Chapter 23
Positional Cloning and Linkage Analysis
FRIEDHELM HILDEBRANDT AND HEYMUT OMRAN
Positional Cloning
Positional cloning is employed for identification of a disease gene if there is no
proteindefectorfunctionaldefectknown,whichmayhelpinexpressioncloning
orcloningbysequence similarity( Chap.16). In positionalcloningadisease gene
may be mapped by information from cytogenetic abnormalities. If no such
information is available, linkage analysis is employed (see Figure 1).
Theory of Linkage Analysis
Recombination in meiosis
Meiosis occurs in the egg or sperm and Ieads to the formation of the gamete.
In the zygotene of the first phase of meiosis, the 23 chromosomes that are
inherited from the individual's father will pair with the 23 homologous
chromosomes that are inherited from the individual's mother. In this phase
each chromosome consists of two chromatids that are identical copies of
each other. The so-called bivalents that are formed by pairing of the homologues, each contain 4 chromatids. In the pachytene that follows the zygotene, crossing over ( or chiasmata) occur between a chromatid of one homologous chromosome and a chromatid of another homologous chromosome.
Crossing over is the process that Ieads to genetic recombination. It can be
observed directly in the pachytene (see Figure 2).
During meiosis (formation of gametes) there is random assortment of
chromosomes. In other words, whether one gamete ends up with the chromosome from the individual's father or with the homologous chromosome
from the individual's mother is random and independent between different
Correspondence to Friedhelm Hildebrandt, Universitäts-Kinderklinik, Mathildenstrasse
1, Freiburg, 79106, Germany (phone +49-761-270-4301; fax +49-761-270-4533; e-mail
hildebra@kkl200.ukl.uni-freiburg.de), Heymut Omran
Positional Cloning and Linkage Analysis
FRIEDHELM HILDEBRANDT AND HEYMUT OMRAN
Positional Cloning
Positional cloning is employed for identification of a disease gene if there is no
proteindefectorfunctionaldefectknown,whichmayhelpinexpressioncloning
orcloningbysequence similarity( Chap.16). In positionalcloningadisease gene
may be mapped by information from cytogenetic abnormalities. If no such
information is available, linkage analysis is employed (see Figure 1).
Theory of Linkage Analysis
Recombination in meiosis
Meiosis occurs in the egg or sperm and Ieads to the formation of the gamete.
In the zygotene of the first phase of meiosis, the 23 chromosomes that are
inherited from the individual's father will pair with the 23 homologous
chromosomes that are inherited from the individual's mother. In this phase
each chromosome consists of two chromatids that are identical copies of
each other. The so-called bivalents that are formed by pairing of the homologues, each contain 4 chromatids. In the pachytene that follows the zygotene, crossing over ( or chiasmata) occur between a chromatid of one homologous chromosome and a chromatid of another homologous chromosome.
Crossing over is the process that Ieads to genetic recombination. It can be
observed directly in the pachytene (see Figure 2).
During meiosis (formation of gametes) there is random assortment of
chromosomes. In other words, whether one gamete ends up with the chromosome from the individual's father or with the homologous chromosome
from the individual's mother is random and independent between different
Correspondence to Friedhelm Hildebrandt, Universitäts-Kinderklinik, Mathildenstrasse
1, Freiburg, 79106, Germany (phone +49-761-270-4301; fax +49-761-270-4533; e-mail
hildebra@kkl200.ukl.uni-freiburg.de), Heymut Omran