Jeffrey L. Doering
The currently available human genome sequence does not include the heterochromatic regions, although these sequences comprise 10-15% of the genome. Containing long domains of tandemly repetitious sequences, heterochromatic regions of the genome are important to the functioning of centromeres, telomeres, and the control of gene expression in the interphase nucleus. We are constructing a detailed physical map of the centromere and short arm of human chromosome 21 (HC21) as a model for understanding the organization of heterochromatic genomic regions. The sequence organization of the short arm of HC21 is particularly important to characterize, since sequences in this region appear to cause some of the aberrant chromosome interactions during meiosis that result in disorders like Down syndrome.
We have a draft map for most of the centromere and short arm at this point, and find the sequence organization to be highly complex with clusters of a large number of different tandemly repeated sequences interspersed with "islands" of low copy number sequences. Work is in progress to expand and enhance the resolution of the map using direct pulsed field gel electrophoresis, yeast artificial chromosome (YAC) mapping and various polymerase chain reaction (PCR) approaches. We are also studying the nature of histone modifications at various positions along the short arm and characterizing the structural basis for the extensive polymorphism in HC21 short arm length in human populations.
Bun, Christopher, William Ziccardi, Jeffrey Doering and Catherine Putonti. 2012. MiIP: The monomer identification and isolation program. Evolutionary Bioinformatics 8: 293-300.
Ennesser, R.E. and Doering, J.L. Beta satellite core sequence in Homo sapiens. 2011. Repbase Reports 11(3):1123-1123.
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.
Baaj, S., Rafidi, G., Krueger, J., Chan, E., Vicker, E., Elfar, A. and Doering, J.L. 2014. 6 kb tandem repeat sequence in Homo sapiens. Repbase Reports 14(7):2086-2086.
Fig. Physical map of the short arm and centromere of chromosome 21 showing relative position of several YAC clones.