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Haplotype
Haplotype DE Bergstrom, The Jackson Laboratory, Bar Harbor, ME, USA
© 2001 Elsevier Inc. All rights reserved.
This article is reproduced from the previous edition, volume 2, pp 911–912, © 2001, Elsevier Inc.
The term ‘haplotype’ refers to a particular set of alleles at linked loci that are present on one of two homologous chromosomes. During the course of a gene-mapping experiment involving backcross or intercross mating schemes, geneticists use a pro cess known as ‘haplotype analysis’ to place genetic markers in a precise order. For purposes of this discussion, we will use a backcross as an example. To initiate a backcross mapping experiment, two inbred parental strains, A and B, are mated to produce an F1 hybrid. By definition, strain A is inbred and can be considered to be homozygous for A alleles (A/A) at all autosomal loci. Likewise, strain B can be considered to be homozygous for B alleles (B/B) at all autosomal loci. F1 hybrids derived from these parental strains must be heterozygous (A/B) at all autosomal loci. Meiotic events within the germline of the F1 hybrid generate recombinant chromosomes in which A and B alleles are placed in new combinations along the length of the chromosome. By backcrossing the F1 hybrid back to an inbred parental strain (of strain B in this case), one can deter mine the haplotype of these recombinant chromosomes by genotyping the resulting progeny. If, for example, five closely linked markers, 1–5, were genotyped in a single offspring and had the haplotype 1A (A at locus 1), 2B, 3A, 4A, and 5B, one can conclude that loci 1, 3, and 4 are on one side of a point of recombination, and that loci 2 and 5 are on the opposite side. Similarly, by determining the haplotypes of additional progeny in which recombination has occurred between different sets of
Brenner’s Encyclopedia of Genetics, 2nd edition, Volume 3
markers, one can begin to subdivide these groups and refine the order of markers even further. By using mapping panels containing DNA from hundreds of progeny that have been previously genotyped with thousands of markers, one can quickly establish the map location of any new genetic marker that is polymorphic between the two parental strains. Two such well-characterized mouse community mapping crosses include The Jackson Laboratory Backcross Mapping Panels and the European Collaborative Interspecific Mouse Backcross Mapping Panel. By utilizing distantly related parental strains, these mapping panels provide useful community resources that exploit polymorphism at a large number of loci. Specialized mapping panels are also frequently established that are segregating for an investigator’s phenotype of interest. Using these mapping panels, a phenotype (for which no mole cular basis has been elucidated) can also be mapped with respect to nearby genetic markers. This provides the basis for position ally cloning the gene underlying the mutant phenotype. The term ‘haplotype’ can also be used to describe particular sets of alleles present at linked loci within naturally occurring populations: for example, t haplotypes occurring within a specialized region of mouse chromosome 17 known as the t complex.
See also: Gene Mapping; Linkage Map; t Haplotype.
doi:10.1016/B978-0-12-374984-0.00681-1
395
© 2001 Elsevier Inc. All rights reserved.
This article is reproduced from the previous edition, volume 2, pp 911–912, © 2001, Elsevier Inc.
The term ‘haplotype’ refers to a particular set of alleles at linked loci that are present on one of two homologous chromosomes. During the course of a gene-mapping experiment involving backcross or intercross mating schemes, geneticists use a pro cess known as ‘haplotype analysis’ to place genetic markers in a precise order. For purposes of this discussion, we will use a backcross as an example. To initiate a backcross mapping experiment, two inbred parental strains, A and B, are mated to produce an F1 hybrid. By definition, strain A is inbred and can be considered to be homozygous for A alleles (A/A) at all autosomal loci. Likewise, strain B can be considered to be homozygous for B alleles (B/B) at all autosomal loci. F1 hybrids derived from these parental strains must be heterozygous (A/B) at all autosomal loci. Meiotic events within the germline of the F1 hybrid generate recombinant chromosomes in which A and B alleles are placed in new combinations along the length of the chromosome. By backcrossing the F1 hybrid back to an inbred parental strain (of strain B in this case), one can deter mine the haplotype of these recombinant chromosomes by genotyping the resulting progeny. If, for example, five closely linked markers, 1–5, were genotyped in a single offspring and had the haplotype 1A (A at locus 1), 2B, 3A, 4A, and 5B, one can conclude that loci 1, 3, and 4 are on one side of a point of recombination, and that loci 2 and 5 are on the opposite side. Similarly, by determining the haplotypes of additional progeny in which recombination has occurred between different sets of
Brenner’s Encyclopedia of Genetics, 2nd edition, Volume 3
markers, one can begin to subdivide these groups and refine the order of markers even further. By using mapping panels containing DNA from hundreds of progeny that have been previously genotyped with thousands of markers, one can quickly establish the map location of any new genetic marker that is polymorphic between the two parental strains. Two such well-characterized mouse community mapping crosses include The Jackson Laboratory Backcross Mapping Panels and the European Collaborative Interspecific Mouse Backcross Mapping Panel. By utilizing distantly related parental strains, these mapping panels provide useful community resources that exploit polymorphism at a large number of loci. Specialized mapping panels are also frequently established that are segregating for an investigator’s phenotype of interest. Using these mapping panels, a phenotype (for which no mole cular basis has been elucidated) can also be mapped with respect to nearby genetic markers. This provides the basis for position ally cloning the gene underlying the mutant phenotype. The term ‘haplotype’ can also be used to describe particular sets of alleles present at linked loci within naturally occurring populations: for example, t haplotypes occurring within a specialized region of mouse chromosome 17 known as the t complex.
See also: Gene Mapping; Linkage Map; t Haplotype.
doi:10.1016/B978-0-12-374984-0.00681-1
395