Genetic linkage

Genetic linkage
It ia functionality of genes to
their location on
chromosomes.

Overview
Neighboring genes on the chromosome
have a tendency to stick together when
passed on to offsprings.
Therefore, if some disease is often passed
to offsprings along with specific markergenes , then it can be concluded that the
gene(s) which are responsible for the
disease are located close on the
chromosome to these markers.

Basic Concepts

Locus
Allele
Genotype
Phenotype

Basic Concepts
Locus
It is specific location of a
gene or DNA sequence
on a chromosome.

Basic Concepts
Allele
A variant of the DNA
sequence at a
given locus is
called an allele

Basic Concepts
Genotype
The genotype is the
genetic makeup of a
cell, an organism, or
an individual (i.e. the
specific allele makeup
of
the
individual)
usually with reference
to a specific character
under consideration

Basic Concepts
Phenotype
A phenotype is an
organism's observable
characteristics or traits:
such as its morphology,
development,
biochemical or
physiological properties,
behavior, and products of
behavior (such as a
bird's nest

Linkage
The further apart two genes on the same
chromosome are, the more it is likely that
a recombination between them will occur.
Two genes are called linked if the
recombination fraction between them is
small (< 50% chance)

Linkage related Concepts

Interference A crossover in one region usually decreases the
probability of a crossover in an adjacent region.
OR
The occurrence of one crossing over interferes
with the coincident occurrence of another
crossing over in the same pair of chromsomes,

Linkage related Concepts

CentiMorgan (cM) 1 cM is the distance between genes for which the recombination
frequency is 1%.
One centimorgan corresponds to about 1 million base pairs in humans on
average.
Plasmodium falciparum has an average recombination distance of ~15 kb
per centimorgan: markers separated by 15 kb of DNA (15,000 nucleotides)
have an expected rate of chromosomal crossovers of 0.01 per generation

Linkage related Concepts

Crossing Over Sometimes in meiosis, homologous chromosomes exchange parts in a
process called crossing-over or recombination.

Linkage related Concepts

Recombination Fraction
The probability for a recombination between two genes
is a monotone, non-linear function of the physical
distance between their loci on the chromosome.

(Linkage) 0 P (Recombination ) 0.5 ( No Linkage)

Linkage related Concepts

Lod Score - a method to calculate linkage distances (to determine the distance between genes).
Positive LOD scores favor the presence of linkage.
Negative LOD scores indicate that linkage is less likely.

Linkage related Concepts

Lod Score Establish a pedigree
Make a number of estimates of recombination frequency
Calculate a LOD score for each estimate
The estimate with the highest LOD score will be considered the best estimate

Linkage related Concepts

Recombination frequency ()
It is the frequency with which a single chromosomal
crossover will take place between two genes during
meiosis.
When two genes are located on the same
chromosome, the chance of a crossover producing
recombination between the genes is related to the
distance between the two genes. Thus, the use of
recombination frequencies has been used to
develop linkage maps or genetic maps.

Linkage related Concepts

Pedigree chart It is a diagram that shows the occurrence and
appearance or phenotypes of a particular gene or
organism and its ancestors from one generation to
the next, most commonly humans, show dogs,
and race horses. The word pedigree is a
corruption of the French "pied de grue" or crane's
foot, because the typical lines and split lines (each
split leading to different offspring of the one parent
line) resemble the thin leg and foot of a crane

Linkage related Concepts

Pied De Grue Or
Crane's Foot

Linkage related Concepts

Pied De Grue Or
Crane's Foot

Linkage related Concepts

Linkage map
A genetic map of a species or experimental
population that shows the position of its
known genes or genetic markers relative to
each other in terms of recombination
frequency, rather than as specific physical
distance along each chromosome. Linkage
mapping is critical for identifying the location
of genes that cause genetic diseases.

Linkage related Concepts

Meiosis Indicators
If the allele from the 'first' copy of the parental chromosome is
transmitted, a '0' might be assigned to that meiosis. If the
allele from the 'second' copy of the parental chromosome is
transmitted, a '1' would be assigned to that meiosis. The
two alleles in the parent came, one each, from two
grandparents. These indicators are then used to determine
identical-by-descent (IBD) states or inheritance states,
which are in turn used to identify genes responsible for
diseases and phenotypes.
With very large pedigrees or with very dense genetic marker
data, such as from whole-genome sequencing, it is
possible to precisely locate and quantify

Research Scope
Its impossible to make controlled crosses in
humans.
Human progenies are rather small.
The human genome is immense. The
distances between genes are large on
average.

Possible Solutions
Make general assumptions:
Hardy-Weinberg Equilibrium :
Assumes certain probability for a certain individual to have a
certain genotype.
Linkage Equilibrium :
Assumes two alleles at different loci are independent of each
other.

Incorporate those assumptions into possible

solutions:
Elston-Stewart method.
Lander-Green method.

Elston-Stewart Method
The ElstonStewart algorithm is an
algorithm for computing the liklehood of
observed genotype data given a pedigree.
It is due to Robert Elston and John
Stewart. It can handle relatively large
pedigrees providing they are (almost)
outbred. Its computation time is
exponential in the number of markers. It is
used in the analysis of genetic linkage.

Lander-Green method
The LanderGreen algorithm is an
algorithm, due to Eric Lander and Philip
Green for computing the liklehood of
observed genotype data given a
pedifgree. It is appropriate for relatively
small pedigrees and a large number of
markers. It is used in the analysis of
genetic linkage.

SuperLink
Combines the covered approaches in one
unified program.
Has other built-in abilities that increase its
computations efficiency.
Claimed to be more capable and faster
than other related programs (by its own
makers).

The End