Array comparative genomic hybridisation on first polar bodies suggests that non-disjunction is not the predominant mechanism leading to aneuploidy in humans

Gabriel, Alem S.; Thornhill, Alan R.; Ottolini, Christian S.; Gordon, Andrew H.; Brown, Anthony P.; Taylor, John; Bennett, Katy; Handyside, Alan H.; Griffin, Darren K.

doi:10.1136/jmg.2010.088070

Cited by 81 publications

(47 citation statements)

References 24 publications

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“…3B) (Pellestor et al 2003). The prevalence of separated sisters has also been confirmed in molecular genetic studies (Gabriel et al 2011;Handyside et al 2012;Fragouli et al 2013), ruling out the possibility that single chromatids were an artifact of chromosome-spreading techniques. The majority of MI errors from older women involve loss or gain of a single chromatid (Pellestor et al 2006;Handyside 2012), indicating that separated sisters segregate equationally during MI (Fig.…”

Section: Toward a Mechanistic Framework For Understanding The Maternamentioning

confidence: 87%

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

Herbert

Kalleas

Cooney

et al. 2015

Cold Spring Harb Perspect Biol

181

175

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In most organisms, genome haploidization requires reciprocal DNA exchanges (crossovers) between replicated parental homologs to form bivalent chromosomes. These are resolved to their four constituent chromatids during two meiotic divisions. In female mammals, bivalents are formed during fetal life and remain intact until shortly before ovulation. Extending this period beyond 35 years greatly increases the risk of aneuploidy in human oocytes, resulting in a dramatic increase in infertility, miscarriage, and birth defects, most notably trisomy 21. Bivalent chromosomes are stabilized by cohesion between sister chromatids, which is mediated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromosomes during female aging. Consistent with this, premature loss of centromeric cohesion is a major source of aneuploidy in oocytes from older women. Here, we propose a mechanistic framework to reconcile data from genetic studies on human trisomy and oocytes with recent advances in our understanding of the molecular mechanisms of chromosome segregation during meiosis in model organisms.

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Section: Toward a Mechanistic Framework For Understanding The Maternamentioning

confidence: 87%

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

Herbert

Kalleas

Cooney

et al. 2015

Cold Spring Harb Perspect Biol

181

175

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“…The genesis of chromosomal aneuploidy has been reviewed in detail elsewhere, 6,7,9,10 but in brief can occur as the result of a meiotic non-disjunction event in gametes, precocious separation of chromatids, [11][12][13] or as a post-zygotic mitotic non-disjunction event in the embryo. It has long been established that advancing maternal age is the highest risk factor for aneuploid conceptions.…”

Section: Chromosomal Aneuploidymentioning

confidence: 99%

Chromosomal disorders and male infertility

Harton¹,

Tempest²

2011

Asian J Androl

148

131

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Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically: chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis (PGD) in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

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“…This is sharply in contrast with our opinion based on our own experience and on available literature, including the two papers reported by Fragouli and Wells as a proof of evidence. The study by Gabriel et al, using aCGH log2 ratio on polar bodies, found that single chromatid errors were much more common than whole chromosome errors (Gabriel et al, 2011). However, the thresholds used in this study were not validated by comparing to the outcome in the embryo (Gabriel et al, 2011).…”

mentioning

confidence: 61%

“…The study by Gabriel et al, using aCGH log2 ratio on polar bodies, found that single chromatid errors were much more common than whole chromosome errors (Gabriel et al, 2011). However, the thresholds used in this study were not validated by comparing to the outcome in the embryo (Gabriel et al, 2011). In the Handyside (2012) paper, they say: 'Although gain or loss of whole chromosomes versus single chromatids in PB1 was apparent in some cases by the extent of the altered ratio following array CGH (especially where examples of both were present in the same plot), this was not systematically analysed and not considered completely reliable'.…”

mentioning

confidence: 99%