grand final atlantic corridor poster presentation [autosaved] [autosaved]

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v To retrieve and compile Traveller mutation data from international literature, both published and unpublished. v To obtain information from hospital cases as well patient reports from colleagues. v To catalogue, document and organise references/data using the correct nomenclature. Irish Travellers are an endogamous, ethnically Irish population whose origins date back to the 12th century 1 . There are approximately 40,000 living in Ireland with up to 10,000 living on mainland Europe 2 . Traveller families tend to be large and have high levels of consanguinity, which increases the possibility of autosomal recessive disease 1 . In 2012, the Academic Centre on Rare Disease estimated over 60 recessive disorders to occur in this group 3 . Mutations tend to cluster among clans with geographical spread 2 . Currently, there is no catalogue of Traveller mutations, their phenotypes, or the associated literature. Identification of genetic alterations within the Traveller population could aid rapid and affordable genetic testing. Conclusion & Discussion Background Results 1. North KE, Martin LJ, Crawford MH: The origins of the Irish Travellers and the genetic structure of Ireland. Annals of Human Biology 2000, 27:453–465. 2. Centre PPT, McGaughey F: Irish Travellers and Roma Shadow Report: A Response to Ireland’s Third and Fourth Report on the International Convention on the Elimination of All Forms of Racial Discrimination (CERD). Pavee Point Travellers’ Centre; 2011. 3. Academic Centre on Rare Diseases [http://www.ucd.ie/medicine/ourresearch/researchcentres/academiccentreonr arediseases/] 4. Murphy M, McHugh B, Tighe O, Mayne P, O’Neill C, Naughten E, Croke DT: Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers. European Journal of Human Genetics 1999, 7. 5. Teebi AS, Teebi SA, Porter CJ, Cuticchia AJ: Arab genetic disease database (AGDDB): a population-specific clinical and mutation database. Hum Mutat 2002, 19:615–621. The phenotypes of the 70 identified mutations affect a broad range of systems. Certain diseases are known to occur more commonly among Travellers, such as Classical Glacatosaemia 4 . However, patients presenting with rare or novel recessive conditions are difficult to diagnose without knowledge from literature reports. In such circumstances gene panels are often requested. This can be a costly and time consuming technique compared to targeting a specific founder mutation within a known gene. Therefore, the catalogued mutations should be considered when Traveller patients present with the conditions listed in figure 2. In addition, the 76 references reported can help facilitate clinical knowledge of these conditions. Data Entry Tool Used Disease Name OMIM Number OMIM Sequence Number UCSC Genome Browser Protein Mutalyzer OMIM = Online Mendelian Inheritance in Man Table 1. Tools used to correct/identify nomenclature of different data. Recommendations Difficulty arose when identifying Traveller patients in reports. Several studies did not disclose case details including nationality or consanguinity. Other problems were encountered with article terminology, for example, use of the word “Gypsy” instead of “Traveller”. Therefore, a number of mutations may have been undetected. Subsequent literature searches should use additional resources such as Google Scholar, EMBASE etc. in addition to broader search term. Future Directions The Arab Genetic Disease Database (AGDDB) is an online catalogue of genetic disorders in Arab populations 5 . The AGDDB contains reports which cover clinical, genomic, reference, and population frequency elements and has over 1,000 unique disorder entries 5 . It has been an instrumental tool in diagnostics and management of genetic diseases. With time we hope to achieve a similar model, which can be updated regularly and accessed by physicians worldwide. Traveller mutations were obtained from various sources (figure 1). Literature searches were carried out using PubMed/MEDLINE, key search terms included “Traveller”, ”mutations”, “consanguineous” etc. Data was documented using Microsoft Excel spreadsheet and the nomenclature was corrected using the appropriated online software tools ( table 1). Figure 1. Sources of Traveller mutations. Aims Methods Figure 2. List of Traveller phenotypes organised by systems. Number of mutations identified = 70. Number of references = 76. References I wish to thank my supervisor and principal investigator Dr Sally Anne Lynch for the opportunity to participate in this project. Many thanks to the staff at the National Rare Disease Office and Department of Metabolic at the Mater Hospital for their guidance, patience and hospitality. Acknowledgements

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Page 1: Grand Final Atlantic Corridor poster presentation  [Autosaved] [Autosaved]

v To retrieve and compile Traveller mutation data from international literature, bothpublished and unpublished.

v To obtain information from hospital cases as well patient reports from colleagues.v To catalogue, document and organise references/data using the correct

nomenclature.

Irish Travellers are an endogamous, ethnically Irish population whose origins date backto the 12th century1. There are approximately 40,000 living in Ireland with up to 10,000living on mainland Europe2. Traveller families tend to be large and have high levels ofconsanguinity, which increases the possibility of autosomal recessive disease1. In2012, the Academic Centre on Rare Disease estimated over 60 recessive disorders tooccur in this group3. Mutations tend to cluster among clans with geographical spread2.Currently, there is no catalogue of Traveller mutations, their phenotypes, or theassociated literature. Identification of genetic alterations within the Traveller populationcould aid rapid and affordable genetic testing.

Conclusion & Discussion

Background Results

1. North KE, Martin LJ, Crawford MH: The origins of the Irish Travellers andthe genetic structure of Ireland. Annals of Human Biology 2000, 27:453–465.2. Centre PPT, McGaughey F: Irish Travellers and Roma Shadow Report: AResponse to Ireland’s Third and Fourth Report on the InternationalConvention on the Elimination of All Forms of Racial Discrimination (CERD).Pavee Point Travellers’ Centre; 2011. 3. Academic Centre on Rare Diseases[http://www.ucd.ie/medicine/ourresearch/researchcentres/academiccentreonrarediseases/] 4. Murphy M, McHugh B, Tighe O, Mayne P, O’Neill C,Naughten E, Croke DT: Genetic basis of transferase-deficient galactosaemiain Ireland and the population history of the Irish Travellers. European Journalof Human Genetics 1999, 7. 5. Teebi AS, Teebi SA, Porter CJ, Cuticchia AJ:Arab genetic disease database (AGDDB): a population-specific clinical andmutation database. Hum Mutat 2002, 19:615–621.

The phenotypes of the 70 identified mutations affect a broad range of systems. Certain diseases are known to occur morecommonly among Travellers, such as Classical Glacatosaemia4. However, patients presenting with rare or novel recessive conditions are difficult to diagnose withoutknowledge from literature reports. In such circumstances gene panels are often requested. This can be a costly and time consuming technique compared to targeting aspecific founder mutation within a known gene. Therefore, the catalogued mutations should be considered when Traveller patients present with the conditions listed in figure2. In addition, the 76 references reported can help facilitate clinical knowledge of these conditions.

Data Entry Tool UsedDisease NameOMIM Number

OMIM

SequenceNumber

UCSC Genome Browser

Protein Mutalyzer

OMIM = Online Mendelian Inheritance in Man Table 1. Tools used to correct/identify nomenclature of different data.

RecommendationsDifficulty arose when identifying Travellerpatients in reports. Several studies did notdisclose case details including nationality orconsanguinity. Other problems wereencountered with article terminology, forexample, use of the word “Gypsy” instead of“Traveller”. Therefore, a number of mutationsmay have been undetected. Subsequentliterature searches should use additionalresources such as Google Scholar, EMBASEetc. in addition to broader search term.

Future DirectionsThe Arab Genetic Disease Database (AGDDB)is an online catalogue of genetic disorders inArab populations5. The AGDDB containsreports which cover clinical, genomic,reference, and population frequency elementsand has over 1,000 unique disorder entries5. Ithas been an instrumental tool in diagnosticsand management of genetic diseases. Withtime we hope to achieve a similar model, whichcan be updated regularly and accessed byphysicians worldwide.

Traveller mutations were obtained from varioussources (figure 1). Literature searches werecarried out using PubMed/MEDLINE, keysearch terms included “Traveller”, ”mutations”,“consanguineous” etc. Data was documentedusing Microsoft Excel spreadsheet and thenomenclature was corrected using theappropriated online software tools ( table 1).

Figure 1. Sources of Traveller mutations.

Aims

Methods

Figure 2. List of Traveller phenotypes organised by systems. Number of mutations identified = 70. Number of references = 76.

References

I wish to thank my supervisor and principalinvestigator Dr Sally Anne Lynch for theopportunity to participate in this project. Manythanks to the staff at the National Rare DiseaseOffice and Department of Metabolic at theMater Hospital for their guidance, patience andhospitality.

Acknowledgements