Predictive use of cpg methylation

A methylation and gene technology, applied in the field of epigenetic markers, can solve problems such as poor adaptability

Inactive Publication Date: 2012-05-02
UNIV OF SOUTHAMPTON +2
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, if nutrient-rich, their offspring are less able to adapt to the rich nutrient supply and may eventually also cause disease (Gluckmann and Hansen (2004), Science, 305, 1733-1736; Gluckman et al. (2008) N. Engl. J. Med, 2008, 359, 61-73)

Method used

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  • Predictive use of cpg methylation
  • Predictive use of cpg methylation
  • Predictive use of cpg methylation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1a

[0103] Childhood fat mass, percent fat mass, body fat distribution, and body mass index in 9-year-old children

[0104] A study of 19 of 37 CpGs / CpG clusters found that the degree of methylation was consistent with total fat mass and / or fractional body fat mass and / or body fat distribution and / or body mass index in 9-year-old children (see Table 1 ). Umbilical cord methylation of retinoic acid X receptor-α (RXRA) chr9: 136355885+ and endothelial nitric oxide synthase (eNOS) chr7: 150315553+ and fat mass in children ( Figure 1a ), percentage of fat mass ( Figure 1b ), trunk / extremity fat ratio ( Figure 1c ), body mass index (respectively r p=0.39, P=0.001 and r p =0.26, P=0.037) all showed a strong positive correlation. The distribution of umbilical cord CpG methylation has a greater impact on obesity, for example, in the lowest quartile RXRA chr9: 136355885+, the sex-adjusted mean fat mass, percent fat mass and trunk / limb fat ratio were 4.8 kg , 17.3% and 0.617, in the...

Embodiment 1b

[0109] Methylation status of specific CpGs associated with obesity in 6- and 9-year-old children

[0110] In an extension of the study reported in Example 1a above, umbilical cord DNA from healthy infants was used to study the 5' methylation status of specific CpGs using dual-energy X-ray absorptiometry (DXA) compared to maternal diet during pregnancy. and later childhood obesity. Selected genes were retinoic acid X receptor-alpha (RXRA), endothelial nitric oxide synthase (eNOS), superoxide dismutase-1 (SOD1), interleukin-8 (IL8), and phosphoinositide -3-kinase, catalytic delta polypeptide (PI3KCD).

[0111] Methylation was measured by the Sequenom MassARRAY system, which varied widely at specific CpG sites. In conclusion, data from a DXA study of 68 CpGs of 9-year-old children showed that 31 had a median methylation of ≥5%, and a range of 5–95% of ≥10%. Methylation of RXRA chr9: 136355885+ and eNOS chr7: 150315553+ was associated with fat mass in children regardless of sex...

Embodiment 2

[0137] Lean body mass, bone mineral content and height in 9-year-old children

[0138] For 20 of the 37 CpGs / CPG clusters, there was evidence that the degree of methylation was associated with total lean body mass and / or lean mass fraction and / or bone mineral content and / or height in children (see Table 4 ). Figure 2a showed a positive association of umbilical cord eNOS chr7: 150315553+ methylation and childhood lean body mass, and a negative association of SOD1 chr21: 31853837+ methylation with childhood lean body mass, adjusted for sex. Figure 2b It showed that eNOS chr7: 150315553+ methylation was positively correlated with bone mass, and SOD1 chr21: 31853837+ methylation was negatively correlated with bone mass, sex adjusted. Similarly, children's height (sex-adjusted) was positively correlated with eNOS chr7:150315553+ methylation and negatively correlated with SOD1 chr21:31853837+ methylation (r p =0.23, P=0.062 and r p=-0.29, P=0.019). Differences in umbilical cor...

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Abstract

Determination of the methylation status of individual selected Cp / G dinucleotides / CpG groups 5' to the coding region of selected genes, preferably in a perinatal tissue sample such as umbilical cord, can be used to predict future development of diverse phenotypic characteristics, such as indices of body composition indicative of, for example, obesity or low bone mineral content, indices of impaired cardiovascular structure or function, ability to learn and cognitive function, neurobehavourial problems and allergic disorders such as atopic eczema.

Description

technical field [0001] The present invention relates to the use of epigenetic markers, more particularly to the use of methylation of one or more selected individual CpGs or CpG clusters at the 5' end of a specific gene to the coding region, especially in the Perinatal tissues, such as the umbilical cord, serve as a means of predicting diverse phenotypic characteristics of individuals later in life. More specifically, methylation of this CpG / CpG cluster in umbilical cord samples from newborns has been found to be associated with various phenotypic features in infancy and later prepubertal childhood, including: Neurodermatitis, cognitive and neurobehavioral features and important phenotypic indicators associated with disease development, such as obesity / adiposity indicators (including total body fat or percentage body fat body fat), and indicators of cardiovascular structure and function, including left ventricular mass, carotid artery intima-media thickness, systolic and dias...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q2523/125C12Q2600/154C12Q1/6883
Inventor K·M·戈弗雷M·A·汉森G·C·伯奇K·A·利利克罗普J·L·斯莱特-杰弗里斯C·库珀P·D·格拉克曼A·M·谢泼德
Owner UNIV OF SOUTHAMPTON
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