Patterns of inter- and intra-group genetic diversity in the Vlax Roma as revealed by Y chromosome and mitochondrial DNA lineages

Previous genetic studies, supported by linguistic and historical data, suggest that the European Roma, comprising a large number of socially divergent endogamous groups, may be a complex conglomerate of founder populations. The boundaries and characteristics of such founder populations and their relationship to the currently existing social stratification of the Roma have not been investigated. This study is an attempt to address the issues of common vs independent origins and the history of population fissioning in three Romani groups that are well defined and strictly endogamous relative to each other. According to linguistic classifications, these groups belong to the Vlax Roma, who account for a large proportion of the European Romani population. The analysis of mtDNA sequence variation has shown that a large proportion of maternal lineages are common to the three groups. The study of a set of Y chromosome markers of different mutability has revealed that over 70% of males belong to a single lineage that appears unique to the Roma and presents with closely related microsatellite haplotypes and MSY1 codes. The study unambiguously points to the common origins of the three Vlax groups and the recent nature of the population fissions, and provides preliminary evidence of limited genetic diversity in this young founder population.     

The value of some Corsican sub-populations for genetic association studies

Background  

Genetic isolates with a history of a small founder population, long-lasting isolation and population bottlenecks represent exceptional resources in the identification of disease genes. In these populations the disease allele reveals Linkage Disequilibrium (LD) with markers over significant genetic intervals, therefore facilitating disease locus identification. In a previous study we examined the LD extension on the Xq13 region in three Corsican sub-populations from the inner mountainous region of the island. On the basis of those previous results we have proposed a multistep procedure to carry out studies aimed at the identification of genes involved in complex diseases in Corsica. A prerequisite to carry out the proposed multi-step procedure was the presence of different degrees of LD on the island and a common genetic derivation of the different Corsican sub-populations. In order to evaluate the existence of these conditions in the present paper we extended the analysis to the Corsican coastal populations.     

Mitochondrial DNA Diversity in the Polish Roma

Mitochondrial DNA variability in the Polish Roma population has been studied by means of hypervariable segment I and II (HVS I and II) sequencing and restriction fragment‐length polymorphism analysis of the mtDNA coding region. The mtDNA haplotypes detected in the Polish Roma fall into the common Eurasian mitochondrial haplogroups (H, U3, K, J1, X, I, W, and M*). The results of complete mtDNA sequencing clearly indicate that the Romani M*‐lineage belongs to the Indian‐specific haplogroup M5, which is characterized by three transitions in the coding region, at sites 12477, 3921 and 709. Molecular variance analysis inferred from mtDNA data reveals that genetic distances between the Roma groups are considerably larger than those between the surrounding European populations. Also, there are significant differences between the Bulgarian Roma (Balkan and Vlax groups) and West European Roma (Polish, Lithuanian and Spanish groups). Comparative analysis of mtDNA haplotypes in the Roma populations shows that different haplotypes appear to demonstrate impressive founder effects: M5 and H (16261–16304) in all Romani groups; U3, I and J1 in some Romani groups. Interestingly, haplogroup K (with HVS I motif 16224‐16234‐16311) found in the Polish Roma sample seems to be specific for Ashkenazi Jewish populations.     

Attitudes of Roma toward smoking: qualitative study in Slovenia

Aim

To understand the reasons for widespread smoking behavior among Roma in Slovenia for the purpose of developing successful smoking cessation interventions.

Method

A qualitative focus group approach using a combination of pre-structured and open-ended questions was applied to collect the data from the representative members of the Roma community in southern Slovenia. The discussions were audiotaped and transcribed, and the collected data analyzed according to qualitative content analysis theory.

Results

The content analysis revealed that smoking was a strong part of the cultural, ethnic, and individual identity of the Roma. Even children smoked. Doctor’s advice to quit smoking was usually not followed and the attempts to quit were usually unsuccessful. Difficult financial situation was never mentioned as a possible motive to quit. Roma held a tenacious belief that the harmful effects of smoking were in the hands of destiny and did not associate the smoking-related illness with the habit.

Conclusions

Traditional strategies for smoking cessation are largely ineffective among the Roma because of their different attitudes toward smoking. Therefore, innovative and culturally acceptable methods need to be developed.According to the 2002 Census, 0.2% of inhabitants in Slovenia are Roma. However, on the basis of reports of social centers and schools, their real number could be up to four times higher than this (1). The socio-economic status, education level, and employment rate among Roma are considerably worse than among other Slovenian population, which places many of them into the category of poor people and thereby, at increased health risk.From the cultural point of view, the Roma are a highly specific ethnic minority. These once nomadic people now mostly live in poor accommodation and have difficult housing situation. The health culture of the Roma and their use of health care are low despite the fact that most of them can obtain full state-provided medical insurance irrespective of their employment status (2). Due to low hygienic and microclimatic conditions, low health education, and excessive smoking, diseases of the respiratory system seem to be among their most important health problems (3-5). Although epidemiologic data hardly exist, the Roma are known to be heavy smokers. The Roma trust in traditional folk medicine and do not believe smoking is a health-threatening habit (2). The percentage of smokers among the Roma in Slovenia is unknown. Studies from other countries show that, similar to other cardiovascular risk factors, smoking is by far more frequent in Roma than in other populations (5,6).Countries with a Roma population, whose health status is usually poor and socioeconomic position the lowest in the country (7-10), realized that research into the health status of the Roma people is needed for the planning of health intervention strategies, such as antismoking campaign (11,12). From everyday practice we know that the Roma never stop smoking and that they smoke heavily. We performed a qualitative study to understand the reasons for widespread and heavy smoking among the Roma in Slovenia for the purpose of developing more successful public health actions against smoking in their community.     

Mortality of Roma population in Serbia, 2002-2005

Aim

To describe and compare mortality and population changes in the Roma and non-Roma population in Serbia in 2002 and 2005.

Methods

The number of cases of death were obtained from the 2002 and 2005 Mortality Database and population data from the Population Census 2002. Standardized sex specific rates of non-traumatic and traumatic mortality in 2002 and 2005 were calculated in relation to the European standard population. We presented population pyramid and aging index for both populations in 2002 and compared sex specific standardized traumatic and non-traumatic mortality rates and the average age of death for 2002 and 2005. The causes of death were coded according to the 10th revision of the International Classification of Diseases (ICD-10) groups, and the proportional mortalities in the year 2002 and 2005 were compared between the Roma and non-Roma population using χ² test.

Results

Standardized mortality rates were higher in the Roma than in the general population. Non-traumatic mortality rate in Roma men in 2002 was 18.2 per 1000 and in slightly decreased to 18.0 per 1000 in 2005; it was significantly higher than in non-Roma men in both years (11.9 per 1000 in 2002 and 12.5 per 1000 in 2005; P<0.001). Standardized non-traumatic mortality rate in Roma women decreased significantly from 16.78 per 1000 in 2002 to 14.89 per 1000 in 2005 (P=0.014), but it was still significantly higher than in non-Roma women (8.46 per 1000 in 2002 and 8.84 per 1000 in 2005; P<0.001). Morbidity structure indicated that the most common causes of death in the Roma population were cardiovascular diseases, neoplasms, and respiratory system diseases. In relation to the general population respiratory system diseases were denoted as main causes of deaths in significantly higher percent (6% vs 3% in 2002 and 7% vs 4% in 2005; P<0.001) and cardiovascular diseases in significantly lower percent (44%:55% in 2002 and 46%:57%; P<0.001).

Conclusions

Our data show that mortality rates in the Roma population are significantly higher than in the general population, and morbidity structure of the most common causes of death significantly different from that of general population.According to the most recent population census in the Serbia from 2002, 108 193 or 1.44% residents declared themselves as Romani. The Roma population is among the most imperiled and potentially most vulnerable groups. Living Standards Measurement Survey (LSMS) conducted in Serbia in 2002-2003 indicated significant differences in living conditions between the Roma and non-Roma population (1). The prevalence of poverty, defined as an average total consumption below the poverty line of 57 euros per month/consumption unit, in the Roma population was as high as 64.4%, which is 6.1 times more frequent than in the general population (10.5%) (1). Extremely low level of education and very high level of unemployment characterize the social status of the Romani people. Almost two thirds (62%) of the Roma older than 15 years did not finish primary school, as opposed to 19% of the general population (1). The unemployment rate is also high, reaching 45%, while in the rest of the Serbian population it amounts to 9% (1). Such findings are not unexpected since these characteristics are highly associated with poverty (1).Although the range of vaccination coverage in Serbian general population is 98%-100%, many Roma children are not included in vaccination programs (2). Twenty nine percent of Roma children aged 18-29 months do not even have vaccination cards. Data regarding the education of Roma children are also discouraging: 62% of them attended pre-school programs one year prior to the first grade, as opposed to 89% children in the general population. Also, the vast majority (98%) of children of primary school age in general population attends school, while the attendance rate among Roma children is significantly lower (74%). The difference between the proportions of Roma children and children in general population who attend secondary schools is even more drastic (only 10% vs 85%).During the last decade, several studies dealing with diverse problems of the Roma population have been conducted in South-Eastern Europe (3-10). Compared with the general populations in Eastern and Central Europe, life expectancy of the Roma population is 10-year shorter because of poor living conditions and poverty (11). A study conducted in the Czechoslovakia in 1989 compared census data and pointed out that life expectancy of the Roma men and women were 12.1 and 14.4 years, respectively, shorter than in the general population (12).The aim of this study was to describe and compare mortality and population changes in the Roma and non-Roma population in Serbia in 2002 and 2005. We present population pyramid and aging index for both populations for the year 2002 and compared sex specific standardized traumatic and non-traumatic mortality rates and the average age of death for 2002 and 2005.     

Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD

Background  

Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD.     

Haplotype analysis suggest common founders in carriers of the recurrent BRCA2 mutation, 3398delAAAAG, in French Canadian hereditary breast and/ovarian cancer families

Background  

The 3398delAAAAG mutation in BRCA2 was recently found to recur in breast and/or ovarian cancer families from the French Canadian population of Quebec, a population that has genetic attributes consistent with a founder effect. To characterize the contribution of this mutation in this population, this study established the frequency of this mutation in breast and ovarian cancer cases unselected for family history of cancer, and determined if mutation carriers shared a common ancestry.     

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

Background  

Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown.     

Genetic variability and population structure of endangered <Emphasis Type="Italic">Panax ginseng</Emphasis> in the Russian Primorye

Background  

The natural habitat of wild P. ginseng is currently found only in the Russian Primorye and the populations are extremely exhausted and require restoration. Analysis of the genetic diversity and population structure of an endangered species is a prerequisite for conservation. The present study aims to investigate the patterns and levels of genetic polymorphism and population structures of wild P. ginseng with the AFLP method to (1) estimate the level of genetic diversity in the P. ginseng populations in the Russian Primorsky Krai, (2) calculate the distribution of variability within a population and among populations and (3) examine the genetic relationship between the populations.     

Loss of balancing selection in the βS globin locus

Background  

Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations.     

Detection of large deletions in the LDL receptor gene with quantitative PCR methods

Background  

Familial Hypercholesterolemia (FH) is a common genetic disease and at the molecular level most often due to mutations in the LDL receptor gene. In genetically heterogeneous populations, major structural rearrangements account for about 5% of patients with LDL receptor gene mutations.     

Absence of association between SERPINE2 genetic polymorphisms and chronic obstructive pulmonary disease in Han Chinese: a case-control cohort study

Background  

Recent studies have proposed that the serine protease inhibitor E2 (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary disease (COPD) in Caucasians. However, this issue still remained controversial. Additional evidences from populations with different environments and/or genetic backgrounds, such as East Asian, would be helpful to elucidate the issue.     

Multiplex SNaPshot for detection of <Emphasis Type="Italic">BRCA1/2</Emphasis> common mutations in Spanish and Spanish related breast/ovarian cancer families

Background  

It is estimated that 5–10% of all breast cancer are hereditary and attributable to mutations in the highly penetrance susceptibility genes BRCA1 and BRCA2. The genetic analysis of these genes is complex and expensive essentially because their length. Nevertheless, the presence of recurrent and founder mutations allows a pre-screening for the identification of the most frequent mutations found in each geographical region. In Spain, five mutations in BRCA1 and other five in BRCA2 account for approximately 50% of the mutations detected in Spanish families.     

Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates

Background  

Autism is a neurobehavioral spectrum of phenotypes characterized by deficits in the development of language and social relationships and patterns of repetitive, rigid and compulsive behaviors. Twin and family studies point to a significant genetic etiology, and several groups have performed genomic linkage screens to identify susceptibility loci.     

