17q12 Recurrent Deletions and Duplications: Description of a Case Series with Neuropsychiatric Phenotype

Syndromic neurodevelopmental disorders are usually investigated through genetics technologies, within which array comparative genomic hybridization (Array-CGH) is still considered the first-tier clinical diagnostic test. Among recurrent syndromic imbalances, 17q12 deletions and duplications are characterized by neurodevelopmental disorders associated with visceral developmental disorders, although expressive variability is common. Here we describe a case series of 12 patients with 17q12 chromosomal imbalances, in order to expand the phenotypic characterization of these recurrent syndromes whose diagnosis is often underestimated, especially if only mild traits are present. Gene content and genotype-phenotype correlations have been discussed, with special regard to neuropsychiatric features, whose impact often requires etiologic analysis.

Expanded catalog of microbial genes and metagenome-assembled genomes from the pig gut microbiome

Gut microbiota plays an important role in pig health and production. Still, availability of sequenced genomes and functional information for most pig gut microbes remains limited. Here we perform a landscape survey of the swine gut microbiome, spanning extensive sample sources by deep metagenomic sequencing resulting in an expanded gene catalog named pig integrated gene catalog (PIGC), containing 17,237,052 complete genes clustered at 90% protein identity from 787 gut metagenomes, of which 28% are unknown proteins. Using binning analysis, 6339 metagenome-assembled genomes (MAGs) were obtained, which were clustered to 2673 species-level genome bins (SGBs), among which 86% (2309) SGBs are unknown based on current databases. Using the present gene catalog and MAGs, we identified several strain-level differences between the gut microbiome of wild boars and commercial Duroc pigs. PIGC and MAGs provide expanded resources for swine gut microbiome-related research.

Mutational landscapes of normal breast during age and pregnancy determine cancer risk

ABSTRACTThe accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood1–10. Similarly, the mutational landscape of both epithelial and stromal components of the mammary gland has not been investigated. Both are relevant for breast cancer (BC), as the interplay between age, pregnancy, and cancer risk has not been fully characterized11. We describe whole genome sequencing analysis of epithelial and stromal compartments from the normal breast. We show that, in a similar way to other normal organs, the mutational burden of the mammary nulliparous epithelium significantly increases with age. In a nulliparous status, mutated clones are maintained at a consistently small size throughout the life of the individual; however, at parity, pre-existent clones significantly increase in size with age. Both epithelial and stromal compartments of the healthy breast contain pre-existing known cancer mutations, albeit at low rate, indicative of subsequent positive selection for mutations in tissue-specific driver genes. In line with this, both compartments also present gene enrichment in preferentially mutated cancer pathways. Our results show that mutational landscapes differ between the parous and nulliparous epithelium and suggest an explanation for both differential breast cancer risk and development of pregnancy-associated BC (PABC).

Germline genomic patterns are associated with cancer risk, oncogenic pathways and clinical outcomes

SummaryGermline genetic polymorphism is prevalent and inheritable. So far mutations of a handful of genes have been associated with cancer risks. For example, women who harbor BRCA1/2 germline mutations have a 70% of cumulative breast cancer risk; individuals with congenital germline APC mutations have nearly 100% of cumulative colon cancer by the age of fifty. At present, gene-centered cancer predisposition knowledge explains only a small fraction of the inheritable cancer cases. Here we conducted a systematic analysis of the germline genomes of cancer patients (n=9,712) representing 22 common cancer types along with non-cancer individuals (n=16,670), and showed that seven germline genomic patterns, or significantly repeatedly occurring sequential mutation profiles, could be associated with both carcinogenesis processes and cancer clinical outcomes. One of the genomic patterns was significantly enriched in the germline genomes of patients who smoked than in those of non-smoker patients of 13 common cancer types, suggesting that the germline genomic pattern was likely to confer an elevated carcinogenesis sensitivity to tobacco smoke. Several patterns were also associated with somatic mutations of key oncogenic genes and somatic-mutational signatures which are associated with higher genome instability in tumors. Furthermore, subgroups defined by the germline genomic patterns were significantly associated with distinct oncogenic pathways, tumor histological subtypes and prognosis in 12 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results demonstrated that genetic cancer risk and clinical outcomes could be encoded in germline genomes in the form of not only mutated genes, but also specific germline genomic patterns, which provided a novel perspective for further investigation.

Expression analysis of acdS-gene of Pseudomonas putida B-37 in transgenic plants Nicotiana tabacum

In current work was realized the transfer of recombinant plasmid pBI121acdS, carring P. putida B-37 bacterial acdSgene to the A. tumefaciens AGL0 cells. Transgenic plants of N. tabacum were created by agrobacterial transformation. Integration of P. putida B-37 bacterial acdS-gene to transgenic plants of N. tabacum was verified by PCR analysis, using specific primers to present gene. Presence of target acdS-gene in transgenic plants genome was proved by RT-PCR analysis. With help of Real-time PCR was shown the difference between reference gene and target P. putida B-37 bacterial acdSgene expression. Expression of target gene exceeded reference gene in 1.27 times, those fact proved expression of acdS-gene in plants on high level. Expression of the heterologous gene in N. tabacum plants was also proved by biochemical method of ACC-deaminase specific activity define.

Gene ORGANizer: Linking Genes to the Organs They Affect

One of the biggest challenges in studying how genes work is understanding their effect on the physiology and anatomy of the body. Existing tools try to address this using indirect features, such as expression levels and biochemical pathways. Here, we present Gene ORGANizer (geneorganizer.huji.ac.il), a phenotype-based tool that directly links human genes to the body parts they affect. It is built upon an exhaustive curated database that links more than 7,000 genes to ∼150 anatomical parts using >150,000 gene-organ associations. The tool offers user-friendly platforms to analyze the anatomical effects of individual genes, and identify trends within groups of genes. We demonstrate how Gene ORGANizer can be used to make new discoveries, showing that chromosome X is enriched with genes affecting facial features, that positive selection targets genes with more constrained phenotypic effects, and more. We expect Gene ORGANizer to be useful in a variety of evolutionary, medical and molecular studies aimed at understanding the phenotypic effects of genes.

Quantitative RT-PCR analyses of five evolutionary conserved genes in Alligator brains during development

Gene expression was investigated in the major brain subdivisions (telencephalon, diencephalon, midbrain and hindbrain) in a representative reptile, Alligator mississipiensis, during the later stages of embryonic development. The following genes were examined: voltage-gated sodium channel isoforms: NaV1.1 and NaV1.2; synaptic vesicle 2a (SV2a); synaptophysin; and calbindin 2. With the exception of synaptophysin, which was only expressed in the telencephalon, all genes were expressed in all brain regions sampled at the time periods examined. For NaV1.1, gene expression varied according to brain area sampled. When compared with NaV1.1, the pattern of NaV1.2 gene expression differed appreciably. The gene expression of SV2a was the most robust of any of the genes examined. Of the other genes examined, although differences were noted, no statistically significant changes were found either between brain part or time interval. Although limited, the present analysis is the first quantitative mRNA gene expression study in any reptile during development. Together with future experiments of a similar nature, the present gene expression results should determine which genes are expressed in major brain areas at which times during development in Alligator. When compared with other amniotes, these results will prove useful for determining how gene expression during development influences adult brain structure.

Novel Gene-Transferring System Using a Laminin-DNA-Apatite Composite Layer

A laminin–DNA–apatite composite layer was successfully formed on the surface of an ethylene–vinyl alcohol copolymer. The immobilized DNA was transferred to the cells adhering onto the laminin–DNA–apatite composite layer more efficiently than those adhering onto a lamininfree DNA–apatite composite layer. It is considered that laminin immobilized in the surface layer enhances cell adhesion and spreading, and DNA locally released from the layer is effectively transferred into the adhering cells, taking advantage of the large contact area. The present gene transferring system, which shows high efficiency and safety, would be useful in gene therapy and tissue engineering.

Phenotypic differentiation of exterior traits in local Criollo Goat Population in Patagonia (Argentina)

The Neuquén-Criollo goat is a significant genetic resource, adapted to the singular harsh environment of North Patagonia. Its present gene pool was built up from different breeds since the Spanish colonization being Angora the latest introduced. High phenotypic diversity and their geographical distribution suggest a subdivision of this goat population into four close sub-areas. As phenotypic characterization was carried out on 827 Criollo adult goats. Analyse were based on fourteen quantitative (morphostructural) and eight qualitative (morphological) variables. Correspondence analyses for qualitative and canonical discriminant analysis for quantitative traits were performed, using hair types as classification variable. Results were consistent in differentiating the four considered sub-areas. Neuquen Criollo breed could be characterized in two ecotypes: Short and Long hair goats, a mixed type area and a crossbred area fulfil the types distribution. Principal divergence factors would be isolation, natural and artificial selection, transhumance and exotic breeds introduction.