Toward a Longitudinal Picture of the Origins and Fates of Specific Chromosome Abnormalities throughout Human Development(PDF - 1.19 MB)
Dr. John Wolstenholme, Institute of Human Genetics, Newcastle Upon Tyne, United Kingdom
Careful analysis of incidences of specific chromosome abnormalities at the various stages of human development, from gametes to birth, will provide an insight into this enormously error- prone process. It has been possible to produce a model of the behaviour of trisomy 16 throughout pregnancy, incorporating our understanding of trisomic zygote rescue, mosaicism, and UPD, but the equivalent of this for other trisomies has been more elusive. Much of this elusiveness is due to the relative heterogeneity of origin of other trisomies and their lower overall incidence. There is a particular gap in knowledge of specific chromosome abnormalities in the first few days of human development, up to the blastocyst stage. In an attempt to fill this gap, a study of almost 700 human blastocysts has been undertaken. This work has demonstrated that most of the pattern of cytogenetic abnormality in continuing pregnancies has been established by the late blastocyst stage, but with the limited numbers of blastocysts which may reasonably be expected to be available, it is inevitable that knowledge of detailed chromosome abnormality specific incidences will lag behind that for inherently more accessible areas, such as CVS and spontaneous pregnancy losses. Other studies have added more data about cleavage stage embryos, with DNA analysis of spontaneous abortion cases adding information about the origins of the essentially "non-viable" trisomies. Combined with a greater understanding of the fates of some of the corrected trisomies seen in CVS, it is now possible to get a much better feel for how other chromosome abnormalities are behaving. This data can be used to identify chromosome abnormality specific characteristics, leading to further studies. Unfortunately, however, the heterogeneous nature of many abnormalities still leaves gaps in any longtitudinal picture, but we are progressing and at least we know which gaps need to be filled.