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Development of a Mitochondrial Disease Profiling Array

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
76259
Program Year/Program:
2005 / STTR
Agency Tracking Number:
GM073407
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
GENEPROTECH,INC.
9103 LAWN AVE ST. LOUIS, MO 63144-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2005
Title: Development of a Mitochondrial Disease Profiling Array
Agency: HHS
Contract: 1R41GM073407-01
Award Amount: $178,265.00
 

Abstract:

DESCRIPTION (provided by applicant): Mitochondrial disease caused by point mutations in mitochondrial DMA (mtDNA) can be a formidable diagnostic challenge. Because clinical presentation can be variable, multisystemic, and mimic many other neurological disorders, ruling out an mtDNA etiology is difficult in patients with suspected myopathies or encephalopathies. DMA microarrays would seem to provide an ideal format for screening patient samples for the approximately200 mtDNA point mutations known or suspected to cause mitochondrial disease (Figure 1). When fabricated from conventional DNA oligonucleotides, however, microarrays often have inadequate power to discriminate, by hybridization, between mutant and wild-type DNAs that differ by a single base mismatch. This problem is aggravated for mtDNA mutations because they are present in most patients as a mixture of wild-type and mutant molecules - often as low as 10% in easily sampled material like peripheral blood. Oligonucleotides synthesized from Locked Nucleic Acid (LNA) nucleotides show much better mismatch detection. LNA-containing oligonucleotides in duplex with normal DNA have a remarkable combination of both high thermal stability (Tm) and enhanced Tm - i.e., the melting temperature difference between a perfect match and single base mismatch. Consequently, short probes (7-9 nt in length) can be used in arrays to maximize discriminatory power between mutant and wild-type DNAs while retaining efficient hybridization and, thus, sensitivity. Here, we propose to develop an array fabricated from LNA oligonucleotides for the detection of all 27 confirmed pathogenic point mutations in mtDNA. Its sensitivity for the detection of mtDNA mutations will be measured in samples containing a mixture of wild-type and mutant molecules. These studies will provide proof of principle for the successful design of an inclusive array to detect all reported pathogenic mtDNA mutations. As new ones are discovered, updated versions would be easy to generate. Towards this goal, the Specific Aims of this proposal are: Specific Aim 1: To develop capture probe pairs towards a set of 27 different mtDNA mutations. Specific Aim 2: To determine the performance of an optimized array to detect mtDNA mutations at varying frequencies.

Principal Investigator:

H. P. Zassenhaus
3149777746
zassenp@slu.edu

Business Contact:


3145835441
Small Business Information at Submission:

Geneprotech, Inc.
Geneprotech, Inc. 9103 Lawn Avenue St. Louis, MO 63144

EIN/Tax ID: 010547942
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
ST. LOUIS UNIVERSITY
SAINT LOUIS UNIVERSITY
221 N GRAND BLVD
SAINT LOUIS, MO 63103
RI Type: Nonprofit college or university