Size at birth, postnatal weight gain, and adult risk for type 2 diabetes may reflect environmental exposures during developmental plasticity and may be mediated by epigenetics. Both low birth weight ...(BW), as a marker of fetal growth restraint, and high birth weight (BW), especially after gestational diabetes mellitus (GDM), have been linked to increased risk of adult type 2 diabetes. We assessed DNA methylation patterns using a bead chip in cord blood samples from infants of mothers with GDM (group 1) and infants with prenatal growth restraint indicated by rapid postnatal catch‐up growth (group 2), compared with infants with normal postnatal growth (group 3). Seventy‐five CpG loci were differentially methylated in groups 1 and 2 compared with the controls (group 3), representing 72 genes, many relevant to growth and diabetes. In replication studies using similar methodology, many of these differentially methylated regions were associated with levels of maternal glucose exposure below that defined by GDM the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study or were identified as changes observed after randomized periconceptional nutritional supplementation in a Gambian cohort characterized by maternal deprivation. These studies provide support for the concept that similar epigenetic modifications may underpin different prenatal exposures and potentially increase long‐term risk for diseases such as type 2 diabetes.—Quilter, C. R., Cooper, W. N., Cliffe, K. M., Skinner, B. M., Prentice, P. M., Nelson, L., Bauer, J., Ong, K. K., Constância, M., Lowe, W. L., Affara, N. A., Dunger, D. B., Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk. FASEB J. 28, 4868–4879 (2014). www.fasebj.org
Low birthweight and reduced height gain during infancy (stunting) may arise at least in part from adverse early life environments that trigger epigenetic reprogramming that may favor survival. We ...examined differential DNA methylation patterns using targeted methyl sequencing of regions regulating gene activity in groups of rural Gambian infants: (a) low and high birthweight (DNA from cord blood (n = 16 and n = 20, respectively), from placental trophoblast tissue (n = 21 and n = 20, respectively), and DNA from peripheral blood collected from infants at 12 months of age (n = 23 and n = 17, respectively)), and, (b) the top 10% showing rapid postnatal length gain (high, n = 20) and the bottom 10% showing slow postnatal length gain (low, n = 20) based on z score change between birth and 12 months of age (LAZ) (DNA from peripheral blood collected from infants at 12 months of age). Using BiSeq analysis to identify significant methylation marks, for birthweight, four differentially methylated regions (DMRs) were identified in trophoblast DNA, compared to 68 DMRs in cord blood DNA, and 54 DMRs in 12‐month peripheral blood DNA. Twenty‐five DMRs were observed to be associated with high and low length for age (LAZ) at 12 months. With the exception of five loci (associated with two different genes), there was no overlap between these groups of methylation marks. Of the 194 CpG methylation marks contained within DMRs, 106 were located to defined gene regulatory elements (promoters, CTCF‐binding sites, transcription factor‐binding sites, and enhancers), 58 to gene bodies (introns or exons), and 30 to intergenic DNA. Distinct methylation patterns associated with birthweight between comparison groups were observed in DNA collected at birth (at the end of intrauterine growth window) compared to those established by 12 months (near the infancy/childhood growth transition). The longitudinal differences in methylation patterns may arise from methylation adjustments, changes in cellular composition of blood or both that continue during the critical postnatal growth period, and in response to early nutritional and infectious environmental exposures with impacts on growth and longer‐term health outcomes.
The serotonin pathways have been implicated in behavioural phenotypes in a number of species, including human, rat, mouse, dog and chicken. Components of the pathways, including the receptors, are ...major targets for drugs used to treat a variety of physiological and psychiatric conditions in humans. In our previous studies we have identified genetic loci potentially contributing to maternal infanticide in pigs, which includes a locus on the porcine X chromosome long arm. The serotonin receptor HTR2C maps to this region, and is therefore an attractive candidate for further study based on its function and its position in the genome.
In this paper we describe the structure of the major transcripts produced from the porcine HTR2C locus using cDNA prepared from porcine hypothalamic and pooled total brain samples. We have confirmed conservation of sites altered by RNA editing in other mammalian species, and identified polymorphisms in the gene sequence. Finally, we have analysed expression and editing of HTR2C in hypothalamus samples from infanticidal and control animals.
The results confirm that although the expression of the long transcriptional variant of HTR2C is raised in infanticidal animals, the overall patterns of editing in the hypothalamus are similar between the two states.Sequences associated with the cDNA and genomic structures of HTR2C reported in this paper are deposited in GenBank under accession numbers FR720593, FR720594 and FR744452.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The serotonin pathways have been implicated in behavioural phenotypes in a number of species, including human, rat, mouse, dog and chicken. Components of the pathways, including ...the receptors, are major targets for drugs used to treat a variety of physiological and psychiatric conditions in humans. In our previous studies we have identified genetic loci potentially contributing to maternal infanticide in pigs, which includes a locus on the porcine X chromosome long arm. The serotonin receptor
HTR2C
maps to this region, and is therefore an attractive candidate for further study based on its function and its position in the genome.
