Chapter 7 – Linkage,
Recombination, and Eukaryotic
Gene Mapping
Genetic Principles
• Principle of Segregation
– Diploid organisms have 2 alleles for each
gene
• Separate during meiosis – only one gamete enters
each gamete
• Principle of Independent Assortment
– 2 alleles of a gene separate independently
from alleles at other loci/other genes
Chromosomes
• Chromosomes follow independent
assortment IF:
– Genes are located of different chromosomes
BUT:
– If genes are on the same chromosome, they
tend to travel together
• Linked genes – close together on the same
chromosome
Sweet peas – dihybrid cross
• P generation purple,
long x red, round
• F1 generation – all
purple,long
• Prediction for F2
generation – ratio of
9:3:3:1
Sweet pea – dihybrid cross cont
• Expected F2 phenotype
ratios is not observed
• Conclusion – genes for
flower color and pollen
shape must be located
close together on the
same chromosome
• Why are any recombinant
progeny seen?
Crossing over
• If 2 genes are on the same chromosome, but far apart,
crossing over can allow for recombination of gametes
• Genes very far apart on the same chromosome will
always be separated by crossing over, and are not
considered to be linked
Notation for linked genes
• Horizontal lines indicate actual
chromosome
A_________B
a
b
*individual heterozygous for 2 different genes where both
dominant alleles are on one chromosome, and both
recessive alleles are on its homologous chromosome
• Can be abbreviated by AB/ab
Testcross for linkage
• For determination if two genes are linked
(close together on the same chromosome)
or not
• Set-up:
– One individual heterozygous for both traits x
individual homozygous recessive for both
traits
Testcross for linkage cont
• MmDd x mmdd
• If not closely linked,
alleles will assort
independently
– MmDd individual can
form 4 different types
of gametes
– 50% recombinant
offspring/50% nonrecombinant offspring
Testcross for linkage cont
• MD/md x md/md
• If closely linked, 2
alleles will always
travel together
– all offspring are nonrecombinant
Testcross for linkage cont
• Can be separated by
crossing over
– Small number of
recombinant
progeny/chromosomes
is seen
Crossing over
• Single cross over produces 50%
nonrecombinant chromosomes (same
configuration as parental chromosome) and 50%
recombinant chromosomes (new allelic
combination)
Recombination frequency
• = number of recombinant progeny x 100
total number of progeny
Values from slide #11
8+7
15
55+53+8+7 = 123 = 12.2% or .122
• Smaller the recombination frequency = more
closely linked
Coupling and Repulsion
• For heterozygous individuals
• Cis configuration/coupling
– Both wildtype alleles are on one chromosome;
both mutant alleles are on the homologous
chromosome
• Trans configuration/repulsion
– Each chromosome has one wildtype allele
and one mutant allele
Recombination
• Interchromosomal
– Between genes on different chromosomes
– Independent assortment/random segregation during
Metaphase/Anaphase I
– Produces 50% recombinant/50% non-recombinant
gametes
• Intrachromosomal
– Between genes on same chromosome
– Crossing over during Prophase I
– Usually produces recombinant gametes less than
50%
• Unless very far apart on the same chromosome
Genetic mapping
• Relative position of different genes based
on recombination rates
• Does NOT state actual chromosome, or
position (locus)
• Distance measured in map units or
centimorgans (cM)
– 1 m.u. (or cM) = 1% recombination
Genetic mapping example
• A and B = 5 m.u.
• A and C = 15 m.u.
• B and C = 10 m.u.
• A and D = 8 m.u.
• B and D = 13 m.u.
• C and D = 23 m.u.
• Any genes with 50% recombination are either on
different chromosomes, or very far apart on the same
chromosome (crossing over always separates them)
Physical mapping
• Locates gene to a specific chromosome/region
of chromosome
• Deletion mapping
– Chromosome deletion studies – how phenotype is
affected/what genes may be missing
– Duchenne m.s.
• X linked disease – but where on X?
• Some affected males have small deletions – common
deleted area must be where gene is located
Somatic cell hybridization
• Fusion of 2 cell types (altered
by viruses or tumor cells to
allow cell lines – uninhibited
growth)
– Somatic cells
• Heterokaryon – 2 distinct
nuclei
– Eventually fuse
• Most chromosomes are lost
(differentially from one type)
– Human chromosomes usually lost,
only a few remain
– Human genes expressed in hybrid
cell lines must be located on
retained chromosomes
• deletion studies can give more
specific location on chromosome
Molecular Analysis
• Fluorescence In Situ
Hybridization (FISH)
– Probe complementary to
gene sequence will bind
to DNA
• Gene sequence/partial
sequence must be
known
• DNA sequencing
– Yields base pair distance
between two genes