Levels Of Linkage Disequilibrium Research Articles

Long-range linkage disequilibrium events on the genome of dromedary camels as a signal of epistatic and directional positive selection

The genome of dromedary camels has been subjected to various evolutionary forces, such as genetic admixture, natural positive selection, and epistatic selection. These forces are considered as main factors associated with the formation of long-range linkage disequilibrium (LRLD) events. We have analyzed whole-genome data of 56 dromedary camel samples from different geographical regions across the Arabian Peninsula for two main purposes: first, to assess the level of linkage disequilibrium, and second, to identify autosomal LRLD events. The analysis revealed a mean r2 value of 0.25 (±0.028) over the dromedary autosomes, with a continuous decay until reaching a plateau at inter-variant distances >400 kb. A total of 1847 LRLD events were identified within the dromedary autosomes, which harbor 36 prevalent haplotypes. A level of genetic admixture was observed among the dromedary populations analyzed, which might be a source for the observed LRLD events. Four functional interactions were revealed among the genes found within the LRLD events, with some genes overlapping with prevalent haplotypes, indicative of potential epistatic selection. Genes related to renal function, fertility, thermal regulation, bone structure, and insulin regulation were found among the LRLD genes. These genes, along with the defined prevalent haplotypes, can be considered as hotspots for natural positive selection associated with the LRLD distribution on dromedary genomes. In this study, we have for the first time analyzed the genome of dromedary camels for LRLD events possibly influenced by forces including genetic admixture, epistatic and positive selection. The revealed LRLD elements and prevalent haplotypes should be accounted for when designing breeding programmes to conserve the genetic stock of this well-adapted domestic species.

Genomic analysis uncovers novel candidate genes related to adaptation to tropical climates and milk production traits in native goats

BackgroundSince domestication, both evolutionary forces and human selection have played crucial roles in producing adaptive and economic traits, resulting in animal breeds that have been selected for specific climates and different breeding goals. Pakistani goat breeds have acquired genomic adaptations to their native climate conditions, such as tropical and hot climates. In this study, using next-generation sequencing data, we aimed to assess the signatures of positive selection in three native Pakistani goats, known as milk production breeds, that have been well adapted to their local climate.ResultsTo explore the genomic relationship between studied goat populations and their population structure, whole genome sequence data from native goat populations in Pakistan (n = 26) was merged with available worldwide goat genomic data (n = 184), resulting in a total dataset of 210 individuals. The results showed a high genetic correlation between Pakistani goats and samples from North-East Asia. Across all populations analyzed, a higher linkage disequilibrium (LD) level (– 0.59) was found in the Pakistani goat group at a genomic distance of 1 Kb. Our findings from admixture analysis (K = 5 and K = 6) showed no evidence of shared genomic ancestry between Pakistani goats and other goat populations from Asia. The results from genomic selection analysis revealed several candidate genes related to adaptation to tropical/hot climates (such as; KITLG, HSPB9, HSP70, HSPA12B, and HSPA12B) and milk production related-traits (such as IGFBP3, LPL, LEPR, TSHR, and ACACA) in Pakistani native goat breeds.ConclusionsThe results from this study shed light on the structural variation in the DNA of the three native Pakistani goat breeds. Several candidate genes were discovered for adaptation to tropical/hot climates, immune responses, and milk production traits. The identified genes could be exploited in goat breeding programs to select efficient breeds for tropical/hot climate regions.

High-throughput and cost-effective genotyping by low-coverage whole genome sequencing with genotype imputation in Pacific oyster, Crassostrea gigas

In order to improve the application of genomic resources in genomic selection breeding of aquaculture species, it is imperative to develop high throughput genotyping methods that are suitable for aquatic species with highly heterozygous and complex genomes. This study aimed to address the issue of accurate genotype imputation for lcWGS (low coverage whole genome sequencing) without reference panel in aquatic species. We performed lcWGS with an average depth of 2.8× on 360 individuals of Crassostrea gigas, then performed genotype imputation through reference-free method to achieve genome-wide genotyping. The results demonstrated that STITCH showed outstanding performance in conducting genotype imputation without reference panel, with R2 of 0.860 ± 0.055 and GC of 0.936 ± 0.022. The comparison of accuracy among different populations indicated that the selected breeding population with higher level of linkage disequilibrium within the population showed significant improvement in imputation accuracy compared to the wild population (P < 0.01). The diminishing marginal utility in accuracy beyond 300 samples suggested that hundreds of individuals were adequate for accurate genotyping by lcWGS. The imputed genotypes showed high accuracy in identifying genetic relationships and potential application in selection breeding. This study provides valuable information toward application of high-throughput and cost-effective genotyping in accelerating genetic analysis and genomic selection of economic traits in aquaculture species.

