Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period

A 4-year-old child born to an HIV-1 seronegative mother was diagnosed with HIV-1, the main risk factor being transmission from the child's father who was seroconverting at the time of the child's birth. In the context of a forensic investigation, we aimed to identify the source of infection of the child and date of the transmission event. Samples were collected from the father and child at two time points about 4 years after the child's birth. Partial segments of three HIV-1 genes (gag, pol, and env) were sequenced and maximum likelihood (ML) and Bayesian methods were used to determine direction and estimate date of transmission. Neutralizing antibodies were determined using a single cycle assay. Bayesian trees displayed a paraphyletic-monophyletic topology in all three genomic regions, with the father's host label at the root, which is consistent with father-to-son transmission. ML trees found similar topologies in gag and pol and a monophyletic-monophyletic topology in env. Analysis of the time of the most recent common ancestor of each HIV-1 gene population indicated that the child was infected shortly after the father. Consistent with the infection history, both father and son developed broad and potent HIV-specific neutralizing antibody responses. In conclusion, the direction of transmission implicated the father as the source of transmission. Transmission occurred during the seroconversion period when the father was unaware of the infection and was likely accidental. This case shows how genetic, phylogenetic, and serological data can contribute for the forensic investigation of HIV transmission.info:eu-repo/semantics/publishedVersio

A novel haemoglobin variant mimicking cyanotic congenital heart disease

Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. However, as this universal newborn screening is implemented, there will be an increasing number of false-positive results. In order to avoid multiple investigations and uncertainty, an haemoglobin (Hb) variant must be included in the differential diagnosis in otherwise well newborns with low oxygen saturation by pulse oximetry. We describe a novel fetal Hb variant (heterozygous γ-globin gene (HBG1) mutation in exon 2 c.202G>A (p.Val68Met)) identified in a newborn with positive pulse oximetry screening for congenital heart disease.info:eu-repo/semantics/publishedVersio

The Ribatejano pig: Rebirth of a local population? First results on growth, and carcass parameters

In order to assess the productive performance of the Ribatejano (RI) pig, resulting from a cross between Alentejano (AL) and Bísaro (BI) breeds, castrated male pigs AL, BI, ALxBI and BIxAL were studied within the framework of the TREASURE project. Ten pigs from each genotype, raised in traditional free-range system and fed commercial diets ad libitum, were slaughtered at ~65 kg live weight (LW). Data obtained show that BI, ALxBI and BIxAL attained slaughter weight faster (P<0.001) than AL pigs. Overall, carcass length (P<0.001), carcass yield (P=0.06), and lean cuts weight (P<0.01) were higher in BI than AL pigs, with intermediate values for both crosses. Conversely, fat cuts weight, ZP fat depth (P<0.01) and average backfat thickness (P<0.001) were higher in AL than in BI, and ALxBI and BIxAL pigs. At 65kg LW, RI crosses presented intermediate characteristics between fatter (AL) and leaner (BI) genotypes. This cross could therefore be an alternative to the use of other (modern) breeds for crossing, helping to increase the revenue of autochthonous pig producers, and also maintain or increase the pure breed populations, contributing to animal biodiversity

Biomonitoring PM using transplanted lichens in an urban-industrial area of the Lisbon Metropolitan Area and integration with reference monitoring method

Trabalho apresentado em 11th International Aerosol Conference (IAC2022), 4-9 setembro 2022, Atenas, GréciaN/

Comparing variant calling algorithms for target-exon sequencing in a large sample

Abstract Background Sequencing studies of exonic regions aim to identify rare variants contributing to complex traits. With high coverage and large sample size, these studies tend to apply simple variant calling algorithms. However, coverage is often heterogeneous; sites with insufficient coverage may benefit from sophisticated calling algorithms used in low-coverage sequencing studies. We evaluate the potential benefits of different calling strategies by performing a comparative analysis of variant calling methods on exonic data from 202 genes sequenced at 24x in 7,842 individuals. We call variants using individual-based, population-based and linkage disequilibrium (LD)-aware methods with stringent quality control. We measure genotype accuracy by the concordance with on-target GWAS genotypes and between 80 pairs of sequencing replicates. We validate selected singleton variants using capillary sequencing. Results Using these calling methods, we detected over 27,500 variants at the targeted exons; >57% were singletons. The singletons identified by individual-based analyses were of the highest quality. However, individual-based analyses generated more missing genotypes (4.72%) than population-based (0.47%) and LD-aware (0.17%) analyses. Moreover, individual-based genotypes were the least concordant with array-based genotypes and replicates. Population-based genotypes were less concordant than genotypes from LD-aware analyses with extended haplotypes. We reanalyzed the same dataset with a second set of callers and showed again that the individual-based caller identified more high-quality singletons than the population-based caller. We also replicated this result in a second dataset of 57 genes sequenced at 127.5x in 3,124 individuals. Conclusions We recommend population-based analyses for high quality variant calls with few missing genotypes. With extended haplotypes, LD-aware methods generate the most accurate and complete genotypes. In addition, individual-based analyses should complement the above methods to obtain the most singleton variants.http://deepblue.lib.umich.edu/bitstream/2027.42/110906/1/12859_2015_Article_489.pd

Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes

We mapped ∼85,000 rare nonsynonymous exonic single nucleotide polymorphisms ( SNPs ) to 17 psychophysiological endophenotypes in 4,905 individuals, including antisaccade eye movements, resting EEG , P 300 amplitude, electrodermal activity, affect‐modulated startle eye blink. Nonsynonymous SNPs are predicted to directly change or disrupt proteins encoded by genes and are expected to have significant biological consequences. Most such variants are rare, and new technologies can efficiently assay them on a large scale. We assayed 247,870 mostly rare SNPs on an Illumina exome array. Approximately 85,000 of the SNPs were polymorphic, rare ( MAF  < .05), and nonsynonymous. Single variant association tests identified a SNP in the PARD 3 gene associated with theta resting EEG power. The sequence kernel association test, a gene‐based test, identified a gene PNPLA 7 associated with pleasant difference startle, the difference in startle magnitude between pleasant and neutral images. No other single nonsynonymous variant, or gene‐based group of variants, was strongly associated with any endophenotype.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109617/1/psyp12349.pd

Comparing variant calling algorithms for target-exon sequencing in a large sample

Abstract Background Sequencing studies of exonic regions aim to identify rare variants contributing to complex traits. With high coverage and large sample size, these studies tend to apply simple variant calling algorithms. However, coverage is often heterogeneous; sites with insufficient coverage may benefit from sophisticated calling algorithms used in low-coverage sequencing studies. We evaluate the potential benefits of different calling strategies by performing a comparative analysis of variant calling methods on exonic data from 202 genes sequenced at 24x in 7,842 individuals. We call variants using individual-based, population-based and linkage disequilibrium (LD)-aware methods with stringent quality control. We measure genotype accuracy by the concordance with on-target GWAS genotypes and between 80 pairs of sequencing replicates. We validate selected singleton variants using capillary sequencing. Results Using these calling methods, we detected over 27,500 variants at the targeted exons; >57% were singletons. The singletons identified by individual-based analyses were of the highest quality. However, individual-based analyses generated more missing genotypes (4.72%) than population-based (0.47%) and LD-aware (0.17%) analyses. Moreover, individual-based genotypes were the least concordant with array-based genotypes and replicates. Population-based genotypes were less concordant than genotypes from LD-aware analyses with extended haplotypes. We reanalyzed the same dataset with a second set of callers and showed again that the individual-based caller identified more high-quality singletons than the population-based caller. We also replicated this result in a second dataset of 57 genes sequenced at 127.5x in 3,124 individuals. Conclusions We recommend population-based analyses for high quality variant calls with few missing genotypes. With extended haplotypes, LD-aware methods generate the most accurate and complete genotypes. In addition, individual-based analyses should complement the above methods to obtain the most singleton variants.http://deepblue.lib.umich.edu/bitstream/2027.42/134735/1/12859_2015_Article_489.pd

Combined Linkage and Association Analyses of the 124-bp Allele of Marker D2S2944 with Anxiety, Depression, Neuroticism and Major Depression

A central issue in psychiatric genetics is whether positive findings replicate. Zubenko et al. (2002b, Mol. Psychiatry 7:460-467) reported an association of the 124-bp allele of D2S2944 with recurrent early-onset major depression for females. We tested for association of this allele to continuous measures of anxiety, depression and neuroticism in a Dutch sample of 347 males and 448 females, and to DSM-IV major depression in a subsample of 210 males and 295 females. The association of the 124-bp allele to depression in females was not replicated, but there were significant associations (not significant after correction for multiple testing) with anxiety and anxious depression in males. However, the association occurred in the absence of evidence for linkage in this region on chromosome 2. © 2006 Springer Science+Business Media, Inc

Chromosome 9: linkage for borderline personality disorder features.

Objective A large-scale twin study implicated genetic influences on borderline personality disorder (BPO) features, with a heritability estimate of 42%. To date, no genome-wide linkage study has been conducted to identify the genomic region(s) containing the quantitative trait loci that influence the manifestation of BPD features. Methods We conducted a family-based linkage study using Merlin regress. The participating families were drawn from the community-based Netherlands Twin Register. The sample consisted of 711 sibling pairs with phenotype and genotype data, and 561 additional parents with genotype data. BPD features were assessed on a quantitative scale. Results Evidence for linkage was found on chromosomes 1, 4, 9, and 18. The highest linkage peak was found on chromosome 9p at marker D9S286 with a logarithm of odds score of 3.548 (empirical P= 0.0001). Conclusion To our knowledge, this is the first linkage study on BPD features and shows that chromosome 9 is the richest candidate for genes influencing BPD. The results of this study will move the field closer to determining the genetic etiology of BPD and may have important implications for treatment programs in the future. Association studies in this region are, however, warranted to detect the actual genes. © 2008 Wolters Kluwer Health|Lippincott Williams & Wilkins

Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited