Five MCT researchers were selected to give oral presentations at RCSI Research Day 2018 – Wednesday 7th March
Category: Early Career Investigators (Post-doctoral Fellows):
Mariana Patricia Cervantes Silva: Those mitochondria have got rhythms! Mitochondrial activity and antigen processing in dendritic cells is dependent on the molecular clock protein BMAL1
Stephanie Annett: The role of FKBPL in LPS induced endothelial barrier dysfunction.
Category: All Postgraduates (Thesis in 3)
Rebecca L Watkin: S. aureus induced miR330-3p expression triggers abnormal permeability in an ex-vivo 2D model of sepsis.
Orla Fox: Uncoupling Activated Protein C Functions by Inhibition of PostTranslational Beta-Hydroxylation.
Edmund Gilbert: The Irish DNA Atlas: Revealing Fine-Scale Population Structure and History within Ireland
The Irish DNA Atlas, a study of Irish genetic history and diversity led by researchers at the Royal College of Surgeons in Ireland (RCSI) and the Genealogical Society of Ireland (GSI), has recently published in findings into the genetics of Ireland in the Nature Publishing journal Scientific Reports (The Irish DNA Atlas: Revealing Fine-Scale Population Structure and History within Ireland). The Irish DNA Atlas is a cohort of individuals with four generations of ancestry from specific regions in Ireland, recruitment is organised and managed by Seamus O’Reilly at the GSI. Mr O’Reilly helps potential recruits finish, or double-check, family history and pedigree charts for the recruitment process, and mails out sample kits and paperwork for their return to RCSI.
The researchers, led by Professor Gianpiero Cavalleri at RCSI, have found; i) different groups of Irish individuals, clustered by genetic similarity alone; ii) the genetic differences between these groups are incredibly small, iii) members of each of these groups share ancestries from similar regions in Ireland (see image below); iv) a migration event(s) is observed in the north of the island of Ireland that dates somewhere in the 17th and 18th centuries and is from Britain; v) a number of genetic barriers within in Ireland, notably; in the north, and between Leinster and Munster; and finally vi) a significant level of Norwegian-like genetic ancestry throughout Ireland is observed for the first time and this is associated with a genetic migration into Ireland around the turn of the first millennium.
Using the Irish DNA Atlas in conjunction with a dataset of British individuals with regional ancestry (the People of the British Isles Study) the project was able to clusters 2,103 individuals from Ireland and Britain based on genetic similarity as 30 distinct genetic groups (see image 1 for clusters within Ireland). People within the same group are more genetically similar to each other than they are to individuals in other groups. When each Irish individual is colour coded by the group and is placed on a map based on where their great-grandparents were born, we generate a map shown below. Shown to the left are the geographic spread of the identified clusters and on the right a map of Irish kingdoms that represent proto-Provinces circa 800AD.
Analysing the Atlas, the broadest groups within Ireland are either; nearly 100% made up of Irish/Northern Irish individuals (i.e. from the island of Ireland), or are a mix between Irish and mainland British individuals. In the case of the latter, this suggests that those (Irish and mainland British) individuals have shared Irish and British genetic ancestry. The Irish individuals within these mixed groups are mainly from the north of Ireland (predominantly those who are blue crosses in the image above), and the British members are predominantly from the north of England and the south-west of Scotland.
These groups/clusters of near 100% Irish membership are interpreted as mainly ‘Gaelic’ Irish, and the genetic differences between these groups are incredibly small. The groups/clusters are grouped geographically and most are remarkably faithful to the boundaries of the Provinces in Ireland (shown on the left map). We compare these clusters and kingdoms from around 800AD in the above image for illustrative purposes. The reflection between the genetic and historical groups suggests that these Provinces and the kingdoms they represent have subtly impacted the genetic landscape of Ireland. Of particular note is within Co. Clare, which has historically been both parts of Munster and Connacht. Individuals with ancestry from Co. Clare reflect this by showing a mix of genetic groups found within both Munster and Connacht.
In addition to identifying different genetic groups within Ireland, the research sought to investigate whether previous migrations into Ireland had a detectable genetic impact on the genetics within Ireland. Having already identified groups of Irish individuals mainly in the north of Ireland who appeared to a mixture of Irish and British genetics, the researchers tested whether this could be due to a specific event creating these mixed groups. They estimated that these mixed groups are from a number of admixture events in the past, dating around the 17th and 18th centuries.
As well as migrations from Britain, the researchers asked whether evidence of migrations from wider afield, i.e. from continental Europe, could be found. A surprisingly larger amount of Scandinavian – specifically Norwegian – looking ancestry in all our Irish clusters was detected (see below image). This image shows along the horizontal axis each of the 30 genetic groups identified in Ireland and Britain. Along the vertical axis is the average proportion of the genome that’s the closest similarity is found in each of the 10 reference European populations. Ireland and Wales share a lot of French-like ancestry, but Ireland shows a lot of Norwegian-like ancestry compared to England or Wales. In fact, in this Norwegian respect, Ireland shows a similarity to Orkney.
This similar pattern of elevated Norwegian-like in Ireland and Orkney is interesting as Orkney is a region with strong evidence of Norwegian Viking genetic migration and mixture. Therefore the researchers investigated whether this Norwegian ancestry in Ireland was due to a mixture event dating from the time of the Viking activities in Ireland. They dated the ancestry to sometime around 1000 AD, which agrees with a ‘Viking Hypothesis’. This result was perhaps the most surprising using the Irish DNA Atlas, as previous work with Y-chromosomes found no evidence of Norse genetics within Ireland. However now, with whole-genome data, the extent of Norwegian mixture within Ireland is able to be shown.
