Biology subjects

Martinez, J.

Publications and source records attributed to Martinez, J..

59 records · Page 4Linked to original sources

bioRxiv2018

Diagnostic outcomes of exome gene panel sequencing in patients with unusual syndromic cleft lip/palate phenotypes

Orofacial clefting (OFC) is a common craniofacial birth defect that has a prevalence of 1.2 in 1,000 live births. Syndromic OFC in which patients present with additional developmental deficits are identified to have a strong genetic component. We applied exome gene panel sequencing in a cohort of 14 Colombian patients identified at Operation Smile in Bogota, Colombia, with syndromic orofacial clefting phenotypes and additional features initially suggesting Aarskog-Scott syndrome (AAS). Gene panel sequencing failed to identify any causal variants in the FGD1 gene which underlies this condition, but variants in a number of genes suggest alternative clinical diagnoses across five patients (~ 36%). The novel variants identified here maps to developmentally important genes including SRCAP, OFD1, NIPBL, GRIN2A and KMT2D6. Our result demonstrates the extensive heterogeneity underlying OFC and emphasises the need for systematic phenotyping of patients with rare conditions. Gene panel sequencing has the potential to cost-effectively resolve ambiguous clinical diagnoses, but rigorous attention should be paid to gene coverage as our results suggest highly variable read depths across individual gene exons and this may reduce the quality of variant calls at specific locations.

genomics↗

bioRxiv2018

Addressing multiple sources of uncertainty in the estimation of parrot abundance from roost counts: a case study with the Vinaceous-breasted Parrot (Amazona vinacea)

Population size is a key predictor of extinction risk and is critical to listing species in IUCN threat categories. The population size of parrots--one of the most threatened bird families--is often assessed using roost counts, which suffer from multiple sources of uncertainty that need to be addressed in monitoring efforts. To improve estimates of abundance for endangered Vinaceous-breasted Parrot (Amazona vinacea), we compared extensive roost counts over the whole range of the species (Argentina, Paraguay, Brazil) with an intensive regional survey designed to address five sources of uncertainty about parrot abundance in western Santa Catarina state (WSC), Brazil, in 2016 and 2017. We estimated regional-scale abundance using a sampling design that minimizes double counting and an N-mixture model of replicated count data, which accounts for imperfect detection, implemented in a Bayesian framework. The whole-range counts amounted to 3,888 and 4,084 individuals in 2016 and 2017, respectively; regional estimates were 945 {+/-} 50 and 1,393 {+/-} 40 individuals, for the same two years. We found no evidence of population growth because the increase in numbers matched an increase in observation effort on both spatial scales. When extrapolating the WSC abundance estimate to three hypothetical geographical range areas of the species, under the simplifying assumption of homogenous density, we obtained values above the whole-range counts, but within the same order of magnitude, putting the global population size of Vinaceous-breasted Parrot in the thousands of individuals. Although our estimates of abundance and geographic range are larger than those currently reported by the IUCN, we suggest that Vinaceous-breasted Parrot remain in the Endangered IUCN threat category pending further investigation of population trends. We recommend that roost-monitoring programs for parrots consider and address sources of uncertainty through field protocols and statistical analysis, to better inform assessments of population size, trends, and threat status.

ecology↗

bioRxiv2018

Divergence in the face of gene flow in two Charadrius plovers along the Chinese coast

