Heterochromatin is a higher order assembly that is characterized by a genome-wide distribution, gene-repression, durability and potential to spread. In this light, it is an appealing mechanism to interpret the neurobiology of complex brain disorders such as schizophrenia where downregulation of expression appears to be the norm. H3K9 methylation (H3K9me) can initiate the seeding of a heterochromatin assembly on an inactive or poorly coordinated promoter as a consequence of a decline in transactivators either from disuse or from misuse. H3K9me can extend its influence by spatial spreading through the mechanism of recursively recruiting adapters, such as heterochromatin protein 1 (HP1) homodimers. HP1 itself serves as a platform for other repressive proteins such as DNA methyltransferases. In full color, heterochromatin can occupy genome-wide gene networks, tissue specific ontologies and even rearrange the nuclear architecture. Heterochromatin in the brain is modified by small molecule pharmacology and serves a physiological role in the functioning of dopamine neurons and the construction of memory. From a therapeutic perspective, the durable nature of heterochromatin implies that it may require disassembly before the full genomic-potential of standard pharmacotherapies is achieved, especially in treatment resistant patients.The Pharmacogenomics Journal advance online publication, 17 January 2012; doi:10.1038/tpj.2011.64.

One hundred and ten inpatients (80 males and 30 females) of Agra Mental Hospital with continuous stay of more than two years formed the study population. Majority of them were schizophrenics. Demographic data of these patients, their current social contacts inside and outside hospital, attitude of hospital staff and family members toward them, self care, sexual problems, future plans, social acceptability and their employability have been reported.

Aberrant neocortical DNA methylation has been suggested to be a pathophysiological contributor to psychotic disorders. Recently, a growth arrest and DNA-damage-inducible, beta (GADD45b) protein-coordinated DNA demethylation pathway, utilizing cytidine deaminases and thymidine glycosylases, has been identified in the brain. We measured expression of several members of this pathway in parietal cortical samples from the Stanley Foundation Neuropathology Consortium (SFNC) cohort. We find an increase in GADD45b mRNA and protein in patients with psychosis. In immunohistochemistry experiments using samples from the Harvard Brain Tissue Resource Center, we report an increased number of GADD45b-stained cells in prefrontal cortical layers II, III, and V in psychotic patients. Brain-derived neurotrophic factor IX (BDNF IXabcd) was selected as a readout gene to determine the effects of GADD45b expression and promoter binding. We find that there is less GADD45b binding to the BDNF IXabcd promoter in psychotic subjects. Further, there is reduced BDNF IXabcd mRNA expression, and an increase in 5-methylcytosine and 5-hydroxymethylcytosine at its promoter. On the basis of these results, we conclude that GADD45b may be increased in psychosis compensatory to its inability to access gene promoter regions.

Single strand conformation polymorphism analysis and DNA sequencing was performed in White Leghorn hens to explore the polymorphisms present in the promoter of the prolactin gene. The effects of different genotypes on egg production and quality traits were determined, and expression of the prolactin gene in different genotypes was quantified by real time-PCR. Five genotypes and four alleles at each of two Fragments of the promoter were found, of which the FG genotype in Fragment 1 and the PQ genotype in Fragment 2 were the most predominant genotypes. The genotypes of Fragment 1 had significant effects (P < 0·05) on Haugh unit, albumen weight, albumen percentage and shell percentage at 40 weeks of age; egg weight and yolk index at 52 weeks of age; and egg weight at 64 weeks of age. Prolactin expression in the genotypes of Fragment 1 differed significantly and GH genotyped birds had the highest level of expression. The genotypes of Fragment 2 did not show any significant differences of expression. It was concluded that the prolactin gene promoter was highly polymorphic, and had significant effects on egg quality traits in White Leghorn hens.

Recent evidence suggests that covalent modifications to the genomic platform in the brain, that is DNA and its surrounding histones, provide a stable potentially lifelong mechanism for remembrance. Consequently, the making and unmaking of memories is accessible through pharmacological manipulations of these modifications. This has implications for psychotherapy and long-term rehabilitation of CNS disorders. We hypothesize that by enhancing learning through pharmacologically manipulating 'epigenetic' parameters, the effects of psychotherapies and rehabilitation can be enhanced.

