Testing the imprinted brain: parent-of-origin effects on empathy and systemizing

Genomic imprinting is a violation of Mendel's laws that enables selection to act on genes, depending on parent of origin, but, even more controversially, on the sex of the offspring. This study tested whether there are parent-of-origin effects on the heritability of empathy and systemizing in the general population as part of a larger question concerning the role of imprinted genes in the evolution of human cognition and behaviour. The measures tested were the Empathy and Systemizing Quotients as proxies for the related terms mentalistic and mechanistic cognition in the imprinted brain theory.To test genomic imprinting hypotheses, correlations in behavioural scores between pairs of full, maternal and paternal siblings were compared. Where scores are influenced by imprinted genes, the actual correlations between pairs of siblings will differ from those expected following classical Mendelian inheritance in a predictable way depending on what kind of imprinting is influencing the trait. These theoretical predictions were used to test the fit of the data against Mendelian and imprinting models using structural equation modeling. The imprinted brain theory proposes a trade-off between maternally influenced mentalistic cognition and paternally influenced mechanistic cognition. However, the results of this study support a model of contrasting maternal and paternal influences on strong and weak empathizing and a maternal influence on systemizing. Although the sample size was insufficient to comprehensively analyse sex-limitation models, there is some evidence that heritability of systemizing is stronger in females than in males.     

Disruption of imprinted X inactivation by parent-of-origin effects at Tsix

In marsupials and in extraembryonic tissues of placental mammals, X inactivation is imprinted to occur on the paternal chromosome. Here, we find that imprinting is controlled by the antisense Xist gene, Tsix. Tsix is maternally expressed and mice carrying a Tsix deletion show normal paternal but impaired maternal transmission. Maternal inheritance occurs infrequently, with surviving progeny showing intrauterine growth retardation and reduced fertility. Transmission ratio distortion results from disrupted imprinting and postimplantation loss of mutant embryos. In contrast to effects in embryonic stem cells, deleting Tsix causes ectopic X inactivation in early male embryos and inactivation of both X chromosomes in female embryos, indicating that X chromosome counting cannot override Tsix imprinting. These results highlight differences between imprinted and random X inactivation but show that Tsix regulates both. We propose that an imprinting center lies within Tsix.     

A parent-of-origin effect on honeybee worker ovary size

Apis mellifera capensis is unique among honeybees in that unmated workers can produce pseudo-clonal female offspring via thelytokous parthenogenesis. Workers use this ability to compete among themselves and with their queen to be the mother of new queens. Males could therefore enhance their reproductive success by imprinting genes that enhance fertility in their daughter workers. This possibility sets the scene for intragenomic conflict between queens and drones over worker reproductive traits. Here, we show a strong parent-of-origin effect for ovary size (number of ovarioles) in reciprocal crosses between two honeybee subspecies, A. m. capensis and Apis mellifera scutellata. In this cross, workers with an A. m. capensis father had 30% more ovarioles than genotypically matched workers with an A. m. scutellata father. Other traits we measured (worker weight at emergence and the presence/absence of a spermatheca) are influenced more by rearing conditions than by parent-of-origin effects. Our study is the first to show a strong epigenetic (or, less likely, cytoplasmic maternal) effect for a reproductive trait in the honeybee and suggests that a search for parent-of-origin effects in other social insects may be fruitful.     

The human gene mutation database.

The Human Gene Mutation Database (HGMD) represents a comprehensive core collection of data on published germline mutations in nuclear genes underlying human inherited disease. By September 1997, the database contained nearly 12 000 different lesions in a total of 636 different genes, with new entries currently accumulating at a rate of over 2000 per annum. Although originally established for the scientific study of mutational mechanisms in human genes, HGMD has acquired a much broader utility to researchers, physicians and genetic counsellors so that it was made publicly available at http://uwcm.ac.uk/uwcm/mg/hgmd0.html in April 1996. Mutation data in HGMD are accessible on the basis of every gene being allocated one web page per mutation type, if data of that type are present. Meaningful integration with phenotypic, structural and mapping information has been accomplished through bi-directional links between HGMD and both the Genome Database (GDB) and Online Mendelian Inheritance in Man (OMIM), Baltimore, USA. Hypertext links have also been established to Medline abstracts through Entrez , and to a collection of 458 reference cDNA sequences also used for data checking. Being both comprehensive and fully integrated into the existing bioinformatics structures relevant to human genetics, HGMD has established itself as the central core database of inherited human gene mutations.     

The androgen receptor gene mutations database.

The androgen receptor gene mutations database is a comprehensive listing of mutations published in journals and meetings proceedings. The majority of mutations are point mutations identified in patients with androgen insensitivity syndrome. Information is included regarding the phenotype, the nature and location of the mutations, as well as the effects of the mutations on the androgen binding activity of the receptor. The current version of the database contains 149 entries, of which 114 are unique mutations. The database is available from EMBL (NetServ@EMBL-Heidelberg.DE) or as a Macintosh Filemaker file (mc33001@musica.mcgill.ca).     

The androgen receptor gene mutations database.

