Assumption Of Hardy-Weinberg Equilibrium Research Articles

Comparison of Val66met Polymorphism of BDNF gene in patients of bipolar disorder and healthy controls.

IntroductionThe study aims to explore the utility of BDNF Val66Met polymorphism as a potential biomarker in Indian bipolar disorder patients and its correlation with clinical characteristics.ObjectivesGenotyping Val66Met in BDNF geneExploring its association with bipolar disorder (BD).Methods150 consenting BD patients and matched controls were recruited using a case-control study design. BD severity was assessed using Young’s mania rating scale and the Clinical Global Impression - Severity (CGI-S) scale. BDNF Val66Met polymorphism was identified through real-time PCR after DNA extraction. Data was tested for normal distribution. Genotype frequencies between two groups were compared and the Hardy-Weinberg equilibrium assumptions were tested using Chi-Square tests. Clinical-genotypic associations were explored using the Kruskal-Wallis test and confirmed using hierarchical regression.ResultsOur sample had more males (60%) than females (40%) with mean age of 35.05 years. Most patients had established bipolar disorder and were severely ill (CGI: 38.75, YMRS). Val66Met SNP genotype frequency differed significantly between cases and controls. Val66Val genotype and Val allele were higher in cases. Results consistent with Hardy-Weinberg equilibrium.Table 1.Genotype frequencies of BDNF (rs6265) in cases and controlsGENOTYPECCCTTTCASES94(62.6%)47(31.3%)9(6%)CONTROL71(47.3%)69(46%)10(6.6%)CHI-SQUARE- 7.431DF(Degree of freedom) - 2p-value- 0.024Table 2.Dominant genotype frequencies in cases and controlsDOMINANT GENOTYPECCCT+TTCASES94(62.6%)56(37.3%)CONTROLS71(47.3%)79(52.6)CHI-SQUARE-7.125DF(Degree of freedom)-1p-value-0.007Table 3.Allelic frequencies of BDNF (rs6265) in BD cases and healthy controlsALLELIC VARIATIONCTCASES235(78.3%)65(21.6%)CONTROLS211(70.3%)89(29.6%)CHI-SQUARE-5.032DF(Degree of freedom)-1p-value- 0.024ConclusionsOur study found that Val66Val genotype and Val allele were higher in cases and could be a potential biomarker for bipolar disorder (BD), which is consistent with previous research conducted on the European population. However, further investigations are required to gain a more comprehensive understanding of its impact on BD, including its association with serum BDNF levels, treatment outcomes, and a more diverse study population.Disclosure of InterestNone Declared

Implications of the Codominance Model for Hardy-Weinberg Testing in Genetic Association Studies

Introduction: The standard way of using tests for compatibility of genetic markers with the Hardy-Weinberg equilibrium (HWE) assumption as a means of quality control in genetic association studies (GAS) is to carry out this step of preliminary data analysis with the sample of non-diseased individuals only. We show that this strategy has no rational basis whenever the genotype-phenotype relation for a marker under consideration satisfies the assumption of codominance. Methods: The justification of this statement is obtained through rigorous analytical arguments. Results: The key result of the paper is that there holds the following proposition: under the codominance model, the genotype distribution of a diallelic marker is in HWE among the controls if and only if the same is true for the cases. Conclusion: The major practical consequence of that theoretical result is that under the codominance model, testing for HWE should be done both for cases and controls aiming to establish the combined (intersection) hypothesis of compatibility of both underlying genotype distributions with the HWE assumption. A particularly useful procedure serving this purpose is obtained through applying the confidence-interval inclusion rule derived by Wellek, Goddard, and Ziegler (Biom J. 2010; 52:253–270) to both samples separately and combining these two tests by means of the intersection-union principle.

The Association of miRNA-146a Gene Variation and Multiple Sclerosis in The Iranian Population.

