New insights into human nondisjunction of chromosome 21 in oocytes.
Tiffany Renee Oliver,Eleanor Feingold,Kai Yu,Vivian G. Cheung,Stuart W. Tinker,Maneesha Yadav-Shah,Nirupama Masse,Stephanie L. Sherman +7 more
TLDR
Analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte, and emphasizes the fact that human nondisJunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors.Abstract:
Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1) a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2) a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors.read more
Citations
More filters
Journal ArticleDOI
Ovarian Aging: Mechanisms and Clinical Consequences
TL;DR: Improved knowledge of the ovarian ageing mechanisms may ultimately provide tools for prediction of menopause and manipulation of the early steps of folliculogenesis for the purpose of contraception and fertility lifespan extension.
Journal ArticleDOI
Human aneuploidy: mechanisms and new insights into an age-old problem
TL;DR: New studies of humans and model organisms have shed new light on the complexity of meiotic defects, providing evidence that the age-related increase in errors in the human female is not attributable to a single factor but to an interplay between unique features of oogenesis and a host of endogenous and exogenous factors.
Journal ArticleDOI
Meiotic Recombination: The Essence of Heredity
TL;DR: This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotics recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase.
Journal ArticleDOI
Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes
Kikuë Tachibana-Konwalski,Jonathan Godwin,Louise van der Weyden,Lysie Champion,Nobuaki Kudo,David J. Adams,Kim Nasmyth +6 more
TL;DR: It is suggested that the inability of oocytes to regenerate cohesion may contribute to age-related meiosis I errors, and little or no cohesin turnover for ≥2 wk during oocyte growth.
Journal ArticleDOI
Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew
TL;DR: It seems likely that there are multiple causes of human age-related nondisjunction, complicating efforts to understand – and, ultimately, to provide preventive measures for – errors associated with increasing maternal age.
References
More filters
Journal ArticleDOI
A high-resolution recombination map of the human genome
Augustine Kong,Daniel F. Gudbjartsson,Jesus Sainz,Gudrun M. Jonsdottir,Sigurjon A. Gudjonsson,Bjorgvin Richardsson,Sigrun Sigurdardottir,John Barnard,Bjorn Hallbeck,Gisli Masson,Adam Shlien,Stefan T Palsson,Michael L. Frigge,Thorgeir E. Thorgeirsson,Jeffrey R. Gulcher,Kari Stefansson +15 more
TL;DR: Recombination rates are significantly correlated with both cytogenetic structures and sequence and paternal chromosomes show many differences in locations of recombination maxima, suggesting that there is some underlying component determined by both genetic and environmental factors that affects maternal recombination rates.
Journal ArticleDOI
BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice.
Darren J. Baker,Karthik B. Jeganathan,J. Douglas Cameron,Michael A. Thompson,Subhash C. Juneja,Alena Kopecka,Rajiv Kumar,Robert B. Jenkins,Piet C. de Groen,Patrick C. Roche,Jan M. van Deursen +10 more
TL;DR: It is shown that mutant mice with low levels of the spindle assembly checkpoint protein BubR1 develop progressive aneuploidy along with a variety of progeroid features, including short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat and impaired wound healing.
Journal ArticleDOI
Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II
Neil E. Lamb,Sallie B. Freeman,Amanda Savage-Austin,Dorothy Pettay,Lisa Taft,Jane Hersey,Yuanchao Gu,Joseph J. Shen,Denise Saker,Kristen M. May,Dimitris Avramopoulos,Michael B. Petersen,Anni Hallberg,Margareta Mikkelsen,Terry J. Hassold,Stephanie L. Sherman,Stephanie L. Sherman +16 more
TL;DR: These findings profoundly affect the understanding of trisomy 21 as they suggest that virtually all maternal non–disjunction results from events occurring in meioisis I.
Journal ArticleDOI
A Genome-Wide Screen Identifies Genes Required for Centromeric Cohesion
TL;DR: The screen described here provides a comprehensive analysis of the genes required for the meiotic cell cycle and identifies three factors important for the stepwise loss of sister chromatid cohesion.
Journal ArticleDOI
Parental Origin of the Extra Chromosome in Trisomy 21 as Indicated by Analysis of DNA Polymorphisms
TL;DR: In trisomy 21 the extra chromosome 21 is maternal in origin in about 95 percent of the cases, and paternal in only about 5 percent--considerably less than has been reported with cytogenetic methods.