Anastasia Miron
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Anastasia Miron has a total of 40 co-authors. Here are the top co-authors by number of shared publications:
- Seema Mital
Ted Rogers Centre for Heart Research, Toronto, Canada (T.P., S.M.).
2 shared publications - Abdelrahman Said
Genetics and Genome Biology Program, The Hospital For Sick Children, Toronto, Canada
1 shared publication - Beth Kaufman
Department of Pediatrics, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, CA (B.K.)
1 shared publication - Bhooma Thiruvahindrapuram
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 1H3, Canada
1 shared publication - Chet R. Villa
Cincinnati Children's Hospital Medical Center University of Cincinnati College of Medicine Cincinnati USA
1 shared publication - Chun-Po Steve Fan
Ted Rogers Computational Program, Peter Munk Cardiac Centre, University Health Network, Toronto, Canada
1 shared publication
Latest Publications
- 16 March 2021
- Published by Wolters Kluwer Health in Circulation
- Vol. 143 (11) , E788-E789
Response by Mital et al to Letter Regarding Article, “A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy”
- 16 March 2021
- Published by Wolters Kluwer Health in Circulation
- Vol. 143 (11) , E788-E789
Response by Mital et al to Letter Regarding Article, “A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy”
- Open Access
Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy
Cardiomyopathy (CMP) is a heritable genetic disorder. Protein-coding variants account for 20-30% of cases. The contribution of variants in non-coding DNA elements that regulate gene expression has not been explored. We performed whole-genome sequencing (WGS) of 228 unrelated CMP families. Besides pathogenic protein-coding variants in known CMP genes, 5% cases harbored rare loss-of-function variants in novel cardiac genes, with NRAP and FHOD3 being strong candidates. WGS also revealed a high burden of high-risk variants in promoters and enhancers of CMP genes in an additional 20% cases (Odds ratio 2.14, 95% CI 1.60-2.86, p=5.26×10 −7 vs 1326 controls) with genes involved in α-dystroglycan glycosylation ( FKTN, DTNA ) and desmosomal signaling ( DSC2, DSG2 ) specifically enriched for regulatory variants (False discovery rate <0.03). These findings were independently replicated in the Genomics England CMP cohort (n=1266). The functional effect of non-coding variants on transcription was functionally validated in patient myocardium and reporter assays in human cardiomyocytes, and that of novel gene variants in zebrafish knockouts. Our results show that functionally active variants in novel genes and in regulatory elements of CMP genes contribute strongly to the genomic etiology of childhood-onset CMP.
Open AccessWhole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy
Cardiomyopathy (CMP) is a heritable genetic disorder. Protein-coding variants account for 20-30% of cases. The contribution of variants in non-coding DNA elements that regulate gene expression has not been explored. We performed whole-genome sequencing (WGS) of 228 unrelated CMP families. Besides pathogenic protein-coding variants in known CMP genes, 5% cases harbored rare loss-of-function variants in novel cardiac genes, with NRAP and FHOD3 being strong candidates. WGS also revealed a high burden of high-risk variants in promoters and enhancers of CMP genes in an additional 20% cases (Odds ratio 2.14, 95% CI 1.60-2.86, p=5.26×10 −7 vs 1326 controls) with genes involved in α-dystroglycan glycosylation ( FKTN, DTNA ) and desmosomal signaling ( DSC2, DSG2 ) specifically enriched for regulatory variants (False discovery rate <0.03). These findings were independently replicated in the Genomics England CMP cohort (n=1266). The functional effect of non-coding variants on transcription was functionally validated in patient myocardium and reporter assays in human cardiomyocytes, and that of novel gene variants in zebrafish knockouts. Our results show that functionally active variants in novel genes and in regulatory elements of CMP genes contribute strongly to the genomic etiology of childhood-onset CMP.