6.7 Unit Summary and Review
Key Takeaways
Taking a family health history is crucial for assessing genetic risks and identifying heritable conditions. It remains the gold standard for initial risk assessment, helping to reveal genetic components, inheritance patterns, and inform testing and treatment decisions.
Constructing a genetic pedigree involves creating a visual representation of a patient’s family health history across multiple generations, which helps in diagnosing inherited conditions, understanding inheritance patterns, and informing clinical decisions. Standardized symbols and lines are used to depict family relationships and medical conditions, making the pedigree easy to read and update for healthcare professionals.
When analyzing pedigree charts to determine genotype, the goal is to identify the most likely mode of inheritance for a trait, which helps in predicting its inheritance in future offspring. This involves considering five major types of inheritance (autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and Y-linked) and making assumptions about complete penetrance and the rarity of the trait in the population. Different modes of inheritance can be identified through characteristic patterns in pedigree charts. These charts help determine how a disease or trait is passed down through generations, aiding in predicting the likelihood of inheritance in future offspring.
Not all diseases are caused by single gene mutations; many have complex inheritance patterns involving multiple genes and environmental factors. Some non-genetic diseases may appear heritable due to shared environmental exposures. Polygenic risk scores, which estimate disease risk based on multiple genetic variants, are emerging tools but currently have limitations, including a lack of diversity in genomic studies. These scores provide relative risk but not absolute certainty, and their use in healthcare is still evolving.
Once the mode of inheritance for a disease is identified, we can infer the genotypes of individuals in a pedigree based on their phenotypes and positions in the family tree. Using Mendelian inheritance rules and probability calculations, we can determine the likelihood of specific genotypes being passed to future generations, which is valuable for genetic counseling and assessing the risk of offspring inheriting certain diseases.
Additional Optional Readings
- Andrusko, D. & Paradiso, C. (2022). Establishing a process to improve the collection of family health history. The Nurse Practitioner, 47 (4), 32-40. https://doi.org/10.1097/01.NPR.0000822532.65525.5a.
- Hays, L. (2023). The three-generation pedigree. Advances in Family Practice Nursing, 5(1), 77–91. https://doi.org/10.1016/j.yfpn.2022.11.006
- Mahon, S.M. (2016). The three-generation pedigree: A critical tool in cancer genetics care. Genetics, Patient Education, Risk Assessment, 43(5), 655-660. https://doi.org/10.1188/16.ONF.655-660
- Stanfill, A. G., & Starlard-Davenport, A. (2018). Primer in genetics and genomics, Article 7—Multifactorial concepts: Gene–gene interactions. Biological Research For Nursing, 20(3), 359-364. https://doi.org/10.1177/1099800418761098
- Wildin, R. S., Messersmith, D. J., & Houwink, E. J. F. (2021). Modernizing family health history: achievable strategies to reduce implementation gaps. Journal of community genetics, 12(3), 493–496. https://doi.org/10.1007/s12687-021-00531-6
- Xiang, R., Kelemen, M., Xu, Y., Harris, L. W., Parkinson, H., Inouye, M., & Lambert, S. A. (2024). Recent advances in polygenic scores: translation, equitability, methods and FAIR tools. Genome Medicine, 16, 33. https://doi.org/10.1186/s13073-024-01304-9
Tools and Resources
Pedigree Analysis
- For a visual walk-through of a pedigree analysis work through this short Khan Academy module on pedigrees which includes practice exercises.
Family History and Pedigree Chart Tools
- Students will use My Family Health Portrait to create a pedigree chart for their chosen case study.
- Another good clinical resource for creating an electronic pedigree is from Progeny Genetics
- For those who prefer a paper template, the Jackson Laboratory provides a template and printable symbol sheet.
- GECKO has also created this family history tool [PDF].
- The NHS Genomics Education Programme has a family history worksheet [PDF]
- Families Sharing Health Assessment and Risk Evaluation (SHARE) helps you and your family learn how your family health history affects your risk for diseases. Includes disease risk worksheets and workbooks in multiple languages.
Variant Classification
Landrum, M. J., Chitipiralla, S., Kaur, K., Brown, G., Chen, C., Hart, J., Hoffman, D., Jang, W., Liu, C., Maddipatla, Z., Maiti, R., Mitchell, J., Rezaie, T., Riley, G., Song, G., Yang, J., Ziyabari, L., Russette, A., & Kattman, B. L. (2024). ClinVar: updates to support classifications of both germline and somatic variants, Nucleic Acids Research, gkae1090, https://doi.org/10.1093/nar/gkae1090
Attribution and References
Key takeaways generated using ChatGPT. Prompt: “summarize this text in a few sentences, ignoring images, captions, citations and web references.” The output was then edited by Andrea Gretchev.
References
ChatGPT: OpenAI. (2024). ChatGPT (Version 4.0) [Large language model]. https://openai.com
