High Performance DNA Probes for Perinatal Detection of Numerical Chromosome Aberrations

Abstract

Human reproduction is a tightly controlled process of stepwise evolution with multiple, mostly yet unknown milestones and checkpoints. Healthy halpoid gametes have to be produced by the parents, which will fuse to form the diploid zygote that implants in the female uterus and grows to become first an embryo, then a fetus and finally matures into a newborn. There are several known risk factors that interfere with normal production of gametes, spermatocytes or oocytes, and often cause embryonic mortality and fetal demise at an early stage. Yet some embryos with chomosomal abnormalities can develop beyond the critical first trimester of pregnancy and, while those with supernumary chromosomes in their hyperdiploid cells will be spontaneously aborted, a small fraction of fetuses with an extra chromosome continues to grow to term and will be delivered as a liveborn baby. While minor clinical symptoms displayed by children with trisomies are manageable for many parents, the burden of caring for a child with numerical chromosome abnormalities can be overwhelming to partners or individual families. It also poses a significant financial burden to the society and poses ethical dilemma. In this communication, we will review the progress that has been made in the development of molecular techniques to test individual fetal cells for chromosomal imbalances. We will focus our discussion on the direct visualization of chromosome-specific DNA sequences in live or fixed specimens using fluorescence in situ hybridization (FISH) and, more specifically, talk about the groundbreaking progress that in recent years has been achieved towards an improved diagnosis with novel, chromosome-specific DNA probes.

Keywords: Aneuploidy; Chromosomal imbalance; DNA probes; Fluorescence in situ hybridization (FISH); Molecular cytogenetics; Perinatal diagnosis; Pregnancy.

Figure 1

The Graphic User Interface (GUI) of the UC Santa Cruz online Genome Browser indicating the position of BAC clone RP11-416F8 (indicated by the blue mark on the left) along the draft sequence of human chromosome 16.

Figure 2

FISH result using a biotinylated probe prepared from BAC clone RP11-416F8. A) DAPI image showing the DNA/metaphase chromosomes; B) Three chromosome-specific green fluorescence signals (arrows) after staining with avidin-FITC; C) Overlay of the DAPI and FITC images.