gene linkage, crossing over & chromosome mapping
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GENE LINKAGE,
CROSSING OVER
& CHROMOSOME MAPPING
Molecular Basis for Mendel’s Postulates
Unit factors in pairs
A pair of genes controls a trait
Dominance / Recessiveness
For different alleles, one will be expressed over
the other
Segregation
Chromosomes separate during meiosis
(each gamete receives 1 copy of a gene)
Independent Assortment
Genes for different traits are assorted
independently of each other during gamete
formation
Linkage
Genes contained on the same chromosome
are “linked”
Do not assort independently
Form linkage groups
Complete linkage = traits always associated together
Why would linked genes NOT assort
together?
Crossing Over
A random exchange of DNA between two
non-sister chromatids of homologous
chromosomes
Occurs during…?
Results in recombination of genetic material
Prevalence of recombination is dependent
on the distance between linked genes
Assortment, Linkage & Crossing Over
Fig. 7-1
Assortment, Linkage & Crossing Over
Fig. 7-1
Assortment, Linkage & Crossing Over
Fig. 8-1
Which of Mendel’s postulates is
violated when genes are linked?
A) Unit factors exist in pairs
B) Law of dominance
C) Law of segregation
D) Law of independent assortment
Single Cross Over (SCO) Events
Occurrence “outside”
linked genes…
Not phenotypically
detectable
Occurrence between
linked genes…
Parental gametes and
recombined gametes
Max. 50% gametes
show recombination
Fig. 8-5
Multiple Cross Over Events
2 or more crossovers between non-sister
chromatids
Ex., DCO’s (double crossovers)
Need 3 linked gene pairs to observe
Fig. 8-7
Which type of crossover event is most
common between two linked genes?
A) Single crossover
B) Double crossover
C) Triple crossover
Chromosome Mapping
Can use the knowledge of gene linkage and
crossover to…
Determine the order of genes on the
chromosome
Determine how far apart genes are on the
chromosome
Construct a map of the chromosome
Estimating Gene Distance
Based on observed crossover frequencies
between two genes
> frequency = > distance
Morgan & Sturtevant
X-linked mutations in Drosophila
Yellow body (y)
White eye (w)
Miniature wings (m)
Yellow, White, Miniature Experiments
Fig. 7-3
Yellow, White, Miniature Experiments
Fig. 7-3
Yellow, White, Miniature Experiments
Recombination frequencies
yellow, white 0.5%
white, miniature 34.5%
yellow, miniature 35.4%
Chromosome map
Distance in map units (mu)
Fig. 7-4
Practice – 2-point mapping
Three-Point Mapping
Three requirements
Organism producing crossover gametes must be
heterozygous for all traits considered
Phenotype must reflect genotype of parental
gametes (cross hetero x homozygous recessive)
Need enough progeny to recover representative
samples of all crossover classes
Practice – 3-point mapping
Phenotype Number
Ly Sb br 404
+ + + 422
Ly + + 18
+ Sb br 16
Ly + br 75
+ Sb + 59
Ly Sb + 4
+ + br 2
Total 1000
Practice – 3-point mapping
• What is the arrangement of alleles
on heterozygous parent?
– Look for most frequent phenotypes
– Not necessarily the right order, but the
right grouping of alleles
Practice – 3-point mapping
• Find correct sequence
– Look for which grouping yields observed
double crossover phenotypes
– Consider one set at a time until you find
the right one
– E.g.,
Practice – 3-point mapping
• Find correct sequence
– Previous wasn’t right. Which of these is?
Practice – 3-point mapping
• Now, find distances between loci
Practice – 3-point mapping
• Put it all together into a map
– Remember, the original problem gave you
assigned locations for two of the loci
already
Linkage & Mapping in Haploid Organisms
Haploid organisms as a genetic model:
Easy & cheap to maintain
Phenotypic expression is simplified
Mating of two strains produces a diploid
zygote, which subsequently undergoes
meiosis to produce tetrads
Tetrad analysis yields information about
frequency of crossing over
Linkage & Mapping in Haploid Organisms
Mapping the centromere
Where is a gene, relative to the centromere of its
chromosome?
Where is a second gene, relative to the
centromere of the same chromosome?
Together, you can deduce the relative location of
the genes with regards to each other
d = (1/2) * crossing over frequency
i.e., d = (1/2) * 30/150 = 0.1 map units
Modern Chromosome Mapping
DNA sequencing
Can produce a physical map of a chromosome
Base pair distance
DNA markers
Restriction fragment length polymorphisms
(RFLPs)
Microsatellites
Single-nucleotide polymorphisms
Sister Chromatid Exchanges
• Exchange of genetic
material between sister
chromatids during
mitosis
• Use BrdU uptake as a
DNA synthesis marker
– Study cells after two
rounds of mitosis to
observe SCE
– *BrdU = bromodeoxyuridine,
a thymidine analog
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