Search

Pedilanthus leaf curl virus (PeLCV) is a monopartite begomovirus (family Geminiviridae) discovered just a few decades ago. Since then, it has become a widely encountered virus, with reports from ca. 25 plant species across Pakistan and India, indicative of its notable evolutionary success. Viruses mutate at such a swift rate that their ecological and evolutionary behaviors are inextricably linked, and all of these behaviors are imprinted on their genomes as genetic diversity. So, all these imprints can be mapped by computational methods. This study was designed to map the sequence variation dynamics, genetic heterogeneity, regional diversity, phylogeny, and recombination events imprinted on the PeLCV genome. Phylogenetic and network analysis grouped the full-length genome sequences of 52 PeLCV isolates into 7 major clades, displaying some regional delineation but lacking host-specific demarcation. The progenitor of PeLCV was found to have originated in Multan, Pakistan, in 1977, from where it spread concurrently to India and various regions of Pakistan. A high proportion of recombination events, distributed unevenly throughout the genome and involving both inter- and intraspecies recombinants, were inferred. The findings of this study highlight that the PeLCV population is expanding under a high degree of genetic diversity (π = 0.073%), a high rate of mean nucleotide substitution (1.54 × 10−3), demographic selection, and a high rate of recombination. This sets PeLCV apart as a distinctive begomovirus among other begomoviruses. These factors could further exacerbate the PeLCV divergence and adaptation to new hosts. The insights of this study that pinpoint the emergence of PeLCV are outlined. [ABSTRACT FROM AUTHOR]

• An updated prehistoric AMH dispersal route in and out of NE India has been unveiled. • TrOC-linked autosomal loci & mtDNA-based marker predicted feasible migration route. • Prehistoric AMH dispersal probably linked with the high TrOC prevalence in NE India. • Back-migration from SE Asia (∼4kya) most likely introduced the TrOC-causing traits. • MtDNA-HG 'R' significantly associated with the risk of TrOC (OR > 9.5) in NE India. Northeast (NE) India is a subject of debate for predicting its involvement in prehistoric anatomically modern human (AMH) dispersal. The unique lifestyle and genetic characteristics of native ethnic groups in this region are believed to be responsible for their susceptibility to tobacco-related oral cancer (TrOC). The present study assessed mitochondrial macro-haplogroup (mHG) diversity and TrOC susceptibility autosomal loci to evaluate the impact of prehistoric AMH dispersal on the present day's high TrOC prevalence in major NE Indian ethnics. We considered 175 unrelated individuals from 35 ethnic groups and previously published 374 sequences for sequencing-based assessment of mtDNA-based marker by subsequent analyses like haplogroup diversity, phylogenetic, genetic structure by AMOVA, and MDS, descriptive statistics of demographic parameters, and migration analysis. Besides, we selected prolonged tobacco-chewing 124 case-control individuals from similar ethnic backgrounds for genotyping 115 autosomal loci in Sequenom iPLEX MassARRAY™ platform and mined 1000genome data (n = 398) for consequent global admixture and ancestry-specific allele frequencies-based analyses. Our mtDNA-based findings suggested that NE populations were distinct from other Indian populations, owing to the first wave of migration from ancient southern China (∼54kya) and two successive spatial expansion events at ∼45kya and ∼43kya. Consequently, it probably acted as another source for prehistoric AMH dispersal in N/NE Asia. Besides, the second wave of back-migration from SE Asia (∼40kya) probably replaced the mitochondrial footprints of survivors from the first migrants and introduced the TrOC susceptibility traits in this region. Afterward, the autosomal marker-based observations on the transition of the disease-associated admixture component 'K6' from SE Asia reconfirmed these results. Moreover, we also observed that the mitochondrial mHG 'R' is significantly associated with the risk of TrOC (OR > 9.5) in NE India. Furthermore, the possible onset of the phenotypic expression of those traits was predicted at ∼4kya, thus, contributing to present-day's TrOC prevalence. This study reflects its uniqueness by revealing an updated AMH dispersal route for the peopling in and out of NE India, which probably introduced the disease-causing traits in the ancestral NE Indian population. Those traits were then imprinted in their genome to get transferred through their respective generations, forming the present-day's TrOC-prevalent NE Indian population. [ABSTRACT FROM AUTHOR]

