Överkalix study
Encyclopedia
The Överkalix study 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 and food prices, in Överkalix
, a small isolated municipality
in northeast Sweden
. The study was of 303 probands, 164 men and 139 women, born in 1920 and their 1,818 parents and grandparents born in 1890, 1905. 44 were still alive in 1995 when mortality follow-up stopped. Mortality
risk ratios (RR) on children and grandchildren were determined based on available food supply
, as indicated by historical data.
Among the sex-specific effects noted; a greater body mass index
(BMI) at 9 years in sons, but not daughters, of fathers who began smoking early. The paternal grandfather's food supply was only linked to the mortality RR of grandsons and not granddaughters. The paternal grandmother's food supply was only associated with the granddaughters' mortality risk ratio. When the grandmother had a good food supply is was associated with a twofold higher motalty (RR).
This transgenerational inheritance was observed with exposure during the slow growth period (SGP). The SGP is the time before the start of puberty
, 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
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 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.
Sex-specific effects are due to parental imprinting a process that results in allele-specific differences in transcription, DNA methylation
, and DNA
replication timing
. 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
as homologous DNA
passes through sperm
or egg
; subsequently during embryogenesis
and into adulthood, alleles of imprinted genes are maintained in two "conformational"/epigenetic states: paternal or maternal. 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 1-2%, currently parental imprinting has been identified in fewer than 100 distinct named genes.
Transgenerational epigenetics
Epigenetic inheritance is the transmittance of information from one generation to the next that affects the traits of offspring without alteration of the primary structure of DNA or from environmental cues...
inheritance. The study was conducted utilizing historical records, including harvests and food prices, in Överkalix
Överkalix
Överkalix is a locality and the seat of Överkalix Municipality in Norrbotten County, Sweden with 946 inhabitants in 2005.- Buildings and Structures :* 330 metres tall guyed mast for FM-/TV-broadcasting at 66°18'5" N, 22°51'13" E...
, a small isolated municipality
Municipality
A municipality is essentially an urban administrative division having corporate status and usually powers of self-government. It can also be used to mean the governing body of a municipality. A municipality is a general-purpose administrative subdivision, as opposed to a special-purpose district...
in northeast Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
. The study was of 303 probands, 164 men and 139 women, born in 1920 and their 1,818 parents and grandparents born in 1890, 1905. 44 were still alive in 1995 when mortality follow-up stopped. Mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
risk ratios (RR) on children and grandchildren were determined based on available food supply
Food security
Food security refers to the availability of food and one's access to it. A household is considered food-secure when its occupants do not live in hunger or fear of starvation. According to the World Resources Institute, global per capita food production has been increasing substantially for the past...
, as indicated by historical data.
Among the sex-specific effects noted; a greater body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
(BMI) at 9 years in sons, but not daughters, of fathers who began smoking early. The paternal grandfather's food supply was only linked to the mortality RR of grandsons and not granddaughters. The paternal grandmother's food supply was only associated with the granddaughters' mortality risk ratio. When the grandmother had a good food supply is was associated with a twofold higher motalty (RR).
This transgenerational inheritance was observed with exposure during the slow growth period (SGP). The SGP is the time before the start of puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as 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
Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during pregnancy can have one or more gestations at the same time ....
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 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.
Sex-specific effects are due to parental imprinting a process that results in allele-specific differences in transcription, DNA methylation
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...
, and DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
replication timing
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 , chromosomes consist of very long linear double-stranded DNA molecules...
. 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
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 division of diploid gametocytes into various gametes,...
as homologous DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
passes through sperm
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
or egg
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
; subsequently during embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
and into adulthood, alleles of imprinted genes are maintained in two "conformational"/epigenetic states: paternal or maternal. 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 1-2%, currently parental imprinting has been identified in fewer than 100 distinct named genes.