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Systems and methods for predicting specific genetic loci that affect phenotypic traits

A technology for genetic loci and phenotypes, applied in the system field of chromosomal regions, which can solve problems such as limiting the identification of genetic loci

Inactive Publication Date: 2006-06-28
SANDHILL BIO CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

With conventional tools, this is a painstaking, expensive and time-consuming process, which greatly limits the speed at which genetic loci can be identified in mice before they can be confirmed in humans

Method used

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  • Systems and methods for predicting specific genetic loci that affect phenotypic traits
  • Systems and methods for predicting specific genetic loci that affect phenotypic traits
  • Systems and methods for predicting specific genetic loci that affect phenotypic traits

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preparation example Construction

[0146] A second preferred method of making microarrays is to make high density oligonucleotide arrays. Techniques are known for fabricating arrays containing thousands of oligonucleotides complementary to known sequences at defined sites on a surface, which are synthesized in situ using photolithographic techniques (see Fodor et al., 1991 , Science 251:767-773; Lockhart et al., 1996, Nature Biotechnology 14:1675; U.S. Pat. & Bioelectronics 11:687-690). When these methods are used, oligonucleotides of known sequence (for example, 20-mers) can be directly synthesized on the surface of a glass slide or the like. Typically, the fabricated arrays are redundant with several oligonucleotide molecules per RNA. Oligonucleotide probes can be selected to detect alternatively spliced ​​mRNAs.

[0147] Other methods can also be used to make microarrays, for example by labeling (Maskos and Southern, 1992, Nuc. Acids. Res. 20: 1679-1684). In general, any array type can be used, such as d...

Embodiment 4

[0169] In Example 1, the characteristics of the haplotype blocks generated using the technique disclosed in FIG. 2 as a function of the number of lines (organisms) present in the genotype database 52 are presented. In Example 2, the systems and methods of the invention were used to correlate phenotypic data obtained from inbred mouse strains with haplotype blocks. In Example 3, the systems and methods of the present invention were used to construct biological pathways. In Example 4, the systems and methods of the present invention were used to determine which chromosomal regions responded to perturbations.

[0170] 1.10.1 Embodiment 1

[0171] An exemplary genotype database 52 used in this example was obtained from (http:\\mouseSNP.Roche.com). An automated high-throughput method of resequencing targeted genomic regions to discover SNPs and characterize alleles, see Grupe et al., 2001, Science 292, 1915-1918. The genomic regions analyzed were all within known biologically im...

Embodiment 2

[0184]U.S. Patent Application 09 / 737,918, filed December 15, 2000, entitled "Systems and Methods for Predicting Chromosomal Regions that Control Phenotypic Traits," and entitled "Predictively Controlling Chromosomal Regions of System and Method for Chromosomal Regions," U.S. Patent Application No. 10 / 015,167, which predicts in silico by correlating phenotypic data obtained from inbred mouse strains with the extent to which alleles are shared within genomic regions. Chromosomal regions that regulate complex traits. It can be determined whether comparing complex phenotypes to the haplotype map of the mouse genome is a better method for in silico analysis of mouse phenotypic traits than the methods disclosed in U.S. Patent Application 09 / 737,918 and U.S. Patent Application 10 / 015,167 method. For each haplotype block within the haplotype map, correlations were calculated by calculating the negative logarithm of the ratio of the average phenotypic difference within haplotype group...

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Abstract

A database of genetic variation was analyzed to generate genomic haplotype maps of single species lines. In silico methods are used to rapidly map complex phenotypes into haplotype blocks within haplotype maps. Specific genetic loci regulating three different biologically important phenotypic traits in mice were identified using these systems and methods.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Application Serial No. 10 / 352,846, filed January 27, 2003, which is hereby incorporated by reference in its entirety. field of invention [0003] The present invention relates to systems and methods for predicting chromosomal regions that affect phenotypic traits. Background of the invention [0004] Identification of genetic loci that modulate disease susceptibility holds promise for understanding pathophysiological mechanisms and leading to new treatments for common human diseases. Family studies clearly demonstrate heritable causes of many common human diseases, such as asthma, autism, schizophrenia, multiple sclerosis, systemic lupus erythematosus, and type I and type II diabetes. See Risch, Nature 405, 847-856, 2000 for an understanding of this. Over the past 20 years, many highly penetrant monogenic (Mendelian) diseases have been identified in human populations by linkage ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/48G16B20/00C12NC12N1/00C12Q1/68G01N33/50G06F19/00G16B20/20G16B25/10G16B30/00
CPCG16B20/00G16B25/00G16B30/00G16B20/20G16B25/10
Inventor 乔纳森·安德鲁·尤索卡廖国春盖瑞·艾伦·佩尔茨
Owner SANDHILL BIO CORP
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