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The North American (NA) Atlantic salmon typically has 27 pairs of chromosomes, whereas the European (EU) subspecies typically has 29. We investigated within-family recombination within three previously identified chromosome rearrangements (Ssa01p/23, Ssa08/29, and Ssa26/28) in NA Atlantic salmon by creating high-density linkage maps using a custom 50K SNP chip developed for the Saint John River aquaculture strain. Linkage maps created for individual purebred and EU hybrid parents in 10 full-sibling families averaged 14337 SNPs per cross, covering 43033 SNPs from the 50K SNP chip. Chromosomal translocation Ssa01p/23 was fixed except in one hybrid female map. In contrast, fusion Ssa08/29 was present in maps in 4 out of 10 females and 8 out of 10 males, whereas fusion Ssa26/28 was present in maps in 6 out of 10 females and 8 out of 10 males. The orientation of Ssa08/29 differed from the previous map; the short arm of the metacentric Ssa08 was fused to the centromere of the acrocentric Ssa29. We detected large regions of recombination suppression in female maps at the fusion of Ssa08 to Ssa29. This suppression may reduce the impacts of aneuploidy resulting from pairing of fused and unfused chromosomes, thereby allowing the persistence of chromosomal polymorphisms in this population. Key words: SNP array, SNP linkage map, chromosome polymorphism, recombination suppression, sex locus, Introduction Recombination between chromosomes with different structural variants can facilitate genome evolution (Bertolotti et al. 2020). Large inversions cause reduced recombination in specific areas of the genome, thereby facilitating local [...]

Bos indicus cattle breeds have been naturally selected for thousands of years for disease resistance and thermo-tolerance. However, the genetic mechanisms underlying these specific inherited characteristics must be elucidated. Hence, in this study, a whole-genome comparative analysis ofthe Bos indicus cattle breeds Kangayam, Tharparkar, Sahiwal, Red Sindhi, and Hariana of the Indian subcontinent was conducted. Genetic variant identification analysis revealed 155 851 012 SNPs and 10 062 805 InDels in the mapped reads across all Bos indicus cattle breeds. The functional annotation of 17252 genes that comprised both SNPs and InDels, with high functional impact on proteins, was carried out. The functional annotation results revealed the pathways involved in the innate immune response, including toll-like receptors, retinoic acid-inducible gene I-like receptors, NOD-like receptors, Jak-STAT signaling pathways, and non-synonymous variants in the candidate immune genes. We also identified several pathways involved in the heat shock response, hair and skin properties, oxidative stress response, osmotic stress response, thermal sweating, feed intake, metabolism, and non-synonymous variants in the candidate thermo-tolerant genes. These pathways and genes directly or indirectly contribute to the disease resistance and thermo-tolerance adaptations of Bos indicus cattle breeds. Key words: Bos indicus, disease resistance, thermo-tolerance, SNPs, InDels. Les races de bovins appartenant a l'espece Bos indicus ont ete selectionnees naturellement au cours de milliers d'annees pour leur resistance aux maladies et leur tolerance a la chaleur. Cependant, le mecanisme genetique expliquant ces caracteres hereditaires n'a pas encore ete decrit. Dans ce travail, les auteurs ont realise une analyse comparee pan-genomique de cinq races du Bos indicus qui sont presentes sur le sous-continent indien (Kangayam, Tharparkar, Sahiwal, Red Sindhi et Hariana). Au total, 155 851 012 SNP et 10 062 805 InDels ont ete identifies a partir des lectures alignees parmi les cinq races. Les auteurs ont realise l'annotation fonctionnelle des 17 252 genes qui comprenaient des SNP ou des InDels dont on a predit qu'ils auraient un impact fonctionnel important sur les proteines. Les resultats de l'annotation fonctionnelle ont revele des sentiers impliques dans les reponses immunitaires innees, comme les recepteurs de type Toll, les recepteurs du type de l'acide retinoique, des recepteurs de type NOD, les sentiers de signalisation Jak-STAT et des variants nonsynonymes dans des genes candidats du systeme immunitaire. De plus, les auteurs ont egalement identifie plusieurs sentiers impliques dans la reponse au choc thermique, lies aux caracteristiques des poils et de la peau, a la reponse aux stress oxydatifs, a la reponse au stress osmotique, la sudation, la prise alimentaire, le metabolisme et des variants non-synonymes dans des genes candidats pour le thermo-tolerance. Ces sentiers et genes pourraient contribuer directement ou indirectement a la resistance aux maladies et aux adaptations liees a la thermo-tolerance chez les races bovines de Bos indicus. [Traduit par la Redaction] Mots-cles: Bosindicus, resistance aux maladies, thermo-tolerance, SNP, InDel., Introduction Bos indicus cattle breeds (Zebu cattle) are characterized by a hump at the withers, pendulous skin in the dewlap and navel, draught ability, fertility at higher temperatures, maintenance of [...]

Malaria remains the deadliest vectorbome infectious disease worldwide (1). Plasmodium spp., most commonly P. falciparum, are responsible for [approximately equal to] 229 million cases and [approximately equal to] 500,000 deaths [...]

Childhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like mesenchymal cell state and a more differentiated sympathetic adrenergic cell state. These cell states are governed by autoregulatory transcriptional loops called core regulatory circuitries (CRCs), which drive the early development of sympathetic neuronal progenitors from migratory neural crest cells during embryogenesis. The adrenergic cell identity of neuroblastoma requires LMO1 as a transcriptional cofactor. Both LMO1 expression levels and the risk of developing neuroblastoma in children are associated with a single nucleotide polymorphism, G/T, that affects a GATA motif in the first intron of LMO1. Here, we showed that WT zebrafish with the GATA genotype developed adrenergic neuroblastoma, while knock-in of the protective TATA allele at this locus reduced the penetrance of MYCN-driven tumors, which were restricted to the mesenchymal cell state. Whole genome sequencing of childhood neuroblastomas demonstrated that TATA/TATA tumors also exhibited a mesenchymal cell state and were low risk at diagnosis. Thus, conversion of the regulatory GATA to a TATA allele in the first intron of LMO1 reduced the neuroblastoma-initiation rate by preventing formation of the adrenergic cell state. This mechanism was conserved over 400 million years of evolution, separating zebrafish and humans., Introduction Across all cell lineages and tissue types, groups of transcription factors act cooperatively in autoregulatory loops to bind to their own and each other's enhancers to regulate gene expression, [...]

Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11,234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH. Analysis of single-nucleotide variants and copy number alterations gives a more complete picture of clonal hematopoiesis and its impact on hematological malignancy and cardiovascular disease., Author(s): Ryunosuke Saiki [sup.1] , Yukihide Momozawa [sup.2] , Yasuhito Nannya [sup.1] , Masahiro M. Nakagawa [sup.1] [sup.3] , Yotaro Ochi [sup.1] , Tetsuichi Yoshizato [sup.1] , Chikashi Terao [sup.4] [...]