Genetic and biochemical study of dual hereditary jaundice: Dubin–Johnson and Gilbert's syndromes. Haplotyping and founder effect of deletion in ABCC2

Dual hereditary jaundice, a combination of Dubin–Johnson and Gilbert''s syndromes, is a rare clinical entity resulting from the compound defects of bilirubin conjugation and transport. We aimed to study the hereditary jaundice in 56 members from seven seemingly unrelated Roma families, to find the causal genetic defect and to estimate its origin in Roma population. On the basis of biochemical results of total and conjugated serum bilirubin and clinical observations, ABCC2 gene, TATA box and phenobarbital enhancer (PBREM) of UGT1A1 gene were analyzed by sequencing, RFLP and fragment analysis. We found a novel variant c.1013_1014delTG in the eighth exon of ABCC2 gene in 17 individuals in homozygous state. Dual defect {"type":"entrez-nucleotide","attrs":{"text":"NG_011798.1","term_id":"226509596","term_text":"NG_011798.1"}}NG_011798.1:c.[1013_1014delTG] {"type":"entrez-nucleotide","attrs":{"text":"NG_002601.2","term_id":"296012512","term_text":"NG_002601.2"}}NG_002601.2:g.[175492_175493insTA] in homozygous state was found in four subjects. Biochemical analyses of porphyrins and coproporphyrin isomers in urine performed by HPLC showed inverted ratio of excreted coproporphyrin, with the predominance of coproporphyrin I (up to 100%), typical for patients with Dubin–Johnson syndrome. Pursuant cultural and social specifics of the population led us to suspect a founder effect; therefore, we performed a haplotype study using genotyping data from Affymetrix Genome-Wide Human SNP Array 6.0. As a result, we detected a common 86 kbp haplotype encompassing promoter and part of the ABCC2 coding region among all families, and estimated the age of the ancestral variant to 178–185 years. In this study, we found a novel deletion in ABCC2 gene, described genetic and biochemical features of dual hereditary jaundice and confirmed the existence of founder effect and common haplotype among seven Roma families.     

Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes

Background  

Although mitochondrial dysfunction is consistently manifested in patients with Type 2 Diabetes mellitus (T2DM), the association of mitochondrial DNA (mtDNA) sequence variants with T2DM varies among populations. These differences might stem from differing environmental influences among populations. However, other potentially important considerations emanate from the very nature of mitochondrial genetics, namely the notable high degree of partitioning in the distribution of human mtDNA variants among populations, as well as the interaction of mtDNA and nuclear DNA-encoded factors working in concert to govern mitochondrial function. We hypothesized that association of mtDNA genetic variants with T2DM could be revealed while controlling for the effect of additional inherited factors, reflected in family history information.     

The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations

Background  

Analysis of the chromosomal background upon which a mutation occurs can be used to reconstruct the origins of specific disease-causing mutations. The relatively common BRCA1 mutation, 1135insA, has been previously identified as a Norwegian founder mutation. We performed haplotype analysis of individuals from breast and ovarian cancer families from four different ethnic backgrounds who had been identified as carriers of the BRCA1: 1135insA mutation.     

The T/G 13915 variant upstream of the lactase gene (LCT) is the founder allele of lactase persistence in an urban Saudi population

Background

The prevalence of lactase persistence is high in Saudi Arabia.

Objective

To identify a DNA variant for the lactase persistence/non‐persistence trait in adult Arabs in Saudi Arabia.

Methods

We sequenced DNA from 432 anonymous neonatal blood donors from five different regions of Saudi Arabia to cover the 400 bp region surrounding the previously identified lactase persistence/non‐persistence variant C/T−13910 residing in intron 13 of the MCM6 gene.

Results

Two anonymous blood donors carried the C/T−13910 genotype. One variant, T/G −13915, residing 5 bp upstream of the C/T−13910 variant, was present in 332 of 432 (76.9%) of the neonatal samples, compatible with previous prevalence figures of lactase persistence in urban Saudi populations. Determination of disaccharidase activities in 25 intestinal biopsy samples showed a highly significant correlation between lactase activity and the T/G−13915 genotypes (p<0.001; Fisher exact test) as well as between the L:S ratio and the aforementioned genotypes (p<0.001; Fisher exact test).

Conclusion

The T/G−13915 variant is the founder mutation of lactase persistence in an urban Saudi population. The results obtained here have implications for genetic testing of adult‐type hypolactasia and to analysis of human evolution, the origin of cattle domestication and migrations of the populations in the Arabian peninsula.     

The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

Background  

The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV).