A Comprehensive Comparison of Haplotype-Based Single-Step Genomic Predictions in Livestock Populations With Different Genetic Diversity Levels: A Simulation Study

The level of genetic diversity in a population is inversely proportional to the linkage disequilibrium (LD) between individual single nucleotide polymorphisms (SNPs) and quantitative trait loci (QTLs), leading to lower predictive ability of genomic breeding values (GEBVs) in high genetically diverse populations. Haplotype-based predictions could outperform individual SNP predictions by better capturing the LD between SNP and QTL. Therefore, we aimed to evaluate the accuracy and bias of individual-SNP- and haplotype-based genomic predictions under the single-step-genomic best linear unbiased prediction (ssGBLUP) approach in genetically diverse populations. We simulated purebred and composite sheep populations using literature parameters for moderate and low heritability traits. The haplotypes were created based on LD thresholds of 0.1, 0.3, and 0.6. Pseudo-SNPs from unique haplotype alleles were used to create the genomic relationship matrix (G) in the ssGBLUP analyses. Alternative scenarios were compared in which the pseudo-SNPs were combined with non-LD clustered SNPs, only pseudo-SNPs, or haplotypes fitted in a second G (two relationship matrices). The GEBV accuracies for the moderate heritability-trait scenarios fitting individual SNPs ranged from 0.41 to 0.55 and with haplotypes from 0.17 to 0.54 in the most (Ne ≅ 450) and less (Ne < 200) genetically diverse populations, respectively, and the bias fitting individual SNPs or haplotypes ranged between −0.14 and −0.08 and from −0.62 to −0.08, respectively. For the low heritability-trait scenarios, the GEBV accuracies fitting individual SNPs ranged from 0.24 to 0.32, and for fitting haplotypes, it ranged from 0.11 to 0.32 in the more (Ne ≅ 250) and less (Ne ≅ 100) genetically diverse populations, respectively, and the bias ranged between −0.36 and −0.32 and from −0.78 to −0.33 fitting individual SNPs or haplotypes, respectively. The lowest accuracies and largest biases were observed fitting only pseudo-SNPs from blocks constructed with an LD threshold of 0.3 (p < 0.05), whereas the best results were obtained using only SNPs or the combination of independent SNPs and pseudo-SNPs in one or two G matrices, in both heritability levels and all populations regardless of the level of genetic diversity. In summary, haplotype-based models did not improve the performance of genomic predictions in genetically diverse populations.

37 Single-step Genomic BLUP Fitting Snps or Haplotypes in Genetically-diverse Populations: A Simulation Study

The successful implementation of genomic selection in more genetically diverse populations (e.g., sheep and goats) require larger training populations. Haplotype-based genomic predictions are hypothesized to perform better in comparison to single-SNP methods mainly due to the possibility of better capturing QTL effects in linkage disequilibrium (LD) with the markers. However, most genomic-prediction studies based on haplotypes were performed in populations with low effective population size (Ne < 150). We aimed to investigate alternative approaches for fitting haplotypes using the single-step GBLUP method (ssGBLUP) in a genetically diverse population (Ne = 400). We simulated a composite sheep population, mimicking real populations based on literature parameters, using the QMSim software, with five replicates. We simulated a HD panel (600K) and two traits with different heritabilites (0.10 and 0.30). Pseudo-SNPs from unique haplotype alleles derived from LD blocks with thresholds of 0.1, 0.3, and 0.6 (LD01, LD03, and LD06, respectively) were used in the analyses. The LD-blocks were constructed using a 50K panel designed from the simulated HD. The training population was composed of 60,000 individuals with phenotypes, 8,000 of them also had genotypes, and 2,000 young genotyped individuals were used as the validation set. The genomic relationship (G) in the ssGBLUP was constructed using both independent markers and pseudo-SNPs (haplotypes). A linear mixed effects model was used to test the effect of the G on the accuracies of prediction, followed by the Tukey test with 5% of significance. No blocks were created with LD06. The accuracies with the 50K panel, LD01, and LD03 for the moderate heritability were 0.41(0.00), 0.40(0.01) and 0.41(0.00), respectively, and 0.24(0.01) 0.23(0.01), and 0.24(0.01) for the low heritability scenario. No statistical differences were observed. Based on our findings, haplotype-based predictions did not improve the accuracy of genomic breeding values in genetically diverse populations.