The current version of the androgen receptor (AR) gene mutations database is described. We have added (if available) data on the androgen binding phenotype of the mutant AR, the clinical phenotype of the affected persons, the family history and whether the pathogenicity of a mutation has been proven. Exonic mutations are now listed in 5'-->3' sequence regardless of type and single base pair changes are presented in codon context. Splice site and intronic mutations are listed separately. The database has allowed us to substantiate and amplify the observation of mutational hot spots within exons encoding the AR androgen binding domain. The database is available from EML (ftp://www.ebi.ac.uk/pub/databases/androgen) or as a Macintosh Filemaker file (MC33@musica.mcgill.ca).     

The effect of Trp53 gene-dosage and parent-of-origin of inheritance on mouse gamete and embryo function in vitro

The transformation-related protein 53 (TRP53) has a canonical role as the "guardian of the genome," serving to protect against the propagation of cells with genomic damage. Autocrine trophic signals act to block the accumulation of TRP53 in the normal preimplantation embryo. Culture of the early embryo at limiting dilutions in simple defined media limits autocrine signaling, resulting in the accumulation of TRP53. This TRP53 reduces the rate of development of embryos. In this study we show that deletion of the Trp53 gene improved development in vitro in a dose-dependent manner. Development to morphological blastocysts increased as the dose of Trp53 was reduced, and this was accompanied by a Trp53-dependent increase in the allocation of cells to the inner cell mass. The intermediate developmental response of heterozygous mice provides evidence for haploinsufficiency of this trait. This haploinsufficiency was evident irrespective of the parent-of-origin of the null allele; however, zygotes with paternal inheritance of the Trp53-null allele had better development in vitro than those with maternal inheritance. There was a beneficial effect of the Trp53-null allele on the number of oocytes released by Trp53(+/-) females, and heterozygous males produced higher fertilization rates than controls, although this was independent of the genotype of the fertilizing sperm. The study shows that ovulation induction or culture of embryos in limiting conditions creates conditions that favor the early development of embryos inheriting loss of Trp53 function. This occurs even in the heterozygous state, showing that the conditions provide a potential basis for accelerated accumulation of deleterious mutations within a population.     

The imprinted gene DIO3 is a candidate gene for litter size in pigs

Genomic imprinting is an important epigenetic phenomenon, which on the phenotypic level can be detected by the difference between the two heterozygote classes of a gene. Imprinted genes are important in both the development of the placenta and the embryo, and we hypothesized that imprinted genes might be involved in female fertility traits. We therefore performed an association study for imprinted genes related to female fertility traits in two commercial pig populations. For this purpose, 309 SNPs in fifteen evolutionary conserved imprinted regions were genotyped on 689 and 1050 pigs from the two pig populations. A single SNP association study was used to detect additive, dominant and imprinting effects related to four reproduction traits; total number of piglets born, the number of piglets born alive, the total weight of the piglets born and the total weight of the piglets born alive. Several SNPs showed significant (q-value < 0.10) additive and dominant effects and one SNP showed a significant imprinting effect. The SNP with a significant imprinting effect is closely linked to DIO3, a gene involved in thyroid metabolism. The imprinting effect of this SNP explained approximately 1.6% of the phenotypic variance, which corresponded to approximately 15.5% of the additive genetic variance. In the other population, the imprinting effect of this QTL was not significant (q-value > 0.10), but had a similar effect as in the first population. The results of this study indicate a possible association between the imprinted gene DIO3 and female fertility traits in pigs.     

昆虫基因组及数据库研究进展

基因组序列为昆虫分子生物学研究提供丰富的数据资源,推动系统生物学在古老的昆虫学中蓬勃发展。昆虫基因组学研究已经成为当前的研究热点,目前在NCBI登录注册的昆虫基因组测序计划有494项,其中已提交原始测序数据的昆虫有225种,完成基因组拼接的有215种,具有基因注释的有65种,公开发表的昆虫基因组有43篇。本文综述了测序技术发展的历史及其对昆虫基因组研究的推动作用、昆虫基因组的组装和注释及其存在的问题、昆虫基因组测序进展、昆虫基因组数据库的发展及基因数据挖掘利用的基本思路和对策,以及昆虫基因大数据在害虫防治和资源昆虫利用中的应用前景。     

Apple gene function and gene family database: an integrated bioinformatics database for apple research

The apple (Malus domestica) is one of the most economically important fruit crops in the world, due its importance to human nutrition and health. To analyze the function and evolution of different apple genes, we developed apple gene function and gene family database (AppleGFDB) for collecting, storing, arranging, and integrating functional genomics information of the apple. The AppleGFDB provides several layers of information about the apple genes, including nucleotide and protein sequences, chromosomal locations, gene structures, and any publications related to these annotations. To further analyze the functional genomics data of apple genes, the AppleGFDB was designed to enable users to easily retrieve information through a suite of interfaces, including gene ontology, protein domain and InterPro. In addition, the database provides tools for analyzing the expression profiles and microRNAs of the apple. Moreover, all of the analyzed and collected data can be downloaded from the database. The database can also be accessed using a convenient web server that supports a full-text search, a BLAST sequence search, and database browsing. Furthermore, to facilitate cooperation among apple researchers, AppleGFDB is presented in a user-interactive platform, which provides users with the opportunity to modify apple gene annotations and submit publication information for related genes. AppleGFDB is available at http://www.applegene.org or http://gfdb.sdau.edu.cn/.     