The Narrow Footprint of Ancient Balancing Selection Revealed by Heterokaryon Incompatibility Genes in Aspergillus fumigatus.

In fungi, fusion between individuals leads to localized cell death, a phenomenon termed heterokaryon incompatibility. Generally, the genes responsible for this incompatibility are observed to be under balancing selection resulting from negative frequency-dependent selection. Here, we assess this phenomenon in Aspergillus fumigatus, a human pathogenic fungus with a very low level of linkage disequilibrium as well as an extremely high crossover rate. Using complementation of auxotrophic mutations as an assay for hyphal compatibility, we screened sexual progeny for compatibility to identify genes involved in this process, called het genes. In total, 5/148 (3.4%) offspring were compatible with a parent and 166/2,142 (7.7%) sibling pairs were compatible, consistent with several segregating incompatibility loci. Genetic mapping identified five loci, four of which could be fine mapped to individual genes, of which we tested three through heterologous expression, confirming their causal relationship. Consistent with long-term balancing selection, trans-species polymorphisms were apparent across several sister species, as well as equal allele frequencies within A. fumigatus. Surprisingly, a sliding window genome-wide population-level analysis of an independent dataset did not show increased Tajima's D near these loci, in contrast to what is often found surrounding loci under balancing selection. Using available de novo assemblies, we show that these balanced polymorphisms are restricted to several hundred base pairs flanking the coding sequence. In addition to identifying the first het genes in an Aspergillus species, this work highlights the interaction of long-term balancing selection with rapid linkage disequilibrium decay.

Hierarchical joint analysis of marginal summary statistics-Part I: Multipopulation fine mapping and credible set construction.

Recent advancement in genome-wide association studies (GWAS) comes from not only increasingly larger sample sizes but also the shift in focus towards underrepresented populations. Multipopulation GWAS increase power to detect novel risk variants and improve fine-mapping resolution by leveraging evidence and differences in linkage disequilibrium (LD) from diverse populations. Here, we expand upon our previous approach for single-population fine-mapping through Joint Analysis of Marginal SNP Effects (JAM) to a multipopulation analysis (mJAM). Under the assumption that true causal variants are common across studies, we implement a hierarchical model framework that conditions on multiple SNPs while explicitly incorporating the different LD structures across populations. The mJAM framework can be used to first select index variants using the mJAM likelihood with different feature selection approaches. In addition, we present a novel approach leveraging the ideas of mediation to construct credible sets for these index variants. Construction of such credible sets can be performed given any existing index variants. We illustrate the implementation of the mJAM likelihood through two implementations: mJAM-SuSiE (a Bayesian approach) and mJAM-Forward selection. Through simulation studies based on realistic effect sizes and levels of LD, we demonstrated that mJAM performs well for constructing concise credible sets that include the underlying causal variants. In real data examples taken from the most recent multipopulation prostate cancer GWAS, we showed several practical advantages of mJAM over other existing multipopulation methods.

Performance of a 74-Microhaplotype Assay in Kinship Analyses.

Microhaplotypes (MHs) consisting of multiple SNPs and indels on short stretches of DNA are new and interesting loci for forensic genetic investigations. In this study, we analysed 74 previously defined MHs in two of the populations that our laboratory provides with forensic genetic services, Danes and Greenlanders. In addition to the 229 SNPs that originally made up the 74 MHs, 66 SNPs and 3 indels were identified in the two populations, and 45 of these variants were included in new definitions of the MHs, whereas 24 SNPs were considered rare and of little value for case work. The average effective number of alleles (Ae) was 3.2, 3.0, and 2.6 in Danes, West Greenlanders, and East Greenlanders, respectively. High levels of linkage disequilibrium were observed in East Greenlanders, which reflects the characteristics of this population that has a small size, and signs of admixture and substructure. Pairwise kinship simulations of full siblings, half-siblings, first cousins, and unrelated individuals were performed using allele frequencies from MHs, STRs and SNPs from Danish and Greenlandic populations. The MH panel outperformed the currently used STR and SNP marker sets and was able to differentiate siblings from unrelated individuals with a 0% false positive rate and a 1.1% false negative rate using an LR threshold of 10,000 in the Danish population. However, the panel was not able to differentiate half-siblings or first cousins from unrelated individuals. The results generated in this study will be used to implement MHs as investigative markers for relationship testing in our laboratory.

