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Mapping Genes in Isolated Populations: Lessons from the Old Order Amish

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Genome Mapping and Genomics in Human and Non-Human Primates

Part of the book series: Genome Mapping and Genomics in Animals ((MAPPANIMAL,volume 5))

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Abstract

The Amish , a socially and religiously isolated population with large communities in Pennsylvania, Ohio, and Indiana, have been frequent participants in genetic studies since the 1960s. Although initial studies focused on rare, recessive diseases, others since the 1990s, largely ours, have focused on common disorders and the genetic underpinnings of their risk factors. We have shown both by simulation and practical case studies that the genetic architecture of the Old Order Amish (OOA) includes rare variants having strong phenotypic effects, some of which have reached non-negligible frequencies due to a founder effect and genetic drift . In this chapter, we review our case studies on variants in four genes: ABCG8, APOB, APOC3, and COL1A2. While traditionally medical genetics studies carried out in isolated populations have focused on individuals who are homozygous for some mutation; the four case studies that we present focus on individuals who are heterozygous carriers of a single mutation. This genetic homogeneity of the Amish and the enrichment of these variants allow us adequate statistical power to characterize the phenotypic variation resulting from a single mutation. These case studies have provided biologic insights into the relevance of these genes to human health and disease reaching beyond the OOA population.

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Acknowledgments

This research has been supported by NIH grants R01 DK54261, R01 AR46838, U01 HL072515, P30 DK072488, U01 HL084756, R01 HL088119, and R01 CA122844. Additional funding for the Amish sitosterol study was provided by an unrestricted research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. The research of A.A.S. on AGDB and PedHunter is supported by the Intramural Research Program of the National Institutes of Health, NLM.

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Authors and Affiliations

  1. Department of Medicine, University of Maryland School of Medicine, 22 S Greene Street, Baltimore, MD, 21201, USA

    Braxton D. Mitchell, Toni I. Pollin, Elizabeth A. Streeten, Richard B. Horenstein, Nanette I. Steinle, Laura Yerges-Armstrong, Alan R. Shuldiner & Jeffrey R. O’Connell

  2. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, DHHS, 8600 Rockville Pike, Bethesda, MD, 20894, USA

    Alejandro A. Schäffer

  3. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, 21201, USA

    Elizabeth A. Streeten & Alan R. Shuldiner

  4. Diabetes and Endocrinology Section, Veterans Administration Medical Center, Baltimore, MD, 21201, USA

    Nanette I. Steinle

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  1. Braxton D. Mitchell
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  2. Alejandro A. Schäffer
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  3. Toni I. Pollin
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  4. Elizabeth A. Streeten
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  5. Richard B. Horenstein
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  6. Nanette I. Steinle
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  7. Laura Yerges-Armstrong
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  8. Alan R. Shuldiner
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  9. Jeffrey R. O’Connell
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Correspondence to Braxton D. Mitchell .

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Editors and Affiliations

  1. South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio, Edinburg, Texas, USA

    Ravindranath Duggirala

  2. South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

    Laura Almasy

  3. South Texas Diabetes and Obesity Institute, Brownsville, Texas, USA

    Sarah Williams-Blangero

  4. Faculty of Biomedical Sciences, Technology & Research, Sri Ramachandra University, Chennai, India

    Solomon F.D. Paul

  5. Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, West Bengal, India

    Chittaranjan Kole

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Mitchell, B.D. et al. (2015). Mapping Genes in Isolated Populations: Lessons from the Old Order Amish. In: Duggirala, R., Almasy, L., Williams-Blangero, S., Paul, S., Kole, C. (eds) Genome Mapping and Genomics in Human and Non-Human Primates. Genome Mapping and Genomics in Animals, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46306-2_10

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