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Bioinformatic Tools Identify Chromosome-Specific DNA Probes and Facilitate Risk Assessment by Detecting Aneusomies in Extra-embryonic Tissues

[ Vol. 13 , Issue. 6 ]

Author(s):

Hui Zeng, Jingly F. Weier, Mei Wang, Haig J. Kassabian, Aris A. Polyzos, Adolf Baumgartner, Benjamin O'Brien and Heinz-Ulli G. Weier   Pages 438 - 445 ( 8 )

Abstract:


Despite their non-diseased nature, healthy human tissues may show a surprisingly large fraction of aneusomic or aneuploid cells. We have shown previously that hybridization of three to six non-isotopically labeled, chromosomespecific DNA probes reveals different proportions of aneuploid cells in individual compartments of the human placenta and the uterine wall. Using fluorescence in situ hybridization, we found that human invasive cytotrophoblasts isolated from anchoring villi or the uterine wall had gained individual chromosomes. Chromosome losses in placental or uterine tissues, on the other hand, were detected infrequently. A more thorough numerical analysis of all possible aneusomies occurring in these tissues and the investigation of their spatial as well as temporal distribution would further our understanding of the underlying biology, but it is hampered by the high cost of and limited access to DNA probes. Furthermore, multiplexing assays are difficult to set up with commercially available probes due to limited choices of probe labels. Many laboratories therefore attempt to develop their own DNA probe sets, often duplicating cloning and screening efforts underway elsewhere. In this review, we discuss the conventional approaches to the preparation of chromosome-specific DNA probes followed by a description of our approach using state-of-the-art bioinformatics and molecular biology tools for probe identification and manufacture. Novel probes that target gonosomes as well as two autosomes are presented as examples of rapid and inexpensive preparation of highly specific DNA probes for applications in placenta research and perinatal diagnostics.

Keywords:

Aneusomy, Gestation, Cytotrophoblast, Fetal-maternal Interface, Bioinformatics, DNA Probes, Bacterial artificial chromosomes, Fluorescence in situ hybridization (FISH), aneusomic, DNA probes

Affiliation:

Dept. of Cancer & DNA Damage Responses, Life Sciences Division, E.O. Lawrence Berkeley National Lab, 1 Cyclotron Road, MS 977, Berkeley, CA 94720, USA.



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