Identification of genomic characteristics and selective signals in Guizhou black goat

BackgroundGuizhou black goat is one of the indigenous black goat breeds in the southwest region of Guizhou, China, which is an ordinary goat for mutton production. They are characterized by moderate body size, black coat, favorite meat quality with tender meat and lower odor, and tolerance for cold and crude feed. However, little is known about the genetic characteristics or variations underlying their important economic traits.ResultsHere, we resequenced the whole genome of Guizhou black goat from 30 unrelated individuals breeding in the five core farms. A total of 9,835,610 SNPs were detected, and 2,178,818 SNPs were identified specifically in this breed. The population structure analysis revealed that Guizhou black goat shared a common ancestry with Shaanbei white cashmere goat (0.146), Yunshang black goat (0.103), Iran indigenous goat (0.054), and Moroccan goat (0.002). However, Guizhou black goat showed relatively higher genetic diversity and a lower level of linkage disequilibrium than the other seven goat breeds by the analysis of the nucleotide diversity, linkage disequilibrium decay, and runs of homozygosity. Based on FST and θπ values, we identified 645, 813, and 804 selected regions between Guizhou black goat and Yunshang black goat, Iran indigenous goat, and cashmere goats. Combined with the results of XP-EHH, there were 286, 322, and 359 candidate genes, respectively. Functional annotation analysis revealed that these genes are potentially responsible for the immune response (e.g., CD28, CD274, IL1A, TLR2, and SLC25A31), humility-cold resistance (e.g., HBEGF, SOSTDC1, ARNT, COL4A1/2, and EP300), meat quality traits (e.g., CHUK, GAB2, PLAAT3, and EP300), growth (e.g., GAB2, DPYD, and CSF1), fertility (e.g., METTL15 and MEI1), and visual function (e.g., PANK2 and NMNAT2) in Guizhou black goat.ConclusionOur results indicated that Guizhou black goat had a high level of genomic diversity and a low level of linkage disequilibrium in the whole genome. Selection signatures were detected in the genomic regions that were mainly related to growth and development, meat quality, reproduction, disease resistance, and humidity-cold resistance in Guizhou black goat. These results would provide a basis for further resource protection and breeding improvement of this very local breed.

Validation of genetic risk scores for hypertension in the Central Russian population

Aim. To validate and evaluate the accuracy of 4 genetic risk scores (GRSs) for hypertension (HTN), previously created on European samples, on a population sample of the Ivanovo Oblast.Material and methods. For genetic analysis, targeted next-generation sequencing was used on a sample of the Central Russia (n=1682) based on the biobank collection. Four GRSs associated with HTN, previously developed for the European population, were selected for validation. The coefficient of determination and the area under the ROC curve were used as quality metrics for regression models. Additional validation was carried out to include all nucleotide sequence variants, regardless of linkage disequilibrium level. A combined GRS was compiled based on coefficients from individual GRSs using the clumping + thresholding (C+T) method.Results. The study demonstrated that the predictive value of previously developed GRSs when used for Central Russian population is lower than in the original studies. The proportion of explained variance was 0,5-0,8%. The best predictive ability (proportion of explained variance — 2,5%) was demonstrated using previously developed GRSs (Evangelou E, et al., 2018), which includes the largest number of nucleotide sequence variants (n=852).Conclusion. GRSs for HTN, developed on European samples, is not recommended for Russian population without preliminary validation. To create original GRSs, combining statistical parameters (β-coefficients and p-value) from different GRS is not recommended.

Evaluation of the Genetic Diversity and Population Structure of Four Native Pig Populations in Gansu Province.

