Whole exome sequencing and homozygosity mapping reveals genetic defects in consanguineous Iranian families with inherited retinal dystrophies

Acknowledgements This research was funded by the Swiss National Science Foundation (Grant #176097 to CR). We would like to express gratitude to the patients and all their family members that participated in this study for their valuable cooperation and participation.Peer reviewedPublisher PD

Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

Funding Information: We would like to thank all of the participating families. We are also grateful to the Swiss Confederation for the award of a PhD fellowship to AUR, to Mashhad University of Medical Sciences for supporting part of the work, in the framework of the PhD thesis of AS, to the Swiss National Science Foundation for grant # 176097 to CR, and to the Fondation Guillaume Gentil for support to ASF.Peer reviewedPublisher PD

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of , has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment

Multidisciplinary management of a patient with van der Woude syndrome : a case report

Introduction: Van der Woude syndrome (VWS) is the most frequent form of syndromic cleft lip and palate (SCLP) accounting for 2% of all patients with CLP. Case presentation: We describe the orthodontic treatment of a girl diagnosed with VWS referred by her family dentist for her cosmetic concerns. Discussion: Comprehensive orthodontic treatment, secondary bone graft, distraction osteogenesis (for a deficient maxilla), secondary palatoplasty and excision of lower lip pits, as well as orthodontic and prosthetic procedures may provide a satisfactory outcome. Genetic testing showed a known putative splice site mutation (c.174 + 1 G/A) as the prime cause of VWS in our patient and her family. Conclusion: SCLP has significant effects on facial aesthetics and the psychosocial status. Parents should be assessed and counseled appropriately. This condition is treatable in the absence of life threatening systemic anomalies. An interdisciplinary team approach is advocated

Diverse genetic origin of Indian Muslims: evidence from autosomal STR loci

The origin and relationships of Indian Muslims is still dubious and are not yet genetically well studied. In the light of historically attested movements into Indian subcontinent during the demic expansion of Islam, the present study aims to substantiate whether it had been accompanied by any gene flow or only a cultural transformation phenomenon. An array of 13 autosomal STR markers that are common in the worldwide data sets was used to explore the genetic diversity of Indian Muslims. The austere endogamy being practiced for several generations was confirmed by the genetic demarcation of each of the six Indian Muslim communities in the phylogenetic assessments for the markers examined. The analyses were further refined by comparison with geographically closest neighboring Hindu religious groups (including several caste and tribal populations) and the populations from Middle East, East Asia and Europe. We found that some of the Muslim populations displayed high level of regional genetic affinity rather than religious affinity. Interestingly, in Dawoodi Bohras (TN and GUJ) and Iranian Shia significant genetic contribution from West Asia, especially Iran (49, 47 and 46%, respectively) was observed. This divulges the existence of Middle Eastern genetic signatures in some of the contemporary Indian Muslim populations. Our study reveals that the spread of Islamic faith in the Indian subcontinent was predominantly cultural transformation associated with minor gene flow from West Asia

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment

The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy

Blue cone monochromacy (BCM) is an X-linked retinal disorder characterized by low vision, photoaversion, and poor color discrimination. BCM is due to the lack of long-wavelength-sensitive and middle-wavelength-sensitive cone photoreceptor function and caused by mutations in the OPN1LW/OPN1MW gene cluster on Xq28. Here, we investigated the prevalence and the landscape of submicroscopic structural variants (SVs) at single-base resolution in BCM patients. We found that about one-third (n = 73) of the 213 molecularly confirmed BCM families carry an SV, most commonly deletions restricted to the OPN1LW/OPN1MW gene cluster. The structure and precise breakpoints of the SVs were resolved in all but one of the 73 families. Twenty-two families—all from the United States—showed the same SV, and we confirmed a common ancestry of this mutation. In total, 42 distinct SVs were identified, including 40 previously unreported SVs, thereby quadrupling the number of precisely mapped SVs underlying BCM. Notably, there was no “region of overlap” among these SVs. However, 90% of SVs encompass the upstream locus control region, an essential enhancer element. Its minimal functional extent based on deletion mapping in patients was refined to 358 bp. Breakpoint analyses suggest diverse mechanisms underlying SV formation as well as in one case the gene conversion-based exchange of a 142-bp deletion between opsin genes. Using parsimonious assumptions, we reconstructed the composition and copy number of the OPN1LW/OPN1MW gene cluster prior to the mutation event and found evidence that large gene arrays may be predisposed to the occurrence of SVs at this locus

Traces of sub-Saharan and Middle Eastern lineages in Indian Muslim populations

Islam is the second most practiced religion in India, next to Hinduism. It is still unclear whether the spread of Islam in India has been only a cultural transformation or is associated with detectable levels of gene flow. To estimate the contribution of West Asian and Arabian admixture to Indian Muslims, we assessed genetic variation in mtDNA, Y-chromosomal and LCT/MCM6 markers in 472, 431 and 476 samples, respectively, representing six Muslim communities from different geographical regions of India. We found that most of the Indian Muslim populations received their major genetic input from geographically close non-Muslim populations. However, low levels of likely sub-Saharan African, Arabian and West Asian admixture were also observed among Indian Muslims in the form of L0a2a2 mtDNA and E1b1b1a and J*(xJ2) Y-chromosomal lineages. The distinction between Iranian and Arabian sources was difficult to make with mtDNA and the Y chromosome, as the estimates were highly correlated because of similar gene pool compositions in the sources. In contrast, the LCT/MCM6 locus, which shows a clear distinction between the two sources, enabled us to rule out significant gene flow from Arabia. Overall, our results support a model according to which the spread of Islam in India was predominantly cultural conversion associated with minor but still detectable levels of gene flow from outside, primarily from Iran and Central Asia, rather than directly from the Arabian Peninsula