Biology subjects

Yoshida, G.

Publications and source records attributed to Yoshida, G..

11 recordsLinked to original sources

bioRxiv2024

m6A-mediated epi-transcriptomic dysregulation underlies synaptic dysfunction in fragile X syndrome

Fragile X syndrome (FXS), the leading genetic cause of intellectual disability, arises from FMR1 gene silencing and loss of the FMRP protein. N6-methyladenosine (m6A) is a prevalent mRNA modification essential for post-transcriptional regulation. FMRP is known to bind to and regulate the stability of m6A-containing transcripts. However, how loss of FMRP impacts on transcriptome-wide m6A modifications in FXS patients remains unknown. To answer this question, we generated cortical neurons differentiated from induced pluripotent stem cells (iPSC) derived from healthy subjects and FXS patients. In electrophysiology recordings, we validated that synaptic and neuronal network defects in iPSC-derived FXS neurons corresponded to the clinical EEG data of the patients from which the corresponding iPSC line was derived. In analysis of transcriptome-wide methylation, we show that FMRP deficiency led to increased translation of m6A writers, resulting in hypermethylation that primarily affecting synapse-associated transcripts and increased mRNA decay. Conversely, in the presence of an m6A writer inhibitor, synaptic defects in FXS neurons were rescued. Taken together, our findings uncover that an FMRP-dependent epi-transcriptomic mechanism contributes to FXS pathogenesis by disrupting m6A modifications in FXS, suggesting a promising avenue for m6A- targeted therapies.

neuroscience↗

bioRxiv2021

Abundances of transfer RNA modifications and transcriptional levels for tRNA-modifying enzymes are sex-specific in mosquitoes

As carriers of multiple human diseases, understanding the mechanisms behind mosquito reproduction may have implications for remediation strategies. Transfer RNA (tRNA) acts as the adapter molecule of amino acids and are key components in protein synthesis and a critical factor in the function of tRNAs is chemical modifications. Here, we provide an assessment of tRNA modifications between sexes for three mosquito species and examine correlated transcript levels underlying key proteins involved in tRNA modification. Thirty-three tRNA modifications were detected among mosquito species and most of these modifications are higher in females compared to males. Analysis of previous male and female RNAseq datasets indicated a similar increase in tRNA modifying enzymes in females, supporting our observed female enrichment of tRNA modifications. Tissues-specific expressional studies revealed high transcript levels for tRNA modifying enzymes in the ovaries for Aedes aegypti, but not male reproductive tissues. These studies suggest that tRNA modifications may be critical to reproduction in mosquitoes, representing a potential novel target for control.

biochemistry↗

bioRxiv2020

Mate selection provides similar genetic progress and average inbreeding than optimum contribution selection in the long-term

Optimum contribution selection (OCS) and mate selection (MS) are alternative strategies to maximize genetic gain under controlled rates of inbreeding. There is evidence in the literature that MS outperforms OCS in controlling inbreeding under the same expected genetic gain in the short-term. It is unclear, however, if the same would occur in the long-term. This study aimed to compare OCS and MS regarding short and long-term genetic progress and inbreeding, using simulated data. The structure of the simulated population aimed to mimic an aquaculture breeding program. Twenty discrete generations were simulated, considering 50 families and 2,000 offspring per generation, and a trait with a heritability of 0.3. OCS and MS were applied using a differential evolution (DE) algorithm, under an objective function that accounted for genetic merit, inbreeding of the future progeny and coancestry among selection candidates. For OCS, the optimization process consisted of selection based on optimum contribution followed by minimum inbreeding mating. Objective functions using different weights on coancestry were tested. For each application, 20 replicates were simulated and the results were compared based on their average. Both strategies, OCS and MS, were very effective in controlling inbreeding over the generations. In the short-term, MS was more efficient than OCS in controlling inbreeding under the same genetic gain. In the long-term, OCS and MS resulted in similar genetic progress and average inbreeding, under the same penalty on coancestry.

genetics↗

bioRxiv2019

Whole genome re-sequencing reveals recent signatures of selection in three strains of farmed Nile tilapia (Oreochromis niloticus)

