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US 5,851,762 AGranted
Genomic mapping method by direct haplotyping using intron sequence analysis
AssigneeGene Type AG
InventorMalcolm J. Simons
Life of this patent
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Abstract
The present invention is an improved genomic mapping method which is able to generate highly informative polymorphic sites throughout the genome. In addition to being highly polymorphic, the sites can be used to generate patterns that identify allelic and sub-allelic haplotypes associated with the region.
Claims23
A genomic mapping method for identifying informative, polymorphic markers and using said markers to identify a chromosomal region associated with a trait, comprising:
- (a) obtaining a first set of genomic DNA samples from a plurality of individuals representing the diversity of a general population;
- (b) amplifying a non-coding sequence from a selected chromosomal region in each of said first set of genomic DNA samples to produce a first set of amplified DNA sequences;
- (c) analyzing said first set of amplified DNA sequences to determine whether said non-coding sequence comprises a plurality of polymorphic regions, wherein said plurality of polymorphic regions defines a plurality of haplotypic patterns detectable by a selected technique for analyzing genetic variation;
- (d) determining the number of haplotypic patterns associated with said non-coding sequence that are distinct as measured by said selected technique, wherein each haplotypic pattern is a marker for a haplotype of said selected chromosomal region;
- (e) repeating steps (a)-(d) to identify a plurality of non-coding sequences, each having a plurality of associated haplotypic patterns, at a series of selected chromosomal regions;
- (f) obtaining a second set of genomic DNA samples from a plurality of individuals with the trait from said general population, wherein said plurality of individuals with the trait is not derived from a single family;
- (g) amplifying said plurality of non-coding sequences from said series of selected chromosomal regions in each genomic DNA sample in said second set to produce a second set of amplified DNA sequences;
- (h) detecting the haplotypic pattern for each amplified DNA sequence in said second set to identify the haplotype of each corresponding selected chromosomal region;
- (i) determining the degree of restriction in haplotype heterogeneity at each selected chromosomal region for said second set of amplified DNA sequences by comparing the number of haplotypic patterns identified for each selected chromosomal region for said first set of amplified DNA sequences and said second set of amplified DNA sequences;
- and
- (j) comparing the degree of haplotype heterogeneity restriction across said selected chromosomal regions, to identify a subseries of adjacent selected chromosomal regions having a greater degree of haplotype heterogeneity restriction at a central selected chromosomal region in said subseries than at selected chromosomal regions at the ends of said subseries as an indication that said central selected chromosomal region is associated with the trait.
8 more elements
A genomic mapping method for identifying a chromosomal region associated with a trait, comprising:
- (a) obtaining genomic DNA samples from a plurality of individuals with the trait from a general population, wherein said plurality of individuals with the trait is not derived from a single family;
- (b) amplifying a plurality of non-coding sequences from a series of selected chromosomal regions in each genomic DNA sample to produce a plurality of amplified DNA sequences, wherein each selected chromosomal region comprises a plurality of polymorphic non-coding regions, and said plurality of polymorphic non-coding regions defines a plurality of haplotypic patterns detectable by a selected technique for analyzing genetic variation;
- (c) analyzing said plurality of amplified DNA sequences to identify the haplotype of each corresponding selected chromosomal region;
- (d) determining the degree of restriction in haplotype heterogeneity at each selected chromosomal region for said plurality of individuals with the trait, as compared to said general population;
- and
- (e) comparing the degree of haplotype heterogeneity restriction across said selected chromosomal regions to identify a subseries of adjacent selected chromosomal regions having a greater degree of haplotype heterogeneity restriction at a central selected chromosomal region in said subseries than at selected chromosomal regions at the ends of said subseries as an indication that said central selected chromosomal region is associated with the trait.
3 more elements
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