Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1997 Jul;61(1):111–119. doi: 10.1086/513894

Identification of the human chromosomal region containing the iridogoniodysgenesis anomaly locus by genomic-mismatch scanning.

F Mirzayans 1, A J Mears 1, S W Guo 1, W G Pearce 1, M A Walter 1
PMCID: PMC1715869  PMID: 9245991

Abstract

Genome-mismatch scanning (GMS) is a new method of linkage analysis that rapidly isolates regions of identity between two genomes. DNA molecules from regions of identity by descent from two relatives are isolated based on their ability to form extended mismatch-free heteroduplexes. We have applied this rapid technology to identify the chromosomal region shared by two fifth-degree cousins with autosomal dominant iridogoniodysgenesis anomaly (IGDA), a rare ocular neurocristopathy. Markers on the short arm of human chromosome 6p were recovered, consistent with the results of conventional linkage analysis conducted in parallel, indicating linkage of IGDA to 6p25. Control markers tested on a second human chromosome were not recovered. A GMS error rate of approximately 11% was observed, well within an acceptable range for a rapid, first screening approach, especially since GMS results would be confirmed by family analysis with selected markers from the putative region of identity by descent. These results demonstrate not only the value of this technique in the rapid mapping of human genetic traits, but the first application of GMS to a multicellular organism.

Full text

PDF
111

Images in this article

114Figure 2
on p.114

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boehnke M. Limits of resolution of genetic linkage studies: implications for the positional cloning of human disease genes. Am J Hum Genet. 1994 Aug;55(2):379–390. [PMC free article] [PubMed] [Google Scholar]
  2. Casna N. J., Novack D. F., Hsu M. T., Ford J. P. Genomic analysis II: isolation of high molecular weight heteroduplex DNA following differential methylase protection and Formamide-PERT hybridization. Nucleic Acids Res. 1986 Sep 25;14(18):7285–7303. doi: 10.1093/nar/14.18.7285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Feingold E., Brown P. O., Siegmund D. Gaussian models for genetic linkage analysis using complete high-resolution maps of identity by descent. Am J Hum Genet. 1993 Jul;53(1):234–251. [PMC free article] [PubMed] [Google Scholar]
  4. Guo S. W. Proportion of genome shared identical by descent by relatives: concept, computation, and applications. Am J Hum Genet. 1995 Jun;56(6):1468–1476. [PMC free article] [PubMed] [Google Scholar]
  5. Jerndal T. Dominant goniodysgenesis with late congenital glaucoma. A re-examination of Berg's pedigree. Am J Ophthalmol. 1972 Jul;74(1):28–33. doi: 10.1016/0002-9394(72)91121-x. [DOI] [PubMed] [Google Scholar]
  6. Lange K., Kunkel L., Aldridge J., Latt S. A. Accurate and superaccurate gene mapping. Am J Hum Genet. 1985 Sep;37(5):853–867. [PMC free article] [PubMed] [Google Scholar]
  7. MORTON N. E. The detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type. Am J Hum Genet. 1956 Jun;8(2):80–96. [PMC free article] [PubMed] [Google Scholar]
  8. Mirzayans F., Pearce W. G., MacDonald I. M., Walter M. A. Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Am J Hum Genet. 1995 Sep;57(3):539–548. [PMC free article] [PubMed] [Google Scholar]
  9. Nelson S. F. Genomic mismatch scanning: current progress and potential applications. Electrophoresis. 1995 Feb;16(2):279–285. doi: 10.1002/elps.1150160144. [DOI] [PubMed] [Google Scholar]
  10. Nelson S. F., McCusker J. H., Sander M. A., Kee Y., Modrich P., Brown P. O. Genomic mismatch scanning: a new approach to genetic linkage mapping. Nat Genet. 1993 May;4(1):11–18. doi: 10.1038/ng0593-11. [DOI] [PubMed] [Google Scholar]
  11. Pearce W. G., Wyatt H. T., Boyd T. A., Ombres R. S., Salter A. B. Autosomal dominant iridogoniodysgenesis: genetic features. Can J Ophthalmol. 1983 Feb;18(1):7–10. [PubMed] [Google Scholar]
  12. Weatherill J. R., Hart C. T. Familial hypoplasia of the iris stroma associated with glaucoma. Br J Ophthalmol. 1969 Jul;53(7):433–438. doi: 10.1136/bjo.53.7.433. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES