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Review
. 2013 Jul;29(7):412-8.
doi: 10.1016/j.tig.2013.01.007. Epub 2013 Feb 17.

Amish revisited: next-generation sequencing studies of psychiatric disorders among the Plain people

Affiliations
Review

Amish revisited: next-generation sequencing studies of psychiatric disorders among the Plain people

Liping Hou et al. Trends Genet. 2013 Jul.

Abstract

The rapid development of next-generation sequencing (NGS) technology has led to renewed interest in the potential contribution of rarer forms of genetic variation to complex non-mendelian phenotypes such as psychiatric illnesses. Although challenging, family-based studies offer some advantages, especially in communities with large families and a limited number of founders. Here we revisit family-based studies of mental illnesses in traditional Amish and Mennonite communities--known collectively as the Plain people. We discuss the new opportunities for NGS in these populations, with particular emphasis on investigating psychiatric disorders. We also address some of the challenges facing NGS-based studies of complex phenotypes in founder populations.

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Figures

Figure 1
Figure 1
One Family-based Sequencing Strategy (adapted from Cirulli & Goldstein [10] with permission). Affected individuals are shaded. Red stars represent the causal variant, stars of other colors represent variants that are shared by the sequenced individuals but do not segregate with disease in the family. The most distantly related cases are sequenced first, with follow-up genotyping of candidate variants in additional relatives. Genes harboring segregating variants are then sequenced in new families and case-control cohorts.
Figure 2
Figure 2
Amish settlements within the continental US. An Amish settlement is defined by three or more Amish households or two or more Amish households with a known bishop, minister, or deacon (source: http://digitalunion.osu.edu/r2/summer07/eellis/Mapshome.html).
Figure 3
Figure 3
Victor McKusick (1921–2008). ‘Father of Medical Genetics” and pioneer of genetic studies in the Amish (Johns Hopkins Chesney Medical Archives).
Figure 4
Figure 4
Identity by Descent. Colored bars represent founder chromosomes. Yellow-boxed segments indicate regions of the genome that descend from the common ancestors and are shared by some individuals in the current generation.
Figure 5
Figure 5
Janice Egeland, who pioneered many studies of psychiatric disorders among the Lancaster County Amish.

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