Parent-of-origin effects in the life-course evolution of cardio-metabolic traits

Objective: Human traits are heritable, and some of these including metabolic and lipid phenotypes show preferential parental transmissions, or parent-of-origin effects. These have been mostly studied in populations comprising adults. We aimed to investigate heritability and parent-of-origin effects on cardiometabolic and anthropometric traits in a birth-cohort with serial measurements to assess if these effects manifested at an early age. Research design and methods: We investigated heritability and parent-of-origin effects on cardiometabolic and anthropometric traits in the Pune Maternal Nutrition Study (PMNS) wherein offspring and parents were studied from birth and followed-up for 18 years. Heritability was estimated by calculating association between mid-parental phenotypes and offspring. Maternal and paternal effects on offspring phenotype were modelled by regression after adjusting for age, sex and BMI. Parent-of-origin effects were calculated by the difference between maternal and paternal effects. Results: Anthropomorphic traits and cardiometabolic traits were robustly heritable. Parent-of-origin effects were observed for glycemic traits at both 6- and 12-years, with a paternal effect at 6-years which transitioned to a maternal effect at 12-years. For insulin and HOMA-S, a negative maternal effect transitioned to a positive one at 12-years. For HOMA-B, a paternal effect at 6- years transitioned to a maternal one at 12-years. Lipid traits consistently showed stronger maternal influence while anthropometric traits did not show any parental biases. Conclusions: Our study highlights that parental programming of cardiometabolic traits is evident from early childhood and can transition during puberty. Further studies are needed to determine the mechanisms of underlying such effects.

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Searching for parent-of-origin effects on cardiometabolic traits in imprinted genomic regions

European Journal of Human Genetics ◽

10.1038/s41431-019-0568-1 ◽

2020 ◽

Vol 28 (5) ◽

pp. 646-655

Author(s):

Einat Granot-Hershkovitz ◽

Peitao Wu ◽

David Karasik ◽

Inga Peter ◽

Gina M. Peloso ◽

...

Keyword(s):

Parent Of Origin ◽

Origin Effects ◽

Genomic Regions ◽

Cardiometabolic Traits

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Artificial and Epigenetic Regulation of the I Factor, a Nonviral Retrotransposon of Drosophila melanogaster

Genetics ◽

10.1093/genetics/156.4.1867 ◽

2000 ◽

Vol 156 (4) ◽

pp. 1867-1878 ◽

Cited By ~ 1

Author(s):

Emmanuel Gauthier ◽

Christophe Tatout ◽

Hubert Pinon

Keyword(s):

Drosophila Melanogaster ◽

Maternal Effect ◽

Copy Number ◽

Hybrid Dysgenesis ◽

Female Sterility ◽

Paternal Effects ◽

Transgene Copy Number ◽

Paternal Effect ◽

Two Generations ◽

I Factor

Abstract The I factor (IF) is a LINE-like transposable element from Drosophila melanogaster. IF is silenced in most strains, but under special circumstances its transposition can be induced and correlates with the appearance of a syndrome of female sterility called hybrid dysgenesis. To elucidate the relationship between IF expression and female sterility, different transgenic antisense and/or sense RNAs homologous to the IF ORF1 have been expressed. Increasing the transgene copy number decreases both the expression of an IF-lacZ fusion and the intensity of the female sterile phenotype, demonstrating that IF expression is correlated with sterility. Some transgenes, however, exert their repressive abilities not only through a copy number-dependent zygotic effect, but also through additional maternal and paternal effects that may be induced at the DNA and/or RNA level. Properties of the maternal effect have been detailed: (1) it represses hybrid dysgenesis more efficiently than does the paternal effect; (2) its efficacy increases with both the transgene copy number and the aging of sterile females; (3) it accumulates slowly over generations after the transgene has been established; and (4) it is maintained for at least two generations after transgene removal. Conversely, the paternal effect increases only with female aging. The last two properties of the maternal effect and the genuine existence of a paternal effect argue for the occurrence, in the IF regulation pathway, of a cellular memory transmitted through mitosis, as well as through male and female meiosis, and akin to epigenetic phenomena.

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Analysis of parent of origin effects in Sorbs using long range phasing algorithms

Diabetologie und Stoffwechsel ◽

10.1055/s-0034-1375033 ◽

2014 ◽

Vol 9 (S 01) ◽

Author(s):

X Liu ◽

M Scholz ◽

A Tönjes ◽

M Stumvoll ◽

PF Stadler ◽

...

Keyword(s):

Long Range ◽

Parent Of Origin ◽

Origin Effects

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Parent-of-origin effects on voluntary exercise levels and body composition in mice

Physiological Genomics ◽

10.1152/physiolgenomics.00139.2009 ◽

2010 ◽

Vol 40 (2) ◽

pp. 111-120 ◽

Cited By ~ 17

Author(s):

Scott A. Kelly ◽

Derrick L. Nehrenberg ◽

Kunjie Hua ◽

Ryan R. Gordon ◽

Theodore Garland ◽

...

Keyword(s):

Body Composition ◽

Body Fat ◽

Wheel Running ◽

Voluntary Exercise ◽

Phenotypic Variance ◽

In Utero Environment ◽

Dependent Activity ◽

Health Related ◽

Parent Of Origin ◽

Origin Effects

Despite the health-related benefits of exercise, many people do not engage in enough activity to realize the rewards, and little is known regarding the genetic or environmental components that account for this individual variation. We created and phenotyped a large G4 advanced intercross line originating from reciprocal crosses between mice with genetic propensity for increased voluntary exercise (HR line) and the inbred strain C57BL/6J. G4 females (compared to males) ran significantly more when provided access to a running wheel and were smaller with a greater percentage of body fat pre- and postwheel access. Change in body composition resulting from a 6-day exposure to wheels varied between the sexes with females generally regulating energy balance more precisely in the presence of exercise. We observed parent-of-origin effects on most voluntary wheel running and body composition traits, which accounted for 3–13% of the total phenotypic variance pooled across sexes. G4 individuals descended from progenitor (F0) crosses of HR♀ and C57BL/6J♂ ran greater distances, spent more time running, ran at higher maximum speeds/day, and had lower percent body fat and higher percent lean mass than mice descended from reciprocal progenitor crosses (C57BL/6J♀ × HR♂). For some traits, significant interactions between parent of origin and sex were observed. We discuss these results in the context of sex dependent activity and weight loss patterns, the contribution of parent-of-origin effects to predisposition for voluntary exercise, and the genetic (i.e., X-linked or mtDNA variations), epigenetic (i.e., genomic imprinting), and environmental (i.e., in utero environment or maternal care) phenomena potentially modulating these effects.

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