Identifying modifier genes of monogenic disease: strategies and difficulties
Open accessAbstract
Substantial clinical variability is observed in many Mendelian diseases, so that patients with the same mutation may develop a very severe form of disease, a mild form or show no symptoms at all. Among the factors that may explain these differences in disease expression are modifier genes. In this paper, we review the different strategies that can be used to identify modifier genes and explain their advantages and limitations. We focus mainly on the statistical aspects but illustrate our points with a variety of examples from the literature.
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Modifier genes can affect pathways downstream or upstream from multiple defective genes, thereby addressing a clinical phenotype without the need for a genetic diagnosis and in a mutation-agnostic manner.
“Modifier genes can affect pathways downstream or upstream from multiple defective genes, thereby addressing a clinical phenotype without the need for a genetic diagnosis and in a mutation-agnostic manner.”
From Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions (2023) · cites this paper as [46]
Modifier therapies rely heavily on identification of modifier genes involved in a particular disease phenotype, which may prove challenging and possibly costly.
“Modifier therapies rely heavily on identification of modifier genes involved in a particular disease phenotype, which may prove challenging and possibly costly.46”
From Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions (2023) · cites this paper as [46]
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A General Test of Association for Quantitative Traits in Nuclear Families
Abecasis, G. R., Cardon, L. R., & Cookson, W. O. C. (2000) · The American Journal of Human Genetics · doi:10.1086/302698 · Cited by 1,126 · see citing works
Discerning the ancestry of European Americans in genetic association studies
Price, A. L., Butler, J., Patterson, N., Capelli, C., Pascali, V. L., Scarnicci, F., Ruiz-Linares, A., Groop, L., Saetta, A. A., Korkolopoulou, P., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.0030236 · Cited by 327 · see citing works
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Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions
Drag, S., Dotiwala, F., & Upadhyay, A. K. (2023) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.64.7.39 · Cited by 145 · see citing works
REGISTRY Investigators of the European Huntington's Disease Network, Bečanović, K., Nørremølle, A., Neal, S. J., Kay, C., Collins, J. A., Arenillas, D., Lilja, T., Gaudenzi, G., Manoharan, S., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4014 · Cited by 135 · see citing works
Philtjens, S., Acri, D. J., Kim, B., Kim, H., & Kim, J. (2021) · doi:10.21203/rs.3.rs-171899/v1 · Cited by 1 · see citing works
“Genes that influence the expression 53 of other genes are called modifiers and can be detected using quantitative trait loci (QTL) 54 mapping [2, 3].”
Background
- Authors
- Génin, E., Feingold, J., & Clerget-Darpoux, F.
- Affiliations
- Université Paris-Sud (FR)
- ORCID
- Génin, Emmanuelle
- Venue
- Human Genetics
- Published
- 2008-09-11
- Volume
- 124
- Issue
- 4
- Pages
- 357-368
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- PMC
- PMC2911473
- OpenAlex
- W2088131585
- Cited by
- 126
- References
- 2
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 6 · 2015: 7 · 2014: 4 · 2013: 11 · 2012: 7
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- genetic modifiers, monogenic disorders, clinical heterogeneity, disease expression, genetic heterogeneity
- MeSH terms
- Genes, Humans, Genetic Linkage, Phenotype, Genetic Predisposition to Disease, Genetic Diseases, Inborn, Mutant Proteins
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