Uniparental disomy: Origin, frequency, and clinical significance

Abstract

Uniparental disomy (UPD) is defined as two copies of a whole chromosome derived from the same parent. There can be multiple mechanisms that lead to UPD; these are reviewed in the context of contemporary views on the mechanism leading to aneuploidy. Recent studies indicate that UPD is rare in an apparently healthy population and also rare in spontaneous abortion tissues. The most common type of UPD is a maternal heterodisomy (both maternal allele sets present). Isodisomy (a duplicated single set of alleles) or segmental loss of heterozygosity is sometimes encountered in SNP‐based microarray referrals. Decisions regarding the most appropriate follow‐up testing should consider the possibility of consanguinity (that will generally involve multiple regions), an imprinted gene disorder (chromosomes 6, 7, 11, 14, 15, 20), expression of an autosomal recessive disorder, and an occult aneuploid cell line that may be confined to the placenta. Upd(16)mat, per se, does not appear to be associated with an abnormal phenotype. UPD provides an insight into the history of early chromosome segregation error and understanding the rates and fate of these events are of key importance in the provision of fertility management and prenatal healthcare.

Chromosomal mosaicism: Origins and clinical implications in preimplantation and prenatal diagnosis

“…In some cases, a combination of two chromosome segregation errors leads to two copies of a chromosome being inherited from a single parent, a phenomenon called uniparental disomy (UPD). A review of mechanisms for UPD can be found elsewhere in this Special Issue 12 . Similar to consanguinity, uniparental isodisomy (two identical [i.e., two homozygous] chromosomes as depicted in Figure 2) leads to an increased risk for autosomal recessive diseases in genes in the homozygous region.…”

“…A review of mechanisms for UPD can be found elsewhere in this Special Issue. 12 Similar to consanguinity, uniparental isodisomy (two identical [i.e., two homozygous] chromosomes as depicted in Figure 2) leads to an increased risk for autosomal recessive diseases in genes in the homozygous region. UPD can also cause aberrant expression levels of genes that are imprinted (only expressed from one parent's chromosome and silenced on the other).…”

The origins of aneuploidy research consortium

“…Benn reviews the multiple etiologic mechanisms for chromosome segregation error that can result in uniparental disomy. 29 For the non-mosaic common autosomal trisomies (21, 18 and 13), as previously noted, maternal age is the main clinical or demographic factor that pre-determines risk. However, a large number of other factors such as paternal age, exposures, and predispositions have been proposed and these are reviewed by Cuckle and Benn.…”

A Novel Genetic Variant in the WFS1 Gene in a Patient with Partial Uniparental Mero-Isodisomy of Chromosome 4

“…The mitotic correction of the resulting aneuploid embryo (trisomy/monosomy rescue) may cause UPD. The UPD phenotypic effects may be due to the involvement of imprinting regions or isodisomy, and can result in a recessive disorder caused by a homozygous pathogenic variant that is present in only one of the parents [ 8 , 9 ].…”