scholarly journals The imprinted gene and parent-of-origin effect database now includes parental origin of de novo mutations

2006 ◽  
Vol 34 (90001) ◽  
pp. D29-D31 ◽  
Author(s):  
R. L. Glaser
Keyword(s):  
De Novo ◽  
Parental Origin ◽  
De Novo Mutations ◽  
Imprinted Gene ◽  
Parent Of Origin ◽  
Origin Effect

scholarly journals Field Study of the Possible Effect of Parental Irradiation on the Germline of Children Born to Cleanup Workers and Evacuees of the Chornobyl Nuclear Accident

2020 ◽  
Vol 189 (12) ◽  
pp. 1451-1460
Author(s):  
Dimitry Bazyka ◽  
Maureen Hatch ◽  
Natalia Gudzenko ◽  
Elizabeth K Cahoon ◽  
Vladimir Drozdovitch ◽  
...  
Keyword(s):  
Atomic Bomb ◽  
De Novo ◽  
Measurement Data ◽  
Nuclear Accident ◽  
Parental Origin ◽  
High Dose ◽  
De Novo Mutations ◽  
Transgenerational Effects ◽  
Genomic Alterations ◽  
Cleanup Workers

Abstract Although transgenerational effects of exposure to ionizing radiation have long been a concern, human research to date has been confined to studies of disease phenotypes in groups exposed to high doses and high dose rates, such as the Japanese atomic bomb survivors. Transgenerational effects of parental irradiation can be addressed using powerful new genomic technologies. In collaboration with the Ukrainian National Research Center for Radiation Medicine, the US National Cancer Institute, in 2014–2018, initiated a genomic alterations study among children born in selected regions of Ukraine to cleanup workers and/or evacuees exposed to low–dose-rate radiation after the 1986 Chornobyl (Chernobyl) nuclear accident. To investigate whether parental radiation exposure is associated with germline mutations and genomic alterations in the offspring, we are collecting biospecimens from father-mother-offspring constellations to study de novo mutations, minisatellite mutations, copy-number changes, structural variants, genomic insertions and deletions, methylation profiles, and telomere length. Genomic alterations are being examined in relation to parental gonadal dose, reconstructed using questionnaire and measurement data. Subjects are being recruited in exposure categories that will allow examination of parental origin, duration, and timing of exposure in relation to conception. Here we describe the study methodology and recruitment results and provide descriptive information on the first 150 families (mother-father-child(ren)) enrolled.

Parent-of-origin-specific signatures of de novo mutations

2016 ◽  
Vol 48 (8) ◽  
pp. 935-939 ◽  
Author(s):  
Jakob M Goldmann ◽  
Wendy S W Wong ◽  
Michele Pinelli ◽  
Terry Farrah ◽  
Dale Bodian ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Mutations ◽  
Parent Of Origin

scholarly journals Author Correction: Parent-of-origin-specific signatures of de novo mutations

2018 ◽  
Vol 50 (11) ◽  
pp. 1615-1615 ◽  
Author(s):  
Jakob M Goldmann ◽  
Wendy S W Wong ◽  
Michele Pinelli ◽  
Terry Farrah ◽  
Dale Bodian ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Mutations ◽  
Parent Of Origin

scholarly journals PWS/AS MS-MLPA Confirms Maternal Origin of 15q11.2 Microduplication

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Angelika J. Dawson ◽  
Janice Cox ◽  
Karine Hovanes ◽  
Elizabeth Spriggs
Keyword(s):  
De Novo ◽  
Clinical Phenotype ◽  
Methylation Status ◽  
Uniparental Disomy ◽  
Proximal Region ◽  
Parental Origin ◽  
Developmental Abnormalities ◽  
Genomic Array ◽  
Parent Of Origin ◽  
Dependent Probe

The proximal region of the long arm of chromosome 15q11.2-q13 is associated with various neurodevelopmental disorders, including Prader-Willi (PWS) and Angelman (AS) syndromes, autism, and other developmental abnormalities resulting from deletions and duplications. In addition, this region encompasses imprinted genes that cause PWS or AS, depending on the parent-of-origin. This imprinting allows for diagnosis of PWS or AS based on methylation status using methylation sensitive (MS) multiplex ligation dependent probe amplification (MLPA). Maternally derived microduplications at 15q11.2-q13 have been associated with autism and other neuropsychiatric disorders. Multiple methods have been used to determine the parent-of-origin for 15q11.2-q13 microdeletions and microduplications. In the present study, a four-year-old nondysmorphic female patient with developmental delay was found to have ade novo~5 Mb duplication within 15q11.2 by oligonucleotide genomic array. In order to determine the significance of this microduplication to the clinical phenotype, the parent-of-origin needed to be identified. The PWS/AS MS-MLPA assay is generally used to distinguish between deletion and uniparental disomy (UPD) of 15q11.2-q13, resulting in either PWS or AS. However, our study shows that PWS/AS MS-MLPA can also efficiently distinguish the parental origin of duplications of 15q11.2-q13.

