Genetic studies of the Roma (Gypsies): a review

Abstract

Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups. Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

Background

Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies.

Results

Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups.

Conclusion

Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

Introduction

]] is rarely discussed and still awaits the attention of the medical profession.

].

], changing the traditional demographic profile of Gypsy minorities across Europe. A predictable consequence of this new diaspora is that medical practitioners in many countries will encounter Romani patients with previously unknown or very rare disorders. A summary of the available information should facilitate diagnostic investigations and counselling in these affected families and stimulate international collaboration.

Materials and Methods

Literature searches were performed using the U.S.A National Library of Medicine PubMed/MEDLINE databases for the period 1960 to December 2000. Database searches using the keyword "Gypsies" identified 297 articles whilst the keyword "Gypsy" produced 573 articles. The discrepancy is due mainly to the inclusion of articles about the "gypsy retransposable element" and the "gypsy moth". Searches using the terms "Roma", "Romani" and "Romany" yielded results that were not relevant to the topic (eg. Roma, the capital of Italy) or else incomplete.

The majority of the 297 articles dealt with issues beyond the focus of this review, namely social problems related to the health of the Roma (28.6%), or general medical problems (29.6%). The remainder were reports on genetic research, of which 41 studies (13.8%) were in the field of clinical genetics, 44 (14.8%) were molecular studies of genetic disorders, and 39 (13.1%) covered population genetic research. In the clinical and molecular genetics fields, we have given preference to publications which were not limited to single case descriptions, and dealt with disorders with public health impact. Population genetics papers were selected on the basis of the compatibility of study design, specifically the analysis of comparable polymorphic systems.

Complementary data on history, linguistics, cultural anthropology and demography were found through standard library and bibliographic searches, and included publications recommended by consulting experts in Romani studies (Drs. Elena Marushiakova and Vesselin Popov from the Bulgarian Academy of Sciences and Dr. Ian Hancock from the University of Texas at Austin).

The "Track Record" of Genetics

]. The Race Hygiene and Population Biology Research Centre, established in 1936, organised thorough records of Jewish and Romani pedigrees and provided "the scientific basis" for the "final solution", the annihilation of millions of Jews and Roma in the concentration camps of Nazi-occupied Europe.

]. Most studies have remained in the realm of scientific exploration, away from the health needs of the Roma. Many publications display judgemental and paternalistic attitudes, that would be considered unacceptable if used with regard to other populations.

]], and the fact that, unlike the Jews, the Finns and the French Canadians, the Roma are still the "object" of investigations conducted by outsiders, are all likely to impact on the attitudes of the Roma towards genetics. Building up the trust and collaboration necessary for both public health programs and research, should become a goal of the health care systems of Europe.

Population Genetics

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]. More importantly, the analysis highlights the internal diversity of the Roma, who appear to be genetically far more heterogeneous than autochthonous European populations.

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Multi-locus reanalysis of previously published data on European Roma

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Diseases and mutations identified to-date

As a result of traditionally low socio-economic status and limited access of the Roma to health care, their unique genetic heritage has long escaped the attention of European medicine and is now being randomly "discovered".

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Mendelian disorders of the Roma caused by private founder mutations

The R306X mutation in PKD2 has been identified in Romani families from Bulgaria. It has not been confirmed in the Hungarian ADPKD families, but appears probable because of a reported common migration history of all affected groups.

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Molecular genetic findings

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], the conserved region of homozygosity (red bars) was found to span only <500 kb. Courtesy of Dr. Tamara Rogers.

Epidemiological data

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Reported carrier rates for single gene disorders among the Roma

Most estimates are based on prevalence figures. *Carrier rates determined through direct mutation detection are indicated in red. **The LGMD2C carrier rates for the general Romani population of Bulgaria are probably an overestimate since the screening was conducted in a geographical region where the high risk groups are clustered. ***The screening for the G985 mutation in Spain, performed in Gypsy groups residing in different parts of the country, revealed substantial differences between groups.

