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Disclosure of Genetic Research Results to Members of a Founder Population

Abstract

There is currently extensive discussion and debate in the literature on how, when, and to whom genetic research results should be returned (see Genetics in Medicine, April 2012 issue). Here, we describe our experience in disclosing genetic information on Mendelian disorders discovered during the course of our research in the Hutterites. We first assessed attitudes toward the disclosure of carrier results, which revealed that many individuals wanted carrier information and that many intended to use the information in family planning. Based on this information, we developed a pilot study to test and disclose cystic fibrosis (CF) carrier status. Next, a larger scale project was developed in order to disclose genetic research results for 14 diseases to those interested in receiving the information. We developed brochures, offered a live interactive educational program, conducted a consent process, and disclosed results in letters mailed to the consented individuals. Overall, ~80 % of individuals who participated in the educational program signed consent forms for the release of their results for 14 diseases. We describe our experience with returning individual genetic research results to participants in a population-based research study.

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References

  • Armistead, J., Khatkar, S., Meyer, B., Mark, B. L., Patel, N., Coghlan, G., et al. (2009). Mutation of a gene essential for ribosome biogenesis, EMG1, causes Bowen-Conradi syndrome. [Comparative Study Research Support, Non-U.S. Gov’t]. American Journal of Human Genetics, 84(6), 728–739. doi:10.1016/j.ajhg.2009.04.017.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M. A., Puffenberger, E. G., Schwartz, C., et al. (2013). Intellectual disability associated with a homozygous missense mutation in THOC6. Orphanet Journal of Rare Diseases, 8(1), 62. doi:10.1186/1750-1172-8-62.

    PubMed Central  PubMed  Article  Google Scholar 

  • Beskow, L. M., & Burke, W. (2010). Offering individual genetic research results: context matters. [Research Support, N.I.H., Extramural]. Science Translational Medicine, 2(38), 38cm20. doi:10.1126/scitranslmed.3000952.

    PubMed Central  PubMed  Article  Google Scholar 

  • Beskow, L. M., Burke, W., Fullerton, S. M., & Sharp, R. R. (2012). Offering aggregate results to participants in genomic research: opportunities and challenges. Genetics in Medicine, 14(4), 490–496. doi:10.1038/gim.2011.62.

    PubMed Central  PubMed  Article  Google Scholar 

  • Bogershausen, N., Shahrzad, N., Chong, J. X., von Kleist-Retzow, J. C., Stanga, D., Li, Y., et al. (2013). Recessive TRAPPC11 mutations cause a disease spectrum of limb girdle muscular dystrophy and myopathy with movement disorder and intellectual disability. American Journal of Human Genetics, 93(1), 181–190. doi:10.1016/j.ajhg.2013.05.028.

    PubMed Central  PubMed  Article  Google Scholar 

  • Bollinger, J. M., Scott, J., Dvoskin, R., & Kaufman, D. (2012). Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. Genetics in Medicine, 14(4), 451–457. doi:10.1038/gim.2011.66.

    PubMed Central  PubMed  Article  Google Scholar 

  • Bookman, E. B., Langehorne, A. A., Eckfeldt, J. H., Glass, K. C., Jarvik, G. P., Klag, M., et al. (2006). Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. [Congresses Guideline]. American Journal of Medical Genetics Part A, 140(10), 1033–1040. doi:10.1002/ajmg.a.31195.

    PubMed Central  PubMed  Article  Google Scholar 

  • Boycott, K. M., Parboosingh, J. S., Chodirker, B. N., Lowry, R. B., McLeod, D. R., Morris, J., et al. (2008). Clinical genetics and the Hutterite population: a review of Mendelian disorders. American Journal of Medical Genetics Part A, 146A(8), 1088–1098.

    PubMed  Article  Google Scholar 

  • Boycott, K. M., Beaulieu, C., Puffenberger, E. G., McLeod, D. R., Parboosingh, J. S., & Innes, A. M. (2010). A novel autosomal recessive malformation syndrome associated with developmental delay and distinctive facies maps to 16ptel in the Hutterite population. [Research Support, Non-U.S. Gov’t]. American Journal of Medical Genetics Part A, 152A(6), 1349–1356. doi:10.1002/ajmg.a.33379.

