Loyola University Chicago

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Professor, Chairman Ph.D., 1975, University of Chicago Human molecular genetics Phone: 773.508.3627 Fax: 773.508.3646 E-Mail: jdoerin@luc.edu

RESEARCH INTERESTS

The presently available human genome sequence does not include the centromeres and other heterochromatic regions, although these sequences comprise 10-15% of the genome. We are constructing a detailed physical map of the centromere and short arm of human chromosome 21 as a model for the organization of heterochromatic regions. Our work is aimed at identifying DNA sequences critical for human centromere function. We are also studying the sequence organization of the short arm, since on chromosome 21 these sequences are involved in chromosome pairing and appear to cause some of the aberrant chromosome interactions that result in disorders like Down syndrome. We have already identified more than 40 different highly repetitious sequences in the centromere and short arm, and have constructed a detailed physical map of about 4 megabases of DNA in the centromere. Work is in progress to expand and enhance the resolution of the map using DNA sequencing as well as direct pulsed field gel electrophoresis and yeast artificial chromosome (YAC) mapping.

Osteogenesis imperfecta (OI) is a genetic disease characterized by extremely fragile bones that fracture under minimum stress. Many forms of OI involve alterations in the structure and/or synthesis of Type I collagen, the major protein involved in bone structure. A number of OI patients have been found with deletions at one or the other of two previously unknown collagen gene loci. Such deletions may prove to be reliable diagnostic markers for certain types of OI and provide useful genetic counseling information. Molecular cloning and sequencing have been used to define the nature of these new collagen loci. We are now characterizing the molecular nature of the deletions and determining how they affect the clinical symptoms of the disease.

REPRESENTATIVE PUBLICATIONS

Korenberg, J.R., Altonen, J., Brahe, C., Cabin, D., Creau, N., Delabar, J.M., Doering, J., et al. 1997. Report of the sixth international workshop on human chromosome 21 mapping 1996. Cytogenet. Cell Genet. 79:21-52. .

Shimizu, N., S.E. Antonarakis, C. Van Broeckhoven, D. Patterson, K. Gardiner, D. Nizetic, N. Creau, J-M. Delbar, J. Korenberg, R. Reeves, J. Doering et al. 1995. Report of the Fifth International Workshop on Human Chromosome 21 Mapping 1994. Cytogenet. Cell Genet. 70:147-182.

Kaplan, F.S., J. Murray, J.E. Sylvester, I.L. Gonzalez, P. O'Connor, J.L. Doering, M. Muenke, B.S. Emanuel and M.A. Zasloff. 1993. The topographic organization of repetitive DNA in the human nucleolus. Genomics 15:123-132.

Doering, J.L., A.E. Burket and L.C. Vogel. 1993. Length polymorphisms in new human collagen-like loci. FEBS Lett. 334:237-240.


Fig. Physical map of the short arm and centromere of chromosome 21 showing relative position of several YAC clones.