TY - JOUR
T1 - Mutation history of the Roma/Gypsies
AU - Morar, Bharti
AU - Gresham, David
AU - Angelicheva, Dora
AU - Tournev, Ivailo
AU - Gooding, Rebecca
AU - Guergueltcheva, Velina
AU - Schmidt, Carolin
AU - Abicht, Angela
AU - Lochmüller, Hanns
AU - Tordai, Attila
AU - Kalmár, Lajos
AU - Nagy, Melinda
AU - Karcagi, Veronika
AU - Jeanpierre, Marc
AU - Herczegfalvi, Agnes
AU - Beeson, David
AU - Venkataraman, Viswanathan
AU - Carter, Kim Warwick
AU - Reeve, Jeff
AU - De Pablo, Rosario
AU - Kučinskas, Vaidutis
AU - Kalaydjieva, Luba
N1 - Funding Information:
We are indebted to the patients, their families, and the members of many Gypsy communities, for making this study possible. We thank the Laboratory of Molecular Pathology of the Medical University in Sofia, Bulgaria, for infrastructure support; Lyle Palmer, for critical reading of the manuscript; Elena Marushiakova and Vesselin Popov, for consultations and guidance in cultural anthropology; Ursula Klutzny, for expert technical assistance; and Dr. Andrew G. Engel (Rochester, NY), for initial mutation testing in Bulgarian patients with CMS. This work was supported by the Australian Research Council, the National Health and Medical Research Council, and The Wellcome Trust of the U.K. We acknowledge support from the Deutsche Forschungsgemeinschaft (to H.L. and A.A.), from the Medical Research Council (U.K.) and the Muscular Dystrophy Campaign/Myasthenia Gravis Association of Great Britain (to D.B.), and from Hungarian-German Oktatasi Miniszterium–Bundesministerium für Bildung und Forschung (OM-BMBF) and Magyar Tudomanyos Akademia–Deutsche Forschungsgemeinschaft (MTA-DFG) Intergovernmental Scientific Cooperation Grants (to V.K. and H.L.).
PY - 2004/10
Y1 - 2004/10
N2 - The 8-10 million European Roma/Gypsies are a founder population of common origins that has subsequently split into multiple socially divergent and geographically dispersed Gypsy groups. Unlike other founder populations, whose genealogy has been extensively documented, the demographic history of the Gypsies is not fully understood and, given the lack of written records, has to be inferred from current genetic data. In this study, we have used five disease loci harboring private Gypsy mutations to examine some missing historical parameters and current structure. We analyzed the frequency distribution of the five mutations in 832-1,363 unrelated controls, representing 14 Gypsy populations, and the diversification of chromosomal haplotypes in 501 members of affected families. Sharing of mutations and high carrier rates supported a strong founder effect, and the identity of the congenital myasthenia 1267delG mutation in Gypsy and Indian/Pakistani chromosomes provided the best evidence yet of the Indian origins of the Gypsies. However, dramatic differences in mutation frequencies and haplotype divergence and very limited haplotype sharing pointed to strong internal differentiation and characterized the Gypsies as a founder population comprising multiple subisolates. Using disease haplotype coalescence times at the different loci, we estimated that the entire Gypsy population was founded ∼32-40 generations ago, with secondary and tertiary founder events occurring ∼16-25 generations ago. The existence of multiple subisolates, with endogamy maintained to the present day, suggests a general approach to complex disorders in which initial gene mapping could be performed in large families from a single Gypsy group, whereas fine mapping would rely on the informed sampling of the divergent subisolates and searching for the shared genomic region that displays the strongest linkage disequilibrium with the disease.
AB - The 8-10 million European Roma/Gypsies are a founder population of common origins that has subsequently split into multiple socially divergent and geographically dispersed Gypsy groups. Unlike other founder populations, whose genealogy has been extensively documented, the demographic history of the Gypsies is not fully understood and, given the lack of written records, has to be inferred from current genetic data. In this study, we have used five disease loci harboring private Gypsy mutations to examine some missing historical parameters and current structure. We analyzed the frequency distribution of the five mutations in 832-1,363 unrelated controls, representing 14 Gypsy populations, and the diversification of chromosomal haplotypes in 501 members of affected families. Sharing of mutations and high carrier rates supported a strong founder effect, and the identity of the congenital myasthenia 1267delG mutation in Gypsy and Indian/Pakistani chromosomes provided the best evidence yet of the Indian origins of the Gypsies. However, dramatic differences in mutation frequencies and haplotype divergence and very limited haplotype sharing pointed to strong internal differentiation and characterized the Gypsies as a founder population comprising multiple subisolates. Using disease haplotype coalescence times at the different loci, we estimated that the entire Gypsy population was founded ∼32-40 generations ago, with secondary and tertiary founder events occurring ∼16-25 generations ago. The existence of multiple subisolates, with endogamy maintained to the present day, suggests a general approach to complex disorders in which initial gene mapping could be performed in large families from a single Gypsy group, whereas fine mapping would rely on the informed sampling of the divergent subisolates and searching for the shared genomic region that displays the strongest linkage disequilibrium with the disease.
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U2 - 10.1086/424759
DO - 10.1086/424759
M3 - Article
C2 - 15322984
AN - SCOPUS:4544388514
SN - 0002-9297
VL - 75
SP - 596
EP - 609
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -