Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Faculty of Communications, Health and Science

First Advisor

Associate Professor Luba Kalaydjieva

Second Advisor

Professor Alan Bittles


The Roma (Gypsies) are a European people composed of a mosaic of culturally heterogeneous populations. Linguistic analyses point to their origins in the Indian subcontinent. Cultural diversity in extant Romani populations suggests that they are descended from a mixture of Indian populations. Previous population genetic studies of the Roma have supported this claim by demonstrating the genetic heterogeneity of Romani populations. More recently, medical genetic research has detected identical founder mutations in separated Romani populations, which provides evidence of their relatedness. In this thesis, the genetic heritage of the Roma and its significance for genetic disease and research is investigated. Male and female lineages were analysed in eight traditionally endogamous Romani populations. Asian specific Y chromosome haplogroup VI-68 and mitochondrial DNA (mtDNA) haplogroup M were detected in all populations and accounted for 39% and 25% of all lineages respectively. Diversity within haplogroups was assessed by genotyping Y chromosome short tandem repeats (YSTRs) and sequencing the mtDNA hypervariable segment 1 (HVSl). Lineages within haplogroups VI-68 and M were found to be closely related suggesting that Romani populations are predominantly descended from a single Indian ethnic population. The differing historical legacies of Romani populations and adherence to endogamous practices have resulted in genetic substructure and limited diversity within populations. Thus, the Roma are shown to comprise a conglomerate of related admixed population isolates. The unique genetic heritage of the Roma provides a powerful tool for the positional cloning of monogenic disease genes. This is demonstrated through the reduction of the critical chromosomal region for a novel genetic disorder, hereditary motor and sensory neuropathy type Lom (HMSNL). In the initial report, the HMSNL disease locus was defined as a 3cM region on chromosome 8q24. In this study, refined genetic mapping utilising historical and parental recombinations observed in Romani individuals from different populations reduced the HMSNL critical interval to 202kb. Sequence analysis of two genes contained within this genomic interval found all affected individuals to be homozygous for a CT mutation in codon 148 of N-myc downstream regulated gene 1 (NDRGJ), resulting in a truncating Rl48X mutation. Investigation of the population distribution of the R148X disease allele shows that it occurs in six of eight separated Romani populations. Another founder mutation, C283Y in the y-sarcoglycan gene (SGCG), which causes limb girdle muscular dystrophy type 2C (LGMD2C), was found in two of eight Romani populations. Profound founder effects are apparent within Romani populations with a carrier frequency of 19.5% determined for the R148X mutation in the Lom population, and 6.25% for the C283Y allele in the Turgovzi population. High carrier frequencies for autosomal recessive diseases can be expected to pose a significant health risk for these communities. Thus, community-wide carrier testing represents a potential means of addressing this health problem. A pilot community based carrier-testing program was implemented in a Romani community of north eastern Bulgaria and relevant attitudes assessed by means of a questionnaire. Community-based carrier screening was demonstrated to be an appropriate approach to improving health amongst the Roma.