Indigenous pig populations, including Bamei pigs (BM), Hezuo pigs (HZ), Huixian Qingni Black pigs (HX), and Minxian Black pigs (MX) in Gansu Province, live in a particular climate and a relatively closed geographical environment. These local pig breeds are characterized by excellent characteristics (e.g., cold tolerance, robust disease resistance, and superior meat quality). In the past few years, pig populations in Gansu Province have decreased significantly because of their poor lean meat percentage, high fat content, and slow growth rate. Maintaining the diversity of these four breeds can act as a source of new alleles to be incorporated into commercial breeds which are more susceptible to disease and less adaptable to changing conditions because of inbreeding. Genomic data analysis is adequate for determining the genetic diversity and livestock breeding population structure, even in local pig populations. However, the genetic diversity and population structure of the four native pig populations in Gansu Province are still unknown. Thus, we used "Zhongxin-I" porcine chip for the SNP detection of 102 individuals living on four pig conservation farms. A total of 57,466 SNPs were identified among the four pig breeds. The linkage disequilibrium (LD) plot showed that MX had the highest level of LD, followed by BM, HZ, and HX. The observed heterozygosity (Ho) in all four populations was higher than the expected heterozygosity (He). A principal component analysis (PCA) demonstrated that the four local pig populations were isolated. The identity displayed by the state matrix and G matrix heat map results indicated that small numbers of individuals among the four pig breeds had a high genetic distance and weak genetic relationships. The results of the population genetic structure of BM, HZ, HX, and MX pigs showed a slight genetic diversity loss. Our findings enabled us to better understand the genome characteristics of these four indigenous pig populations, which will provide novel insights for the future germplasm conservation and utilization of these indigenous pig populations.

#209 : The Association Between Autoimmune Diseases and Gestational Diabetes Mellitus: A Mendelian Randomization Study

Background and Aims: As a common complication of pregnancy, gestational diabetes mellitus (GDM) may lead to a serious negative impact on pregnant women and their children. Autoimmune diseases are chronic pathologies triggered by abnormal responses of the human immune system that result in damage and disorders in the body. Recently, several studies have demonstrated that autoimmune diseases could be related to the risk of GDM. However, several other studies of this relationship have yielded conflicting results. We explored the causal relationship between autoimmune diseases and GDM risk through a two-sample Mendelian randomization (2SMR) study. Method: We obtained exposure data for rheumatoid arthritis (RA) from a genome-wide association study (GWAS) pooled dataset, which consisted of 361,194 participants. We selected single-nucleotide polymorphisms (SNPs) that had a relationship with RA and were at a significance level of not only p &lt; 5 × 10[Formula: see text] but also at a low linkage disequilibrium (LD) level (r2 &lt; 0.01). The results included 5,687 GDM cases and 117,892 controls. For detailed Methods, please see the Methods section in this article’s Online Repository at https://www.jacionline.org Results: The results of inverse variance weight (IVW) analysis suggested a positive correlation between RA and GDM risk. In addition, no validity was observed in the statistical models for heterogeneity and pleiotropy. However, for multiple sclerosis (MS), no causal relationship between it and GDM risk was found in our study. Conclusion: Our results suggest a strong casual association between RA and the risk of GDM. The results suggested the importance of enhanced antenatal care and early intervention among pregnant women with RA as well as clues for novel risk factors for GDM.

Molecular evidence depicts genetic divergence among Agropyron elongatum and A. cristatum accessions from gene pool of Iran.

The genus Agropyron has an important role in soil protection and forage production in rangelands. The investigation utilized 37 ISSR primers, resulting in the detection of 956 loci within the A. elongatum genome and 705 loci within the A. cristatum genome. The findings revealed a high level of polymorphism, with 97% of loci in A. elongatum and 84% of loci in A. cristatum exhibiting variability. Notably, the primer (AC)8GCT emerged as a promising candidate for evaluating genetic diversity due to its ability to amplify numerous loci in both species. Using both the UPGMA algorithm and Bayesian analysis, the examined Agropyron accessions were categorized into two subgroups based on their respective species. The Q values associated with these subgroups suggested that certain accessions, namely "G16," "G19," "G20," "G21," "G22," "G23," "G24," and "G25," displayed potential admixture genomes. An analysis of molecular variance (AMOVA) underscored the significance of within-species variability, which accounted for 69% of the overall diversity, compared to between-species variability at 31%. Various genetic diversity parameters, including Na, Ne, I, He, and the number of private loci, were found to be higher in A. elongatum when compared to A. cristatum. Furthermore, Jaccard similarity coefficients ranged from 0.33 to 0.66 in A. cristatum and from 0.25 to 0.7 in A. elongatum, indicating the extent of genetic relatedness among these species. Intriguingly, the study identified two and three heterotic groups in A. cristatum and A. elongatum, respectively, which could be harnessed in the development of synthetic varieties to exploit heterosis. The results also indicated that a small proportion of ISSR loci pairs (5.2% in A. elongatum and 0.5% in A. cristatum) exhibited significant levels of linkage disequilibrium (LD) (P≤0.05), suggesting the potential utility of LD-based association mapping in Agropyron species. In conclusion, this research sheds light on the genetic diversity of Agropyron species and provides valuable insights into their potential applications in soil protection and forage production, as well as the prospects for enhancing genetic variability and heterosis in these species.

The causal relationship between pure hypercholesterolemia and psoriasis: A bidirectional, two-sample Mendelian randomization study.

Several studies have reported the association between pure hypercholesterolemia (PH) and psoriasis, but the causal effect remains unclear. We explored the causal effect between PH and psoriasis using two-sample bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies. Single nucleotide polymorphisms related with exposures at the genome-wide significance level (p<5×10-8 ) and less than the linkage disequilibrium level (r2 <0.001) were chosen as instrumental variables. Subsequently, we used inverse variance weighting (IVW), MR-Egger and weighted median (WM) methods for causal inference. p<0.05 was considered statistically significant. Heterogeneity was tested using Cochran's Q-test, and horizontal pleiotropy was examined using the MR-Egger intercept. Leave-one-out analyses were performed to assess the robustness and reliability of the results. MR results showed a positive causal effect of PH on psoriasis [IVW: odds ratios (OR): 1.139, p=0.032; MR-Egger: OR: 1.434, p=0.035; WM: OR: 1.170, p=0.045] and psoriatic arthritis (PsA) (IVW: OR: 1.210, p=0.049; MR-Egger regression: OR: 1.796, p=0.033; WM: OR: 1.317, p=0.028). However, there is no causal relationship between PH and psoriasis vulgaris as well as other unspecified psoriasis. Inverse MR results suggested a negative causal relationship between PsA and PH (IVW: OR: 0.950, p=0.037). No heterogeneity and horizontal pleiotropy exist, and these results were confirmed to be robust. PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.

Divergent mechanisms of reduced growth performance in Betula ermanii saplings from high-altitude and low-latitude range edges

The reduced growth performance of individuals from range edges is a common phenomenon in various taxa, and considered to be an evolutionary factor that limits the species’ range. However, most studies did not distinguish between two mechanisms that can lead to this reduction: genetic load and adaptive selection to harsh conditions. To address this lack of understanding, we investigated the climatic and genetic factors underlying the growth performance of Betula ermanii saplings transplanted from 11 populations including high-altitude edge and low-latitude edge population. We estimated the climatic position of the populations within the overall B. ermanii’s distribution, and the genetic composition and diversity using restriction-site associated DNA sequencing, and measured survival, growth rates and individual size of the saplings. The high-altitude edge population (APW) was located below the 95% significance interval for the mean annual temperature range, but did not show any distinctive genetic characteristics. In contrast, the low-latitude edge population (SHK) exhibited a high level of linkage disequilibrium, low genetic diversity, a distinct genetic composition from the other populations, and a high relatedness coefficient. Both APW and SHK saplings displayed lower survival rates, heights and diameters, while SHK saplings also exhibited lower growth rates than the other populations’ saplings. The low heights and diameters of APW saplings was likely the result of adaptive selection to harsh conditions, while the low survival and growth rates of SHK saplings was likely the result of genetic load. Our findings shed light on the mechanisms underlying the reduced growth performance of range-edge populations.

Comparative assessment of the effective population size and linkage disequilibrium of Karan Fries cattle revealed viable population dynamics.