The filamentous fungal gene expression database (FFGED)

Filamentous fungal gene expression assays provide essential information for understanding systemic cellular regulation. To aid research on fungal gene expression, we constructed a novel, comprehensive, free database, the filamentous fungal gene expression database (FFGED), available at http://bioinfo.townsend.yale.edu. FFGED features user-friendly management of gene expression data, which are assorted into experimental metadata, experimental design, raw data, normalized details, and analysis results. Data may be submitted in the process of an experiment, and any user can submit multiple experiments, thus classifying the FFGED as an “active experiment” database. Most importantly, FFGED functions as a collective and collaborative platform, by connecting each experiment with similar related experiments made public by other users, maximizing data sharing among different users, and correlating diverse gene expression levels under multiple experimental designs within different experiments. A clear and efficient web interface is provided with enhancement by AJAX (Asynchronous JavaScript and XML) and through a collection of tools to effectively facilitate data submission, sharing, retrieval and visualization.     

A new model for parent-of-origin effect analyses applied to Brown Swiss cattle slaughterhouse data

Genomic imprinting is a phenomenon that arises when the expression of genes depends on the parental origin of alleles. Epigenetic mechanisms may induce the full or partial suppression of maternal or paternal alleles, thereby leading to different types of imprinting. However, imprinting effects have received little consideration in animal breeding programmes, although their relevance to some agricultural important traits has been demonstrated. A recently proposed model (imprinting model) with two path-of-transmission (male and female)-specific breeding values for each animal accounts for all types of imprinting simultaneously (paternal, maternal, full and partial). Imprinting effects (or more generally: parent-of-origin effects (POE)) are determined by taking the difference between the two genetic effects in each animal. However, the computation of their prediction error variance (PEV) is laborious; thus, we propose a new model that is equivalent to the aforementioned imprinting model, which facilitates the direct estimation of imprinting effects instead of taking the differences and the PEV is readily obtained. We applied the new model to slaughterhouse data for Brown Swiss cattle, among which imprinting has never been investigated previously. Data were available for up to 173 051 fattening bulls, where the pedigrees contained up to 428 710 animals representing the entire Brown Swiss population of Austria and Germany. The traits analysed comprised the net BW gain, fat score, EUROP class and killing out percentage. The analysis demonstrated that the net BW gain, fat score and EUROP class were influenced significantly by POE. After estimating the POE, the new model yielded estimates with reliabilities ranging between 0.4 and 0.9. On average, the imprinting variances accounted for 9.6% of the total genetic variance, where the maternal gamete was the main contributor. Moreover, our results agreed well with those obtained using linear models when the EUROP class and fat score were treated as categorical traits by applying a GLMM with a logit link function.     

PHLDA2 is an imprinted gene in cattle

Genomic imprinting is an epigenetic non-Mendelian phenomenon found predominantly in placental mammals. Imprinted genes display differential expression in the offspring depending on whether the gene is maternally or paternally inherited. Currently, some 100 imprinted genes have been reported in mammals, and while some of these genes are imprinted across most mammalian species, others have been shown to be imprinted in only a few species. The PHLDA2 gene that codes for a pleckstrin homology-like domain, family A (member 2), protein has to date been shown to be a maternally expressed imprinted gene in humans, mice and pigs. Genes subject to imprinting can have major effects on mammalian growth, development and disease. For instance, disruption of imprinted genes can lead to aberrant growth syndromes in cloned domestic mammals, and it has been demonstrated that PHLDA2 mRNA expression levels are aberrant in the placenta of somatic clones of cattle. In this study, we demonstrate that PHLDA2 is expressed across a range of cattle foetal tissues and stages and provide the first evidence that PHLDA2 is a monoallelically expressed imprinted gene in cattle foetal tissues, and also in the bovine placenta.     

maternally expressed gene1 Is a novel maize endosperm transfer cell-specific gene with a maternal parent-of-origin pattern of expression

Growth of the maize (Zea mays) endosperm is tightly regulated by maternal zygotic and sporophytic genes, some of which are subject to a parent-of-origin effect. We report here a novel gene, maternally expressed gene1 (meg1), which shows a maternal parent-of-origin expression pattern during early stages of endosperm development but biallelic expression at later stages. Interestingly, a stable reporter fusion containing the meg1 promoter exhibits a similar pattern of expression. meg1 is exclusively expressed in the basal transfer region of the endosperm. Further, we show that the putatively processed MEG1 protein is glycosylated and subsequently localized to the labyrinthine ingrowths of the transfer cell walls. Hence, the discovery of a parent-of-origin gene expressed solely in the basal transfer region opens the door to epigenetic mechanisms operating in the endosperm to regulate certain aspects of nutrient trafficking from the maternal tissue into the developing seed.