A unique Toxoplasma gondii haplotype under strong selection has accompanied domestic cats in their global expansion

ABSTRACTToxoplasma gondii is a cyst-forming apicomplexan parasite of virtually all warm-blooded species, with all true cats (Felidae) as definitive hosts. It is the etiologic agent of toxoplasmosis, a disease causing substantial public health burden worldwide. Its wide range of host species and its global occurrence probably complicate the study of its evolutionary history, and conflicting scenarios have been proposed to explain its current global distribution. In this study, we analyse a global set of 156 genomes (including 105 new genomes) and we provide the first direct estimate of T. gondii mutation rate and the first estimate of its generation time. We elucidate how the evolution of T. gondii populations is intimately linked to the major events that have punctuated the recent history of cats. We show that a unique haplotype —whose length represents only 0.16% of the whole T. gondii genome— is common to all domestic T. gondii strains worldwide and has accompanied wild cats (Felis silvestris) during their emergence from the wild to domestic settlements, their dispersal in the Old World and their recent expansion to the Americas in the last six centuries. By combining environmental and functional data to selection inference tools, we show that selection of this domestic haplotype is most parsimoniously explained by its role in initiation of sexual reproduction of T. gondii in domestic cats.

First Record of a Novel Mitochondrial DNA Haplotype of a Marble Trout Lineage of Salmo Trutta in Turkey

A new record of a marble trout mtDNA haplotype known to be restricted to Adriatic basin (called marmoratus lineage within Salmo trutta complex) has been reported from Eşen Stream in the Aegean Sea basin of southeastern Turkey, based on sequence data of the mitochondrial DNA control region. The results of this study showed a single unique haplotype from this population, called MATR1. Phylogenetic analyses of this haplotype along with other haplotypes belonging to different mitochondrial DNA lineages of the S. trutta complex confirmed the existence of the marmoratus lineage in Turkey, suggesting a possible river capture between the Adriatic and Aegean Sea basins until the last (Würmian) marine regression.

Highly Elevated Prevalence of Spinobulbar Muscular Atrophy in Indigenous Communities in Canada Due to a Founder Effect

ObjectiveSpinobulbar muscular atrophy (SBMA) is an X-linked adult-onset neuromuscular disorder that causes progressive weakness and androgen insensitivity in hemizygous males. This condition is reported to be extremely rare, but has higher prevalence in certain populations due to multiple founder effects. Anecdotal observations of a higher prevalence of SBMA in patients of Indigenous descent in Saskatchewan led us to perform this study, to estimate the disease prevalence, and to attempt to identify a founder effect.MethodsFor our prevalence estimation, we identified patients with confirmed SBMA diagnosis from the Saskatoon neuromuscular clinic database for comparison with population data available from Statistics Canada. For our haplotype analysis, participants with SBMA were recruited from 2 neuromuscular clinics, as well as 5 control participants. Clinical data were collected, as well as a DNA sample using saliva kits. We performed targeted quantification of DXS1194, DXS1111, DXS135, and DXS1125 microsatellite repeats and the AR GGC repeat to attempt to identify a disease haplotype and compare it with prior studies.ResultsWe estimate the prevalence of SBMA among persons of Indigenous descent in Saskatchewan as 14.7 per 100,000 population. Although we believe that this is an underestimate, this still appears to be the highest population prevalence for SBMA in the world. A total of 21 participants were recruited for the haplotype study, and we identified a unique haplotype that was shared among 13 participants with Indigenous ancestry. A second shared haplotype was identified in 2 participants, which may represent a second founder haplotype, but this would need to be confirmed with future studies.ConclusionsWe describe a very high prevalence of SBMA in western Canadians of Indigenous descent, which appears to predominantly be due to a founder effect. This necessitates further studies of SBMA in these populations to comprehensively ascertain the disease prevalence and allow appropriate allocation of resources to support individuals living with this chronic disease.