Results
In this paper we describe the structure of the major transcripts produced from the porcine
HTR2C
locus using cDNA prepared from porcine hypothalamic and pooled total brain samples. We have confirmed conservation of sites altered by RNA editing in other mammalian species, and identified polymorphisms in the gene sequence. Finally, we have analysed expression and editing of
HTR2C
in hypothalamus samples from infanticidal and control animals.
Conclusions
The results confirm that although the expression of the long transcriptional variant of
HTR2C
is raised in infanticidal animals, the overall patterns of editing in the hypothalamus are similar between the two states.
Sequences associated with the cDNA and genomic structures of
HTR2C
reported in this paper are deposited in GenBank under accession numbers FR720593, FR720594 and FR744452.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A combination of FISH and RH mapping was used to study the evolution of sex chromosome genes in the pig. In total, 19 genes were identified, including 3 PAR genes (STS, KAL, PRK). The gene order of ...the porcine X Chromosome (Chr) closely resembled the human X Chr (PRK/STS/KAL-AMELX-EIF2s3X/ZFX-USP9X-DBX-SMCX), suggesting that the porcine X has undergone very little rearrangement during evolution. For the porcine Y Chr, two linkage groups of 10 NRY genes were found, and the following order was established: Ypter-(AMELY-EIF2S3Y/ZFY-USP9Y-DBY/UTY)-(TSPY-SMCY-UBE1Y-SRY)-CEN. This gene order showed greater conservation with the murine Y than with the human Y Chr. In addition, all porcine Y Chr genes mapped to Yp, which is similar to the mouse and included EIF2s3Y and UBE1Y, which are not present in humans. Interestingly, complete conservation of X/Y homologous gene order was found between the pig X and Y Chrs, indicating that the porcine Y Chr has not undergone extensive reorganisation with respect to the X. This suggests that the order of the X/Y homologous genes of the porcine X and Y Chrs may closely resemble the ancestral gene order of the eutherian sex chromosomes.
To assess whether to perform routine cytogenetic and Y chromosome microdeletion screening on all infertile male patients.
A cytogenetic and Y microdeletion study of a random group of infertile men.
...University department.
In total, 40 patients had azoospermia (21 nonidiopathic), 27 had severe oligozoospermia/oligoasthenozoospermia (≤5 × 106/mL) (5 nonidiopathic), 20 had oligozoospermia/oligoasthenozoospermia (5–20 × 106/mL) (6 nonidiopathic), and 16 had asthenozoospermia (5 nonidiopathic). Many were candidates for intracytoplasmic sperm injection (ICSI).
Collection of blood samples from all patients and buccal cells from one patient.
Karyotype analysis, polymerase chain reaction (PCR) screening for Y chromosome microdeletions, and fluorescence in situ hybridization of abnormal chromosomes.
Ten (9.7%) subjects, including one nonidiopathic patient, were found to have an abnormal karyotype. Two idiopathic azoospermic patients were missing large portions of Y chromosome euchromatin, confirmed by PCR analysis and an additional idiopathic azoospermic patient had a Y chromosome microdeletion.
Routine cytogenetic analysis of all infertile male patients is required but it may be advisable to limit routine Y chromosome microdeletion screening to patients with severe male factor infertility (≤5 × 106/mL).
: A combination of FISH and RH mapping was used to study the evolution of sex chromosome genes in the pig. In total, 19 genes were identified, including 3 PAR genes (STS, KAL, PRK). The gene order of ...the porcine X Chromosome (Chr) closely resembled the human X Chr (PRK/STS/KAL–AMELX–EIF2s3X/ZFX–USP9X–DBX–SMCX), suggesting that the porcine X has undergone very little rearrangement during evolution. For the porcine Y Chr, two linkage groups of 10 NRY genes were found, and the following order was established: Ypter–(AMELY–EIF2S3Y/ZFY–USP9Y–DBY/UTY)–(TSPY–SMCY–UBE1Y–SRY)–CEN. This gene order showed greater conservation with the murine Y than with the human Y Chr. In addition, all porcine Y Chr genes mapped to Yp, which is similar to the mouse and included EIF2s3Y and UBE1Y, which are not present in humans. Interestingly, complete conservation of X/Y homologous gene order was found between the pig X and Y Chrs, indicating that the porcine Y Chr has not undergone extensive reorganisation with respect to the X. This suggests that the order of the X/Y homologous genes of the porcine X and Y Chrs may closely resemble the ancestral gene order of the eutherian sex chromosomes.
Summary
Sex chromosome abnormalities are common in mammals and humans and are often associated with subfertility. In this study a boar with normal sperm parameters was indicated to have reduced ...prolificacy from figures obtained for return rate, farrowing rate and total number of piglets born. G‐banded cytogenetic analysis of peripheral blood identified an abnormal mosaic sex chromosome constitution 39,XYY74/38,XY23/37,X3. Cytogenetic analysis of fibroblasts confirmed this mosaic karyotype with similar percentages of cell lines observed 39,XYY76/38,XY19/37,X5. External genitalia revealed a poorly developed scrotum with the right testicle being smaller than the left. To the best of our knowledge this is the first time that this chromosome constitution has been reported in the pig. It is of particular interest that this karyotype is associated with reduced boar fertility, which could lead to potential economic losses if such a boar were selected for breeding purposes.
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