Abstract
BackgroundMaternal uniparental disomy (UPD) of chromosome 7 (upd(7)mat) accounts for approximately 10% of patients with Silver-Russell syndrome (SRS). For upd(7)mat and trisomy 7, a significant number of mechanisms have been proposed to explain the postzygotic formation of these chromosomal compositions, but all have been based on as small number of cases. To obtain the ratio of isodisomy and heterodisomy in UPDs (hUPD, iUPD) and to determine the underlying formation mechanisms, we analysed a large cohort of upd(7)mat patients (n = 73) by SNP array typing. Based on these data, we discuss the UPDs and their underlying trisomy 7 formation mechanisms.ResultsA whole chromosome 7 maternal iUPD was confirmed in 28.8%, a mixture or complete maternal hUPD in 71.2% of patients.ConclusionsWe could demonstrate that nondisjunction mechanism affecting chromosome 7 are similar to that of the chromosomes more frequently involved in trisomy (and/or UPD), and that mechanisms other than trisomic rescue have a lower significance than previously suspected. Furthermore, we suggest SNP array typing for future parent- and cell-stage-of origin studies in human aneuploidies as they allow the definite classification of trisomies and UPDs, and provide information on recombinational events and their suggested association with aneuploidy formation.
Highlights
Maternal uniparental disomy (UPD) of chromosome 7 (upd(7)mat) accounts for approximately 10% of patients with Silver-Russell syndrome (SRS)
Chromosomal regions were classified as iUPD in case of a loss of heterozygosity (LOH), the non-LOH parts of the chromosomes 7 were defined as hUPD
In the group of 73 carriers of whole chromosome upd(7)mat tested by SNP array analysis, we determined a SNP array analysis in the three segmental upd(7q)mat carriers revealed a iUPD for the whole uniparental regions and confirmed the sizes of the UPD segments obtained from previous microsatellite studies [13, 14]
Summary
Maternal uniparental disomy (UPD) of chromosome 7 (upd(7)mat) accounts for approximately 10% of patients with Silver-Russell syndrome (SRS). To obtain the ratio of isodisomy and heterodisomy in UPDs (hUPD, iUPD) and to determine the underlying formation mechanisms, we analysed a large cohort of upd(7)mat patients (n = 73) by SNP array typing. Based on these data, we discuss the UPDs and their underlying trisomy 7 formation mechanisms. With the increasing number of reported cases with uniparental disomies (UPDs), this ascertainment problem could at least in part be circumvented for some of the rare trisomies in particular those which significantly contribute to the high reproductive failure in humans and/or can frequently be detected in prenatal testing. Other mechanisms of UPD formation are conceivable but are rare because they require a lot of events
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