DFNA5 (GSDME) c.991-15_991-13delTTC: Founder Mutation or Mutational Hotspot?

Deafness due to mutations in the DFNA5 gene is caused by the aberrant splicing of exon 8, which results in a constitutively active truncated protein. In a large family of European descent (MORL-ADF1) segregating autosomal dominant nonsyndromic hearing loss, we used the OtoSCOPE platform to identify the genetic cause of deafness. After variant filtering and prioritization, the only remaining variant that segregated with the hearing loss in the family was the previously described c.991-15_991-13delTTC mutation in DFNA5. This 3-base pair deletion in the polypyrimidine of intron 7 is a founder mutation in the East Asian population. Using ethnicity-informative markers and haplotype reconstruction within the DFNA5 gene, we confirmed family MORL-ADF1 is of European ancestry, and that the c.991-15_991-13delTTC mutation arose on a unique haplotype, as compared to that of East Asian families segregating this mutation. In-depth audiometric analysis showed no statistical difference between the audiometric profile of family MORL-ADF1 and the East Asian families. Our data suggest the polypyrimidine tract in intron 7 may be a hotspot for mutations.

Genetic diversity of blue swimming crab (Portunus pelagicus Linn 1758) from Indonesian waters (Sunda and Sahul Shelf, Wallacea region): Phylogenetic approach

Hidayani AA, Fujaya Y, Trijuno DD, Rukminasari N, Alimuddin A. 2020. Genetic diversity of blue swimming crab (Portunus pelagicus Linnaeus 1758) from Indonesian waters (Sunda and Sahul Shelf, Wallacea region): Phylogenetic approach. Biodiversitas 21: 2097-2102. Blue swimming crab is one of the exploited fisheries commodities in Indonesia. This condition has contributed to the decline of their genetic diversity. The information on genetic diversity assumes importance for the conservation and the cultural purposes of species. The study aimed to determine the genetic diversity of blue swimming crabs from Indonesian waters using phylogenetic analysis. We conducted sampling of crab from several Indonesian waters, such the Aceh and Semarang (representing Sunda Shelf), Barru, South Sulawesi, and Maumere, Flores (representing Wallacea region) and Sorong, Raja Ampat and Kaimana (representing Sahul Shelf). Genetic diversity in this study using mitochondrial DNA (mtDNA) by implementing the method of Cytochrome c Oxidase Subunit I (COI). According to the findings, the blue swimming crabs from our study sites had a high genetic diversity variation. Three groups of crabs were determined using phylogenetic tree which formed three different unique clades. There was the same haplotype of crab observed from different locations, barring a sample from the Sahul Shelf which has a unique haplotype. There was no genetic speciation of crab samples from the Sunda Shelf and the Wallacea region were observed, except samples from the Sahul Shelf. Hybridization might occur between species of the crabs due to the finding of a cryptic species.

A fortuitous find: a unique haplotype of Ooencyrtus nezarae Ishii (Encyrtidae: Encyrtinae) discovered in Florida

The adventive arrival of biological control agents circumvents the regulatory process by introducing exotic species to control invasive pests and is generally followed by post hoc risk evaluation. The bean plataspid, Megacopta cribraria (Fabricius) (Hemiptera: Plataspidae), is an invasive pest of leguminous crops in the south-eastern United States that was eventually followed by two parasitoid wasps from its range in the eastern hemisphere, Paratelenomus saccharalis (Dodd) (Scelionidae) and Ooencyrtus nezarae Ishii (Encyrtidae). In North Central Florida, sentinel egg masses, intended to capture Paratelenomus saccharalis, instead yielded Ooencyrtus nezarae, which was previously known only from Alabama (Ademokoya et al. 2018). Two generations of O. nezarae were subsequently reared in the laboratory. COI sequences from the Florida population of O. nezarae differed by 1.3% from the Alabama population and the presence of a different haplotype suggests the possibility of a separate introduction. Laboratory parasitism rates, sex ratios, morphology, molecular diagnosis and implications for agriculture are discussed.

