A molecular model for sporadic human aneuploidy.
Aneuploidy is a leading cause of birth defects and a significant contributor to infertility in humans. Maternal age is the only well-established risk factor for gametic aneuploidy in the general population, with the underlying cause(s) yet to be identified. Here we present an extension of the 'two-hit' model for sporadic human aneuploidy. An important implication of this model is that the genetic makeup of an individual will influence the threshold where recombinationally at-risk oocytes (hit-1 events) become sensitive to the effects of advancing age (hit-2 events). Consequently, the age-related risk of gametic aneuploidy in many individuals is likely to differ significantly from the population average, and single nucleotide polymorphisms (SNPs) associated with altered risk should be identifiable.
Comparative Genomics Centre, James Cook University, Townsville, QLD 4811, Australia. bill.warren@jcu.edu.au
William D
WD
Warren
Kylie L
KL
Gorringe
D000328:Adult; D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D005260:Female; D006801:Humans; D008423:Maternal Age; D008540:Meiosis; D008957:Models, Genetic; D009630:Nondisjunction, Genetic; D009687:Nuclear Proteins / Q000235:genetics*; D009865:Oocytes / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011995:Recombination, Genetic; D012307:Risk Factors; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000097722:Cohesins; C090464:Bub1 spindle checkpoint protein