Multiple sclerosis (MS) is a complex human autoimmune-type inflammatory disease of the central nervous system (CNS). MicroRNA-146a (miR-146a) belongs to an endogenous and non-coding RNA family with 18-22 nucleotides long, which modulates the innate and adaptive immune response. Our study aimed to investigate a possible association between rs2910164 and rs2431697 polymorphisms of the miR-146a gene and multiple sclerosis in the Iranian population. A total of 60 MS cases and 100 controls were recruited. Single nucleotide polymorphism (SNP) rs2431697 was genotyped by utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and SNP rs2910164 was genotyped by using Tetra-primer ARMS-PCR. Statistical Analysis conducted by the chi-squared test utilizing SPSS version 21.0 Software. The Hardy-Weinberg equilibrium assumption was evaluated. The results of the present study suggest the miR-146a gene rs2431697 polymorphism is not associated with multiple sclerosis. However, there is a significant relationship between polymorphism rs2910164 of the miR-146a gene and multiple sclerosis in the population studied (P = 0.012). Our data provide evidence that the miR-146a gene may be involved in creating the susceptibility to MS in the Iranian population.

Distribution of ABO and Rh (D) Blood Groups and their Genotypes in Amran Governorate, Yemen

Background: The ABO and Rh blood group system is essential for blood bank inventory, blood transfusion services, and organ transplants. Relatively very little data is available about ABO and Rh (D) blood groups distributions in the Amran governorate. Therefore, this study aimed to determine the distribution of ABO and Rh (D) blood group and their genotypes in the Amran governorate, Yemen. Methods: A cross-sectional prospective and retrospective study was carried out from January 2020 to December 2021, on 1949 volunteer blood donors; 414 medical students were obtained from Amran University and 1535 from clinical records in the blood bank of Maternity and childhood hospital at Amran Governorate. The ABO and RhD grouping was done by using commercially available monoclonal antibodies (anti-A, anti-B, and anti-D) by slide methods. The allele and genotype frequency of the donors was determined by the Hardy-Weinberg equilibrium assumption. Descriptive statistics were analyzed using the SPSS program. The difference between the observed and expected frequency was tested by an online Chi-square calculator. A P-value of <0.05 was considered statistically significant. Results: Out of 1949 participants; were 78.8% of hospital donors, 92.2% of males, and 63.5% of rural areas. Blood group O was the most prevalent (51.2%), followed by A (31.5%), B (13.9%), and AB (3.5%) with statistically significant differences (P= 0.002). The Rh (D) positive was present in 86.8% of participants and 13.2% were Rh (D) negative. Moreover, the allele frequencies were in the order of (IO > IA > IB > AB), where (IO i = 0.513, IA = 0.313, IB = 0.138, and AB= 0.035). While the Rh(D) and d allelic frequencies were 0.868 and 0.132, respectively. Also, there was no statistically significant difference between observed and expected allele and genotype frequency (P-value >0.05). Conclusion: The frequency of distribution of ABO and Rh (D) blood group and their genotypes among the study population was found to be similar to those reported from most Asian populations. This crucial information may be helpful in planning for future health challenges, particularly planning with regard to blood transfusion services.

Phenotype, allele and genotype frequency distribution of ABO and Rh(D) blood group among blood donors attending regional blood transfusion centre in Delhi, India.

