Theoretical Framework for the Study of Genetic Diseases Caused by Dominant Alleles
We propose a theoretical basis for analyzing several features of genetic diseases caused by dominant alleles, including: disease prevalence, genotype penetrance, and the relationship between causal genotype frequency and disease frequency. In addition, we provide a theoretical framework for accurate...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/13/3/733 |
| _version_ | 1797610649725960192 |
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| author | Michael F. Roberts Stephen E. Bricher |
| author_facet | Michael F. Roberts Stephen E. Bricher |
| author_sort | Michael F. Roberts |
| collection | DOAJ |
| description | We propose a theoretical basis for analyzing several features of genetic diseases caused by dominant alleles, including: disease prevalence, genotype penetrance, and the relationship between causal genotype frequency and disease frequency. In addition, we provide a theoretical framework for accurate diagnosis and clinical approaches for disease study, including two examples in which inaccurate and incomplete diagnoses affect the estimates of disease prevalence: First, the disease iceberg effect shows that disease prevalence is often underestimated due to errors introduced by inaccurate diagnosis; second, because lifetime risk of disease is cumulative, and therefore an increasing function of age, measurements of prevalence are inaccurate if people of all ages are not included. Finally, we discuss the aggregation of genetic diseases. We identify theoretical and computational deficiencies associated with using the sibling recurrence-risk ratio as a measure of familial aggregation. We develop an alternative concept of aggregation and propose an associated measure that does not experience the deficiencies. Throughout, we provide clinicians and researchers practical implications of our theoretical framework. |
| first_indexed | 2024-03-11T06:17:12Z |
| format | Article |
| id | doaj.art-5fe9f6ada35e4d44b5a433f1d14d5f06 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T06:17:12Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-5fe9f6ada35e4d44b5a433f1d14d5f062023-11-17T12:11:36ZengMDPI AGLife2075-17292023-03-0113373310.3390/life13030733Theoretical Framework for the Study of Genetic Diseases Caused by Dominant AllelesMichael F. Roberts0Stephen E. Bricher1Department of Biology, Linfield University, McMinnville, OR 97128, USADepartment of Mathematics and Computer Science, Linfield University, McMinnville, OR 97128, USAWe propose a theoretical basis for analyzing several features of genetic diseases caused by dominant alleles, including: disease prevalence, genotype penetrance, and the relationship between causal genotype frequency and disease frequency. In addition, we provide a theoretical framework for accurate diagnosis and clinical approaches for disease study, including two examples in which inaccurate and incomplete diagnoses affect the estimates of disease prevalence: First, the disease iceberg effect shows that disease prevalence is often underestimated due to errors introduced by inaccurate diagnosis; second, because lifetime risk of disease is cumulative, and therefore an increasing function of age, measurements of prevalence are inaccurate if people of all ages are not included. Finally, we discuss the aggregation of genetic diseases. We identify theoretical and computational deficiencies associated with using the sibling recurrence-risk ratio as a measure of familial aggregation. We develop an alternative concept of aggregation and propose an associated measure that does not experience the deficiencies. Throughout, we provide clinicians and researchers practical implications of our theoretical framework.https://www.mdpi.com/2075-1729/13/3/733genetic diseaseprevalencepenetranceaccurate diagnosisdisease iceberg effectcumulative lifetime risk |
| spellingShingle | Michael F. Roberts Stephen E. Bricher Theoretical Framework for the Study of Genetic Diseases Caused by Dominant Alleles Life genetic disease prevalence penetrance accurate diagnosis disease iceberg effect cumulative lifetime risk |
| title | Theoretical Framework for the Study of Genetic Diseases Caused by Dominant Alleles |
| title_full | Theoretical Framework for the Study of Genetic Diseases Caused by Dominant Alleles |
| title_fullStr | Theoretical Framework for the Study of Genetic Diseases Caused by Dominant Alleles |
| title_full_unstemmed | Theoretical Framework for the Study of Genetic Diseases Caused by Dominant Alleles |
| title_short | Theoretical Framework for the Study of Genetic Diseases Caused by Dominant Alleles |
| title_sort | theoretical framework for the study of genetic diseases caused by dominant alleles |
| topic | genetic disease prevalence penetrance accurate diagnosis disease iceberg effect cumulative lifetime risk |
| url | https://www.mdpi.com/2075-1729/13/3/733 |
| work_keys_str_mv | AT michaelfroberts theoreticalframeworkforthestudyofgeneticdiseasescausedbydominantalleles AT stephenebricher theoreticalframeworkforthestudyofgeneticdiseasescausedbydominantalleles |