scholarly journals Sex-specific recombination predicts parent of origin for recurrent genomic disorders

2020 ◽  
Author(s):  
Trenell Mosley ◽  
H. Richard Johnston ◽  
David J Cutler ◽  
Michael E Zwick ◽  
Jennifer G Mulle
Keyword(s):  
Large Scale ◽  
Structural Variation ◽  
De Novo ◽  
Copy Number Variants ◽  
Parental Origin ◽  
Structural Rearrangements ◽  
Recombination Rates ◽  
Pathogenic Cnvs ◽  
Parent Of Origin ◽  
Genomic Disorders

Abstract Genomic disorders are caused by structural rearrangements of the genome that generally occur during meiosis. Often the rearrangements result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications ≥ 1 kb). Recurrent pathogenic CNVs harbor similar breakpoints in multiple unrelated individuals and are primarily formed via non-allelic homologous recombination (NAHR). Several pathogenic NAHR-mediated recurrent CNV loci demonstrate biases for parental origin of de novo CNVs. However, the mechanism underlying these biases is not well understood. Here we have curated parent of origin data for multiple pathogenic CNV loci and demonstrate a significant association between sex-specific differences in meiotic recombination and parental origin biases at these loci. Our results suggest that parental-origin of CNVs is largely controlled by sex-specific recombination rates, and highlight the need to consider these differences when investigating mechanisms that cause structural variation.

scholarly journals Sex-specific recombination predicts parent of origin for recurrent genomic disorders

2020 ◽  
Author(s):  
Trenell Mosley ◽  
H. Richard Johnston ◽  
David J. Cutler ◽  
Michael E. Zwick ◽  
Jennifer G. Mulle
Keyword(s):  
Large Scale ◽  
Structural Variation ◽  
De Novo ◽  
Copy Number Variants ◽  
Parental Origin ◽  
Recombination Rates ◽  
Pathogenic Cnvs ◽  
Parent Of Origin ◽  
Genomic Disorders ◽  
Underlying Risk

SUMMARYGenomic disorders are caused by structural rearrangements of the genome that generally occur during meiosis1. Often the rearrangements result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications ≥ 1 kb)2,3. Recurrent pathogenic CNVs harbor similar breakpoints in multiple unrelated individuals and are primarily formed via non-allelic homologous recombination (NAHR)3,4. Several pathogenic NAHR-mediated recurrent CNV loci demonstrate biases for parental origin of de novo CNVs5–9. However, the mechanism underlying these biases is not well understood. Here we have curated parent of origin data for multiple pathogenic CNV loci and demonstrate a significant association between sex-specific differences in meiotic recombination and parental origin biases at these loci. Our results suggest that parental-origin of CNVs is largely controlled by sex-specific recombination rates and bring into light the need to consider these differences when seeking to determine the factors underlying risk for structural variation.

scholarly journals Sex-specific recombination patterns predict parent of origin for recurrent genomic disorders

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Trenell J. Mosley ◽  
H. Richard Johnston ◽  
David J. Cutler ◽  
Michael E. Zwick ◽  
Jennifer G. Mulle
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Copy Number Variants ◽  
Parental Origin ◽  
Recombination Rates ◽  
Pathogenic Cnvs ◽  
Parent Of Origin ◽  
Genomic Disorders ◽  
The Relationship ◽  
Male To Female

Abstract Background Structural rearrangements of the genome, which generally occur during meiosis and result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications ≥ 1 kb), underlie genomic disorders. Recurrent pathogenic CNVs harbor similar breakpoints in multiple unrelated individuals and are primarily formed via non-allelic homologous recombination (NAHR). Several pathogenic NAHR-mediated recurrent CNV loci demonstrate biases for parental origin of de novo CNVs. However, the mechanism underlying these biases is not well understood. Methods We performed a systematic, comprehensive literature search to curate parent of origin data for multiple pathogenic CNV loci. Using a regression framework, we assessed the relationship between parental CNV origin and the male to female recombination rate ratio. Results We demonstrate significant association between sex-specific differences in meiotic recombination and parental origin biases at these loci (p = 1.07 × 10–14). Conclusions Our results suggest that parental origin of CNVs is largely influenced by sex-specific recombination rates and highlight the need to consider these differences when investigating mechanisms that cause structural variation.

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