The ABO and Rh blood group phenotypes, alleles, and genotype frequencies have many biological and medical implications. The frequency differs broadly according to races, geographical borders and ethnicity, even within the same region. This study was designed to determine the frequency of ABO and Rh blood groups among blood donors attending the regional blood transfusion centre in Delhi. The gel card method was used to determine the ABO and Rh(D) blood groups of donors who donated blood between January 1, 2020, and June 30, 2022. The assumption of Hardy-Weinberg equilibrium was used to determine allele and genotype frequencies of blood donors. A total of 16,925 blood units were donated during the study period. Donors phenotype frequencies of ABO were as follows: 'A' (23.88%), 'B' (37.38%), 'AB' (9.97%) and 'O '(29.27%). Rh(D)+Ve (D) were (94.9%) and Rh(D)-Ve (d) were (5.01%), which follow an order of B > O > A > AB and Rh-D > d for Rh. Donors ABO and Rh (D) allele frequencies were IA-0.183, IB-0.277, IO-0.541 and ID-0.776, Id-0.224 respectively. Allele frequencies follow an order of IO > IB > IA and Rh- ID > Id. Donors ABO genotype frequencies were AA-0.0333, AO-0.198, BB-0.0768, BO-0.30, AB-0.101, OO-0.293 and Rh(D) genotype frequencies were DD-0.602, Dd-0.347, dd-0.0501. Genotype frequencies follow an order of BO > OO > AO > AB > BB > AA and DD > Dd > dd. Among our donors, which were mostly from northern India, the ABO and Rh(D) blood groups have the highest proportion of ABO-B and Rh(D)+Ve and the lowest proportion of ABO-AB and Rh(D)-Ve, with a stable order of B > O > A > AB and D > d for phenotype, IO > IB > IA and ID > Id for allele and BO > OO > AO > AB > BB > AA and DD > Dd > dd for genotype.

Novel Microsatellite Markers for Osmia lignaria (Hymenoptera: Megachilidae): A North American Pollinator of Agricultural Crops and Wildland Plants

Comprehensive decisions on the management of commercially produced bees, depend largely on associated knowledge of genetic diversity. In this study, we present novel microsatellite markers to support the breeding, management, and conservation of the blue orchard bee, Osmia lignaria Say (Hymenoptera: Megachilidae). Native to North America, O. lignaria has been trapped from wildlands and propagated on-crop and used to pollinate certain fruit, nut, and berry crops. Harnessing the O. lignaria genome assembly, we identified 59,632 candidate microsatellite loci in silico, of which 22 were tested using molecular techniques. Of the 22 loci, 12 loci were in Hardy-Weinberg equilibrium (HWE), demonstrated no linkage disequilibrium (LD), and achieved low genotyping error in two Intermountain North American wild populations in Idaho and Utah, USA. We found no difference in population genetic diversity between the two populations, but there was evidence for low but significant population differentiation. Also, to determine if these markers amplify in other Osmia, we assessed 23 species across the clades apicata, bicornis, emarginata, and ribifloris. Nine loci amplified in three species/subspecies of apicata, 22 loci amplified in 11 species/subspecies of bicornis, 11 loci amplified in seven species/subspecies of emarginata, and 22 loci amplified in two species/subspecies of ribifloris. Further testing is necessary to determine the capacity of these microsatellite loci to characterize genetic diversity and structure under the assumption of HWE and LD for species beyond O. lignaria. These markers will inform the conservation and commercial use of trapped and managed O. lignaria and other Osmia species for both agricultural and nonagricultural systems.

Association of D299G Polymorphism of TLR4 Gene and CagA Virulence Factor of H. pylori among the Iranian Patients with Colorectal Cancer.

Background: Colorectal cancer (CRC) represents 9% of all malignancies globally. TLR4 gene defenses against Helicobacter pylori infection (HPI), so its mutations are a risk factor for CRC. As there is a correlation between (HPI) and gastric cancer, we investigated whether there is an association between CagA virulence factor in HPI and D299G polymorphism of TLR4 gene with developing CRC among Iranians. Methods: This retrospective study included 85 biopsies of confirmed colorectal lesions out of 230 subjects, which were divided into two age groups. Single nucleotide polymorphism (SNP) D299G in the TLR4 gene was assessed using Tetra-primer ARMS-PCR. The expression of TLR4 and the CagA virulence factor in H.pylori was assessed using real-time PCR (RT-PCR). Results: Chi-squared test showed genotype frequencies of GG were 79% and 62%in patients 51> and 51<years, respectively. Logistic regression showed a positive association between the presence of CagA and a high GG allele (p=0.002). The odd ratio was predicted as 4.80 using the Hardy-Weinberg equilibrium assumption. Iranians with CagA and high GG of D299G were four times more likely to develop CRC than their peers with AA allele. Conclusion: H. pylori-positive CagA has a higher ability to escape from the immune response. D299G polymorphism of TLR4 gene full of GG allele is an influential risk factor in developing CRC. Hence finding H. pylori-positive CagA should be noticed as a marker of the TLR4 gene full of GG allele in screening plans.

