Recent research

Uncovering the Genetic History of the Present-Day Greenlandic Population

TreeMix
TreeMix

New research sheds light on the genetic history of the Greenlandic population. Research from Copenhagen University, Steno Diabetes Center and National Institute of Public Health, University of Southern Denmark just published in American Journal of Human Genetics reconstructs the genetic ancestry of present day Greenlanders and provides a genetic map of recent and ancient migrations into the Island.
Within the last 5000 years the world’s largest Island has been colonized many times both by different arctic populations and by European settlers such as the Vikings. Additionally, the Greenlandic population size has increased almost tenfold within the last two hundred years mainly by natural growth but also by migration from Denmark. In this study the researchers study the genetic impact of these migrations and determine which populations have contributed to the genetic composition of modern Greenlanders.

Impact from recent European migration

Based on more than 10% of the adult population and two hundred thousand genetic markers the study finds that 75% of the genetic ancestry is of Inuit origin while the remaining 25% is European. However the amount of European ancestry varies greatly between the different regions in Greenland.
In most locations in Greenland almost everybody has some European ancestry. However, some regions stand out. For example in Tasiilaq and villages in the East most individuals do not have any European ancestry while in cities in West Greenland such as Aasiaat, Maniitsoq and Nuuk all but a few percent have some European ancestry explains post doc Ida Moltke who is the first author of the study.
It is not just the amount of European ancestry that varies between regions in Greenland. There are also genetic differences between the individuals from the different regions. Using statistical methods the researchers were able distinguish individuals from North, West and East Greenland.
Due to the historically small size of the population, the settlements in the different regions of the Island diverged a fair amount in a short time. The impact is so pronounced that based on only genetic information it is possible to determine if a person is from Qaanaaq in the North, Tasiilaq in the East or from somewhere in the West. Surprisingly people from Qaanaaq are more genetically distant to people in Tasiilaq than Danish individuals are to people from the southern part of Italy says Associate professor Anders Albrechtsen from the Bioinformatics Centre at the University of Copenhagen.

Ancient migration routes and meeting of cultures

The most recent arctic colonization of Greenland happened around 700 years ago by the Thule culture which is the Inuit ancestors of the current population. However, at the time they were not the only people on the Island. There were still people of the Dorset culture from a previous arctic colonization as well as the Norse – the Viking settlers.

We know from archeological evidence that the cultures met and traded with each other which raises the question of whether the Greenlandic Dorset people or the Vikings settlers interbred with the Thule population. However, we found no evidence that either the Dorset or the Vikings contributed to the gene pool of present day Greenlanders explains Rasmus Nielsen, University of California Berkeley who together with Anders Albrechtsen is a corresponding author of the work.

In addition to investigating previous encounters of cultures the researches were also able to determine the route that was used by the Thule population when colonizing the Island. Many previous studies have suggested that the Thule population reached Tasiilaq in the East using the northern route around the Island. However, the genetic data was not consistent with such a route. Instead the ancestors of the present day individuals living in East Greenland came from the south
Based solely on the genetic data we can see each village splitting off one by one starting in the North, then down the west coast all the way to the south tip of the Island and then up again on the East coast. Therefore, the individuals who migrated north on the Island do not appear to have left any genetic trace in the current Tasiilaq population says Anders Albrechtsen.

Small population and genetic risk factors

In addition to describing the genetic history of the Greenlandic population the study also provides a foundation for investigating genetic risk factors for disease. The historically small population size of Greenlanders has had a large impact on the genetic landscape. There are fewer genetic variations in the population compared to large populations such as Chinese or European. However, the variations that exist are more common than in other populations.
The consequence for genetic disease susceptibility is that a lower number of genetic markers will have an impact on disease but the markers that exist will have a higher impact. With the information we have gained from this study we can better understand the genetic risk factors that affect the Greenlandic population. We will use this information in future studies to identify new disease markers with the goal of providing better diagnoses and ultimately treatment of diseases says Ida Moltke

ANGSD: Analysis of Next Generation Sequencing Data

Finally the paper describing the ANGSD software is out. Do you have low or medium depth NGS data. Then this software is for you. No genotype calling only base analysis on genotype likelihoods or read sampling.