Objectives To evaluate if the parental origin of X-chromosome has an impact on the phenotype and biochemical profile in Turner syndrome (TS). Result of the previous studies have been equivocal and could be attributable to the multicentric study design with different experts examining heterogeneous TS population of various ethnic background. Methods A cross-sectional single center study from Northern India. Fifty nine diagnosed subjects of TS and their parents participated in the study. Parental origin of intact X-chromosome was determined using 12 highly polymorphic short tandem repeats (STR) on X-chromosome. For the evaluation of parent-of-origin effects, typical phenotypic traits including congenital malformations, anthropometry, body composition by dual energy X-ray absorptiometry (DXA) and biochemical profile were compared. Clinical stigmata of TS in all subjects were examined by a single expert. Results The intact X-chromosome was of maternal origin (Xm) in 49.1% subjects while 50.9% had paternal origin (Xp). Skeletal anomalies were more common in Xm group, out of which prevalence of short neck and short fourth metatarsal reached statistical significance (p=0.04 and 0.01 respectively). A strong correlation was observed between subject's baseline height standard deviation score (Ht SDS) and paternal height (r=0.593, p<0.001), maternal height (r=0.564, p<0.001) and mid-parental height (MPH) (r=0.372, p=0.047) in Xp group. This effect was not seen in Xm subjects whose baseline Ht SDS showed no significant correlation with maternal height, paternal height or MPH. No differences were detected between the groups with regard to biochemical profile or body composition. Conclusions We speculate that the differences in skeletal anomalies and height correlations between Xm and Xp groups could be due to the modifying effect of epigenetic signature on short stature homeobox (SHOX) gene of Xm. SHOX gene is not modified on Xp thereby explaining the paucity of skeletal changes and height correlations in Xp subjects.

Objectives: To report a phenotypic series of eight patients of Beckwith-Wiedemann Syndrome (BWS) with abnormalities of 11p15.5 region to highlight the spectrum of phenotypic manifestations., Methods: All the cases were evaluated using Methylation Specific Multiplex Ligation Dependent Probe Amplification (MS-MLPA) of 11p15.5 region to detect the abnormal methylation status of ICR1 (H19DR) and ICR2 (KvDMR) regions., Results: The median age at diagnosis was 5.7 mo (range 1.5-13 mo) with female preponderance. Macroglossia, ear creases and abdominal wall defects were the major features. Hypomethylation at ICR2 and hypermethylation at ICR1 was observed in 6/8 and 2/8 patients respectively. No specific genotype and phenotype correlation was observed., Conclusions: This report highlights the major clinical features of BWS that should prompt pediatricians to offer genetic testing to evaluate the epigenetic abnormalities using MS-MLPA, as it not only helps in appropriate counseling but also provides further guidance about the tumor risk surveillance.

Objective: To study H19 ICR methylation levels in association with sperm parameters routinely analyzed in idiopathic recurrent spontaneous miscarriage cases., Design: Case-control study., Setting: Academic research setting., Patient(s): Male partners of couples with a history of idiopathic recurrent spontaneous miscarriage (RSM group) and male partners of couples with proven fertility (control group)., Intervention(s): None., Main Outcome Measure(s): Paternal age, sperm concentration, motility, chromatin compaction status, morphology, and H19 ICR methylation were assessed in control and idiopathic RSM group participants., Result(s): Paternal age and basic semen parameters analyzed did not show any significant difference between the two groups; however H19 ICR methylation levels were reduced significantly in the idiopathic RSM group compared with the control group., Conclusion(s): Significant reduction in the H19 ICR methylation without significant difference in the sperm parameters demonstrates aberrant imprinting to be associated with idiopathic RSM., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

In 79 South Indian nuclear pedigrees ascertained via probands with NIDDM and both parents living, parental diabetic status was established through previously diagnosed NIDDM (n = 97) or oral glucose tolerance testing (n = 61). There was no significant difference between diabetes prevalence in mothers and fathers (60 vs 53 (76% vs 67%), respectively, p = 0.22). 'Age at diabetes diagnosis' survival curves did differ according to parental gender (p = 0.02) but this may reflect gender differences in health provision rather than pathophysiology. No maternal excess effects of the magnitude evident in previous studies were detected, suggesting either ethnic differences or overestimation of the maternal effect when reported histories of parental diabetes have been used. The tRNA(Leu(UUR) gene region was studied for diabetes-associated variation given the role of mutations in this gene in some pedigrees displaying maternal transmission of NIDDM. None of 142 unrelated South Indian NIDDM subjects displayed the MELAS mutation at nt3243. However, sequencing identified two variants of potential importance: (a) at nt3290 in the tRNA(Leu(UUR) gene, seen in 7/142 diabetic and 1/85 control subjects (p = 0.11), (b) at nt3316 in the ND1 gene (4/142 vs 1/85 subjects, respectively (p = 0.51)). Further studies are needed to determine the relevance of these variants to the development of NIDDM.

The family histories of 976 South Indian Type 2 diabetic patients were recorded in a questionnaire-based survey to establish whether the excess maternal transmission of Type 2 diabetes reported in low prevalence Europid populations was also evident in this medium prevalence population. In 450 families (46.1%), no parental history of diabetes was reported. In 423 families with one parent diabetic, 222 fathers (52.5%) and 201 (47.5%) mothers were diabetic. In the remaining 103 (10.6%) families, both parents were diabetic. In contrast to previous studies, we found no evidence for substantial maternal excess in the transmission of diabetes (325 diabetic fathers vs 304 mothers; p = 0.4; p = 0.07 when compared using life table methods). The age of diagnosis of diabetes in probands was lower than that of their diabetic parents (p < 0.001): furthermore increasing parental history of diabetes was associated with an earlier diagnosis of diabetes in probands (p < 0.001). These results emphasize the extensive familial aggregation of Type 2 diabetes in this population but fail to replicate the evidence for excess maternal transmission evident in lower prevalence Europid populations, suggesting ethnic differences in the extent of this phenomenon.