Karan Fries (KF), a high-producing composite cattle was developed through crossing indicine Tharparkar cows with taurine bulls (Holstein Friesian, Brown Swiss, and Jersey), to increase the milk yield across India. This composite cattle population must maintain sufficient genetic diversity for long-term development and breed improvement in the coming years. The level of linkage disequilibrium (LD) measures the influence of population genetic forces on the genomic structure and provides insights into the evolutionary history of populations, while the decay of LD is important in understanding the limits of genome-wide association studies for a population. Effective population size (Ne) which is genomically based on LD accumulated over the course of previous generations, is a valuable tool for e valuation of the genetic diversity and level of inbreeding. The present study was undertaken to understand KF population dynamics through the estimation of Ne and LD for the longterm sustainability of these breeds. The present study included 96 KF samples genotyped using Illumina HDBovine array to estimate the effective population and examine the LD pattern. The genotype data were also obtained for other crossbreds (Santa Gertrudis, Brangus, and Beefmaster) and Holstein Friesian cattle for comparison purposes. The average LD between single nucleotide polymorphisms (SNPs) was r2 = 0.13 in the present study. LD decay (r2 = 0.2) was observed at 40 kb inter-marker distance, indicating a panel with 62,765 SNPs was sufficient for genomic breeding value estimation in KF cattle. The pedigree-based Ne of KF was determined to be 78, while the Ne estimates obtained using LD-based methods were 52 (SNeP) and 219 (genetic optimization for Ne estimation), respectively. KF cattle have an Ne exceeding the FAO's minimum recommended level of 50, which was desirable. The study also revealed significant population dynamics of KF cattle and increased our understanding of devising suitable breeding strategies for longterm sustainable development.

Association Analysis of Tiller-Related Traits with EST-SSR Markers in Psathyrostachys juncea.

Psathyrostachys juncea is a long-lived perennial Gramineae grass with dense basal tillers and soft leaves. It is used widely in cold and dry areas of Eurasia and North America to establish grazing pasture and is even used as an ideal plant for revegetation and ecological restoration. Plant architecture, especially tillering traits, is critical for bunch grasses in breeding programs, and these traits in plants are mostly quantitative traits. In this study, the genetic diversity, population structure, and linkage disequilibrium of 480 individual lines were analyzed using 127 pairs of the EST-SSR marker, and a significant association between ten plant-architecture-related traits of P. juncea and molecular markers was found. The results of the genetic diversity analysis showed that the number of observed alleles was 1.957, the number of effective alleles was 1.682, Shannon's information index was 0.554, observed heterozygosity was 0.353, expected heterozygosity was 0.379, and the polymorphism information content was 0.300. A total of 480 individual lines were clustered into five groups based on population genetic structure, principal coordinate analysis, and unweighted pair group method with arithmetic mean analysis (UPGMA). The linkage disequilibrium coefficient (r2) was between 0.00 and 0.68, with an average of 0.04, which indicated a relatively low level of linkage disequilibrium among loci. The results of the association analysis revealed 55 significant marker-trait associations (MTA). Moreover, nine SSR markers were associated with multiple traits. This study provides tools with promising applications in the molecular selection and breeding of P. juncea germplasm.

Linkage disequilibrium, historical effective population size and haplotype blocks in selected native sheep breeds

This study was conducted to investigate linkage disequilibrium (LD), historical effective population size (Ne) and haplotype blocks structure in genomes of nine Polish conserved sheep breeds or varieties: Black-headed (BH), Colored Mountain Sheep (CMS), Old-type Merino (MPOT), Podhale Zackel (PZ), Polish Merino of Coloured Variety (MPC), Polish Mountain Sheep (PMS), Świniarka (SW), Uhruska (UHR) and Wrzosówka (WRZ), based on single nucleotide polymorphisms (SNPs) from the OvineSNP50 DNA Analysis Kit (Illumina, San Diego, CA). LD analysis was performed based on the pairwise r2 statistic of SNPs at a distance up to 5 Mb. At a short distance, up to 100 kb, the lower average r2 was observed in PZ (0.10) breed and the highest average r2 was observed in MPC (0.21) breed. At a distance of 4–5 Mb, the highest average r2 was observed in SW (0.08) breed and the lowest average r2 was observed in PZ (0.02) and PMS (0.02) breeds. All studied Polish sheep breeds, showed mean r2 > 0.3 (‘useful’ LD level for QTL mapping) at shorter distances than average distances between adjacent SNP markers and only for MPC, SW, UH, WRZ breeds mean r2 > 0.2 (high enough to attain an accuracy of 0.85 for genomic breeding value estimation) was observed at similar or longer distances than average distances between adjacent SNP markers. Obtained results showed that the Illumina OvineSNP50 BeadChip assay is not a suitable tool to perform reliable genome-wide association for all studied Polish sheep breeds and only for MPC, SW, UH and WRZ it is potentially possible to perform reliable genomic breeding value estimation. For most of the studied sheep breeds, effective population size 5 generations ago was close or less to the FAO recommended Ne of 50 per generation required to maintain fitness in breed. From 2,051 (SW) to 1,265 (PZ) haplotype block structures, spanning from 148.9 (SW) to 26.3 (PZ) of the genome were detected. Across all studied sheep breeds the highest average block length was observed in MPC (82.5 ± 114 kb) breed and the lowest average block length was observed in PZ (20.9 ± 43 kb) breed. For all studied Polish sheep breeds, as many as 280 haplotype block structures with overlapping segments were detected, within which 182 genes were identified.