]. This clustering should be borne in mind in diagnostic studies, where assumptions based on pedigree structure should be avoided and independent clinical and genetic assessment should be conducted in all cases.

).

]. Such collaboration will be essential for future research into new disorders, founder mutations and factors modifying disease severity, and for understanding the epidemiology of genetic diseases of the Roma. The first steps to European collaboration have been made, with the founding of the Gypsy Genetic Heritage Consortium in 1997, and the forthcoming ENMC workshop on neuromuscular disorders in Gypsies.

collaborative studies and are not likely to represent the true spread of Romani founder mutations. The distribution of LGMD2C in Western Europe and in Bulgaria leads to the prediction that the disorder occurs and awaits detection along the entire European migration route, spanning the Balkans and Central Europe. Filling the gaps in the map will be particularly useful in the case of treatable disorders which are strong candidates for newborn screening, such as galactokinase deficiency and congenital myasthenia.

Discussion

The pattern emerging from genetic research is that of a conglomerate of founder populations which extend across Europe but at the same time differ within individual countries, and whose demographic history, internal structure and relationships are poorly understood. An insight is provided by the social sciences.

] origins proposed by linguists. Translated into the language of genetics, this is a relevant question related to the homogeneity or diversity of the founding population.

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century was estimated at only 17,000.

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Linguistics, history and cultural anthropology suggest two major, equally plausible historical scenarios that could lead to a "jigsaw puzzle" of founder populations: (i) a genetically substructured ancestral population, where the old social traditions of strict endogamy have been retained and subsequent splits of the comprising groups have enhanced the original genetic differences; (ii) a small homogeneous ancestral population spawning numerous subgroups where strong drift effects have resulted in substantial genetic divergence. Genetic research has indeed faced the "jigsaw puzzle" and has thus far been unable to resolve it. The genetic data provide evidence of population stratification, however a closer examination is precluded by the random cross-section sampling design of most population genetic studies, where the traditional social organisation and self-identity of the Roma have been ignored and subjects classified on the basis of the political boundaries of Europe. The relationship between social organisation and genetic structure does not appear to be straightforward and is still to be addressed in population genetic research based on the long standing identity of Gypsy groups. The issue is of relevance to public health policies and the targeted prevention of mendelian disorders, as well as to future studies of genetically complex disorders.

]. Unlike the above examples however, genetic studies of the Roma have failed to take the immediate benefits of research back to the individuals and families that have been the object of research. Yet by now it should be obvious that genetics has an important role to play in improving the quality of health care for the Roma. Treatable disorders such as galactokinase and MCAD deficiency, with an expected incidence of affected births in the range of 1:1,000 to 1:5,000, meet the standard criteria for newborn screening more than does phenylketonuria, with its average incidence of 1:10,000. Adding the simple, sensitive and specific mutation tests to existing newborn screening programs would be technically simple and highly efficient due to the homogeneous genetic basis of the disorders.

]. This component would be particularly important for a population like the Roma, which has been subject to racism and persecution throughout its co-existence with European societies.

]. This forgotten people of Europe can be regarded as a test case for the capacity of genetics to provide better health.

Pre-publication history

The pre-publication history for this paper can be accessed here:

Acknowledgements

We thank the Romani families and communities, and the numerous colleagues in different countries who have made our research into the genetics of the Roma possible, the members of the Gypsy Genetic Heritage Consortium Prof. J.-C. Kaplan, Prof. A. Urtizberea, Prof. J.-P. Liegeois, Drs. M. Jeanpierre and L. Merlini for their commitment to international collaboration, and Drs. E. Marushiakova, V. Popov and I. Hancock for enlightening discussions of the ethnology, history and linguistics of the Roma. Special thanks to the research team at the Centre for Human Genetics of Edith Cowan University.

L.K. wishes to acknowledge funding from The Wellcome Trust, The National Health and Medical Research Council of Australia, The Muscular Dystrophy Association of the US, L'Assoçiation Française contre les Myopathies, The Australian Research Council and Edith Cowan University.