, or Interference
- Quantification of this Interference is
- I = 1 - C where C is the coefficient of coincidence
C=Observed DOC/Expected DOC
In our example
6/6.34=0.946
Therefore, 1-0.946=0.054
If observed DCO=0
I=1
Complete interference
If observed DCO=expected DCO
I=0
No interference
If observed DCO < expected DCO
I>0
Positive interference
If observed DCO > expected DCO
I<0
Negative interference
Interference is not equivalent
in all parts of a chromosome or among the different chromosomes of a given compliment