Lemke Kalistyn H, Weier Jingly F, Weier Heinz-Ulrich G, Lawin-O'Brien Anna R
Life Sciences Division, University of California, E.O. Lawrence Berkeley National Laboratory (LBNL), Berkeley, USA.
Life Sciences Division, University of California, E.O. Lawrence Berkeley National Laboratory (LBNL), Berkeley, USA; Dermatopathology Service, School of Medicine, University of California, San Francisco, USA.
Adv Tech Biol Med. 2015 Nov;3(3). doi: 10.4172/2379-1764.1000155. Epub 2015 Dec 3.
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.
人类生殖是一个受到严格控制的逐步演化过程,有多个大多仍不为人知的里程碑和检查点。父母必须产生健康的单倍体配子,这些配子融合形成二倍体受精卵,受精卵植入女性子宫,首先发育成胚胎,然后是胎儿,最终成熟为新生儿。有几种已知的风险因素会干扰配子、精母细胞或卵母细胞的正常产生,并常常在早期导致胚胎死亡和胎儿夭折。然而,一些染色体异常的胚胎能够在怀孕关键的头三个月之后继续发育,虽然超二倍体细胞中具有额外染色体的胚胎会自然流产,但一小部分具有一条额外染色体的胎儿会继续发育至足月并作为活产婴儿出生。虽然许多父母能够应对三体患儿表现出的轻微临床症状,但照顾患有染色体数目异常孩子的负担对伴侣或单个家庭来说可能难以承受。这也给社会带来了巨大的经济负担,并引发伦理困境。在本交流中,我们将回顾在开发用于检测单个胎儿细胞染色体失衡的分子技术方面所取得的进展。我们将把讨论重点放在使用荧光原位杂交(FISH)对活标本或固定标本中染色体特异性DNA序列进行直接可视化上,更具体地说,会谈论近年来在使用新型染色体特异性DNA探针改进诊断方面所取得的突破性进展。