Nile tilapia (Oreochromis niloticus Linnaeus, 1758) belong to the second most cultivated group of fish in the world, mainly because of its favorable characteristics for production. Genetic improvement programs in this species began in the late 1980s to enhance some traits of commercial interest. The resulting domestication process of Nile tilapia may have modified the genome through selective pressure, leaving signals that can be detected at the molecular level. In this work, signatures of selection were identified using genome-wide SNP data, using two complementary methods based in extended haplotype homozygosity (EHH)._Whole-genome sequencing of 326 individuals from three strains (A, B and C) of farmed tilapia from two countries (Brazil and Costa Rica) was carried out using Illumina HiSeq 2500 technology. After applying conventional SNP-calling and quality-control pipelines, a total of ~1.3M high-quality SNPs were inferred and used as input for the Integrated Haplotype Score (|iHS|) and standardized log-ratio of integrated EHH between pairs of populations (Rsb) methods. We detected 16, 174 and 96 candidate genes subjected to selection in strain A, B, and C, respectively. These candidate genes represent putative genomic landmarks that could contain functions of biological and commercial interest.

genomics↗

bioRxiv2019

High-throughput single nucleotide polymorphism (SNP) discovery and validation through whole-genome resequencing of hundreds of individuals in Nile tilapia (Oreochromis niloticus)

Nile Tilapia (Oreochromis niloticus) is the second most important farmed fish in the world and a sustainable source of protein for human consumption. Several genetic improvement programs have been established for this species in the world and so far, they are mainly based on conventional selection using genealogical and phenotypic information to estimate the genetic merit of breeders and make selection decisions. Genome-wide information can be exploited to efficiently incorporate traits that are difficult to measure in the breeding goal. Thus, SNPs are required to investigate phenotype-genotype associations and determine the genomic basis of economically important traits. We performed de novo SNP discovery in three different populations of farmed tilapias. A total of 29.9 million non-redundant SNPs were identified through Illumina (HiSeq 2500) whole-genome resequencing of 326 individual samples. After applying several filtering steps including removing SNP based on genotype and site quality, presence of Mendelian errors, and non unique position in the genome, a total of high quality 50,000 SNP were selected for validation purposes. These SNPs were highly informative in the three populations analyzed showing between 43,869 (94%) and 46,139 (99%) SNP in HWE; 37,843 (76%) and 45,171(90%) SNP with a MAF higher than 0.05 and; 43,450 (87%) and 46,570 (93%) SNPs with a MAF higher than 0.01. The final list of 50K SNPs will be very useful for the dissection of economically relevant traits, enhancing breeding programs through genomic selection as well as supporting genetic studies in farmed populations Nile tilapia using dense genome-wide information.

genomics↗

bioRxiv2019

Fine mapping using whole-genome sequencing confirms anti Mullerian hormone as a major gene for sex determination in farmed Nile tilapia (Oreochromis niloticus L.)

Nile tilapia (Oreochromis niloticus) is one of the most cultivated and economically important species in world aquaculture. Faster male development during grow-out phase is considered a major problem that generate heterogeneous sizes of fish at harvest. Identifying genomic regions associated with sex determination in Nile tilapia is a research topic of great interest. The objective of this study was to identify genomic variants associated with sex determination in three commercial populations of Nile tilapia. Whole-genome sequencing of 326 individuals was performed, and a total of 2.4 million high-quality bi-allelic single nucleotide polymorphisms (SNPs) were identified. A genome-wide association study (GWAS) was conducted to identify markers associated with the binary sexual trait (males = 0; females = 1). A mixed logistic regression GWAS model was fitted and a genome-wide significant signal comprising 36 SNPs, located on chromosome 23 spanning a genomic region of 536 kb, was identified. Ten out of these 36 genetic variants, intercept the anti-Mullerian hormone gene. Other significant SNPs were located in the neighboring Amh gene region. This gene has been strongly associated with sex determination in several vertebrate species, playing an essential role in the differentiation of male and female reproductive tissue in early stages of development. This finding provides useful information to better understand the genetic mechanisms underlying sex determination in Nile tilapia.

genomics↗

bioRxiv2019

Genome-wide association study and low-cost genomic predictions for growth and fillet yield in Nile tilapia (Oreochromis niloticus)