ANGSD pipeline
ANGSD pipeline

DivA: Detection of non-homologous and very divergent regions in protein sequence alignments. BMC Research Notes, in press

Software for detecting and masking problematic regions in protein sequence alignments.

Download DivA

The genetic prehistory of the New World Arctic

We participated in a large project that unraveled the genetic history of the new world arctic populations and showed how all of the paleo-eskimo populations have been completely replaced by the current Inuit cultures.

figure of migration
figure of migration

A recessive mutation explains more than 10% of all cases of type 2 diabetes in Greenland

In a recent publication we identified a genetic variation that has an extremely large impact on the Greenlandic population. The variation affects a muscle specific isoform of the Gene TBC1D4 which reduces the GLUT4a ctivity which affects postprandial glucose levels.

Moltke et al . A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. In press. DOI: 10.1038/nature13425

The genome of a Late Pleistocene human from a Clovis burial site in western Montana

Ida Moltke, Thorfinn Korneliusen and Anders Albrechtsen helped analysing the Ancient DNA samples in a study led by Morten Rasmussen and Eske Willeslev. This study shows that the 13000 year old individual was part of the population that where ancestors of most contemporary Native Americans.

Rasmussen M et al. The genome of a Late Pleistocene human from a Clovis burial site in western Montana. Nature, 2014, vol. 506, no. 7487, pp. 225-229

Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans

Ida Moltke and Anders Albrechtsen helped analyse the data in a large study led Maanasa Raghaven and Eske Willerslev. Here we showed that there was additional geneflow from the Mal'ta population into the Native Americans. This explains the link between Europeans and Native Americans.

Raghavan M, et al. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans. Nature, 2014, vol. 505, no. 7481, pp. 87-91

Admixture analysis from low and medium depth sequencing data is now possible.

Line Skotte, Thorfinn Korneliussen and Anders Albrechtsen shows that it is possible in accurately infer admixture proportions even with low depth sequencing data.

Skotte* L, Korneliussen* TS, Albrechtsen A. Estimating individual admixture proportions from next generation sequencing data. Genetics, 2013, vol. 195, no. 3, pp. 693-702

Relatedness estimation is now possible for admixed individuals

Ida Molke and Anders Albrechtsen gives a maximum likelihood solution for estimating pairwise relatedness coefficient for admixed individuals.

Moltke I, Albrechtsen A. RelateAdmix: a software tool for estimating relatedness between admixed individuals. Bioinformatics, 2013

Large scale exome sequencing and genotyping reviels novel loci associated with diabetes and lipid levels

Anders Albrechtsen, Thorfinn Korneliussen and Line Skotte performed the first large scale sequencing based association studies.

Albrechtsen A et a.. Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes. Diabetologia, 2013, vol. 56, no. 2, pp. 298-310

Skotte L, Korneliussen TS, Albrechtsen A. Association testing for next-generation sequencing data using score statistics. Genetic epidemiology, 2012, vol. 36, no. 5, pp. 430-437

Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome

Lohmueller KE, Albrechtsen A, Li Y, Kim SY, Korneliussen T, Vinckenbosch N, Tian G, Huerta-Sanchez E, Feder AF, Grarup N, Jørgensen T, Jiang T, Witte DR, Sandbæk A, Hellmann I, Lauritzen T, Hansen T, Pedersen O, Wang J, Nielsen R. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome. PLoS genetics, 2011, vol. 7, no. 10, pp. e1002326

Local IBD inference estimated joint from multiple individuals

Moltke I, Albrechtsen A, Hansen TV, Nielsen FC, Nielsen R. A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics. Genome research, 2011, vol. 21, no. 7, pp. 1168-1180

Review of NGS data

Nielsen R, Paul JS, Albrechtsen A, Song YS, Nature reviews. Genetics, 2011, vol. 12, no. 6, pp. 443-451 Genotype and SNP calling from next-generation sequencing data.