A homozygosity-based investigation of the South African feral Tankwa goat population

The Tankwa goat is a known feral goat landrace that originated in the Karoo region of South Africa. These goats are able to thrive with no managerial intervention, and prosper in the harsh, arid conditions that characterizes their natural habitat. This study aimed to use a ROH-approach to describe the Tankwa goat in terms of autozygosity and to identify possible signatures of selection. Genome-wide SNP data for 360 Tankwa goats were used to calculate diversity statistics, detect runs of homozygosity and estimate individual genetic inbreeding coefficients. SNP genotypes of 48 Angora and 40 Dairy individuals were compared using the FST approach to detect signatures of selection. Relatively low minor allele frequency (0.249), and high linkage disequilibrium (r2 = 0.469) levels were estimated for the Tankwa population, with moderate levels of heterozygosity (HE = 0.368; HO = 0.367). The results for both the detected runs of homozygosity and inbreeding estimate, indicates an ancient origin of inbreeding for the Tankwa goats with low levels of autozygosity. Signatures of selection were identified in 50 SNPs, of which 0.1% was considered significant. A total of 49 genes were identified that may possibly be significant in various biological pathways. Three of these genes, namely GJB2, GJB6 and GJA3 on CHI12, were previously associated with adaptation to heat and drought resistance in other breeds. Genes GJB2 and GJB6 are known to be linked to the sensory perception of sound, while GJA3 and OPA3 are linked to visual perception. These genes could play an important role in the survival of an individual existing in a harsh environment in terms of foraging and evading predators. Understanding the genetic background of these genes, as well as the metabolic pathways that they control, could assist in further investigating production efficiency of domesticated species in a climate change environment.

Population structure and genomic analyses of carcass back Length, shoulder width and leg width in purebred and crossbred German Merino sheep

In order to derive suitable breeding strategies for complex traits, it is indispensable that their genetic architecture as well as population specific parameters are thoroughly investigated. Large samples of genotyped individuals are required in order to produce reliable results and to draw adequate inferences. Whereas in cattle, pig and chicken such data are available for many populations, such datasets are rare for sheep. Except for some sheep breeding nations where genomic selection is applied to sheep, the majority of datasets of genotyped sheep come from experiments with often small sample sizes. Pooling data from different breeds and crosses is one way to increase the sample size for genomic analyses but is somehow challenging due to the multi-breed composition of the datasets. Population structure and genetic diversity has an impact on the results of genomic analyses but is often not studied in the populations in which genomic analyses are conducted. Genetically diverse populations as found in sheep often compromise the analyses and the interpretation of results. Here, we investigated the genetic diversity and population structure of purebred Merino and several Merino crossbred lambs as well as in their pooled data and conducted separate and joint genetic analyses. Linkage disequilibrium was studied in the pooled data as well as in the single datasets. Consistency of phase was calculated among crosses. Population structure assessed by principal component analysis. Variance components were estimated and genome-wide association studies were performed for three carcass traits. All investigations based on 50k genotype data. Large genetic diversity was found between and also within crosses. The populations showed low levels of linkage disequilibrium (average r² between 0.155 and 0.171 within crosses and 0.138 in the pooled dataset for inter-marker distances up to 0.059 Mbp) which decayed fast with increasing inter-marker distance which was particularly pronounced when the data were pooled. The population genetic structure of the purebred Merino sample was similar as in Merino crosses and the genetic differentiation between the different populations were small. Variance components could solely be estimated at acceptable standard errors for some of the single crosses and hence genome-wide association studies could not be performed for all crosses. Pooling data drastically reduced standard errors in variance component estimation but did only marginally improve gene mapping results in terms of power but not precision. The heritabilities estimated in the pooled dataset were 0.30, 0.18 and 0.18 for back length, shoulder width and leg width. Only one genome-wide significant SNP for shoulder width was detected. Further, across all traits and datasets, 25 SNPs were found to be putatively trait associated. Larger datasets and denser marker panels are required to utilize such datasets for gene mapping analyses at high power and precision and would improve population genetic investigations. If possible, and to avoid the application of too complex models, data pooling should rather be done by combining several populations of the same breed instead of multiple crosses.