This research has been funded through a Career Development Award from Science Foundation Ireland. RCSI is ranked among the top 250 (top 2%) of universities worldwide in the Times Higher Education World University Rankings (2018) and its research is ranked first in Ireland for citations. It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide. RCSI is a signatory of the Athena SWAN Charter.
Reported by Edmund Gilbert
Edmund Gilbert reports
A new study, led by Prof. Gianpiero Cavalleri at MCT and Prof. Jim Wilson at the University of Edinburgh, has examined the population history of the Irish Travellers and has confirmed that the Irish Travellers share a common Irish origin with the settled Irish population. The work has also for the first time estimated the date which this divergence occurred.
The Irish Travellers are a small nomadic population, making up about 0.6% of the total population on the island of Ireland, or between 29,000 and 40,000 individuals. Within the population cousin marriages (consanguineous marriages) are common, and the population is socially isolated from the surrounding settled Irish population.
The researchers, who also include MCT PhD student Edmund Gilbert, Shai Carmi of the Hebrew University of Jerusalem, and Sean Ennis of University College Dublin, used SNP-array based genotype data to compare the population genetics of the Irish Travellers to neighbouring Irish and British populations, as well as world-wide groups and European Roma Gypsies.
The study found that although the Irish Travellers were genetic closest to the settled Irish population, they showed significant differences. The study also confirmed the lack of recent shared genetic ancestry between the Irish Travellers and Roma Gypsies. The Irish Travellers, therefore, represent a subset of Irish genetic diversity, and the significant differences can be attributed to genetic drift, brought on by hundreds of years of genetic isolation and a decreasing population size. The analysis showed Irish Travellers also exhibit within-population sub-structure with four apparently distinct groups emerging, and interestingly these groups mirror different forms of the Shelta language and sociological groups within the Irish Travellers.
The dating of the origin of the Irish Travellers is of considerable interest, but this is a distinct date from the genetic origins of each population. This study has estimated a time of genetic divergence of the Irish Travellers and the settled Irish population using genomic tracts of shared identity. This method estimated the divergence to about 12 generations (360 years) ago, which is far older than common belief that the Irish Traveller population arose from the time of the Great Famine. The size of the dataset limited the authors to exploring the relatively simple model of one divergence event, future work is required to expand the study to explore more complex demographic models. The Irish Traveller population was shown to have high proportions of the genome where both maternal and paternal copies are identical, at similar levels to other consanguineous populations around the world.
The research was also welcomed by author and Traveller activist, Michael McDonagh said, “As a Traveller who has spoken on the history and identity of Irish Travellers to many groups ranging from children to academics, you sometimes rely on anecdotal information in trying to put across a serious message about Irish Traveller history. I am delighted that now we have qualified evidence that substantiates the argument I have made for many years, which is that Travellers did not descend from the Famine in Ireland. This research allows us to bring Irish Traveller history back many and gives us a factual identity.”
MCT Research Talk – 12th December
The Human Genetic Variation Research Group
The Monday 12th December MCT Seminar Series will feature presentations from Amy Cole and Edmund Gilbert, of the Human Genetic Variation Research Group at RCSI. Led by Prof. Gianpiero Cavalleri, this research group studies large genetic datasets to investigate population structure, natural selection and the genetic basis of human disease.
Amy Cole’s research focuses on identifying adaptive genetic variants in high altitude populations. There are more than 140 million people living at high altitude who are exposed to two primary environmental extremes; hypobaric hypoxia and cold. At altitudes >2500 m individuals have between 11-14% effective oxygen availability, instead of the 21% available at sea level. Previous studies have identified genetic signals of selection across the genome, which have facilitated an adaptive phenotype for survival in this hypoxic environment. Studying these indigenous high altitude populations will enable us to shed light on genes and molecular mechanisms involved in the response to hypoxia. This insight can help shed light on a number of illnesses associated with hypoxic states in low altitude populations, such as pneumonia, chronic obstructive pulmonary disease, asthma and cancer.
Today Amy presented research on a whole genome sequencing project on native high altitude Quechua individuals, recruited from the city of Cerro de Pasco, Peru, during a field trip in 2015. Amy recently completed a three-month lab placement at MD Anderson Cancer Center with Professor Chad Huff’s research group. Here Amy performed a number of computational analyses to identify regions of the genome that are under selection in this cohort.
Edmund Gilbert’s research involves investigating the genetic structure and diversity found within the Irish. As an island population on the west of Europe, the Irish population is, from the genetic perspective, relatively homogenous compared to populations of the European mainland. As a results of this elevated homogeneity, the Irish population is well suited to studies of genetic disease. Such studies have recently shifted focus towards rare variants, which are more geographically stratified than more common variants. Therefore understanding the population structure within Ireland is key for the optimal design of genetic disease causing rare variant identification within the Irish.
Today Edmund will be presenting research investigating the extent of fine-scale population structure found within Ireland. He has been using SNP-array genotype data from the genetic ancestry DNA cohort called the “Irish DNA Atlas”. The Atlas is a cohort of individuals with Irish ancestry from three generations ago who have all eight of their great-grandparents born within 50 km. Edmund will be presenting analysis based on the suite of software known as fineStructure; investigating both fine-scale structure as well as the genetic ancestry of this structure.
Amy Cole, Edmund Gilbert, Gianpiero Cavalleri