High efficiency in the attribution of parental origin of non-disjunction in trisomy 21 by both cytogenetic and molecular polymorphisms

Bricarelli, Franca Dagna; Pierluigi, Mauro; Perroni, L; Grasso, Marina; Arslanian, A; Sacchi, Nicoletta

doi:10.1007/bf00280549

Cited by 20 publications

(7 citation statements)

References 13 publications

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“…Through the use of quinacrine fluorescence variants [Juberg and Mowrey, 19831, quinacrine and NOR variants [Mikkelsen et al, 1980;Jackson-Cook et al, 19851 and fluorescent R-banding [Verma et al, 19861, cytogenetic heteromorphisms have been used for the identification of the parental origin of the extra chromosome 21 in Down syndrome. Restriction fragment length polymorphisms have been used more recently to assign the parental origin and meiotic stage of the nondisjunctional error resulting in trisomy 21 [Davies et al, 1984;Stewart et al, 1985;Hamers et al, 1987;Stewart et al, 1988;Dagna Bricarelli et al, 1988;Rudd et al, 1988;Galt et al, 1989;Antonarakis et al, 19911. Additionally, RFLPs have become helpful for studying nondisjunction, especially in cases where the cytogenetic markers were uninformative or ambiguous [Stewart et al, 1988;Millington Ward and Pearson, 1988;Antonarakis et al, 19913.…”

Section: Discussionmentioning

confidence: 99%

Parental origin determination in thirty de novo Robertsonian translocations

Shaffer¹,

Jackson‐Cook²,

Stasiowski³

et al. 1992

Am. J. Med. Genet.

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Cytogenetic heteromorphisms and restriction fragment length polymorphisms were used to assign the parental origins of 30 de novo non-homologous Robertsonian translocations. The balanced and unbalanced translocations studied included 20 rob(14q21q) four rob(13q14q)four rob(15q21q) one rob(13q15q), and one rob(13q21q). Significantly more maternally (26/30) than paternally (4/30) derived de novo translocations were noted and all rob(14q21q) ascertained through unbalanced probands (20/20) were maternal in origin. Interestingly, 12/13 probands who were trisomic and informative for proximal chromosome 21q loci were homozygous for the markers tested. Segregation (2:1) of the Robertsonian translocation into one daughter cell in meiosis I and subsequent failure of the chromosome 21 chromatids to separate in meiosis II may account for our observation of homozygosity for proximal chromosome 21 loci in the majority of de novo rearrangements tested.

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Section: Discussionmentioning

confidence: 99%

Parental origin determination in thirty de novo Robertsonian translocations

Shaffer¹,

Jackson‐Cook²,

Stasiowski³

et al. 1992

Am. J. Med. Genet.

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“…The assignment of the haplotypes was possible in the majority of cases for groups A and B, combining both the cytogenetic and -molecular data of the father (F), mother (M), and children (DS or NC) (8). The criteria used are exemplified in Fig.…”

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confidence: 99%

“…2b) was helpful in determining the linkage phase. A few recombinational events preceding the NDJs at meiosis I and II were recognized by combining both the cytogenetic and the molecular analysis (8 …”

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confidence: 99%

Lack of evidence for association of meiotic nondisjunction with particular DNA haplotypes on chromosome 21.

