Jacobs, Patricia - University of Southampton

个人简介

My 56 years of research have been devoted to human cytogenetics. I entered the field at an exciting time in the late 1950s. I made the first observation of a human chromosome abnormality in 1959 namely the additional X chromosome in Klinefelter syndrome. My main interests have always been in the population aspects of human chromosome abnormalities. I have also published widely on the frequency and mechanisms of origin of chromosome abnormalities. One of the main aspects of this research was the cytogenetic study of spontaneous fetal loss; this occurs in about 15% of all human pregnancies that are clinically recognised and 50% of all such pregnancies have a cytogenetic abnormality recognisable at the level of the light microscope. My recent research has focused on the mechanism of origin of structural chromosome abnormalities detected by aCGH. We examined 173 patients and their parents with physical and/or neurological abnormalities and a de novo imbalance identified by aCGH. Breakpoint intervals were screened for the presence of low copy repeats (LCRs) to distinguish between rearrangements resulting from non-allelic homologous recombination (NAHR) and those due to other mechanisms. We identified significant differences in both size and parental origin between the LCR-mediated and non-LCR groups. Non-LCR imbalances were evenly distributed among the four size intervals we defined, whereas LCR-mediated rearrangements had a narrow size distribution, between 1 and 5Mb. Among the LCR-mediated rearrangements there were equal numbers of maternally and paternally derived cases, while the non-LCR rearrangements showed a significant excess of paternal cases over a wide size range. The paternal imbalances were evenly distributed among all size groups, but in contrast there were very few maternal imbalances either <1 Mb or > 10 Mb. Furthermore, a lower proportion of paternal imbalances are LCR mediated (13/71) compared with the maternal imbalances (12/30). We hypothesise that imbalances of maternal origin arise predominantly through NAHR during meiosis, while the majority of those of paternal origin arise through male-specific mechanisms other than NAHR. This suggests that mitotic divisions of testicular germ cells are important in the formation of chromosome imbalances, however, surprisingly we found no association with increased paternal age.

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Temporal changes in chromosome abnormalities in human spontaneous abortions: results of 40 years of analysis - Hardy, Kathy, Hardy, Philip J., Jacobs, Patricia, Lewallen, Kevin and Hassold, Terry J. Published:2016Publication:American Journal of Medical Genetics Part AVolume:170, (10)Page Range:2671-2680doi:10.1002/ajmg.a.37795PMID:27287007