Inter and intra population phenotypic variability of Lippia integrifolia(Verbenaceae) and its natural situation in the west-center of Argentina

The species Lippia integrifoliais an aromatic, sub-woody shrub, distributed from Northwest and Central Argentina to Bolivia. It is among the most important native aromatic species. It presents medicinal properties, some of which have been scientifically proven. As an alternative to harvesting, the process of domestication of the species was initiated. The objective of this work was to assess the phenotypic variability based on botanical-taxonomic and morpho-agronomic descriptors and the use of indicators to evaluate its natural situation in the west-center of Argentina. We worked in five wild populations, registering morphological variables, phenology, natural regeneration, herbivory and presence of diseases. L. integrifoliapresents a wide morphological variability, which can be explained with three morphological descriptors. Natural regeneration ́s rate is very low to zero, in four of the sites. The results obtained are of importance to make decisions related to the sustainable use in situ, and to begin a program of domestication of the species.

Short structural variants as informative genetic markers for ALS disease risk and progression

There is considerable variability in disease progression for patients with amyotrophic lateral sclerosis (ALS) including the age of disease onset, site of disease onset, and survival time. There is growing evidence that short structural variations (SSVs) residing in frequently overlooked genomic regions can contribute to complex disease mechanisms and can explain, in part, the phenotypic variability in ALS patients. Here, we discuss SSVs recently characterized by our laboratory and how these discoveries integrate into the current literature on ALS, particularly in the context of application to future clinical trials. These markers may help to identify and differentiate patients for clinical trials that have a similar ALS disease mechanism(s), thereby reducing the impact of participant heterogeneity. As evidence accumulates for the genetic markers discovered in SQSTM1, SCAF4, and STMN2, we hope to improve the outcomes of future ALS clinical trials.

Epigenomic analysis of KLF1 haploinsufficiency in primary human erythroblasts

Haploinsufficiency for the erythroid-specific transcription factor KLF1 is associated with hereditary persistence of fetal hemoglobin (HPFH). Increased HbF ameliorates the symptoms of β-hemoglobinopathies and downregulation of KLF1 activity has been proposed as a potential therapeutic strategy. However, the feasibility of this approach has been challenged by the observation that KLF1 haploinsufficient individuals with the same KLF1 variant, within the same family, display a wide range of HbF levels. This phenotypic variability is not readily explained by co-inheritance of known HbF-modulating variants in the HBB, HBS1L-MYB and/or BCL11A loci. We studied cultured erythroid progenitors obtained from Maltese individuals in which KLF1 p.K288X carriers display HbF levels ranging between 1.3 and 12.3% of total Hb. Using a combination of gene expression analysis, chromatin accessibility assays and promoter activity tests we find that variation in expression of the wildtype KLF1 allele may explain a significant part of the variability in HbF levels observed in KLF1 haploinsufficiency. Our results have general bearing on the variable penetrance of haploinsufficiency phenotypes and on conflicting interpretations of pathogenicity of variants in other transcriptional regulators such as EP300, GATA2 and RUNX1.

Genetic and Social Transmission of Parental Sex Roles in Zebra Finch Families

Parental care plays a central, reinforcing role in the evolution of sex roles and its development is often reported to be driven by genetic, rather than environmental effects. Based on these studies, however, genetic inheritance does not account fully for the often-significant phenotypic variability observed within species, a variation that we hypothesized may be explained by social effects from parents. Following a full cross-fostering design, here we aimed at disentangling genetic and social parental effects in the ontogeny of parental behaviours. Clutches of eggs were swapped, and we monitored parental behaviours in two consecutive generations of a captive population of the socially monogamous, biparental zebra finch (Taeniopygia guttata). Using nest box cameras, parental behaviour was recorded for 3 h in two reproductive stages: on day 8 of incubation and day 10 post-hatching. These fostered birds, after becoming fully matured, received a pair randomly and we observed parental care of this second generation too, following the same protocol. We then compared various parental behaviours (such as time spent incubating, or number of nest attendances during offspring provisioning) in the second generation to those of their genetic and social parents. Based on the results of our experiment, both genetic and social effects can contribute to intergenerational transmission of specific parental behaviours, with various weights. However, the strongest and most consistent effect that we found is that of the current mate; a social effect that can manifest both in negative and positive directions, depending on the behavioural trait. Our study suggests context-specific and sexually different genetic, social and non-social environmental effects in the ontogeny of parental sex roles and outline the importance of parental negotiation in explaining individual variation of parental behaviour in biparental species.

Morphological and Chemical Variation of Wild Sweet Chestnut (Castanea sativa Mill.) Populations

Sweet chestnut (Castanea sativa Mill., Fagaceae) is one of the oldest cultivated tree species in the Mediterranean, providing multiple benefits, and, since it has edible seeds, it represents an interesting model species for the research of morphological and chemical variability. In this study, morphometric methods and chemical analyses were used to quantify the extent of differences in phenotypic and nutritional traits between eight natural populations of sweet chestnut from different environmental conditions, where different management types are applied, high-forest and coppice. The samples were collected from the Prealps in Italy to the western part of Bosnia and Herzegovina. In total, 31 nut and kernel morphometric and nutritional traits were studied on 160 trees, and various multivariate statistical analyses were used to study intra- and interpopulation variations. Both analyses, morphometric and chemical, revealed a similar pattern of diversity, with morphological and chemical variability not associated with geographic or environmental variables. In addition, we found significant correlations between morphometric and chemical data. High phenotypic variability was determined both among and within the studied populations, and all populations had a similar level of diversity. The results of the analysis of morphological and chemical diversity can have many practical applications for the management, production, and conservation of the sweet chestnut genetic resources for nut production.

Evaluation of the phenotypic and genomic background of variability based on litter size of Large White pigs

Background The genetic background of trait variability has captured the interest of ecologists and animal breeders because the genes that control it could be involved in buffering various environmental effects. Phenotypic variability of a given trait can be assessed by studying the heterogeneity of the residual variance, and the quantitative trait loci (QTL) that are involved in the control of this variability are described as variance QTL (vQTL). This study focuses on litter size (total number born, TNB) and its variability in a Large White pig population. The variability of TNB was evaluated either using a simple method, i.e. analysis of the log-transformed variance of residuals (LnVar), or the more complex double hierarchical generalized linear model (DHGLM). We also performed a single-SNP (single nucleotide polymorphism) genome-wide association study (GWAS). To our knowledge, this is only the second study that reports vQTL for litter size in pigs and the first one that shows GWAS results when using two methods to evaluate variability of TNB: LnVar and DHGLM. Results Based on LnVar, three candidate vQTL regions were detected, on Sus scrofa chromosomes (SSC) 1, 7, and 18, which comprised 18 SNPs. Based on the DHGLM, three candidate vQTL regions were detected, i.e. two on SSC7 and one on SSC11, which comprised 32 SNPs. Only one candidate vQTL region overlapped between the two methods, on SSC7, which also contained the most significant SNP. Within this vQTL region, two candidate genes were identified, ADGRF1, which is involved in neurodevelopment of the brain, and ADGRF5, which is involved in the function of the respiratory system and in vascularization. The correlation between estimated breeding values based on the two methods was 0.86. Three-fold cross-validation indicated that DHGLM yielded EBV that were much more accurate and had better prediction of missing observations than LnVar. Conclusions The results indicated that the LnVar and DHGLM methods resulted in genetically different traits. Based on their validation, we recommend the use of DHGLM over the simpler method of log-transformed variance of residuals. These conclusions can be useful for future studies on the evaluation of the variability of any trait in any species.

OCULO-AURICULO-VERTEBRAL SPECTRUM ASSOCIATED WITH ABERRANT SUBCLAVIAN ARTERY IN AN INFANT WITH RECURRENT RESPIRATORY DISTRESS

ABSTRACT Objective: To describe an infant with craniofacial microsomia and recurrent respiratory distress associated with aberrant right subclavian artery in order to review its most frequent congenital anomalies and alert the pediatrician to its rarer and more severe complications. Case description: This case report involves an 18-month-old male infant, only son of non-consanguineous parents. At birth, the child presented craniofacial dysmorphisms (facial asymmetry, maxillary and mandibular hypoplasia, macrostomia, grade 3 microtia, and accessory preauricular tag) restricted to the right side of the face. Additional tests showed asymmetric hypoplasia of facial structures and thoracic hemivertebrae. No cytogenetic or cytogenomic abnormalities were identified. The patient progressed to several episodes of respiratory distress, stridor, and nausea, even after undergoing gastrostomy and tracheostomy in the neonatal period. Investigation guided by respiratory symptoms identified compression of the esophagus and trachea by an aberrant right subclavian artery. After surgical correction of this anomaly, the infant has not presented respiratory symptoms and remains under multidisciplinary follow-up, seeking rehabilitation. Comments: Craniofacial microsomia presents a wide phenotypic variability compared to both craniofacial and extracraniofacial malformations. The latter, similarly to the aberrant right subclavian artery, is rarer and associated with morbidity and mortality. The main contribution of this case report was the identification of a rare anomaly, integrating a set of malformations of a relatively common condition, responsible for a very frequent complaint in pediatric care.

Identification of a PROM1 mutation in a Spanish family with inherited retinal dystrophies

Background: We report a Spanish family, comprising an affected mother and daughter, respectively diagnosed with retinitis pigmentosa and Stargardt-like macular dystrophy, in whom we identified a PROM1 mutation. Methods: A custom gene panel consisting of 119 inherited retinal dystrophies (IRD)-genes was applied in the two affected individuals of this family and sequenced using the Illumina´s NextSeq500 platform. Results: The analysis of the resulting data allowed us to identify the pathogenic PROM1 mutation c.1117C>T (p.Arg373Cys) as the primary cause of the disease in both patients. No additional variants contributing to the extent of retinal dysfunction were detected. Conclusion: The variable expressivity of the detected PROM1 mutation is the most likely responsible for the intrafamilial phenotypic variability observed in this family. Screening of this mutation should be considered in patients with compatible clinical manifestations, especially when accompanied by an autosomal dominant family history.