Speciation with gene flow is an alternative to the nascence of new taxa in strict allopatric separation. Indeed, many taxa have parapatric distributions at present. It is often unclear if these are secondary contacts, e.g. caused by past glaciation cycles or the manifestation of speciation with gene flow, which hampers our understanding of how different forces drive diversification. Here we studied genetic, phenotypic and ecological aspects of divergence in a pair of incipient species, the Kentish (Charadrius alexandrinus) and the white-faced Plovers (C. dealbatus), shorebirds with parapatric breeding ranges along the Chinese coast. We assessed divergence based on molecular markers with different modes of inheritance and quantified phenotypic and ecological divergence in aspects of morphometric, dietary and climatic niches. These analyses revealed small to moderate levels of genetic and phenotypic distinctiveness with symmetric gene flow across the contact area at the Chinese coast. The two species diverged approximately half a million years ago in dynamical isolation and secondary contact due to cycling sea level changes between the Eastern and Southern China Sea in the mid-late Pleistocene. We found evidence of character displacement and ecological niche differentiation between the two species, invoking the role of selection in facilitating divergence despite gene flow. These findings imply that the ecology can indeed counter gene flow through divergent selection and thus contribute to incipient speciation in these plovers. Furthermore, our study highlights the importance of using integrative datasets to reveal the evolutionary history and underlying mechanisms of speciation.

evolutionary biology↗

bioRxiv2018

Programmatic Detection of Diploid-Triploid Mixoploidy via Whole Genome Sequencing

PurposeMixoploidy is a type of mosaicism where an organism is a mixture of cells with different numbers of chromosomes. There are a broad range of phenotypes associated with mixoploidy that vary greatly depending on the fraction of cells that are non-diploid, their chromosome number, their distribution, and presumably the specific variation present in the patient. Clinical detection of mixoploidy is important for diagnosis.\n\nMethodsWe developed a method to detect mixoploidy from clinical whole genome sequencing (WGS) data through the identification of excess of variant calls centered on unusual B-allele frequencies. Our method isolates the signal from these variants using trio calls and then solves a basic linear equation to estimate levels of diploid-triploid mixoploidy within the sample.\n\nResultsWe show that our method reflects the results from a cytogenetic test. We provide examples detailing how our method has been used to identify diploid-triploid mixoploid individuals from within the NIH Undiagnosed Diseases Network. We present confirmatory findings obtained by clinical cytogenetic testing and show that our method can be used to identify the diploid-triploid ratio in these cases.\n\nConclusionWGS data from patients with rare diseases can be used to identify mixoploid individuals. Individuals with certain characteristics as discussed should be tested for mixoploidy as part of standard clinical pipeline procedures. Scripts that perform this calculation are publicly available at https://github.com/HudsonAlpha/mixoviz.

genomics↗

bioRxiv2017

Low-Cost HPV Screening And The Prevalence Of Cervical Infection In Asymptomatic Populations In Guatemala

BackgroundA low cost and accurate method for detecting high-risk (HR) HPV is important to permit HPV testing for cervical cancer prevention. We validated a low-cost commercially available HPV method (H13, Hybribio, Hong Kong) and determined the distribution of HPV infections in over 1717 cancer-free women in Guatemala.\n\nMethodsH13 results were compared with two more established HPV tests: (Xpert (Cepheid) and SPF10-LIPA25 (DDL)) in 40 mainly known positive specimens. HR-HPV was detected in cervical samples from 1717 cancer-free women receiving Pap smears using the Hybribio realtime PCR assay of 13 HR types. Selected HPV positive samples were sequenced to determine viral type.\n\nResultsThe Hybribio H13 Assay showed 93% identical results with Xpert, and 89% with SPF10-LIPA25. A total of 13% (226/1717) of women tested HPV+. The highest prevalence was found in younger women (<30 years, 22 %) and older ones ([≥]60 years, 15%). The six most common HR-HPV types among the 148 HPV+ typed were HPV16 (22%), HPV18 (11%), HPV39 (11%), HPV58 (10%), HPV52 (8%), and HPV45 (8%).\n\nConclusionsThe Hybribio Assay was low cost, and accurate in testing for HR-HPV infection. As in most places, HPV16 was the most prevalent HR type in Guatemala and the age-specific prevalence curve peaked in younger ages.\n\nHighlightsO_LIA low cost and accurate method, Hybribio Assay, could be used for CC testing in low income regions.\nC_LIO_LIA total of 13% of cancer-free women were HPV+ and positivity was associated with younger age (<30 years old) in Guatemala.\nC_LIO_LIHPV16 was the major prevalent type.\nC_LI

molecular biology↗