Expression of prolactin hormone is a crucial event in regulating egg production in chickens for which promoter plays the vital role in expressing the prolactin gene. The objective of the present study was to identify haplotypes in the prolactin promoter and their effects on egg production and egg quality traits in White Leghorn chicken. Single stranded conformation polymorphism followed by sequencing was conducted to explore polymorphism at 561 bp promoter of prolactin gene. The effect of haplotype combinations on egg production and quality traits were estimated following general linear model technique. The expression of prolactin by different haplogroups was quantified by qPCR. Total 28 haplotypes were found in White Leghorn chicken of which h1 haplotype possessed the highest frequency of 0.46 and h8, h14, h16, h25, h26, and h28 haplotypes had the lowest frequency (0.1%). The egg production up to 52 and 64 weeks of age were found to be significantly (p < 0.05) associated with haplotype combinations where the highest 52-w (52 weeks) egg production was found in animals with h1/h22 combination and the lowest production was observed in the birds with h1/h2 haplogroup. The haplotype combinations had the significant effect (p < 0.05) on Haugh Unit, yolk index and albumen weight at 40 weeks of age; Haugh Unit and albumen weight at 52 weeks of age and Haugh unit, yolk weight and yolk percentage at 64 weeks of age. The prolactin expression in h1/h22 birds was found to be the lowest and in h1/h5 birds to be the highest. The prolactin expression showed significant effect on 52-w egg production and albumin weight at 52 weeks age. In conclusion, it may be stated that the prolactin promoter was highly polymorphic and had the significant association with egg production and quality traits in White Leghorn chicken.

The juvenile growth and carcass traits were evaluated in a 4 × 4 full diallel crossing involving four colored broiler chicken lines viz., Naked neck (NN), Dwarf, Punjab Broiler-1 (PB-1), and Punjab Broiler-2 to study the performance and crossbreeding parameters. The data on 2,280 chicks were analyzed using least squares techniques to assess the effect of genetic group, and the significant traits were further analyzed for crossbreeding parameters. Genetic group had significant influence on the body weights and carcass traits. The cross of PB-1 × NN recorded significantly (p ≤ 0.05) higher body weight at 6 weeks of age. The data revealed that general combining ability (GCA), specific combining ability (SCA), maternal ability (MA), sex-linked effect (SE), and purebred effects significantly influenced the growth and carcass traits in the broiler crosses. The crossbred PB-1 × NN showed positive heterosis for growth as well as carcass traits. The results suggest that GCA, SCA, SE, and MA are important in the inheritance of the body weights and carcass traits indicating the presence of both additive and nonadditive genetic variation along with reciprocal effects. Therefore, pure line selection along with development of specialized sire and dam lines followed by crossing will improve the growth performance and benefit the poultry farmers. It is concluded that PB-1 as a male line and NN as a female line performed significantly higher, therefore, may be used for improving the performance of colored broilers.

The study of CpG methylation of genomic DNA in neurons has emerged from the shadow of cancer biology into a fundamental investigation of neuronal physiology. This advance began with the discovery that catalytic and receptor proteins related to the insertion and recognition of this chemical mark are robustly expressed in neurons. At the smallest scale of analysis is the methylation of a single cytosine base within a regulatory cognate sequence. This singular alteration in a nucleotide can profoundly modify transcription factor binding with a consequent effect on the primary 'transcript'. At the single promoter level, the methylation-demethylation of CpG islands and associated alterations in local chromatin assemblies creates a type of cellular 'memory' capable of long-term regulation of transcription particularly in stages of brain development, differentiation, and maturation. Finally, at the genome-wide scale, methylation studies from post-mortem brains suggest that CpG methylation may serve to cap the genome into active and inactive territories introducing a 'masking' function. This may facilitate rapid DNA-protein interactions by ambient transcriptional proteins onto actively networked gene promoters. Beyond this broad portrayal, there are vast gaps in our understanding of the pathway between neuronal activity and CpG methylation. These include the regulation in post-mitotic neurons of the executor proteins, such as the DNA methyltransferases, the elusive and putative demethylases, and the interactions with histone modifying enzymes.

Variability of microsatellites and a possible relationship with growth, egg production, and immunocompetence traits were estimated for six crossbred chicken populations of White Leghorn. Nine microsatellite markers were explored; an association study used the least square maximum-likelihood method on 170 birds of six genetic groups. Seven microsatellites were polymorphic, with two to four alleles. The polymorphism information content (PIC) of five markers was more than 52%. Microsatellites MCW0041, ADL0210, and MCW0110 were significantly (P < 0.05) associated with egg production traits. Genotype 33 of MCW0041 had the highest egg production, up to 64 and 72 weeks of age. Genotypes 11 and 13 of this marker produced the lowest number of eggs. The heterozygous genotype 34 of ADL0210 had the highest egg production, up to 52, 64, and 72 weeks of age. Homozygote 11 of MCW0110 produced the highest number of eggs, up to 28 weeks of age. MCW0041 was significantly (P < 0.05) associated with body weight at 28 and 40 weeks of age. No microsatellite was significantly associated with egg weight at any age, with age at sexual maturity, or with immune response to sheep RBC.