Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. 1996

N E Lamb, and S B Freeman, and A Savage-Austin, and D Pettay, and L Taft, and J Hersey, and Y Gu, and J Shen, and D Saker, and K M May, and D Avramopoulos, and M B Petersen, and A Hallberg, and M Mikkelsen, and T J Hassold, and S L Sherman
Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

The cause of non-disjunction of chromosome 21 remains largely unknown. Advanced maternal age is associated with both maternal meiosis I (MI) and meiosis II (MII) non-disjunction events. While reduced genetic recombination has been demonstrated in maternal MI errors, the basis for MII errors remains uncertain. We studied 133 trisomy 21 cases with maternal MII errors to test the hypothesis that segregation at MII may also be influenced by genetic recombination. Our data support a highly significant association: MII non-disjunction involves increased recombination that is largely restricted to proximal 21q. Thus, while absence of a proximal recombination appears to predispose to non-disjunction in MI, the presence of a proximal exchange predisposes to non-disjunction in MII. These findings profoundly affect our understanding of trisomy 21 as they suggest that virtually all maternal non-disjunction results from events occurring in meiosis I.

UI MeSH Term Description Entries
D008297 Male Males
D008423 Maternal Age The age of the mother in PREGNANCY. Age, Maternal,Ages, Maternal,Maternal Ages
D008540 Meiosis A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells. M Phase, Meiotic,Meiotic M Phase,M Phases, Meiotic,Meioses,Meiotic M Phases,Phase, Meiotic M,Phases, Meiotic M
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D009630 Nondisjunction, Genetic The failure of homologous CHROMOSOMES or CHROMATIDS to segregate during MITOSIS or MEIOSIS with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none. Genetic Non-Disjunction,Genetic Nondisjunction,Non-Disjunction, Genetic,Genetic Non Disjunction,Genetic Non-Disjunctions,Genetic Nondisjunctions,Non Disjunction, Genetic,Non-Disjunctions, Genetic,Nondisjunctions, Genetic
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002891 Chromosomes, Human, Pair 21 A specific pair of GROUP G CHROMOSOMES of the human chromosome classification. Chromosome 21
D004314 Down Syndrome A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213) Mongolism,Trisomy 21,47,XX,+21,47,XY,+21,Down Syndrome, Partial Trisomy 21,Down's Syndrome,Partial Trisomy 21 Down Syndrome,Trisomy 21, Meiotic Nondisjunction,Trisomy 21, Mitotic Nondisjunction,Trisomy G,Downs Syndrome,Syndrome, Down,Syndrome, Down's
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females

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