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