VNTR DNA Variation in Siberian Indigenous Populations

This is the published version. Copyright 1995 Wayne State University Press.The VNTR loci D7S104, D11S129, D18S17, D20S15, and D21S112 in three indigenous Siberian populations were analyzed to determine the populations' genetic structure. Using the Kolmogorov- Smirnov test, we found that the Siberian indigenous populations of Surinda and Sulamai are separated at the D1 IS 129 locus (p < 0.05). However, the population of Poligus is genetically homogeneous compared with the villages of Sulamai and Surinda. Principal component plots for the sets of VNTR loci cluster the Siberian groups together, reflecting the homogeneity of these populations. An analysis of mean per locus heterozygosity versus the distance from the centroid of distribution suggests gene flow into Sulamai but little genetic exchange with Surinda and Poligus. Ultimately, the VNTR data reflect the genetic distinctiveness of the Kets and the Evenki

ANALYSIS OF THE RESULTS OF SURGICAL PROCEDURES ADVISABLE FOR CHRONIC PANCREATITIS WITH THE PREDOMINANT LESION OF THE PANCREATIC HEAD

Recently, studies comparing various variants of operations to establish the optimal method of surgical treatment for chronic pancreatitis with pancreatic head lesions from the point of view of evidence-based medicine have been carried out in the world. However, these comparative studies do not take into account differences in the clinical and morphological forms of the disease, in particular, chronic pancreatitis with a predominant and isolated lesion of the head. Subtotal resection of the pancreatic head with proximal pancreatojejunostomy, suitable for an isolated lesion of the head, does not solve all the problems of chronic pancreatitis with a predominant lesion of the head. In this case, the violation of the outflow of pancreatic juice along the pathologically changed main pancreatic duct from the left half of the gland is not eliminated. It is impossible to unambiguously support the hypothesis of the feasibility of performing subtotal resection of the pancreatic head with proximal pancreatojejunostomy in chronic pancreatitis with a predominant lesion of the head with a uniformly expanded main pancreatic duct. With this form of chronic pancreatitis, cicatricial strictures can form in the main pancreatic duct, which can lead to ductal hypertension and serve as an indication for reoperation. The feasibility of using Beger operation in chronic pancreatitis with a predominant lesion of the head is doubtful, since the intersection of the isthmus and the need for a T-shaped longitudinal pancreatojejunostomy makes this intervention technically difficult and unsafe. Based on the studies performed, it is impossible to say with certainty about the reliable advantages of one type of operations over another. To obtain reliable results, it’s necessary to conduct evidence-based studies comparing subtotal resection of the pancreatic head with longitudinal pancreatojejunostomy with other types of interventions only for chronic pancreatitis with a predominant head lesion, excluding from the study patients with chronic pancreatitis with isolated head lesion

Distinct physiological and behavioural functions for parental alleles of imprinted Grb10

Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development1, but also postnatal functions including energy homeostasis2 and behaviour3, 4. When the two parental alleles are unequally represented within a social group (when there is sex bias in dispersal and/or variance in reproductive success)5, 6, imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules7. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue-specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues

Patterns of Hybrid Loss of Imprinting Reveal Tissue- and Cluster-Specific Regulation

Background: Crosses between natural populations of two species of deer mice, Peromyscus maniculatus (BW), and P. polionotus (PO), produce parent-of-origin effects on growth and development. BW females mated to PO males (bw6po) produce growth-retarded but otherwise healthy offspring. In contrast, PO females mated to BW males (PO6BW) produce overgrown and severely defective offspring. The hybrid phenotypes are pronounced in the placenta and include PO6BW conceptuses which lack embryonic structures. Evidence to date links variation in control of genomic imprinting with the hybrid defects, particularly in the PO6BW offspring. Establishment of genomic imprinting is typically mediated by gametic DNA methylation at sites known as gDMRs. However, imprinted gene clusters vary in their regulation by gDMR sequences. Methodology/Principal Findings: Here we further assess imprinted gene expression and DNA methylation at different cluster types in order to discern patterns. These data reveal PO6BW misexpression at the Kcnq1ot1 and Peg3 clusters, both of which lose ICR methylation in placental tissues. In contrast, some embryonic transcripts (Peg10, Kcnq1ot1) reactivated the silenced allele with little or no loss of DNA methylation. Hybrid brains also display different patterns of imprinting perturbations. Several cluster pairs thought to use analogous regulatory mechanisms are differentially affected in the hybrids. Conclusions/Significance: These data reinforce the hypothesis that placental and somatic gene regulation differs significantly, as does that between imprinted gene clusters and between species. That such epigenetic regulatory variatio

