The National down Syndrome Project: Design and Implementation

Freeman, Sallie B.; Allen, Emily G.; Oxford-Wright, Cindy L.; Tinker, Stuart W.; Druschel, Charlotte M.; Hobbs, Charlotte A.; O’Leary, Leslie A.; Romitti, Paul A.; Royle, Marjorie H.; Torfs, Claudine P.; Sherman, Stephanie L.

doi:10.1177/003335490712200109

Cited by 74 publications

(93 citation statements)

References 14 publications

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“…Our findings confirm the model for DS origin found in other populations (Antonarakis, 1991;Gó mez et al, 2000;Petersen and Mikkelsen, 2000;Machatkova et al, 2005;Freeman et al, 2007;Ramírez et al, 2007;Ghosh et al, 2010). The obtained frequencies of maternal MIderived (86%) and MII-derived (14%) trisomy 21 were different from the study reported by Freeman et al (2007), but similar to the studies on Mediterranean and Eastern Europe populations (Gó mez et al, 2000;Machatkova et al, 2005). The discrepancy was probably due to both the small sample size and maternal age distribution covered by the study.…”

Section: Discussionsupporting

confidence: 91%

“…The discrepancy was probably due to both the small sample size and maternal age distribution covered by the study. As the sample size increases, the results are more similar to that obtained by Freeman et al (2007), which included an impressive number of cases. Allen et al (2009) found that the ratio of maternal MI-to MII-derived trisomy 21 cases was less in the youngest ( < 15) and the oldest (40-50) maternal age groups compared with that in the other maternal age groups.…”

Section: Discussionsupporting

confidence: 77%

“…The reaction products were subsequently separated on an ABI 3130 genetic analyzer and analyzed with GeneMapper software (Pavlinić et al, 2008). The detection of parental origin and stage of nondisjunction (meiotic/mitotic) and the analysis of recombination events were done as previously described (Freeman et al, 2007).…”

Section: Dna Analysismentioning

confidence: 99%

“…The majority of full trisomy 21 is caused by chromosomal nondisjunction occurring during maternal meiotic division (*90%). Errors occur more frequently in the first maternal meiotic division than the second (73% vs. 25%) (Antonarakis, 1991;Antonarakis et al, 1992;Yoon et al, 1996;Hassold and Sherman, 2000;Freeman et al, 2007;Ghosh et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Down Syndrome: Parental Origin, Recombination, and Maternal Age

Vraneković

Božović²,

Grubić³

et al. 2012

Genetic Testing and Molecular Biomarkers

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The aims of the present study were to assess (1) the parental origin of trisomy 21 and the stage in which nondisjunction occurs and (2) the relationship between altered genetic recombination and maternal age as risk factors for trisomy 21. The study included 102 cases with Down syndrome from the Croatian population. Genotyping analyses were performed by polymerase chain reaction using 11 short tandem repeat markers along chromosome 21q. The vast majority of trisomy 21 was of maternal origin (93%), followed by paternal (5%) and mitotic origin (2%). The frequencies of maternal meiotic I (MI) and meiotic II errors were 86% and 14%, respectively. The highest proportion of cases with zero recombination was observed among those with maternal MI derived trisomy 21. A higher proportion of telomeric exchanges were presented in cases with maternal MI errors and cases with young mothers, although these findings were not statistically significant. The present study is the first report examining parental origin and altered genetic recombination as a risk factor for trisomy 21 in a Croatian population. The results support that trisomy 21 has a universal genetic etiology across different human populations.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 77%

Section: Dna Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Down Syndrome: Parental Origin, Recombination, and Maternal Age

Vraneković

Božović²,

Grubić³

et al. 2012

Genetic Testing and Molecular Biomarkers

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show abstract

“…Shared Genetic Susceptibility-Nondisjunction, or the failure of chromosome pairs to separate properly during meiosis or mitosis, is the principal cause of Down syndrome, and is of maternal origin over 90% of the time (Freeman et al, 2007). Schupf and her associates (Schupf et al, 1994;Schupf, Kapell et al, 2001) therefore postulated that if there was a shared genetic susceptibility for Down syndrome and Alzheimer's disease, it should only be most evident among mothers and maternal relatives of individuals with Down syndrome.…”

Section: Risk Factorsmentioning

confidence: 99%

Chapter 4 Alzheimer's Disease in Adults with Down Syndrome

Zigman¹,

Devenny²,

Krinsky‐McHale³

et al. 2008

International Review of Research in Mental Retardation

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Etiology of Down syndrome: Evidence for consistent association among altered meiotic recombination, nondisjunction, and maternal age across populations

Ghosh

Feingold

Dey

2009

American J of Med Genetics Pt A

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Down syndrome caused by meiotic nondisjunction of chromosome 21 in humans, is well known to be associated with advanced maternal age, but success in identifying and understanding other risk factors has been limited. Recently published work in a U.S. population suggested intriguing interactions between the maternal age effect and altered recombination patterns during meiosis, but some of the results were counter-intuitive. We have tested these hypotheses in a population sample from India, and found that essentially all of the results of the U.S. study are replicated even in our ethnically very different population. We examined meiotic recombination patterns in a total of 138 families from the eastern part of India, each with a single free trisomy 21 child. We genotyped each family with a set of STR markers using PCR and characterized the stage of origin of nondisjunction and the recombination pattern of maternal chromosome 21 during oogenesis. Our sample contains 107 maternal meiosis I errors and 31 maternal meiosis II errors and we subsequently stratified them with respect to maternal age and the number of detectable crossover events. We observed an association between meiosis I nondisjuncion and recombination in the telomeric 5.1 Mb of chromosome 21. By contrast, in meiosis II cases we observed preferential peri-centromeric exchanges covering the proximal 5.7 Mb region, with interaction between maternal age and the location of the crossover. Overall reduction of recombination irrespective of maternal age is also evident in meiosis I cases. Our findings are very consistent with previously reported data in a U.S. population and our results are the first independent confirmation of those previous reports. This not only provides much needed confirmation of previous results, but it suggests that the genetic etiology underlying the occurrence of trisomy 21 may be similar across human populations.

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The National down Syndrome Project: Design and Implementation

Cited by 74 publications

References 14 publications

Down Syndrome: Parental Origin, Recombination, and Maternal Age

Down Syndrome: Parental Origin, Recombination, and Maternal Age

Chapter 4 Alzheimer's Disease in Adults with Down Syndrome

Etiology of Down syndrome: Evidence for consistent association among altered meiotic recombination, nondisjunction, and maternal age across populations

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