CD33 polymorphisms and Parkinson’s disease Parkinson’s disease in northern Chinese Han population: A case-control study

ObjectiveParkinson's disease (PD) represents the multisystem illness involving immunological and neuroinflammatory dysfunction. The present work focused on evaluating link of CD33 single nucleotide polymorphisms (SNPs) with PD vulnerability of the northern Chinese Han people, considering CD33’s role as a critical immunoregulatory receptor in neuroinflammatory responses. MethodsThe present case-control study included 475 PD cases together with 475 normal controls. A further division of PD patients into two categories was made: 74 patients with early-onset PD (EOPD; onset age ≤ 50 years) and 401 patients with late-onset PD (LOPD; onset age > 50 years). DNA extraction was conducted, followed by genotyping for 2SNPs of CD33 polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). ResultsAlleles (G vs. A, P = 0.028) and AA genotypes (P = 0.042) of rs12985029 were significantly different between the groups. Distinctions were observed between the two groups in the recessive, co-dominant, and additive models (nominal P = 0.030, nominal P = 0.045, and P = 0.032). AA genotype frequency among male PD was higher compared to corresponding male controls (P = 0.034), and in the male group allele A was a factor causing the disease (P = 0.026). The rs12985029 genotypes and allele frequency were different in EOPD compared with LOPD (P = 0.002, P = 0.002, respectively), and in LOPD group relative to healthy control group (P = 0.020 and P = 0.004, separately). Regarding the rs3826656 polymorphism, the frequency of GA genotype was higher in the control group than in the case group (nominal P = 0.036). Overdominance and co-dominant models were different between these groups (P = 0.026, nominal P = 0.030). Subgroup analysis revealed genotype frequency differences between rs3826656 LOPD group and control group (P = 0.018). Furthermore, relationship between rs3826656 and rs12985029 (D' = 0.162, r2 = 0.021) did not reach a complete level of linkage disequilibrium (LD) of northern Chinese Han people. ConclusionThis study establishes an association between CD33 rs12985029 and rs3826656 polymorphisms and PD risk among the selected northern Chinese Han people. The GA genotype, rs3826656, may act as a protective factor against PD, while the A allele, rs12985029,could be genetic risk factor related to PD. Future research should include larger sample sizes and other human populations to further investigate how CD33 polymorphisms contribute to PD.

Population genomic analysis reveals distinct demographics and recent adaptation in the black flying fox (Pteropus alecto)

As the only mammalian group capable of powered flight, bats have many unique biological traits. Previous comparative genomic studies in bats have focused on long-term evolution. However, the micro-evolutionary processes driving recent evolution are largely under-explored. Using resequencing data from 50 black flying foxes (Pteropus alecto), one of the model species for bats, we find that black flying fox has much higher genetic diversity and lower levels of linkage disequilibrium than most of the mammalian species. Demographic inference reveals strong population fluctuations (>100 fold) coinciding with multiple historical events including the last glacial change and Toba super eruption, suggesting that the black flying fox is a very resilient species with strong recovery abilities. While long-term adaptation in the black flying fox is enriched in metabolic genes, recent adaptation in the black flying fox has a unique landscape where recently selected genes are not strongly enriched in any functional category. The demographic history and mode of adaptation suggest that black flying fox might be a well-adapted species with strong evolutionary resilience. Taken together, this study unravels a vibrant landscape of recent evolution for the black flying fox and sheds light on several unique evolutionary processes for bats comparing to other mammalian groups.