    PubMed  Google Scholar 

  • Caliskan, M., Chong, J. X., Uricchio, L., Anderson, R., Chen, P., Sougnez, C., et al. (2011). Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. [Research Support, N.I.H., Extramural]. Human Molecular Genetics, 20(7), 1285–1289. doi:10.1093/hmg/ddq569.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Chong, J. X., Oktay, A. A., Dai, Z., Swoboda, K. J., Prior, T. W., & Ober, C. (2011). A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites. European Journal of Human Genetics, 19(10), 1045–1051. doi:10.1038/ejhg.2011.85.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., & Ober, C. (2012). A population-based study of autosomal-recessive disease-causing mutations in a founder population. American Journal of Human Genetics, 91(4), 608–620. doi:10.1016/j.ajhg.2012.08.007.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Fabsitz, R. R., McGuire, A., Sharp, R. R., Puggal, M., Beskow, L. M., Biesecker, L. G., et al. (2010). Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. [Practice Guideline Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Circulation. Cardiovascular Genetics, 3(6), 574–580. doi:10.1161/CIRCGENETICS.110.958827.

    PubMed Central  PubMed  Article  Google Scholar 

  • Gerull, B., Kirchner, F., Chong, J., Tagoe, J., Chandrasekharan, K., Strohm, O., et al. (2013). A homozygous founder mutation in Desmocollin-2 (DSC2) causes arrhythmogenic cardiomyopathy in the hutterite population. Circulation. Cardiovascular Genetics. doi:10.1161/CIRCGENETICS.113.000097.

    PubMed  Google Scholar 

  • Henneman, L., Bramsen, I., van der Ploeg, H. M., & ten Kate, L. P. (2002). Preconception cystic fibrosis carrier couple screening: impact, understanding, and satisfaction. [Research Support, Non-U.S. Gov’t]. Genetic Testing, 6(3), 195–202. doi:10.1089/109065702761403351.

    CAS  PubMed  Article  Google Scholar 

  • Heshka, J. T., Palleschi, C., Howley, H., Wilson, B., & Wells, P. S. (2008). A systematic review of perceived risks, psychological and behavioral impacts of genetic testing. [Research Support, Non-U.S. Gov’t Review]. Genetics in Medicine, 10(1), 19–32. doi:10.1097/GIM.0b013e31815f524f.

    PubMed  Article  Google Scholar 

  • Hostetler, J. A. (1974). Hutterite society. Baltimore: Johns Hopkins University Press.

    Google Scholar 

  • Huang, L., Szymanska, K., Jensen, V. L., Janecke, A. R., Innes, A. M., Davis, E. E., et al. (2011). TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone. [Research Support, American Recovery and Reinvestment Act Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. American Journal of Human Genetics, 89(6), 713–730. doi:10.1016/j.ajhg.2011.11.005.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Knoppers, B. M., Joly, Y., Simard, J., & Durocher, F. (2006). The emergence of an ethical duty to disclose genetic research results: international perspectives. [Historical Article Research Support, Non-U.S. Gov’t]. European Journal of Human Genetics, 14(11), 1170–1178. doi:10.1038/sj.ejhg.5201690.

    PubMed  Article  Google Scholar 

  • Kosova, G., Abney, M., & Ober, C. (2010). Colloquium papers: heritability of reproductive fitness traits in a human population. Proceedings of the National Academy of Sciences of the United States of America, 107(Suppl 1), 1772–1778. doi:10.1073/pnas.0906196106.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Lakeman, P., Plass, A. M., Henneman, L., Bezemer, P. D., Cornel, M. C., & ten Kate, L. P. (2009). Preconceptional ancestry-based carrier couple screening for cystic fibrosis and haemoglobinopathies: what determines the intention to participate or not and actual participation? European Journal of Human Genetics, 17(8), 999–1009. doi:10.1038/ejhg.2009.1.

    PubMed Central  PubMed  Article  Google Scholar 

  • Martin, A. O. (1970). The founder effect in a human isolate: evolutionary implications. American Journal of Physical Anthropology, 32, 351–368.

    CAS  PubMed  Article  Google Scholar 

  • Murphy, J., Scott, J., Kaufman, D., Geller, G., LeRoy, L., & Hudson, K. (2008). Public expectations for return of results from large-cohort genetic research. [Multicenter Study Research Support, N.I.H., Extramural]. The American Journal of Bioethics, 8(11), 36–43. doi:10.1080/15265160802513093.

    PubMed Central  PubMed  Article  Google Scholar 

  • Ober, C., Hyslop, T., Elias, S., Weitkamp, L. R., & Hauck, W. W. (1998). Human leukocyte antigen matching and fetal loss: results of a 10-year prospective study. Human Reproduction, 13, 33–38.

    CAS  PubMed  Article  Google Scholar 

  • Ober, C., Tsalenko, A., Parry, R., & Cox, N. J. (2000). A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. American Journal of Human Genetics, 67(5), 1154–1162. doi:10.1016/S0002-9297(07)62946-2.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ober, C., Abney, M., & McPeek, M. S. (2001). The genetic dissection of complex traits in a founder population. American Journal of Human Genetics, 69(5), 1068–1079.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Payne, Y., Williams, M., Cheadle, J., Stott, N. C., Rowlands, M., Shickle, D., et al. (1997). Carrier screening for cystic fibrosis in primary care: evaluation of a project in South Wales. The South Wales Cystic Fibrosis Carrier Screening Research Team. [Research Support, Non-U.S. Gov’t]. Clinical Genetics, 51(3), 153–163.

