Children of the Dutch Hunger Winter of 1944 survived thanks to adapted genes

Children of the Famine of 1944, known in Dutch as the Hunger Winter, may have survived the adverse conditions in the womb thanks to adaptations to their DNA. However, these changes also made them more prone to health problems later in life. This is what LUMC researchers write in Nature Communications, together with colleagues from Columbia University and Harvard.

Different configuration of the growth genes

During the Hunger Winter of 1944–1945, the quantity of available food plummeted to a bar quarter of what a person actually needs. And yet, some children were conceived at that time and were born with a normal birth weight. Extensive DNA research on children born during this famine now shows that in these children, the genes that promote growth are configured differently. That explains also why they are more prone to health problems when they reach middle age.

Health decades later

‘The adapted growth genes helped these children to endure the difficult circumstances in the womb. But these adaptations have a maladjusted metabolism as a side effect. The altered way that these genes are set is coupled with such problems as higher blood cholesterol level at the age of 60,’ says Dr Bas Heijmans, who heads the research team. Heijmans is an epigeneticist in the department of Molecular Epidemiology at LUMC.

Adapted growth genes

The researchers examined a million different points in the DNA of children who were conceived during the famine, and they compared them with those of their brothers and sisters. This allowed them to map out very precisely differences in the way their genes were configured. Although the famine was acute, the configuration of most genes in the children at the time were found to be intact.

A different configuration from their siblings

Epigeneticists study the influence of reversible hereditary changes in gene expression without altering the molecular DNA structure.

Epigeneticists study the influence of reversible hereditary changes in gene expression without altering the molecular DNA structure.

These adaptations to the DNA that occurred seem to follow a special pattern: groups of genes that work together to promote growth in the womb are configured differently in these people than in siblings who were conceived and born before or after the famine.

Conditions in the womb

Food drop carried out by the Allied Forces (Photo: NIOD)

Food drop carried out by the Allied Forces (Photo: NIOD)

The children born during the Hunger Winter who were studied were all about sixty years old when they contributed DNA for the study. This means that the growth genes of people conceived during the famine maintain their distinct configuration throughout their lifetime. ‘By and large, a person’s genes get set during the first weeks after fertilisation. The operating system that determines which genes are switched on and off gets installed at that point. This operating system, also known as epigenetics, consists of molecular dimmer switches on the DNA. Conditions in the womb, such as too little food or stress undergone by the mother, can lead to permanent changes in the operating system of the unborn child,’ says Heijmans.

Critical stages during pregnancy

What happens in early pregnancy can have consequences for one’s health later in life. ‘Thanks to research on children of the famine, we can point to critical stages in early development that are significant in every pregnancy. As part of a European team we are now studying whether adverse conditions endured by unborn children today lead to modifications to the operating systems comparable to those caused by exposure to the Famine of 1944,’ says Dr Elmar Tobi, who is the lead author of the article.

The article appeared in Nature Communications on 26 November.

(3 December 2014)

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Last Modified: 04-12-2014