Phenotype, Allele and Genotype Frequency of ABO and Rhesus D Blood Groups of Blood Donors at the North Gondar District Blood Bank, Northwest Ethiopia.

BackgroundKnowledge of the ABO and RhD group distribution is essential for blood banks inventory and assuring quality blood transfusion services. The objective of this study was to determine the frequency of ABO and RhD phenotype, allele, and genotype among blood donors at North Gondar District Blood Bank from 2010 to 2012, Northwest Ethiopia.MethodsThe data of the current study were obtained from registration logbooks of blood donors registered. The ABO and RhD grouping was done by using commercially available monoclonal antibodies (anti-A, anti-B and anti-D) by slide methods. Results with no agglutination by anti-D antibody were confirmed using anti-human globulin test. Descriptive statistics were analyzed using SPSS version 20. The allele and genotype frequency of the donors was determined by Hardy–Weinberg equilibrium assumption. The difference between the observed and expected frequency was tested by online Chi-square calculator. P-value of <0.05 was considered statistically significant.ResultsAmong 6471 blood donors, 82.1%, 94.1% and 55.4% were males, replacement donors and in the age group of 21–30 years, respectively. Blood group O (47.04%) and blood group AB (4.81%) were the dominant and least common, respectively. The distribution of the RhD negative blood group was 5.76%. The distribution of A, B and O alleles was 0.1714, 0.1433 and 0.6859, respectively. Moreover, the genotype frequency of AA, AO, BB, BO, AB and OO was 0.0294, 0.2350, 0.0205, 0.1966, 0.0491 and 0.4704, respectively. The genotype frequency of DD, Dd and dd was 0.5774, 0.3649 and 0.0576, respectively. The result showed that there was no statistically significant difference between observed and expected allele and genotype frequency (P-value >0.05).ConclusionBlood group O and AB were the most and least prevalent, respectively. The allele and genotype frequency of the population was fulfilled the Hardy–Weinberg equilibrium assumption. This finding might be useful for blood transfusion services.

HLA haplotype frequency estimation for heterogeneous populations using a graph-based imputation algorithm

HLA haplotype frequencies are estimated from ambiguous unphased HLA genotyping data using Expectation-Maximization (EM) algorithms. Current population genetics methods require independent EM frequency estimates for each population, and assume that each population is in Hardy-Weinberg Equilibrium (HWE). The HWE assumption of EM has thus far resulted in the exclusion of individuals from mixed or unknown ethnic backgrounds from reference datasets. Multi-region populations are currently poorly served by stem cell donor registry HLA imputation and matching implementations due to the inability of such algorithms to incorporate admixture into their population genetics models. To address this unmet need, we have expanded the imputation component of our GRaph IMputation and Matching (GRIMM) framework, where imputation becomes the expectation step in an iterative EM algorithm. Our novel multi-region EM implementation considers region as a Bayesian prior, enabling integration of HLA information from multiple single-region population groups, and for the first time including individuals with ambiguous or mixed ethnic backgrounds. We show that our multi-region EM produces much higher likelihood values and better haplotype recovery as measured by Kullback-Leibler divergence than all evaluated EM implementations when tested on real datasets of US donor registry HLA typings as well as simulated multi-region datasets of ambiguous HLA typings.

Assessment of association between HLA alleles and acquired aplastic anemia in Iranian population

Aplastic anemia is regarded as an immune-related disorder in which T lymphocytes have a prominent role in destroying bone marrow cells. Previous studies have assessed the role of HLA alleles in development of this disorder. In the current investigation, we genotyped HLA-A/-B/DRB1 alleles in 22 Iranian patients with acquired aplastic anemia and the same number of matched healthy subjects. Frequencies of HLA genotypes were in agreement with the Hardy-Weinberg Equilibrium assumption in aplastic anemia patients and healthy controls. Although some HLA alleles and genotypes were represented with different frequencies between patients and controls, the differences did not reach the level of significance. Thus, we suggest conduction of further studies in larger samples sizes to find whether the observed associations in other populations can be found in Iranian patients as well.

