Related Experiment Videos
[Uniparental disomy: a review of causes and clinical sequelae]
1Division de Génétique Médicale, Centre Médical Universitaire, Genève, Suisse.
Insights
Uniparental disomy (UPD) occurs when a child inherits both chromosomes of a pair from a single parent, potentially causing genetic disorders through altered imprinting or increased recessive disease risk.
Area of Science:
- Genetics
- Epigenetics
- Human Biology
Context:
- Uniparental disomy (UPD) is a rare genetic condition where an individual inherits two copies of a chromosome from one parent and none from the other.
- UPD can arise from various chromosomal mechanisms and has been observed across numerous human chromosomes, including sex chromosomes.
Purpose:
- To elucidate the mechanisms and phenotypic consequences of Uniparental Disomy (UPD).
- To highlight the impact of UPD on genomic imprinting and the risk of genetic disorders.
- To discuss the clinical implications of UPD in relation to Mendelian inheritance and evolution.
Summary:
- UPD results from inheriting a chromosome pair solely from one parent, leading to potential health issues via isodisomy (homozygous state), genomic imprinting disruption, or residual aneuploidy.
- Isodisomy increases the risk of recessive genetic disorders like cystic fibrosis and thalassemia, while both iso- and heterodisomy can disrupt imprinting, causing syndromes such as Angelman and Prader-Willi.
- UPD can cause morbidity or lethality by affecting imprinting, mimicking deletions/duplications, triggering recessive disorders, or promoting cancer, challenging traditional inheritance patterns and raising questions about genomic imprinting's evolutionary role.
Impact:
- UPD contributes to a spectrum of congenital disorders and genetic diseases, underscoring the importance of parental origin in gene expression.
- Understanding UPD is crucial for accurate genetic diagnosis, counseling, and comprehending the complex interplay between inheritance, imprinting, and disease.
- This research sheds light on the fundamental processes of inheritance and gene regulation, with potential implications for developmental biology and personalized medicine.
Abstract:
1) Uniparental disomy (UPD) results from the exceptional derivation of a pair of the offspring chromosome from one parent only and has been documented thus far for chromosomes 2, 4, 5, 6, 7, 11, 13, 14, 15, 20, 21, 22 both X's and the XY pair. Its consequences on the phenotype may result from three potentially harmful effects, namely isodisomy, interference with genomic imprinting and, occasionally the vestigial aneuploidy from which UPD may have originated. 2) In isodisomy, the uniparental pair is partially or entirely homozygous, through the duplication of a same chromosomal DNA template, thus bringing about an increased risk of recessive disorders. As a result, conditions such as cystic fibrosis, a type of osteogenesis imperfecta, thalassemia alpha or beta, retinoblastoma, rod monochromacy, etc., have now been reported. 3) Duplication of both homologues of a parental pair in a diploid genome is called heterodisomy. Both iso- and heterodisomy may also cause disruption of the genomic imprints normally modifying the differential expression of some maternal and paternal genes or gene sequences needed for eugenic growth and development, in the course of normal biparental inheritance. Such a disturbance can be one of the causes of congenital clinical entities as well defined as Angelman, Prader-Willi or Beckwith-Wiedemann syndromes and some new syndromes, for instance for UPD 7 mat, UPD 14 mat and, probably also 14 pat. 4) All in all, UPD can cause morbidity or lethality by altering imprinting processes, mimicking certain deletions or duplications, generating recessive disorders or prompting malignant tumor development. 5) In the clinical field, UPD occasionally upsets some mendelian tenets of traditional inheritance, and raises, the question of the evolutional role plaid by genomic imprinting (GI). An hypothetical opinion is that one of GI potential side effects is a biased intergenerational preferential display or skip of parental features. This could be so because some of the inherited genes or gene domains only gain maternal or paternal expression in the offspring, as a function of their parental imprint.