    CAS  PubMed  Article  Google Scholar 

  • Steinberg, A. G., Bleibtreu, H. K., Kurczynski, T. W., Martin, A. O., & Kurczynski, E. M. (1967). Genetic studies in an inbred human isolate. In J. F. Crow & J. V. Neel (Eds.), Proceedings of the Third International Congress of Human Genetics (pp. 267–290). Baltimore: Johns Hopkins University Press.

    Google Scholar 

  • Tambor, E. S., Bernhardt, B. A., Chase, G. A., Faden, R. R., Geller, G., Hofman, K. J., et al. (1994). Offering cystic fibrosis carrier screening to an HMO population: factors associated with utilization. [Research Support, U.S. Gov’t, P.H.S.]. American Journal of Human Genetics, 55(4), 626–637.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trinidad, S. B., Fullerton, S. M., Bares, J. M., Jarvik, G. P., Larson, E. B., & Burke, W. (2010). Genomic research and wide data sharing: views of prospective participants. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Genetics in Medicine, 12(8), 486–495. doi:10.1097/GIM.0b013e3181e38f9e.

    PubMed Central  PubMed  Article  Google Scholar 

  • Wiltshire, K. M., Hegele, R. A., Innes, A. M., & Brownell, A. K. (2013). Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy. [Research Support, Non-U.S. Gov’t]. Neuromuscular Disorders, 23(3), 265–268. doi:10.1016/j.nmd.2012.11.011.

    PubMed  Article  Google Scholar 

  • Wolf, S. M. (2012). The past, present, and future of the debate over return of research results and incidental findings. Genetics in Medicine, 14(4), 355–357. doi:10.1038/gim.2012.26.

    PubMed  Article  Google Scholar 

  • Wolf, S. M., Crock, B. N., Van Ness, B., Lawrenz, F., Kahn, J. P., Beskow, L. M., et al. (2012). Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genetics in Medicine, 14(4), 361–384. doi:10.1038/gim.2012.23.

    PubMed Central  PubMed  Article  Google Scholar 

  • Yao, T. C., Du, G., Han, L., Sun, Y., Hu, D., Yang, J. J., et al. (2013). Genome-wide association study of lung function phenotypes in a founder population. Journal of Allergy and Clinical Immunology. doi:10.1016/j.jaci.2013.06.018.

    Google Scholar 

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Acknowledgments

The authors acknowledge Dr. Elizabeth McNally and Dr. Amy Lemke for guidance and helpful discussions; Dr. Cheryl Rockman-Greenberg for advising us on the Town Hall format; Ms. Amanda Schleif for designing the Cystic Fibrosis informational brochure; Dr. Preeti Sharma, Ms. Kathleen Shanovich, Ms. Michelle Stein, Ms. Donata Russell, and Ms. Tara Newcomb for field trip assistance, Mr. William Wentworth-Sheilds for computational support, and the Hutterites for their continued enthusiasm and support for our studies. This research was supported in part by grants R01 HD21244 and R01 HL085197.

Conflict of Interest

Authors Rebecca L. Anderson, Kathleen Murray, Jessica X. Chong, Rebecca Ouwenga, Marina Antillon, Peixian Chen, Lorena Diaz de Leon, Lucille A. Lester, Soma Das, Carole Ober, and Darrel J. Waggoner declare that they have no conflict of interest.

Kathryn J. Swoboda has grant funding from NINDS U10 NS077305, NICHD R01 HD69045 and Families of SMA for SMA-related studies; she has contracts for SMA clinical trials and studies with F. Hoffmann-La Roche Genetech and ISIS.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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Correspondence to Darrel J. Waggoner.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

Brochure on Cystic Fibrosis (CF) in the Hutterites. (PDF 279 kb)

Online Resource 2

CF results letter sent to CF carriers who were married. (PDF 69 kb)

Online Resource 3

Brochure distributed at the Town Hall describing 14 genetic diseases in the Hutterites. (PDF 311 kb)

Online Resource 4

Disclosure letter for 14 conditions. (PDF 84 kb)

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Anderson, R.L., Murray, K., Chong, J.X. et al. Disclosure of Genetic Research Results to Members of a Founder Population. J Genet Counsel 23, 984–991 (2014). https://doi.org/10.1007/s10897-014-9721-8

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  • DOI: https://doi.org/10.1007/s10897-014-9721-8

Keywords

  • Disclosure
  • Genetic
  • Results
  • Research
  • Individual
  • Hutterite