Robust method of estimating of odd ratios in case-control association studies

In case-control studies, association of a disease with a genetic trait can be studied in terms of Single Nucleotide Polymorphisms (SNP). Prospective and retrospective likelihoods are the two common approaches used to study this association. In this paper, a method based on Preliminary test, has been proposed, which is efficient than prospective approach by exploiting model assumptions of Hardy Weinberg Equilibrium (HWE) and robust against failure of model assumptions as compared to retrospective approach (2015-16). In this proposed approach, a Preliminary Test Estimator (PTE) has been suggested based on both prospective and retrospective approach for estimating of association of a disease with genetic marker. The proposed PTE has been empirically evaluated through a simulation study. The Preliminary Test Estimator developed was found to be robust against the deviation from HWE.

Incorporating information from markers in LD with test locus for detecting imprinting and maternal effects

Numerous statistical methods have been developed to explore genomic imprinting and maternal effects by identifying parent-of-origin patterns in complex human diseases. However, because most of these methods only use available locus-specific genotype data, it is sometimes impossible for them to infer the distribution of parental origin of a variant allele, especially when some genotypes are missing. In this article, we propose a two-step approach, LIMEhap, to improve upon a recent partial likelihood inference method. In the first step, the distribution of the missing genotypes is inferred through the construction of haplotypes by using information from nearby loci. In the second step, a partial likelihood method is applied to the inferred data. To substantiate the validity of the proposed procedures, we simulated data in a genomic region of gene GPX1. The results show that, by borrowing genetic information from nearby loci, the power of the proposed method can be close to that with complete genotype data at the locus of interest. Since the inference on the genotype distribution is made under the assumption of Hardy-Weinberg Equilibrium (HWE), we further studied the robustness of LIMEhap to violation of HWE. Finally, we demonstrate the utility of LIMEhap by applying it to an autism dataset.

Exploiting gene-environment independence in haplotype-based inferences for population-based case-control studies with complex sampling.

The use of complex sampling in population-based case-control studies is becoming more common. Although most single nucleotide polymorphism-based association studies with complex sampling account for the design complications, many of haplotype-based genetic association studies with complex sampling tend to ignore them when estimating haplotype frequencies, regression coefficients, or both. In this article, we develop innovative one-step and two-step statistical methods that account for the design complications in haplotype-based association studies when cases and/or controls are sampled with complex sampling. Attracted by the efficiency advantage of the retrospective method, we explore the assumptions of Hardy-Weinberg equilibrium and gene-environment independence in the underlying population. Results of our simulation studies demonstrate superior performance of the proposed methods over selected existing methods under various complex sampling designs. An application of the proposed methods is illustrated using a population-based case-control study of kidney cancer.

