Genome mapping

1. By: TENZIN
Division of Biochemistry
1
CONCEPT OF
GENOME MAPPING

2.  It is the creation of a genetic map assigning
DNA fragments to chromosomes
 A genome map provides a guide for the
sequencing experiments by showing the
positions of genes and other distinctive
features

3.  Genome mapping methods can be divided into two
categories.
• Genetic mapping: uses genetic techniques to
construct maps showing the positions of genes and
other sequence features on a genome. Genetic
techniques include crossbreeding experiments or, in
the case of humans, the examination of family
histories (pedigrees).
• Physical mapping uses molecular biology techniques
to examine DNA molecules directly in order to
construct maps showing the positions of sequence
features, including genes.

4. Cytogenetic map
Linkage mapping
Physical mapping
DNA sequencing
Overlapping
fragments

5.  Gene mapping determines the order of genes and the relative
distances between them in map units
 Gene mapping describes the methods used to identify
the locus of a gene and the distances between genes
 1 map unit = 1 cM (centimorgan)
 Gene mapping methods use recombination
frequencies between alleles in order to determine the relative
distances between them
 Recombination frequencies between genes are inversely
proportional to their distance apart
 Distance measurement: 1 map unit = 1 percent recombination
(true for short distances)
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6.  Genes with recombination frequencies less than 50 percent are
on the same chromosome = linked)
 Linkage group = all known genes on a chromosome
 Two genes that undergo independent assortment have
recombination frequency of 50 percent and are located on
nonhomologous chromosomes or far apart on the same
chromosome = unlinked
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7.  Morgan found that linked traits are on the
same chromosome.
 Chromosomes, not genes, assort
independently during meiosis.

8.  Chromosomes exchange homologous genes
during meiosis.

9.  The closer together two genes are, the more
likely they will be inherited together.
 Cross-over frequencies are related to
distances between genes.
 The higher the frequency, the further the
genes are apart. Linkage maps show the
relative locations of genes.

10. • Cross-over frequencies can be converted into map units.
• Ex: A 5% cross-over frequency equals 5 map units.
– gene A and gene B cross over 6.0 percent of
the time
– gene B and gene C cross over
12.5 percent of the time
– gene A and gene C cross over 18.5 percent of the time

11. The percentage of recombinant progeny
produced in a cross is called the
recombination frequency, which is calculated
as follows:

12. 12

13.  Imperfect pedigrees are analyzed statistically,
using a measure called the lod score (Morton,
1955). This stands for logarithm of the odds
that the genes are linked and is used
primarily to determine if the two markers
being studied lie on the same chromosome,
in other words if the genes are linked or not.
If the lod analysis establishes linkage then it
can also provide a measure of the most likely
recombination frequency

14. The LOD score is calculated as follows:
LOD = Z = Log10 probability of birth sequence with a given linkage
probability of birth sequence with no linkage
By convention, a LOD score greater than 3.0 is considered evidence for
linkage.
On the other hand, a LOD score less than -2.0 is considered evidence
to
exclude linkage.

15. As with gene markers, a DNA marker must have at
least two alleles to be useful. There are three
types of DNA sequence feature that satisfy this
requirement:
Restriction fragment length polymorphisms
(RFLPs),
Simple sequence length polymorphisms (SSLPs),
and Single nucleotide polymorphisms (SNPs).

16.  The presence in a population of two or more relatively
common forms of a gene or a chromosome is called
polymorphism
 Changes in DNA fragment length produced by
presence or absence of the cleavage sites in DNA
molecules are known as restriction fragment length
polymorphism (RFLP)
 A prevalent type of polymorphism is a single base pair
difference, simple-nucleotide polymorphism (SNP)
 A genetic polymorphism resulting from a tandemly
repeated short DNA sequence is called a simple
sequence repeat (SSR)
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17.  Restriction endonucleases are used to map genes as
they produce a unique set of fragments for a gene
 There are more than 200 restriction endonucleases
in use, and each recognizes a specific sequence of
DNA bases
 EcoR1 cuts double-stranded DNA at the sequence
5’-GAATTC-3’ wherever it occurs
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18. 18

19.  Differences in DNA sequence generate different recognition
sequences and DNA cleavage sites for specific restriction
enzymes
 Two different genes will produce different fragment patterns
when cut with the same restriction enzyme due to differences
in DNA sequence
19Fig. 4.19

21.  Gene map is the anatomy of human genome.
 Helps in analysis of the heterogeneity and
segregation of human genetic diseases.

 Helps to develop methods for gene therapy.
 Provides clinically useful information about
linkage