Genetic studies of Romani populations (Gypsies) in Europe have provided insights into their origins and population history. Y-chromosome and mitochondrial DNA analyses indicate Romani paternal and maternal lineages originated in South Asia, likely arriving in Europe between the 9th-15th centuries AD. Subsequent isolation and endogamy led to reduced genetic diversity and increased frequencies of disease-causing mutations inherited from a small number of founding ancestors. At least 9 Mendelian disorders have been identified through private mutations shared across European Romani communities. Future studies incorporating Romani culture and history can improve understanding of their population genetics and help design public health programs.

1. Genetic studies of
Gypsies

2. Who are they??
 The Gypsies (a misnomer, derived from an early legendabout Egyptian
origins) defy the conventional definition of a population.
 Referred to as ‘‘the invisible minority’’.
 Founder populations derived from a small number of ancestors with
subsequent isolation(geographic,cultural etc.) leading to limited
immigration and demographic growth mainly from with in.

3.  Reduced genetic diversity and founder effect gave rise to more
homogeneous basis of inherited disorders make it possible for genetic
studies to treat the whole population as one large family since more likely
to share same ancestral disease causing DNA variants.
 Private disease causing mutations and evidence of founder effect where
published in 2 independent studies in 1996
1. novel heridatory motor and sensory neuropathy type lom (HMSNL).
2 . Limb-girdle muscular dystrophy 2C.

4.  Further studies in private mutations and molecular epidemiology has
revealed peculiar combination of genetic homogeneity and mutation
sharing by affected subjects across the Europe.

5. GYPSIES through the eye of social scientists
 Potential of founder populaitons to contribute to understanding gentic
basis of human biengs is determined by historial demography.
 Current gypsy population in Europe is 10 million under different names like
ROMA,SINTI ,ROMANICHALS,KALO etc..
 200 year old linguistic theory of indian origins of gypsies is widely accepted
which states : 1 . Arrival in byzantine emperor to the 9-11th century AD.
2 . Settling in Balkans has taken place in13 -14th century AD,
early diaspora into rest of Europe.

7. Romani population size in different European countries The collection of this type of data depends on declared ethnic
identity which, in the case of the Roma, can be affected by a number of political and social circumstances. The estimates in the
figure are the average of the numbers provided by different sources, such as census data, ministries of internal affairs and human rights organizations

8.  Balkans have trditonally hosted large prortion of
European gypsies referred to as Balkan and Vlax Roma
 They are classified on the basis of history of migration
 Slavery not only played an important role in biological
history of Vlax roma,but lead to mass migrations at the
time of Austrian-Turkish war in early 18th century, social
and economic changes in eastern Europe in 1990’s

9. Did they come from central asia?
 The primary unit of social organization of gypsy group resemble the
professional JATIS in india.
 Identity is defined by group ethonym (usally reflecting a traditional trade.
 Hypothesis on origins of proto range from lowest strata of indian caste
system,to mixed society of warriors fitting of the early Islamic incursions.

10. Figure 2
Multilocus comparison between Romani populations from different European countries, autochthonous Euro- pean
populations and populations from north India The polymorphic systems included in the analysis comprised
A1A2BO, MN, haptoglobin and Rh (CDE), with a total of 11 independent alleles. Information on these markers was available
for the Roma in Slovakia (n = 350) [26], Hungary (n = 507) [11], England (n = 109) [23], Slovenia (n = 350) [27], Sweden (n
=
115) [24] and Wales (n = 84) [22], for non-Roma Europeans (n = 5169) and for two north Indian populations, Rajput (n = 175)
[34,35] and Punjabi (n = 140) [35,36]. Genetic distances between pairs of populations were computed by means of Reynold's
coancenstry coefficient [84] and displayed as a neighbour-joining tree [85]. The robustness of the branches in the tree
was
assessed with a bootstrap approach [86]. The analysis was conducted using the PHYLIP 3.57c package [87].