PHENOTYPIC FREQUENCIES OF ABO AND RH(D) BLOOD GROUPS AMONGST HEALTHY BLOOD DONORS IN BIKANER, RAJASTHAN

Background &amp; Objective: Practically, most important blood groups are A, B, O, AB and RhD(+/-), which are essential for right blood supply to the recipients and in various studies. The incidence of ABO and Rhesus (Rh) groups varies markedly in different parts of the world and in different races. The present study was aimed at determining the prevalence of ABO &amp; RhD blood groups among healthy blood donors in Western Rajasthan.&#x0D; Material and Methods: At our centre, all the healthy blood donors were assessed and analyzed for ABO-Rh blood grouping during a period of previous 4 years (from January, 2015 to December, 2018). 119200 samples were checked for ABO and RhD blood grouping by manual saline antigen-antibody agglutination method using commercially prepared antisera antiA, antiB, antiAB, antiD, in house prepared reagent cells Acell, Bcell, Ocell and negative control. The results were reconfirmed on fully automated immunohematology analyzer (Galileo Neo, USA) with direct hemagglutination micro-well plates using antiA, antiB, antiD series-5, antiD Novaclone, Monoclonal control, Acell, Bcell and Ocell provided by the manufacturer. Discrepant samples were cross checked separately by column agglutination technique using DG Gel ABO/Rh-2D cards (Diagnostic Grifols S.A.) and tube technique.&#x0D; Results: We found that the most common blood group was B+ 39758 (33.35%) followed by O+, A+, AB+, B-, O-, A- and AB-. RhD negative donors were 10504 (8.81%) among the total donors. Phenotypic frequencies were expressed under the standard assumption of Hardy-Weinberg equilibrium.&#x0D; Conclusion: Present study concludes that the most common ABO phenotype found among healthy blood donors in Western Rajasthan (India) is group B with RhD negativity being 8.81%. Larger studies should be conducted to calculate antigenic, phenotypic and allelic frequencies in general population.&#x0D; Keywords: ABO-RhD blood group, Phenotype, Allele, Blood donors, hemagglutination.

Examining the rare disease assumption used to justify HWE testing with control samples.

Many statistical methods for analyzing genetic data, such as those used in genome-wide association studies, assume Hardy-Weinberg Equilibrium (HWE). Therefore, to use such methods, one must check whether the HWE assumption is valid. For a case-control study, researchers have recognized that Hardy Weinberg proportions will be distorted if the marker being tested happens to be associated with the disease. To alleviate this problem, many studies carry out HWE testing on controls only. A number of papers in the literature have justified this practice by making the rare disease assumption without providing rigorous theoretical basis for this justification. Even though many of the diseases studied today are common, whether it is justifiable to use controls to test for HWE when the disease is indeed rare remains an outstanding issue. In this study, we address the rare disease assumption as well as potential problems associated with testing for HWE using controls only, regardless of the prevalence of the disease. We carried out theoretical derivations and numerical studies; the latter were performed using simulated genotypes as well as data from the 1000 Genomes Project. The results from our study are striking: the type I error can be severely inflated, regardless of whether the disease being investigated is rare or common. This study shows that, based on the common practice of using controls only to test for HWE, many genetic variants will be discarded erroneously, wasting valuable information and hindering the ability to detect disease-associated variants.

Geographic distribution of the 3435C>T polymorphism of the MDR1 gene in Peruvian populations.

Background The MDR1 gene presents several genetic polymorphisms with pharmacological implications. Therefore, the aim of the present study is to establish the genotype and allele frequencies of 3435C>T polymorphism of MDR1 gene into Peruvian populations (Coastal, Andean and Amazonian ecoregions), even considering the altitude (lowland <2500 m and highland >2500 m). Methods The polymorphism was analyzed by TaqMan genotyping assays in a group of 181 healthy unrelated Peruvian individuals. The comparison of genotype and allele frequencies of 3435C>T polymorphism was made with the Pearson test (X2), and, to calculate the genotype distributions, the Hardy-Weinberg equilibrium (HWE) was used. Results In all populations evaluated in this study, the genotype frequency distributions met HWE assumptions. The comparison between genotype and allele frequencies showed significant differences (p < 0.05), when the Andean, Coastal and Amazonian populations were compared. Also, significant differences (p < 0.05) were obtained when these populations were compared considering their altitudes. Likewise, in comparison with countries like USA, Finland, Nigeria and Kenya, the results showed significant differences (p < 0.05). Conclusions This investigation allowed us to establish the genotype and allele frequencies of 3435C>T polymorphism in different Peruvian populations, considering the geographic localization and even the altitude.

