Transmission ratio distortion in the myotonic dystrophy locus in human preimplantation embryos
Abstract
One form of myotonic dystrophy, dystrophia myotonica 1 (DM1), is caused by the expansion of a (CTG)(n) repeat within the dystrophia myotonica-protein kinase (DMPK) gene located in chromosome region 19q13.3. Unaffected individuals carry alleles with repeat size (CTG)(5-37), premutation carriers (CTG)(38-49) and DM1 affected individuals (CTG)(50-6,000). Preferential transmission both of expanded repeats from DM1-affected parents and larger DMPK alleles in the normal-size range have been reported in live-born offspring. To determine the moment in development when transmission ratio distortion (TRD) for larger normal-size DMPK alleles is generated, the transmission from heterozygous parents with one repeat within the (CTG)(5-18) range (Group I repeat) and the other within the (CTG)(19-37) range (Group II repeat) to human preimplantation embryos was analysed. A statistically significant TRD of 59% (95% confidence interval of 54-64) in favour of Group II repeats from both mothers and fathers was observed in preimplantation embryos, which remained significant when female embryos were considered separately. In contrast, no significant TRD was detected for repeats from informative Group I/Group I parents. Our analysis showed that Group II repeats specifically were preferentially transmitted in human preimplantation embryos. We suggest that TRD, in Group II repeats at the DMPK locus, is likely to result from events occurring at or around the time of fertilisation.
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Preferential transmission of premutated or expanded repeats to unaffected, subclinical, and affected individuals occurs in many repeat diseases.
“Preferential transmission of premutated or expanded repeats to unaffected, subclinical, and affected individuals has been observed in many different repeat-related diseases42–44.”
From Genome-wide detection of tandem DNA repeats that are expanded in autism (2020) · cites this paper as [44]
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- Authors
- Dean, N. L., Loredo-Osti, J. C., Fujiwara, T. M., Morgan, K., Tan, S. L., Naumova, A. K., & Ao, A.
- Affiliations
- McGill University (CA)
- Research Institute of the McGill University Health Centre (CA)
- Corresponding author
- Ao, Asangla
- Venue
- European Journal of Human Genetics
- Published
- 2006-01-04
- Volume
- 14
- Issue
- 3
- Pages
- 299-306
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- OpenAlex
- W2029859027
- Cited by
- 29
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- Canadian Institutes of Health Research (36391_1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- myotonic dystrophy type 1, segregation distortion, CTG repeat expansion, DMPK gene, preimplantation embryo, premutation, fertilisation (biology), trinucleotide repeat instability, chromosome 19q13.3
- MeSH terms
- Alleles, Blastocyst, Chromosome Mapping, Chromosomes, Human, Pair 19, Embryo, Mammalian, Fathers, Female, Fertilization, Fertilization in Vitro, Gene Frequency, Genotype, Heterozygote, Humans, Male, Mothers, Mutation, Myotonic Dystrophy, Repetitive Sequences, Nucleic Acid, Spermatozoa, Protein Serine-Threonine Kinases, Trinucleotide Repeat Expansion, Myotonin-Protein Kinase
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