Sacchi¹,

Gusella²,

Perroni³

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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The hypothesis of a predisposition to meiotic nondisjunction for chromosome 21 carrying a specific molecular haplotype has been tested. The haplotype in question is defined by the restriction fragment length polymorphisms for the D21S1/D21S11 loci. Our results obtained on a sample of Northern Italian families with the occurrence of trisomy 21 (Down syndrome) failed to support this hypothesis, contradicting a previous study [Antonarakis, S. E., Kittur, S. D., Metaxotou, C., Watkins, P. C. & Patel, A. S. (1985) Errors in the transmission ofgenetic material-a process that must occur with a high degree of precision-lead to aneuploidy in eukaryotic. organisms. Little is known about the causes for incorrect pairing and aberrant segregation of chromosomes, but these mechanisms are likely to be influenced by both genetic and environmental factors (1). It has been proposed that correct chromosome pairing or synapsis plays a critical role in ensuring appropriate segregation, although the evidence to date is not conclusive. Therefore, genes encoding proteins involved in controlling or carrying out chromosome pairing and segregation might be involved in abnormal meioses. Studies of mutants in Drosophila point to a large number of loci that can affett segregation of chromosome pairs and suggest an inverse relationship between recombination and nondisjunction (NDJ) (2, 3). Genetic effects on meiosis might also be expected to operate through particular DNA sequences that eukaryotes have evolved to fulfill specific meiotic functions. In the yeast Saccharomyces cerevisiae, centromeric DNA sequences essential for both reductional and equational meiotic divisions have been defined (4). In Lilium, DNA sequences have been found that may play a role in the chromosome pairing or synapsis (5). No specific gene loci or structural DNA segments in man have yet been implicated in chromosome NDJ, although aneuploidy is the basis of many severe human disorders.The most common human disorder resulting from aberrant chromosome segregation is Down syndrome (DS) or trisomy 21, affecting " 1 birth in 1000 (6). Recently, an association has been reported between NDJ of chromosome 21 and a haplotype defined by restriction fragment length polymorphism (RFLP) at an anonymous DNA locus on this autosome (7). In view of the profound impact of such a finding for genetic counseling and prevention ofDS, we investigated the general validity ofthis observation. In contrast to the previous study, we did not observe any particular haplotype on chromosome 21 associated with NDJ chromosomes-i.e., chromosomes that did not undergo disjunction (DJ). MATERIALS AND METHODSFamily Samples. We examined 23 Italian families (group A) as a control group and 37 families with a DS child (group B). All of the control families consisted of mother, father, and one normal child (NC). Of 37 families with a DS child, 23 consisted of mother, father, and the DS child, and the remaining 14 consisted of the parents and two children, one NC and one with DS; of the 37 families, 3...

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“…However, we have shown that a large proportion of parental origins of de novo rearrangements can be determined using combined QFQ/NOR heteromorphism data (75%). Restriction fragment length polymorphisms have been used by other investigators to assign the parental origin and meiotic stage of the nondisjunctional error resulting in trisomy 21 (Davies et al 1984;Stewart et al 1985Stewart et al , 1988Hamers et al 1987;Dagna Bricarelli et al 1988;Rudd et al 1988;Galt et al 1989;Meijer et al 1989). Using a sufficient number of DNA markers spanning the length of the chromosome, it is theoretically possible to assign the parental origin of nondisjunction in virtually all cases of trisomy 21 Chakravarti 1989).…”

Section: Discussionmentioning

confidence: 96%

A molecular genetic approach to the identification of isochromosomes of chromosome 21

Shaffer

et al. 1991

Hum Genet

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The largest class of de novo chromosomal rearrangements in Down syndrome are rea(21q21q). Classically, these rearrangements have been termed Robertsonian translocations, implying an attachment of two different chromosome 21 homologues. Additionally, a Robertsonian translocation between two chromosomes 21 cannot be distinguished from an isochromosome composed of genetically identical arms by cytogenetic analyses. Therefore, we have used molecular techniques to differentiate between true Robertsonian translocations and isochromosomes. Samples were obtained from 12 probands, ascertained for de novo rearrangements between homologous chromosomes 21 [11 rea(21q21q) and 1 rea (21;21)(q22;q22)], their parents (n = 24) and available siblings (n = 7). The parental origins of the de novo rearrangements were assigned using molecular and cytogenetic analyses. Although not statistically significant, there was a two-fold increase in the number of paternally derived de novo rearrangements (n = 8) as compared with maternally derived rearrangements (n = 4). To distinguish between rob(21q21q) and i(21q), we used restriction fragment length polymorphisms (RFLPs) spanning the length of chromosome 21. Using all informative and partially informative RFLPs, we used the method of maximum likelihood to assign the most likely rearrangement definition (i or rob) and parental origin in each family. The maximum likelihood estimates indicated that all rearrangements tested (n = 8) were isochromosomes. C-banding revealed two centromeres in three cases indicating that a U-type exchange occurred between sister chromatids in these rearrangements. Our results suggest that the majority of de novo rea(21q21q) are isochromosomes derived from a single parental chromosome 21.

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High efficiency in the attribution of parental origin of non-disjunction in trisomy 21 by both cytogenetic and molecular polymorphisms

Cited by 20 publications

References 13 publications

Parental origin determination in thirty de novo Robertsonian translocations

Parental origin determination in thirty de novo Robertsonian translocations

Lack of evidence for association of meiotic nondisjunction with particular DNA haplotypes on chromosome 21.

A molecular genetic approach to the identification of isochromosomes of chromosome 21

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