| Complex Trait Mapping in the Hutterites |
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in conjunction with the University of South Dakota The Hutterites of South DakotaThe Hutterites are a religious sect that originated in the Tyrolean Alps in the 1500's. Between the mid-1700's to mid-1800's, during their tenure in Russia, the population grew in size from approximately 120 to over 1,000 members (Hostetler 1974). In the 1870's approximately 900 of these members migrated to what is now South Dakota and roughly half settled on three communal farms. Due to a high natural fertility rate and the proscription of contraception among communal Hutterites (Sheps 1965), the population expanded dramatically since migrating to the United States. Today there are >35,000 Hutterites living on >350 communal farms (called colonies) in the northern United States and western Canada. Genealogical records, collected by Steinberg and his students in the 1950's and 1960's (Bleibtreu 1964; Mange 1964; Steinberg et al. 1967), trace all extant Hutterites to fewer than 90 ancestors who lived in the early 1700's to the early 1800's (Martin 1970). The relationships between these ancestors are unknown, but some of them may have been related. The three original South Dakota colonies have given rise to the three major subdivisions of Hutterite population structure, called the Schmiedeleut (S-leut), Dariusleut (D-leut), and Leherleut (L-leut) and members of each leut have remained reproductively isolated from each other since 1910 (Bleibtreu 1964). The subjects of our studies, the S-leut Hutterites of South Dakota, are descendants of 64 Hutterite ancestors. The average coefficient of inbreeding among the subjects in our study is 0.0327 (s.d. 0.016), slightly greater than that of 1½ cousins. Thus, the small number of ancestral genomes present in the current population should result in a smaller number of asthma susceptibility alleles at any given locus, and possibly a smaller number of loci, than in outbred populations and facilitate the search for genes underlying this complex phenotype. The relatively recent origins of the population enhances the ability to detect linkage disequilibrium between asthma-susceptibility alleles and marker alleles over approximately 5-10 cM distances (Hall et al. 1997). Furthermore, the Hutterite communal lifestyle ensures that all members are exposed to a relatively uniform environment. In particular, the Hutterites prepare and eat meals in a communal kitchen and dining room, respectively, and smoking is prohibited (and rare) in the population. Thus, primary or secondary exposure to cigarette smoke does not complicate diagnoses of asthma or lung disease in the Hutterites as it does in other populations. Founder Populations are Useful for Mapping Complex TraitsThe advantages of
inbred or founder populations for genetic studies were first noted over
30 years ago (McKusick et al. 1964; Neel 1970; Steinberg et al. 1967).
Interest in these populations has recently been renewed as a result of
the explosion of molecular biological techniques and the initiation of
the Human Genome Project (Collins 1995; de la Chapelle 1993; Lander and
Schork 1994). The relatively small number of founders and recent ancestries
that are characteristic of these populations facilitate the search for
human disease genes and make them particularly amenable to novel analytic
strategies. Indeed, founder populations have proven useful for mapping
genes that underlie Mendelian disorders (eg., (Hästbacka et al. 1992;
Höglund et al. 1995; Houwen et al. 1994; Kestilä et al. 1994;
Sulisalo et al. 1994) and multigenic disorders that segregate as Mendelian
conditions in specific populations (Mahtani et al. 1996; Puffenberger
et al. 1994). The same features of population history that advanced the
search for Mendelian conditions in founder populations should also facilitate
the search for genes that influence susceptibility to complex traits (Ober
et al. 1998).
Bleibtreu HK (1964)
Marriage and residence patterns in a genetic isolate Anthropology. Harvard,
Cambridge de la Chapelle A (1993) Disease gene mapping in isolated human populations: the example of Finland. Am J Med Genet 30:857-865 Hall
D, Cho J, Hill A, Spedini G, Ober C, Di Rienzo A (1997) Comparison of
linkage disequilibrium within and between ethnic groups. Amer J Hum
Genet 61:A200 Hostetler
JA (1974) Hutterite Society. Johns Hopkins University Press, Baltimore Sheps
MC (1965) An analysis of reproductive patterns in an American isolate.
Popul Stud 19:65-80 Results of ongoing research
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