Researchers map genetic make-up of Danish population

A new study by the GenomeDenmark research consortium has produced the first catalogue of its kind of the genetic make-up of the average Dane. In future, the catalogue can be used to identify gene variations leading to genetically determined diseases.

The study, which has just been published in the leading scientific journal Nature, has been undertaken jointly by the University of Copenhagen, Technical University of Denmark, Aarhus University and the company BGI Europe. The study mapped the genes of 150 carefully selected Danes. The result is a new Danish reference genome seen as representative of the genetic make-up of the average Danish person.

Reference genome

A reference genome is a kind of average genome consisting of DNA information from a large number of individuals from the same geographical area. Two individuals whose families have lived in Denmark for generations are expected to share more DNA traits than two from far-apart regions.

Source: GenomeDenmark

Increased understanding of heritability of diseases
The new reference genome for the normal population can be used for comparing with other results. When examining the genetic material of individuals suffering from a specific disease, it is now possible to eliminate a whole range of variations as being irrelevant to the development of the disease, if you can see that they are very normal in the population. Instead, it allows us to focus on the gene variations that may have caused the disease in question.

“We’re really keen to identify patterns in people’s genetic material which cause disease. But first, we need to understand what are normal and harmless patterns or variations in our DNA. The study is helping us do this, and it paves the way for studies of the genome of sufferers from specific groups of diseases,” says one of the main authors behind the study, Professor Søren Brunak from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen and at DTU Bioinformatics.

New and important knowledge about rare gene variations behind common preventable diseases
The new Danish reference genome is crucial to being able to map the importance of the more rare gene variations behind, for example, obesity, type 2 diabetes, cardiovascular diseases, and other common preventable diseases among Danes, explains Professor Oluf Borbye Pedersen from the Novo Nordisk Foundation Center for Basic Metabolic Research.

“With the chip-based methods we’ve been using in our genetic studies of lifestyle diseases at the Novo Nordisk Foundation Center for Basic Metabolic Research Center in recent years, we’ve been able to identify vulnerability variations in the genome occurring in more than 5% of the population. However, these frequently occurring variations explain only a few per cent of the hereditary causes of these common preventable diseases,” he says.

“Uniquely, the new Danish reference genome makes it possible to multiply the number of genetic markers for each and every individual we examine. Also, it increases our knowledge of the more rare mutations causing type 2 diabetes, obesity and arteriosclerotic diseases. In fact, the more rare mutations are believed to be more closely associated with the occurrence of diseases than the frequent ones,” he explains.

“Furthermore, it will be really interesting and quite challenging to analyse the impact of the more complex gene variations—in the form of both missing and extra DNA material—on the risk of disease. The reference genome contains a lot of information about complex Danish gene variations, brand new knowledge,” concludes Professor Oluf Borbye Pedersen. 

Different countries, different genomes
In the past, we have been able to use international reference genomes, but this is the first Danish reference genome. Having a Danish reference genome is important because genetic variations between Danish genomes and an international reference genome may be due to the fact that your average Danish genome differs anyway, explains Professor Søren Brunak.

“There are lots of variations in the genome which are only found among Danes or Scandinavians, but which may not be particularly common in Spain. And so without a Danish reference genome, we could be led to believe that certain variations might have something to do with a particular disease,” he says.

Deeper analysis than normal
The study is based on genetic material from 150 individuals. Fifty fathers, mothers, and children were selected from the Copenhagen Family Bank, a biobank established in the 1970s by Associate Professor Hans Eiberg from the Faculty of Health and Medical Sciences, University of Copenhagen, who is also a co-author of the study.

The 150 individuals were selected to reflect the composition of the Danish population, for example in terms of height and blood group. 

Sequencing

Sequencing is a technology which shows how the genetic material of organisms is structured. The genetic material of most organisms consists of very long molecules of the substance DNA (deoxyribonucleic acid). The DNA is subdivided into genes which can be illustrated as long strings of genetic letters in a particular order. The order of these genetic letters determines an organism’s development, appearance and response to, for example, the external environment and disease. Sequencing shows the structure of the genetic material by reading the sequence of the genetic letters in the DNA one letter at a time. Sequencing can (via additional methods) also be used to analyse an organism’s RNA expression, providing insight into the activity of specific genes at a certain point in time.

Source: GenomeDenmark

 

The genetic material was then analysed in-depth through sequencing, which roughly speaking involves cutting the DNA into pieces and reading the order or sequence of the nucleotides in the DNA strand. In this study, each nucleotide was sequenced an average of 78 times. This greatly increases the validity of the conclusions.

Important genetics behind immune system mapped
These very thorough efforts have also produced new discoveries. For example, previously unknown regions of the genetic material of humans have been mapped.

“We’ve been able to map 100 new complete MHC haplotypes which are extremely important for the human immune system. We used to have only two of this quality, which means that we’ve substantially increased our knowledge of the genetics of our different immune systems,” says Søren Brunak.

Read more about the research project at the GenomeDenmark website, or read the scientific article ‘ Sequencing and de novo assembly of 150 genomes from Denmark as a population reference’