Transcriptome-Wide Identification of Novel Imprinted Genes in Neonatal Mouse Brain

Imprinted genes display differential allelic expression in a manner that depends on the sex of the transmitting parent. The degree of imprinting is often tissue-specific and/or developmental stage-specific, and may be altered in some diseases including cancer. Here we applied Illumina/Solexa sequencing of the transcriptomes of reciprocal F1 mouse neonatal brains and identified 26 genes with parent-of-origin dependent differential allelic expression. Allele-specific Pyrosequencing verified 17 of them, including three novel imprinted genes. The known and novel imprinted genes all are found in proximity to previously reported differentially methylated regions (DMRs). Ten genes known to be imprinted in placenta had sufficient expression levels to attain a read depth that provided statistical power to detect imprinting, and yet all were consistent with non-imprinting in our transcript count data for neonatal brain. Three closely linked and reciprocally imprinted gene pairs were also discovered, and their pattern of expression suggests transcriptional interference. Despite the coverage of more than 5000 genes, this scan only identified three novel imprinted refseq genes in neonatal brain, suggesting that this tissue is nearly exhaustively characterized. This approach has the potential to yield an complete catalog of imprinted genes after application to multiple tissues and developmental stages, shedding light on the mechanism, bioinformatic prediction, and evolution of imprinted genes and diseases associated with genomic imprinting

The importance of imprinting in the human placenta.

As a field of study, genomic imprinting has grown rapidly in the last 20 years, with a growing figure of around 100 imprinted genes known in the mouse and approximately 50 in the human. The imprinted expression of genes may be transient and highly tissue-specific, and there are potentially hundreds of other, as yet undiscovered, imprinted transcripts. The placenta is notable amongst mammalian organs for its high and prolific expression of imprinted genes. This review discusses the development of the human placenta and focuses on the function of imprinting in this organ. Imprinting is potentially a mechanism to balance parental resource allocation and it plays an important role in growth. The placenta, as the interface between mother and fetus, is central to prenatal growth control. The expression of genes subject to parental allelic expression bias has, over the years, been shown to be essential for the normal development and physiology of the placenta. In this review we also discuss the significance of genes that lack conservation of imprinting between mice and humans, genes whose imprinted expression is often placental-specific. Finally, we illustrate the importance of imprinting in the postnatal human in terms of several human imprinting disorders, with consideration of the brain as a key organ for imprinted gene expression after birth

Antagonistic roles in fetal development and adult physiology for the oppositely imprinted Grb10 and Dlk1 genes

BACKGROUND: Despite being a fundamental biological problem the control of body size and proportions during development remains poorly understood, although it is accepted that the insulin-like growth factor (IGF) pathway has a central role in growth regulation, probably in all animals. The involvement of imprinted genes has also attracted much attention, not least because two of the earliest discovered were shown to be oppositely imprinted and antagonistic in their regulation of growth. The Igf2 gene encodes a paternally expressed ligand that promotes growth, while maternally expressed Igf2r encodes a cell surface receptor that restricts growth by sequestering Igf2 and targeting it for lysosomal degradation. There are now over 150 imprinted genes known in mammals, but no other clear examples of antagonistic gene pairs have been identified. The delta-like 1 gene (Dlk1) encodes a putative ligand that promotes fetal growth and in adults restricts adipose deposition. Conversely, Grb10 encodes an intracellular signalling adaptor protein that, when expressed from the maternal allele, acts to restrict fetal growth and is permissive for adipose deposition in adulthood. RESULTS: Here, using knockout mice, we present genetic and physiological evidence that these two factors exert their opposite effects on growth and physiology through a common signalling pathway. The major effects are on body size (particularly growth during early life), lean:adipose proportions, glucose regulated metabolism and lipid storage in the liver. A biochemical pathway linking the two cell signalling factors remains to be defined. CONCLUSIONS: We propose that Dlk1 and Grb10 define a mammalian growth axis that is separate from the IGF pathway, yet also features an antagonistic imprinted gene pair. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-014-0099-8) contains supplementary material, which is available to authorized users