Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients
Abstract Background Uniparental disomy (UPD) is the inheritance of two homologous chromosomes from the same parent. UPD may result in clinical phenotypes when occurring on chromosomes with specific imprinting pattern, when leading to homozygosity of a deleterious recessive allele inherited from one...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Wiley
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/33740cb3ed954d878e2eff95e6e8e6b0 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:33740cb3ed954d878e2eff95e6e8e6b0 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:33740cb3ed954d878e2eff95e6e8e6b02021-11-21T19:38:53ZContribution of uniparental disomy in a clinical trio exome cohort of 2675 patients2324-926910.1002/mgg3.1792https://doaj.org/article/33740cb3ed954d878e2eff95e6e8e6b02021-11-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1792https://doaj.org/toc/2324-9269Abstract Background Uniparental disomy (UPD) is the inheritance of two homologous chromosomes from the same parent. UPD may result in clinical phenotypes when occurring on chromosomes with specific imprinting pattern, when leading to homozygosity of a deleterious recessive allele inherited from one carrier parent, or when associated with a mosaic aneuploidy. Due to the importance of UPD in genetic disease etiology, UPD analysis has started to be implemented in the context of exome sequencing (ES) or genome sequencing. Methods We developed an in‐house algorithm TRIPS (Trio Parentage/UPD Studies) to identify UPD events in trio ES cases. This method identifies regions with uniparental inheritance by utilizing the trio genotyping data obtained from the concurrent SNP array to delineate the parental origin of the SNPs in the proband. Results We identified 16 UPD events from 2675 ES trios. Among those, four events led to imprinting disorders, seven unmasked a pathogenic/likely pathogenic variant in a recessive disease gene, and two were consistent with a mosaic genome wide paternal UPD pattern. Twelve of these UPD events directly contributed to the molecular diagnosis of the patients. Conclusion Our study demonstrated the contribution of UPD to the molecular diagnosis in one clinical ES cohort, thus UPD analysis should be incorporated into routine clinical ES interpretation.Lei WangPengfei LiuWeimin BiTeresa SimXia WangMagdalene WalkiewiczMagalie Sophie LeducLinyan MengFan XiaChristine M. EngYaping YangBo YuanHongzheng DaiWileyarticlealgorithmSNP arraytrio exome sequencinguniparental disomyGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
algorithm SNP array trio exome sequencing uniparental disomy Genetics QH426-470 |
| spellingShingle |
algorithm SNP array trio exome sequencing uniparental disomy Genetics QH426-470 Lei Wang Pengfei Liu Weimin Bi Teresa Sim Xia Wang Magdalene Walkiewicz Magalie Sophie Leduc Linyan Meng Fan Xia Christine M. Eng Yaping Yang Bo Yuan Hongzheng Dai Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients |
| description |
Abstract Background Uniparental disomy (UPD) is the inheritance of two homologous chromosomes from the same parent. UPD may result in clinical phenotypes when occurring on chromosomes with specific imprinting pattern, when leading to homozygosity of a deleterious recessive allele inherited from one carrier parent, or when associated with a mosaic aneuploidy. Due to the importance of UPD in genetic disease etiology, UPD analysis has started to be implemented in the context of exome sequencing (ES) or genome sequencing. Methods We developed an in‐house algorithm TRIPS (Trio Parentage/UPD Studies) to identify UPD events in trio ES cases. This method identifies regions with uniparental inheritance by utilizing the trio genotyping data obtained from the concurrent SNP array to delineate the parental origin of the SNPs in the proband. Results We identified 16 UPD events from 2675 ES trios. Among those, four events led to imprinting disorders, seven unmasked a pathogenic/likely pathogenic variant in a recessive disease gene, and two were consistent with a mosaic genome wide paternal UPD pattern. Twelve of these UPD events directly contributed to the molecular diagnosis of the patients. Conclusion Our study demonstrated the contribution of UPD to the molecular diagnosis in one clinical ES cohort, thus UPD analysis should be incorporated into routine clinical ES interpretation. |
| format |
article |
| author |
Lei Wang Pengfei Liu Weimin Bi Teresa Sim Xia Wang Magdalene Walkiewicz Magalie Sophie Leduc Linyan Meng Fan Xia Christine M. Eng Yaping Yang Bo Yuan Hongzheng Dai |
| author_facet |
Lei Wang Pengfei Liu Weimin Bi Teresa Sim Xia Wang Magdalene Walkiewicz Magalie Sophie Leduc Linyan Meng Fan Xia Christine M. Eng Yaping Yang Bo Yuan Hongzheng Dai |
| author_sort |
Lei Wang |
| title |
Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients |
| title_short |
Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients |
| title_full |
Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients |
| title_fullStr |
Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients |
| title_full_unstemmed |
Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients |
| title_sort |
contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/33740cb3ed954d878e2eff95e6e8e6b0 |
| work_keys_str_mv |
AT leiwang contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT pengfeiliu contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT weiminbi contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT teresasim contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT xiawang contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT magdalenewalkiewicz contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT magaliesophieleduc contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT linyanmeng contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT fanxia contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT christinemeng contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT yapingyang contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT boyuan contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients AT hongzhengdai contributionofuniparentaldisomyinaclinicaltrioexomecohortof2675patients |
| _version_ |
1718418693612896256 |