Effect of Bitter Compounds on the Expression of Bitter Taste Receptor T2R7 Downstream Signaling Effectors in cT2R7/pDisplay-Gα16/gust44/pcDNA3.1 (+) Cells

Bitterness is an important taste sensation for chickens, which provides useful sensory information for acquisition and selection of diet, and warns them against ingestion of potentially harmful and noxious substances in nature. Bitter taste receptors (T2Rs) mediate the recognition of bitter compounds belonging to a family of proteins known as G-protein coupled receptors. The aim of this study was to identify and evaluate the expression of T2R7 in chicken tongue tissue and construct cT2R7-1 and cT2R7-2-expressing HEK-293T cells to access the expression of PLCβ2 and ITPR3 after exposure with different concentrations of the bitter compounds. Using real-time PCR, we show that the relative expression level of T2R7 mRNA in 5, 1, 0.1, and 10−3 mM of camphor and erythromycin solutions and 5 mM of chlorpheniramine maleate solutions was significantly higher than that in 50 mM KCL solutions. We confirmed that the bitter taste receptor T2R7 and downstream signaling effectors are sensitive to different concentrations of bitter compounds. Moreover, T2R7-1 (corresponding to the unique haplotype of the Tibetan chicken) had higher sensitivity to bitter compounds compared with that of T2R7-2 (corresponding to the unique haplotype of the Jiuyuan black-chicken). These results provide great significance of taste response on dietary intake to improve chicken feeding efficiency in poultry production and have certain reference value for future taste research in other bird species.

Trans-acting non-synonymous variant of FOXA1 predisposes to hepatocellular carcinoma through modulating FOXA1-ERα transcriptional program and may have undergone natural selection

Interplay of pioneer transcription factor forkhead box A1 (FOXA1) and estrogen receptor has been implicated in sexual dimorphism in hepatocellular carcinoma (HCC), but etiological relevance of its polymorphism was unknown. In the case control study (1152 patients versus1242 controls), we observed significant increase in HCC susceptibility in hepatitis B virus carriers associated with a non-synonymous Thr83Ala variant of FOXA1 (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.11−1.48, for Ala83-containing genotype, after validation in an independent population with 933 patients versus 1030 controls), a tightly linked (CGC)5/6or7 repeat polymorphism at its promoter (OR 1.32; 95% CI 1.10–1.60, for (CGC)6or7-repeat-containing genotype), and their combined haplotype (OR 1.50; 95% CI 1.24–1.81, for (CGC)6or7−Ala83 haplotype). The susceptible FOXA1-Ala83 impairs its interaction with ERα, attenuates transactivation toward some of their dual target genes, such as type 1 iodothyronine deiodinase, UDP glucuronosyltransferase 2 family, polypeptide B17 and sodium/taurocholate cotransporting polypeptide, but correlates with strengthened cellular expression of α-fetoprotein (AFP) and elevated AFP serum concentration in HCC patients (n = 1096). The susceptible FOXA1 cis-variant with (CGC)6or7 repeat strengthens the binding to transcription factor early growth response 1 and enhances promoter activity and gene expression. Evolutionary population genetics analyses with public datasets reveal significant population differentiation and unique haplotype structure of the derived protective FOXA1-Thr83 and suggest that it may have undergone positive natural selection in Chinese population. These findings epidemiologically highlight the functional significance of FOXA1-ERα transcriptional program and regulatory network in liver cancer development.