| 1. |
- Anney, Richard, et al.
(författare)
-
A genome-wide scan for common alleles affecting risk for autism.
- 2010
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
-
Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
|
|
| 2. |
- Mahawar, Lovely, et al.
(författare)
-
GABA as a signalling molecule: Possible mechanism for its enhanced commercial production by cyanobacteria
- 2022
-
Ingår i: Journal of Applied Phycology. - : Springer. - 0921-8971 .- 1573-5176. ; 34, s. 2355-2369
-
Forskningsöversikt (refereegranskat)abstract
- γ-aminobutyric acid (GABA) is a ubiquitous non-protein amino acid widely distributed in prokaryotes and eukaryotes. Recently, it is gaining momentum to treat several human diseases. It is synthesized from glutamate, by glutamate decarboxylase a key enzyme in GABA shunt pathway and has been considered as one of the important bioactive compounds produced in response to several environmental stresses. GABA works as a signalling molecule that plays crucial role in biological organisms under adverse conditions. So far, the metabolism of GABA is extensively studied in plants and other eukaryotes, although in cyanobacteria GABA is less studied than in other prokaryotes. Hence the present review highlights the metabolic pathways of GABA production in cyanobacteria particularly the possible ways (via modifying the exogenous growth conditions and regulating gene expression) to enhance the endogenous GABA pool and its extraction in cost effective way to meet the rising demand due to its diverse physiological functions on human health. Alternatively, we discuss the effects of various environmental stresses in augmenting intracellular production in algal cells. Besides this, the review also emphasizes on different commercial applications of this compound in various industrial sectors such as pharmaceutical industry, food, beverages and dairy industry, bioplastics and biofuel production.
|
|
| 3. |
- Mahawar, Lovely, et al.
(författare)
-
Iron deficiency in plants : an update on homeostasis and its regulation by nitric oxide and phytohormones
- 2023
-
Ingår i: Plant growth regulation (Print). - : Springer. - 0167-6903 .- 1573-5087. ; 100, s. 283-299
-
Forskningsöversikt (refereegranskat)abstract
- Iron is an essential micronutrient for plants as it involves in several important physiological processes. Understanding iron homeostasis in plants is pivotal, not only for improving their growth and development but also for enhancing human nutrition as plants are the principal dietary source of iron. This calls for the need to enrich bioavailable iron in crops to resolve iron starvation issue especially in low income and rural populations who have limited access to food markets and proper health facilities. The uptake of iron from rhizosphere, its transporters and transcription factors that regulate iron acquisition are well characterized. Here, the present review emphasizes on the role of signalling molecules particularly phytohormones and nitric oxide and their interactive co-ordination in iron homeostasis in agriculturally important crops that grow at pH 6.0-7.5 and have limited access to Fe2+. The involvement of these signalling molecules in up-regulating iron acquisition genes (FRO2 and IRT1), iron translocation to the cellular compartments and accessibility of iron storage which are important for proper iron homeostasis hence can be considered as vital biofortification strategy for crop plants to address hidden hunger.
|
|
| 4. |
- Pinto, Dalila, et al.
(författare)
-
Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants
- 2011
-
Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 29:6, s. 512-521
-
Tidskriftsartikel (refereegranskat)abstract
- We have systematically compared copy number variant (CNV) detection on eleven microarrays to evaluate data quality and CNV calling, reproducibility, concordance across array platforms and laboratory sites, breakpoint accuracy and analysis tool variability. Different analytic tools applied to the same raw data typically yield CNV calls with <50% concordance. Moreover, reproducibility in replicate experiments is <70% for most platforms. Nevertheless, these findings should not preclude detection of large CNVs for clinical diagnostic purposes because large CNVs with poor reproducibility are found primarily in complex genomic regions and would typically be removed by standard clinical data curation. The striking differences between CNV calls from different platforms and analytic tools highlight the importance of careful assessment of experimental design in discovery and association studies and of strict data curation and filtering in diagnostics. The CNV resource presented here allows independent data evaluation and provides a means to benchmark new algorithms.
|
|
| 5. |
- Pinto, Dalila, et al.
(författare)
-
Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
-
Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
|
|
| 6. |
- Sato, Daisuke, et al.
(författare)
-
SHANK1 Deletions in Males with Autism Spectrum Disorder.
- 2012
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 90:5, s. 879-887
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies have highlighted the involvement of rare (<1% frequency) copy-number variations and point mutations in the genetic etiology of autism spectrum disorder (ASD); these variants particularly affect genes involved in the neuronal synaptic complex. The SHANK gene family consists of three members (SHANK1, SHANK2, and SHANK3), which encode scaffolding proteins required for the proper formation and function of neuronal synapses. Although SHANK2 and SHANK3 mutations have been implicated in ASD and intellectual disability, the involvement of SHANK1 is unknown. Here, we assess microarray data from 1,158 Canadian and 456 European individuals with ASD to discover microdeletions at the SHANK1 locus on chromosome 19. We identify a hemizygous SHANK1 deletion that segregates in a four-generation family in which male carriers-but not female carriers-have ASD with higher functioning. A de novo SHANK1 deletion was also detected in an unrelated male individual with ASD with higher functioning, and no equivalent SHANK1 mutations were found in >15,000 controls (p = 0.009). The discovery of apparent reduced penetrance of ASD in females bearing inherited autosomal SHANK1 deletions provides a possible contributory model for the male gender bias in autism. The data are also informative for clinical-genetics interpretations of both inherited and sporadic forms of ASD involving SHANK1.
|
|
