Abstract

Identification of genes causing human genetic diseases will lead to new methods of diagnosis and treatment of many disorders. The screening of candidate genes for mutations is rapidly becoming the rate-limiting step in the disease gene identification process (positional cloning). Thus, new methods for mutation detection are needed. In addition, new cost efficient methods for high throughput genotyping are needed for screening populations for genetic risk factors, for studies to identify polygenic disease loci, and for more efficient linkage analysis of single g,ene disorders. The goals of this project are to evaluate and develop methods for identifying mutations in DNA and to develop methods and resources necessary for high throughput genotyping. To achieve these goals, we will determine factors currently limiting the sensitivity of single strand conformation polymorphism (SSCP) analysis for detection of single base changes, and seek to improve the sensitivity of this technique by modification of gel matrices, electrophoresis conditions, and the nucleotide composition of the DNA sample to be analyzed. In addition, new mutation detection methods will be developed by taking advantage of mismatch binding proteins and endonucleases. Finally, cost effective strategies and reagents for high throughput genotyping will be developed using tetranucleotide repeat polymorphic markers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG000457-05
Application #
2208845
Study Section
Genome Study Section (GNM)
Project Start
1991-09-30
Project End
1997-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

Green, Glenn E; Scott, Daryl A; McDonald, Joshua M et al. (2002) Performance of cochlear implant recipients with GJB2-related deafness. Am J Med Genet 109:167-70
Campbell, C; Cucci, R A; Prasad, S et al. (2001) Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat 17:403-11
Scott, D A; Drury, S; Sundstrom, R A et al. (2000) Refining the DFNB7-DFNB11 deafness locus using intragenic polymorphisms in a novel gene, TMEM2. Gene 246:265-74
Green, G E; Scott, D A; McDonald, J M et al. (1999) Carrier rates in the midwestern United States for GJB2 mutations causing inherited deafness. JAMA 281:2211-6
Scott, D A; Wang, R; Kreman, T M et al. (1999) The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 21:440-3
Brennan, T M; Landau, D; Shalev, H et al. (1998) Linkage of infantile Bartter syndrome with sensorineural deafness to chromosome 1p. Am J Hum Genet 62:355-61
Parvari, R; Hershkovitz, E; Kanis, A et al. (1998) Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43. Am J Hum Genet 63:163-9
Scott, D A; Kraft, M L; Carmi, R et al. (1998) Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss. Hum Mutat 11:387-94
Heaney, C; Shalev, H; Elbedour, K et al. (1998) Human autosomal recessive osteopetrosis maps to 11q13, a position predicted by comparative mapping of the murine osteosclerosis (oc) mutation. Hum Mol Genet 7:1407-10
Haider, N B; Carmi, R; Shalev, H et al. (1998) A Bedouin kindred with infantile nephronophthisis demonstrates linkage to chromosome 9 by homozygosity mapping. Am J Hum Genet 63:1404-10

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