The Överkalix study ( sv, Överkalixstudien) was a study conducted on the physiological effects of various environmental factors on transgenerational epigenetic inheritance. The study was conducted utilizing historical records, including

harvests Harvesting is the process of gathering a ripe crop from the fields. Reaping is the cutting of grain or pulse for harvest, typically using a scythe, sickle, or reaper. On smaller farms with minimal mechanization, harvesting is the most labor-i ...

and

food prices Food prices refer to the average price level for food across countries, regions and on a global scale. Food prices have an impact on producers and consumers of food. Price levels depend on the food production process, including food marketing an ...

, in

Överkalix Överkalix (; fi, Ylikainuu) is a locality and the seat of Överkalix Municipality in Norrbotten County, Sweden with 975 inhabitants in 2010. Climate Överkalix has a subarctic climate with significant temperature differences between the warm sho ...

, a small isolated

municipality A municipality is usually a single administrative division having corporate status and powers of self-government or jurisdiction as granted by national and regional laws to which it is subordinate. The term ''municipality'' may also mean the go ...

in northeast

Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...

. The study was of 303

probands In medical genetics and other medical fields, a proband, proposito (male proband), or proposita (female proband)Bennett, RL. The Language of the Pedigree. In: ''The Practical Guide to the Genetic Family History''. Wiley-Liss. is a particular subjec ...

, 164 men and 139 women, born in 1890, 1905, or 1920, and their 1,818 children and grandchildren. 44 were still alive in 1995 when mortality follow-up stopped.

Mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...

risk ratios (RR) on children and grandchildren were determined based on available

food supply Food security speaks to the availability of food in a country (or geography) and the ability of individuals within that country (geography) to access, afford, and source adequate foodstuffs. According to the United Nations' Committee on World ...

, as indicated by historical data. Among the sex-specific effects noted; a greater

body mass index Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...

(BMI) at 9 years in sons, but not daughters, of fathers who began smoking early. The paternal grandfather's severe change in food supply was only linked to the cardiovascular mortality RR of grandsons and not granddaughters. The paternal grandmother's food supply was only associated with the granddaughters' cardiovascular mortality risk ratio. The grandmother having a severe change in food supply (especially from good to poor) was associated with a twofold higher cardiovascular mortality (RR). This transgenerational inheritance was observed with exposure during the

slow growth period In everyday use and in kinematics, the speed (commonly referred to as ''v'') of an object is the magnitude of the change of its position over time or the magnitude of the change of its position per unit of time; it is thus a scalar quantit ...

(SGP). The SGP is the time before the start of

puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...

, when environmental factors have a larger impact on the body. The ancestors' SGP in this study, was set between the ages of 9-12 for boys and 8–10 years for girls. This occurred in the SGP of both grandparents, or during the

gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...

period/infant life of the grandmothers, but not during either grandparent's puberty. The father's poor food supply and the mother's good food supply were associated with a lower risk of

cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

death. Only the female probands experienced a twofold higher mortality RR when the paternal grandmother had good food availability during her SGP, compared to the mortality risk of those whose paternal grandmothers had poor food supply during the SGP. Using the same data, another investigation highlighted that a sharp change in food availability in paternal grandmothers' resulted in an increased risk of cardiovascular mortality in granddaughters adults' life. Such an effect was not observed in other grandparents. The grandparents were considered exposed if they experienced drastic change in their early life ranging from embryo to 13 years old. Sex-specific effects can be due to parental imprinting, a process that results in allele-specific differences in transcription,

DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...

, and DNA

replication timing Replication timing refers to the order in which segments of DNA along the length of a chromosome are duplicated. DNA replication In eukaryotic cells (cells that package their DNA within a nucleus), chromosomes consist of very long linear doubl ...

. Imprinting is an important process in human development, and its deregulation can cause certain defined disease states of other imprinted human disease loci. The establishment of parental imprints occurs during

gametogenesis Gametogenesis is a biological process by which diploid or haploid precursor cells undergo cell division and differentiation to form mature haploid gametes. Depending on the biological life cycle of the organism, gametogenesis occurs by meiotic d ...

as homologous DNA passes through

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...

egg An egg is an organic vessel grown by an animal to carry a possibly fertilized egg cell (a zygote) and to incubate from it an embryo within the egg until the embryo has become an animal fetus that can survive on its own, at which point the a ...

; subsequently during

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

and into adulthood,

alleles An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

of imprinted genes are maintained in two "conformational"/epigenetic states:

paternal A father is the male parent of a child. Besides the paternal bonds of a father to his children, the father may have a parental, legal, and social relationship with the child that carries with it certain rights and obligations. An adoptive fathe ...

maternal ] A mother is the female parent of a child. A woman may be considered a mother by virtue of having given birth, by raising a child who may or may not be her biological offspring, or by supplying her ovum for fertilisation in the case of gestat ...

. Thus, genomic imprints template their own replication, are heritable, can be identified by molecular analysis, and serve as markers of the parental origin of genomic regions. The estimation of percentage of human genes subject to parental imprinting is approximately one to two percent, currently parental imprinting has been identified in fewer than 100 distinct named genes.

References

{{DEFAULTSORT:Overkalix Study Genetics studies Environmental research

See also

References