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.

Full Karyotype Interphase Cell Analysis

“…Improving the coverage of all the chromosomes and devising sophisticated, fast, and reliable methods to evaluate these single cells is favorable as not all of the possible numerical abnormalities can be currently assessed due to the limited number of available chromosome-specific probes and the limited number of suitable fluorochromes. 21,22 Here, we present the selection of human probe DNA and a technique using multistep FISH employing four sets of six labeled FISH probes able to delineate all 24 human chromosomes in interphase cells. This full karyotype analysis approach will provide additional diagnostic potential for single-cell analysis.…”

“…Improving the coverage of all the chromosomes and devising sophisticated, fast, and reliable methods to evaluate these single cells is favorable as not all of the possible numerical abnormalities can be currently assessed due to the limited number of available chromosome-specific probes and the limited number of suitable fluorochromes. 21,22…”