Uniparental disomy is a chromosomic disorder in the first place

• Published in: Molecular cytogenetics 2022-02, Vol.15 (1), p.5-12, Article 5
• Main Author: Liehr, Thomas
• Format: Article
• Language: English
• Subjects: Analysis; Aneuploidy; Chromosome; Chromosome rearrangements; Cytogenetics; DNA methylation; Epigenetics; Gene mutations; Genes; Genetic aspects; Genomes; Genomic imprinting; Imprinting; Isodisomy; Mosaic; Mosaicism; Mutation; Point mutation; Uniparental disomy; Uniparental disomy (UPD); Y chromosomes
• ISSN: 1755-8166; 1755-8166
• DOI: 10.1186/s13039-022-00585-2

Uniparental disomy (UPD) is well-known to be closely intermingled with imprinting disorders. Besides, UPD can lead to a disease by 'activation' of a recessive gene mutation or due to incomplete (cryptic) trisomic rescue. Corresponding to all common theories how UPD forms, it takes place as a consequence of a "chromosomic problem", like an aneuploidy or a chromosomal rearrangement. Nonetheless, UPD is rarely considered as a cytogenetic, but most often as a molecular genetic problem. Here a review on the ~ 4900 published UPD-cases is provided, and even though being biased as discussed in the paper, the following insights have been given from that analysis: (1) the rate of maternal to paternal UPD is 2~3 to 1; (2) at most only ~ 0.03% of the available UPD cases are grasped scientifically, yet; (3) frequencies of single whole-chromosome UPDs are non-random, with UPD(16) and UPD(15) being most frequent in clinically healthy and diseased people, respectively; (4) there is a direct correlation of UPD frequency and known frequent first trimester trisomies, except for chromosomes 1, 5, 11 and 18 (which can be explained); (5) heterodisomy is under- and UPD-mosaicism is over-represented in recent reports; and (6) cytogenetics is not considered enough when a UPD is identified. As UPD is diagnosed using molecular genetic approaches, and thus by specialists considering chromosomes at best as a whim of nature, most UPD reports lack the chromosomal aspect. Here it is affirmed and substantiated by corresponding data that UPD is a chromosomic disorder in the first place and cytogenetic analyses is indicated in each diagnosed UPD-case.