ArticleAmerican journal of human genetics2014
Parent of origin, mosaicism, and recurrence risk: probabilistic modeling explains the broken symmetry of transmission genetics.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed.
- A Synonymous DLG4 Variant (c.771G>A) Causes Exon 9 Skipping via Paternal Germline Mosaicism in DLG4-Related Synaptopathy.Molecular genetics & genomic medicine · 2026Article
- Mucopolysaccharidosis II with diverse genetic origins in a single family: a case series and literature review.BMC pediatrics · 2026Review
- Complete Androgen Insensitivity Syndrome (CAIS) Genetic Counseling: Navigating Germline Mosaicism Concerns.Case reports in genetics · 2026Article
- From Overgrowth to Complex Malformations: A NovelChildren (Basel, Switzerland) · 2025Article
- De novo somatic mosaicisms of INF2 and TRPV4 in patients with Charcot-Marie-Tooth disease.Genes & genomics · 2025Article
- [Expert consensus on auditory intervention and language rehabilitation of CHARGE syndrome].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Article
- Parental germline mosaicism in genome-wide phased de novo variants: Recurrence risk assessment and implications for precision genetic counselling.PLoS genetics · 2025Article
- Chromoanasynthesis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The clinical application and challenges of preimplantation genetic testing.Frontiers in genetics · 2025Review
- Prenatal diagnosis of fetal skeletal anomalies via whole-exome sequencing in a tertiary referral center.Scientific reports · 2024Article
- A Family With Nail-Patella Syndrome Caused by a Germline Mosaic Deletion ofAnnals of laboratory medicine · 2024Article
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics.NPJ genomic medicine · 2024Article
- [Sperm Mosaic Variants and Their Influence on the Offspring].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- Case report: Deep sequencing and long-read genome sequencing refine prior genetic analyses in families with apparent gonadal mosaicism inFrontiers in immunology · 2024Article
- Revealing parental mosaicism: the hidden answer to the recurrence of apparent de novo variants.Human genomics · 2023Article
- The contribution of mosaicism to genetic diseases and de novo pathogenic variants.American journal of medical genetics. Part A · 2023Article
- Parental mosaicism detection and preimplantation genetic testing in families with multiple transmissions of de novo mutations.Journal of medical genetics · 2023Article
- Clinical application of next generation sequencing-based haplotype linkage analysis in the preimplantation genetic testing for germline mosaicisms.Orphanet journal of rare diseases · 2023Article
- Genome-wide identification of copy neutral loss of heterozygosity reveals its possible association with spatial positioning of chromosomes.Human molecular genetics · 2023Article
15 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
Most new mutations are observed to arise in fathers, and increasing paternal age positively correlates with the risk of new variants. Interestingly, new mutations in X-linked recessive disease show elevated familial recurrence rates. In male offspring, these mutations must be inherited from mothers. We previously developed a simulation model to consider parental mosaicism as a source of transmitted mutations. In this paper, we extend and formalize the model to provide analytical results and flexible formulas. The results implicate parent of origin and parental mosaicism as central variables in recurrence risk. Consistent with empirical data, our model predicts that more transmitted mutations arise in fathers and that this tendency increases as fathers age. Notably, the lack of expansion later in the male germline determines relatively lower variance in the proportion of mutants, which decreases with paternal age. Subsequently, observation of a transmitted mutation has less impact on the expected risk for future offspring. Conversely, for the female germline, which arrests after clonal expansion in early development, variance in the mutant proportion is higher, and observation of a transmitted mutation dramatically increases the expected risk of recurrence in another pregnancy. Parental somatic mosaicism considerably elevates risk for both parents. These findings have important implications for genetic counseling and for understanding patterns of recurrence in transmission genetics. We provide a convenient online tool and source code implementing our analytical results. These tools permit varying the underlying parameters that influence recurrence risk and could be useful for analyzing risk in diverse family structures.
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