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Dotan Schreiber
According to a series of presentations by M. Fishelson
OutLine
Introduction.
Basic concepts and some background.
Motivation for linkage analysis.
Linkage analysis: main approaches.
Latest developments.
Genetic linkage analysis is a statistical
method that is used to associate
functionality of genes to their location on
chromosomes.
http://bioinfo.cs.technion.ac.il/superlink/
The Main Idea/usage:
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 marker-
genes , 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
Dominant Vs. Recessive Allele
:
heterozygote
homozygote
(se)X-Linked Allele
Most human cells contain 46 chromosomes:
2 sex chromosomes (X,Y):
XY in males.
XX in females.
22 pairs of chromosomes named autosomes.
X-linked dominant.
Affected males pass the disorder to all daughters but to none of
their sons.
Affected heterozygous females married to unaffected males pass
the condition to half their sons and daughters.
Example
1 2 3 4 5 6 7 8 9 10
leaf
1/2
11 12 13 14
a/b a/b
21 22 23 24
a/b a/b a/c b/d
Example Descent Graph
1 2
11 12 13 14
a/b a/b
21 22 23 24
a/b a/b a/c b/d
Descent Graph 3 4 5 6
1 2 7 8
(a,b) (a,b)
1 2 7 8
(a,b) (a,b)
1 2 7 8
(a,b) (a,b)
Founder Graph
(a,b) (a,b)
5 3 6 4
(a,b) (b,d) (a,c)
2 1 8 7
Find compatible allelic assignments
for non-singleton components
1. Identify the set of compatible alleles for each vertex.
This is the intersection of the genotypes.
(a,b) (a,b)
5 3 6 4
(a,b) (b,d) (a,c)
2 1 8 7
Possible Allelic Assignments
{b} {a}
{a,b} {a,b}
(a,b) (a,b)
5 3 6 4
(a,b) (b,d) (a,c)
2 1 8 7
Pr[Ci ] Pr[a
{h:ah iAi }
hi ] 2 terms at most
m
Pr[ m | v ] Pr[C
i 1
i ] Linear in the number of founders
Latest News: 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).
http://bioinfo.cs.technion.ac.il/superlink/
The
End