Fillet yield (FY) and harvest weight (HW) are economically important traits in Nile tilapia production. Genetic improvement of these traits, especially for FY, are lacking, due to the absence of efficient methods to measure the traits without sacrificing fish and the use of information from relatives to selection. However, genomic information could be used by genomic selection to improve traits that are difficult to measure directly in selection candidates, as in the case of FY. The objectives of this study were: (i) to perform genome-wide association studies (GWAS) to dissect the genetic architecture of FY and HW, (ii) to evaluate the accuracy of genotype imputation and (iii) to assess the accuracy of genomic selection using true and imputed low-density (LD) single nucleotide polymorphism (SNP) panels to determine a cost-effective strategy for practical implementation of genomic information in tilapia breeding programs. The data set consisted of 5,866 phenotyped animals and 1,238 genotyped animals (108 parents and 1,130 offspring) using a 50K SNP panel. The GWAS were performed using all genotyped and phenotyped animals. The genotyped imputation was performed from LD panels (LD0.5K, LD1K and LD3K) to high-density panel (HD), using information from parents and 20% of offspring in the reference set and the remaining 80% in the validation set. In addition, we tested the accuracy of genomic selection using true and imputed genotypes comparing the accuracy obtained from pedigree-based best linear unbiased prediction (PBLUP) and genomic predictions. The results from GWAS supports evidence of the polygenic nature of FY and HW. The accuracy of imputation ranged from 0.90 to 0.98 for LD0.5K and LD3K, respectively. The accuracy of genomic prediction outperformed the estimated breeding value from PBLUP. The use of imputation for genomic selection resulted in an increased relative accuracy independent of the trait and LD panel analyzed. The present results suggest that genotype imputation could be a cost-effective strategy for genomic selection in tilapia breeding programs.

genomics↗

bioRxiv2019

Genome-wide association analysis for resistance to infectious pancreatic necrosis virus identifies candidate genes involved in viral replication and immune response in rainbow trout (Oncorhynchus mykiss)

Infectious pancreatic necrosis (IPN) is a viral disease with considerable negative impact on the rainbow trout (Oncorhynchus mykiss) aquaculture industry. The aim of the present work was to detect genomic regions that explain resistance to infectious pancreatic necrosis virus (IPNV) in rainbow trout. A total of 2,278 fish from 58 full-sib families were challenged with IPNV. Of the challenged fish, 768 individuals were genotyped (488 resistant and 280 susceptible), using a 57K single nucleotide polymorphisms (SNPs) panel Axiom(R), Affymetrix(R). A genome-wide association study (GWAS) was performed using the phenotypes time to death (TD) and binary survival (BS), along with the genotypes of the challenged fish using a Bayesian model (Bayes C). Heritabilities for resistance to IPNV estimated using pedigree information, were 0.39 and 0.32 for TD and BS, respectively. Heritabilities for resistance to IPNV estimated using genomic information, were 0.50 and 0.54 for TD and BS, respectively. The Bayesian GWAS detected a SNP located on chromosome 5 explaining 18% of the genetic variance for TD. A SNP located on chromosome 23 was detected explaining 9% of the genetic variance for BS. The proximity of Sentrin-specific protease 5 (SENP5) to a significant SNP makes it a candidate gene for resistance against IPNV. However, the moderate-low proportion of variance explained by the detected marker leads to the conclusion that the incorporation of all genomic information, through genomic selection, would be the most appropriate approach to accelerate genetic progress for the improvement of resistance against IPNV in rainbow trout.

genomics↗

bioRxiv2019

Genome-wide patterns of population structure and linkage disequilibrium in farmed Nile tilapia (Oreochromis niloticus)

Nile tilapia (Oreochromis niloticus) is one of the most produced farmed fish in the world and represents an important source of protein for human consumption. Farmed Nile tilapia populations are increasingly based on genetically improved stocks, which have been established from admixed populations. To date, there is scarce information about the population genomics of farmed Nile tilapia, assessed by dense single nucleotide polymorphism (SNP) panels. The patterns of linkage disequilibrium (LD) may affect the success of genome-wide association studies (GWAS) and genomic selection and can also provide key information about demographic history of farmed Nile tilapia populations. The objectives of this study were to provide further knowledge about the population structure and LD patterns, as well as, estimate the effective population size (Ne) for three farmed Nile tilapia populations, one from Brazil (POP A) and two from Costa Rica (POP B and POP C). A total of 55, 56 and 57 individuals from POP A, POP B and POP C, respectively, were genotyped using a 50K SNP panel selected from a whole-genome sequencing (WGS) experiment. Two principal components explained about 20% of the total variation and clearly discriminated between the three populations. Population genetic structure analysis showed evidence of admixture, especially for POP C. The contemporary Ne values calculated based to LD values, ranged from 71 to 141. No differences were observed in the LD decay among populations, with a rapid decrease of r2 when increasing inter-marker distance. Average r2 between adjacent SNP pairs ranged from 0.03 to 0.18, 0.03 to 0.17 and 0.03 to 0.16 for POP A, POP B and POP C, respectively. Based on the number of independent chromosome segments in the Nile tilapia genome, at least 4.2 K SNP are required for the implementation of GWAS and genomic selection in farmed Nile tilapia populations.

