Search

ABSTRACT: Tibetan chicken is one of the most common and widely distributed highland breeds, and is often used as a model organism for understanding genetic adaptation to extreme environments in Tibet. Despite its apparent geographical diversity and large variations in plumage patterns, the genetic differences within breed were not accounted for in most studies and have not been systematically investigated. In order to reveal and genetically differentiate the current existing TBC sub-populations that might have major implications for genomic research in TBCs, we systematically evaluated the population structure and demography of current TBC populations. Based on 344 whole-genome sequenced birds including 115 Tibetan chickens that were mostly sampled from family-farms across Tibet, we revealed a clear separation of Tibetan chickens into 4 sub-populations that broadly aligns with their geographical distribution. Moreover, population structure, population size dynamics, and the extent of admixture jointly suggest complex demographic histories of these sub-populations, including possible multiple origins, inbreeding, and introgressions. While most of the candidate selected regions found between the TBC sub-populations and Red Jungle fowls were nonoverlapping, 2 genes RYR2 and CAMK2D were revealed as strong selection candidates in all 4 sub-populations. These 2 previously identified high altitude associated genes indicated that the sub-populations responded to similar selection pressures in an independent but functionally similar fashion. Our results demonstrate robust population structure in Tibetan chickens that will help inform future genetic analyses on chickens and other domestic animals alike in Tibet, recommending thoughtful experimental design.

Although hematologic malignancies (HM) are no longer considered exclusively sporadic, additional awareness of familial cases has yet to be created. Individuals carrying a (likely) pathogenic germline variant (e.g., in ETV6, GATA2, SAMD9, SAMD9L, or RUNX1) are at an increased risk for developing HM. Given the clinical and psychological impact associated with the diagnosis of a genetic predisposition to HM, it is of utmost importance to provide high-quality, standardized patient care. To address these issues and harmonize care across Europe, the Familial Leukemia Subnetwork within the ERN PaedCan has been assigned to draft an European Standard Clinical Practice (ESCP) document reflecting current best practices for pediatric patients and (healthy) relatives with (suspected) familial leukemia. The group was supported by members of the German network for rare diseases MyPred, of the Host Genome Working Group of SIOPE, and of the COST action LEGEND. The ESCP on familial leukemia is proposed by an interdisciplinary team of experts including hematologists, oncologists, and human geneticists. It is intended to provide general recommendations in areas where disease-specific recommendations do not yet exist. Here, we describe key issues for the medical care of familial leukemia that shall pave the way for a future consensus guideline: (i) identification of individuals with or suggestive of familial leukemia, (ii) genetic analysis and variant interpretation, (iii) genetic counseling and patient education, and (iv) surveillance and (psychological) support. To address the question on how to proceed with individuals suggestive of or at risk of familial leukemia, we developed an algorithm covering four different, partially linked clinical scenarios, and additionally a decision tree to guide clinicians in their considerations regarding familial leukemia in minors with HM. Our recommendations cover, not only patients but also relatives that both should have access to adequate medical care. We illustrate the importance of natural history studies and the need for respective registries for future evidence-based recommendations that shall be updated as new evidence-based standards are established., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

NIMA-related kinase 1(NEK1) gene was related to amyotrophic lateral sclerosis (ALS). However, genetic spectrum and clinical characteristics of ALS patients with NEK1 variants was largely unknown. We conducted genetic analysis on 1587 Chinese ALS patients and used software to predict the pathogenicity of NEK1 missense variant. We searched the literatures in PubMed, Embase, and Web of Science. In our ALS cohort, 42 ALS patients (2.6%) carried NEK1 variants, including 10 novel loss-of-function (LoF) variant carriers and 32 missense variant carriers. 90% of the NEK1 LoF variant carriers had upper limbs onset. The median survival time of LoF variant carriers tend to be shorter than that of probably pathogenic variant carriers (23.80 vs. 42.77 months). In 16 related studies, 167 different NEK1 variants, including 62 LoF and 105 missense variants, were found in 237 reported ALS patients. It was found that the survival time of LoF variant carriers was significantly shorter than that of missense variant carriers. Our study expanded the genotype and phenotype spectrum of ALS patients with NEK1 variants., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The structural base of all membranes of symbiotic dinoflagellates (SD) is composed of glycolipids and betaine lipids, whereas triacylglycerols (TG) constitute an energy reserve and are involved in biosynthesis of glycolipids. Since data on the SD lipidome and the host's influence on symbionts' lipidome are scanty, we analyzed and compared the lipidomes of SD isolated from the zoantharian Palythoa tuberculosa and the alcyonarian Sinularia heterospiculata. A sequencing of nuclear gene regions showed that both cnidarians hosted the dinoflagellates Cladocopium sp. (subclades C1 and C3), but the zoantharian also contained the dinoflagellates Durusdinium trenchii (clade D). The presence of the thermotolerant D. trenchii resulted in a higher unsaturation of mono- and digalactosyldiacylglycerols (MGDG and DGDG), but a lower unsaturation of sulfoquinovosyldiacylglycerol (SQDG). The same features were earlier described for same SD from a reef-building coral. Hence, the profile of glycolipid molecules, which form SD thylakoid membranes, seems to be species-specific and does not depend on the host's taxonomic position. In contrast, the betaine lipid molecular species profile of diacylglyceryl-3-O-carboxyhydroxymethylcholine (DGCC), which forms SD cell membranes, can be influenced by the host. The profiles of the TG molecular species from freshly isolated SD have been determined for the first time. These molecular species can be divided on the basis of the acyl group in sn-2 position. The TG with 16:0 acyl group in sn-2 position may enrich total TG of a cnidarian colony and originate from SD cytoplasm. In contrast, TG 18:3/18:4/18:3 may be biosynthetically related with DGDG and concentrated in SD plastoglobules. Our data may be useful for further investigations of natural and technogenic variations in microalgal lipids and symbiont-host interactions in marine ecosystems., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Digital PCR enabled high-sensitivity and quantitative measurements of rare biological variants. A new digital droplet-enabled PCR technology was introduced in this paper, which partitioned genetic targets into a planar nanoliter droplet array by using a microfluidic impact printer (MIP) with a disposable microfluidic chip. The accuracy of this MIP-enabled PCR technology was verified by detecting a series of concentration gradients of GAPDH gene across spanning four orders of magnitude (from 0.464 copies/μL to 464 copies/μL). Furthermore, this technology was applied to detect the expressions of p53 gene in colon cancer tissues and adjacent nontumorous tissues, from which the copies of the nucleic acids could be absolute-quantitatively determined. The outcomes were consistent with the results of using the conventional real-time PCR, demonstrating a great potential of the MIP-enabled digital PCR in detecting gene expression in clinical samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)