Biology subjects

de Gennaro, L.

Publications and source records attributed to de Gennaro, L..

5 recordsLinked to original sources

bioRxiv2024

Aquaporin-4 expression levels and mis-localization are inversely linked to peritumoral edema in gliomas of varying aggressiveness

Aquaporin-4 (AQP4) and its extended isoform, AQP4ex, are crucial for regulating brain water homeostasis. Mis-localization of these isoforms is implicated in various brain tumors, including glioblastoma multiforme (GBM). This study explores AQP4 isoform expression and localization in Pilocytic Astrocytomas (PA), a circumscribed astrocytic low-grade glioma, compared to GBM, an adult-type diffuse high grade glioma. We found significant upregulation of AQP4 and AQP4ex in PA, with notable mis-localization deviating from the typical perivascular localization seen in healthy tissue. This mis-localization mirrors the phenotype observed in AQP4ex knockout models, where impaired AQP4 localization is linked to disrupted water homeostasis and reduced waste clearance, despite overall increased AQP4 levels. Interestingly, PA shows minimal peritumoral edema and a relatively intact blood-brain barrier (BBB), with elevated phosphorylated AQP4ex (pAQP4ex) suggesting a role in stabilizing AQP4 function. In contrast, GBM exhibits reduced AQP4/AQP4ex expression, significant peritumoral edema, and BBB disruption. GFAP isoforms, GFAP{kappa} and GFAP{delta}, are upregulated in PA, associated with Rosenthal fibers, indicating a stabilizing astrocytic response. GBM, however, shows generalized GFAP increase, reflecting aggressive gliosis and disrupted water homeostasis. In conclusion, both AQP4 expression levels and mis-localization are important factors influencing peritumoral edema and tumor aggressiveness in gliomas. This study positions AQP4 as a potential biomarker for glioma progression, offering insights into astrocytic function and paving the way for targeted therapies.

cancer biology↗

bioRxiv2024

Genomic sequencing to detect cross-breeding quality in dogs: an example studying disorders in sexual development

BackgroundDisorders of Sexual Development (DSD) in dogs, similar to humans, arise from irregularities in genetic determinants, gonadal differentiation, or phenotypic sex development. The French Bulldog, a breed that has seen a surge in popularity and demand, has also shown a marked increase in DSD incidence. This study aims to characterize the genetic underpinnings of DSD in a French Bulldog named Brutus, exhibiting ambiguous genitalia and internal sexual anatomy, and to explore the impact of breeding practices on genetic diversity within the breed. MethodsWe utilized a comprehensive approach combining conventional cytogenetics, molecular techniques, and deep sequencing to investigate the genetic profile of Brutus. The sequence data were compared to three other male French Bulldogs genome sequences with typical reproductive anatomy, including Brutuss father, and the canine reference genome (CanFam6). FindingsOur findings revealed a 22% mosaicism (78, XX/77, XX), the absence of the SRY gene, and the presence of 43 unique Single Nucleotide Variants (SNVs) not inherited from the father. Notably, the Run of Homozygosity (ROH) analysis showed Brutus has a significantly higher number of homozygous segments compared to other Bulldogs, with a total length of these fragments 50% greater than the average, strongly suggesting this dog is the product of the mating between siblings. While no direct causative genes for the DSD phenotype were identified four candidate loci warranting further investigation were highlighted. ConclusionsOur study highlighted the need for a better annotated and curated reference dog genome to define genes causative of any specific phenotype, suggests a potential genetic basis for the DSD phenotype in dogs, and underscores the consequences of uncontrolled breeding practices in French Bulldogs. These findings highlight the importance of implementing strategic genetic management to preserve genetic health and diversity in canine populations.

genomics↗

bioRxiv2024

Fast and reliable ancestral reconstruction on ancient genotype data with non-negative Least square and Principal Component Analysis

The history of human populations has been strongly shaped by admixture events, contributing to the patterns of observed genetic diversity across populations. Given its significance for evolutionary and medical studies, many algorithms focusing on the inference of the genetic composition of admixed populations have been developed. In particular, the recent development of new ancestry estimation methods that consider the fragmentary nature of ancient genotype data, such as the f-statistics family and its derivations, have radically changed our understanding of the past. F-statistics capture similar genetic similarity information as Principal Component Analysis (PCA), which is widely used in population genetics to quantify genetic affinity between populations or individuals. In this study, we introduce ASAP (ASsessing ancestry proportions through Principal component Analysis) method that leverages PCA and Non-Negative Least Square (NNLS) to assess the ancestral compositions of admixed individuals given a large set of populations. We tested ASAP on different simulated models, incorporating high levels of missingness. Our results show its ability to reliably estimate ancestry across numerous scenarios, even those with a significant proportion of missing genotypes, in a fraction of the time required when using other tools. When harnessed on Eurasias genotype data, ASAP helped replicate and extend findings from previous studies proving to be a fast, efficient, and straightforward new ancestry estimation tool.

genomics↗

bioRxiv2024

The Genomic portrait of the Picene culture: new insights into the Italic Iron Age and the legacy of the Roman expansion in Central Italy.

BackgroundThe Italic Iron Age was characterized by the presence of various ethnic groups partially examined from a genomic perspective. To explore the evolution of Iron Age Italic populations and the genetic impact of Romanization, we focused on the Picenes, one of the most fascinating pre-Roman civilizations, who flourished on the Middle Adriatic side of Central Italy between the 9th and the 3rd century BCE, until the Roman colonization. ResultsWe analyzed more than 50 samples, spanning more than 1,000 years of history from the Iron Age to Late Antiquity. Despite cultural diversity, our analysis reveals no major differences between the Picenes and other coeval populations, suggesting a shared genetic history of the Central Italian Iron Age ethnic groups. Nevertheless, a slight genetic differentiation between populations along the Adriatic and Tyrrhenian coasts can be observed, possibly due to genetic contacts between populations residing on the Italian and Balkan shores of the Adriatic Sea. Additionally, we found several individuals with ancestries deviating from their general population. Lastly, In the Late Antiquity period, the genetic landscape of the Middle Adriatic region drastically changed, indicating a relevant influx from the Near East. ConclusionsOur findings, consistently with archeological hypotheses, suggest genetic interactions across the Adriatic Sea during the Bronze/Iron Age and a high level of individual mobility typical of cosmopolitan societies. Finally, we highlighted the role of the Roman Empire in shaping genetic and phenotypic changes that greatly impacted the Italian peninsula.

genomics↗

bioRxiv2023

The Complete Sequence and Comparative Analysis of Ape Sex Chromosomes

Apes possess two sex chromosomes--the male-specific Y and the X shared by males and females. The Y chromosome is crucial for male reproduction, with deletions linked to infertility1. The X chromosome carries genes vital for reproduction and cognition2. Variation in mating patterns and brain function among great apes suggests corresponding differences in their sex chromosomes. However, due to their highly repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (chimpanzee, bonobo, gorilla, Bornean and Sumatran orangutans) and a lesser ape, the siamang gibbon. These assemblies allowed us to untangle the intricacies of ape sex chromosome evolution. We found that, compared to the Xs, the ape Ys vary greatly in size and have low alignability and high levels of structural rearrangements. This divergence on the Y arises from the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements, and satellites. Our analysis of Y chromosome genes revealed expansions of multi-copy gene families and signatures of purifying selection. Thus, the Y exhibits dynamic evolution, while the X is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of >100 great ape individuals. These reference assemblies are expected to inform human evolution and conservation genetics of nonhuman apes, all of which are endangered species.

genomics↗