genomics↗

bioRxiv2018

Population genomic structure and genome-wide linkage disequilibrium in farmed Atlantic salmon (Salmo salar L.) using dense SNP genotypes

Chilean Farmed Atlantic salmon (Salmo salar) populations were established with individuals of both European and North American origins. These populations are expected to be highly genetically differentiated due to evolutionary history and poor gene flow between ancestral populations from different continents. The extent and decay of linkage disequilibrium (LD) among single nucleotide polymorphism (SNP) impacts the implementation of genome-wide association studies and genomic selection and provides relevant information about demographic processes of fish populations. We assessed the population structure and characterized the extent and decay of LD in three Chilean commercial populations of Atlantic salmon with North American (NAM), Scottish (SCO) and Norwegian (NOR) origin. A total of 151 animals were genotyped using a 159K SNP Axiom(R) myDesign Genotyping Array. A total of 40K, 113K and 136 K SNP markers were used for NAM, SCO and NOR populations, respectively. The principal component analysis explained 86.7% of the genetic diversity between populations, clearly discriminating between populations of North American and European origin, and also between European populations. Admixture analysis showed that the Scottish and North American populations likely come from one ancestral population, while the Norwegian population probably originated from more than one. NAM had the lowest effective size, followed by SCO and NOR. Large differences in the LD decay were observed between populations of North American and European origin. A r2 threshold of 0.2 was estimated for marker pairs separated by 8,000 Kb, 42 and 64 Kb in the NAM, NOR and SCO populations, respectively. In this study we show that this SNP panel can be used to detect association between markers and traits of interests and also to capture high-resolution information for genome-enabled predictions. Also, we suggest the feasibility to achieve higher prediction accuracies by using a small SNP data set as was used with the NAM population.

genomics↗

bioRxiv2018

Whole genome linkage disequilibrium and effective population size in a coho salmon (Oncorhynchus kisutch) breeding population

The estimation of linkage disequilibrium between molecular markers within a population is critical when establishing the minimum number of markers required for association studies, genomic selection and for inferring historical events influencing different populations. This work aimed to evaluate the extent and decay of linkage disequilibrium in a coho salmon breeding population using ddRAD genomic markers.\n\nLinkage disequilibrium was estimated between a total of 7,505 SNPs found in 62 individuals (33 dams and 29 sires) from the breeding population. The makers encompass all 30 coho salmon chromosomes and comprise 1,655.19 Mb of the genome. The average density of markers per chromosome ranged from 3.45 to 6.11 per 1 Mbp. The minor allele frequency averaged 0.20 (with a range from 0.08 to 0.50). The overall average linkage disequilibrium among SNPs pairs measured as r2 was 0.054. The Average r2 value decreased with increasing physical distance, with values ranging from 0.37 to 0.054 at distances lower than 1 kb and up to 10 Mb, respectively. An r2 threshold of 0.1 was reached at distance of approximately 1.3 Mb. Chromosomes Okis05, Okis15 and Okis28 showed high levels of linkage disequilibrium (> 0.20 at distances lower than 1 Mb). Average r2 values were lower than 0.1 for all chromosomes at distances greater than 4 Mb. Linkage disequilibrium values suggest that whole genome association and selection studies could be performed using about 75,000 SNPs in aquaculture populations (depending on the trait under investigation). From the identified SNPs, an effective population size of 100 was estimated for the population 10 generation ago, and 1,000, for 139 generations ago.\n\nBased on the extent of r2 decay, we suggest that at least 75,000 SNPs would be necessary for an association mapping study. Over 100,000 SNPs would be necessary for a high power study, in the current coho salmon population.

genomics↗