11. Picture emerging from recent genetic
studies
 Genetic variation of gypsy has been studied in divergent gypsy groups.
 The analysis include polymorphisms on parentally inherited
1) Y CHROMOSOME 2)MITOCHONDRIAL (mt) DNA
(haplogroup H-M82) (haplogroup M)
3)BIPARENTALLY INHERITED AUTOSOMAL MARKERS
(pathogenic 1267deIG mutation in CHRNE)

12.  Y chromosome and mt DNA haplogroups reflect the ancient human history
which is used to compare global diversity data to trace continental origins
of gypsy lineages.
 Y chromosomal minisatellite mm (MSY1) and sequence variation in
mitochondrial control region were used asses current diversity and recent
population history.
 ARLEQUIN is a population genetics analysis tool used to examine genetic
diversity using (parameters like observed no. of haplotypes,polymorphic
sites)test demographic models based on mt DNA sequence variation and
assess genetic distances between populations using no. of pairwise
differences as molecular distance
 The dating of historical events are based upon coalescene time analysis of
Ychromosome and autosomal haplotypes

13.  The above method gives us a strong evidence that 47.3% of men carry H-
M82 Y-chromosomes,mt DNA haplogroup M accounts almost 30% of gypsy
subjects and the mutation of1267deIG has 4% of average carrier rates .
 Analysis of highly mutatable MSY1 minisatellite in Y chromosome provide
further evidence of limited variatins with diversity values lower in finns,
basques.
 The most recent common ancestor of gypsy men lived around 39
generations ago.
 The process of gradual separation carried till 6 to 8 generations ago.

14. Figure 2. The origins of Gypsy Y chromosome and mtDNA haplogroups. Linguistic analysis has charted the
Gypsy migration from India to Europe through the Hindu Kush, along Persia and the southern shoreline
of the Caspian Sea, through the southern Caucasus (Armenia) and westwards to Anatolia and Byzantium.
Genetic evidence of the geographical origins of paternal and maternal lineages in the Gypsies is based on
thestudy of unique event polymorphisms of the Y chromosome (left panel) and mtDNA (right panel),
compared to published data on other populations.(51 – 62)
Y chromosome haplogroup H-M82 and mtDNA
haplogroup M can be unambiguously assigned to Asia and the Indian subcontinent. The wide geographical
distribution of the remaining lineages precludes the tracing of their origins in the Gypsy population.
The internal diversity of the latter lineages points to multiple admixture events during the journey or after
the arrival of the Gypsies in Europe.

16. Evolution of gypsy groups into
genetic subisolates
 The blood purity laws are applied more rigorously between roma groups
than surrounding population.
 Mixed marriages can result in formation of new gypsy group
EX. Jewish roma was born in the common deportation camps during WW II.
 Strongest genetic indication of severly lmited inherited migration is
provided by the study of chromosomal haplotypes surrounding R148X
founder mutation in Vlax roma groups,carrier rates ranging from 10-16%.
 The lack of strict sharing of haplotypes is evidence for inter-group
endogamy.
 Harsh conditions of nomadic life affected the life expectancy,population
growth and genetic diversity.

17. Figure 3. Paternal and maternal lineages in Roma groups from Bulgaria.
Proportions of Indian Y chromosome H-M82, mtDNA haplogroup M5 and
of other, admixed lineages in the Vlax Roma with a recent history of
nomadism (left panel) and in the sedentary Balkan groups from Bulgaria.
Ethnonym abbreviations are as shown in Figure 1. Preservation of the
ancestral Y chromosome lineage is particularly strong in the Vlax compared to
the Balkan Roma (two-tailed permutation test P ¼ 0.017). mtDNA lineages
show greater overall diversity in
not reaching statistical significance (P ¼ 0.071). A rank-test comparison of the
mean growth rate values, estimated using Batwing, shows a

18. impact of genetic diseases
 To date 9 mendelian disorders caused by primate mutations have been
discovered.


19.  The above list is not exhaustive and existence of no,of additional rare single
gene disorders whose molecular bases yet to be studied.
 Currently available frequency data shows that 1 in 8 subjects in gypsy
population is carrier of 1 of 5 mutations tested.
 These carrier rates can range from 5-16%,
 These mendelian disorders are considerd to be health burden,making
community –based carrier testing programs highly beneficial to public
health initiative.
 Reported gene frequency are high for private mutations and often exeed
by an order of magnitude those for global population.
Ex: galactokinase deficiency frequencies in global population is 1:150000-
1:1000000 where as in romani children it is 1:5000.

20.  Incorporating population history in gene cloning stratergies has prompt the
novel “Not-quite identical by descent(NQIBD) approach.
 In this approach identification of mutated gene is greatly facilitated by
tracing origin of mutation to recent occurring haplotype background
which allowed the detection of mutation by comparing sequence of small
part of critical gene region between two chromosomes of single carrier
parent.

21. conclusions
 Medical genetics has a role to play in improving health of underprivileged
and forgotten people of Europe.
 Future studies of epidemiology of single gene disorder should take social
organization and cultural anthropology into consideration thus targeting
public health programs and contributing to understandingdemographic
history of roma.

22.  thank you