FitTetra 2.0 \u2013 improved genotype calling for tetraploids with multiple population and parental data support

BackgroundGenetic studies in tetraploids are lagging behind in comparison with studies of diploids as the complex genetics of tetraploids require much more elaborated computational methodologies. Recent advancements in development of molecular techniques and computational tools facilitate new methods for automated, high-throughput genotype calling in tetraploid species. We report on the upgrade of the widely-used fitTetra software aiming to improve its accuracy, which to date is hampered by technical artefacts in the data.ResultsOur upgrade of the fitTetra package is designed for a more accurate modelling of complex collections of samples. The package fits a mixture model where some parameters of the model are estimated separately for each sub-collection. When a full-sib family is analyzed, we use parental genotypes to predict the expected segregation in terms of allele dosages in the offspring. More accurate modelling and use of parental data increases the accuracy of dosage calling. We tested the package on data obtained with an Affymetrix Axiom 60 k array and compared its performance with the original version and the recently published ClusterCall tool, showing that at least 20% more SNPs could be called with our updated.ConclusionOur updated software package shows clearly improved performance in genotype calling accuracy. Estimation of mixing proportions of the underlying dosage distributions is separated for full-sib families (where mixture proportions can be estimated from the parental dosages and inheritance model) and unstructured populations (where they are based on the assumption of Hardy-Weinberg equilibrium). Additionally, as the distributions of signal ratios of the dosage classes can be assumed to be the same for all populations, including parental data for some subpopulations helps to improve fitting other populations as well. The R package fitTetra 2.0 is freely available under the GNU Public License as Additional file with this article.

Assessing non-additive effects in GBLUP model.

Understanding non-additive effects in the expression of quantitative traits is very important in genotype selection, especially in species where the commercial products are clones or hybrids. The use of molecular markers has allowed the study of non-additive genetic effects on a genomic level, in addition to a better understanding of its importance in quantitative traits. Thus, the purpose of this study was to evaluate the behavior of the GBLUP model in different genetic models and relationship matrices and their influence on the estimates of genetic parameters. We used real data of the circumference at breast height in Eucalyptus spp and simulated data from a population of F2. Three commonly reported kinship structures in the literature were adopted. The simulation results showed that the inclusion of epistatic kinship improved prediction estimates of genomic breeding values. However, the non-additive effects were not accurately recovered. The Fisher information matrix for real dataset showed high collinearity in estimates of additive, dominant, and epistatic variance, causing no gain in the prediction of the unobserved data and convergence problems. Estimates presented differences of genetic parameters and correlations considering the different kinship structures. Our results show that the inclusion of non-additive effects can improve the predictive ability or even the prediction of additive effects. However, the high distortions observed in the variance estimates when the Hardy-Weinberg equilibrium assumption is violated due to the presence of selection or inbreeding can converge at zero gains in models that consider epistasis in genomic kinship.

Frequencies of red blood cell major blood group antigens and phenotypes in the Chinese Han population from Mainland China.

Alloantibodies directed to red blood cell (RBC) antigens play an important role in alloimmune-mediated haemolytic transfusion reactions and haemolytic disease of the foetus and newborn. The frequencies and phenotypes of RBC antigens are different in populations from different geographic areas and races. However, the data on major blood group antigens in the Chinese Han population from Mainland China are still very limited; thus, we aimed to investigate them in this study. A total of 1412 unrelated voluntary Chinese Han blood donors were randomly recruited. All donors were typed for blood group antigens: D, C, c, E, e, C(w) , Jk(a) , Jk(b) ,M, N, S, s, Le(a) , Le(b) , K, k. Kp(a) , Kp(b) , Fy(a) , Fy(b) , Lu(a) , Lu(b) , P1 and Di(a) using serological technology. Calculations of antigen and phenotype frequencies were expressed as percentages and for allele frequencies under the standard assumption of Hardy-Weinberg equilibrium. Amongst the Rh antigens, D was the most common (98.94%) followed by e (92.28%), C (88.81%), c (58.43%), E (50.78%) and C(w) (0.07%) with DCe/DCe (R1 R1 , 40.72%) being the most common phenotype. In the Kell blood group system, k was present in 100% of the donors and a rare phenotype, Kp (a+b+), was found in 0.28% of the donors. For the Kidd and Duffy blood group systems, Jk (a+b+) and Fy (a+b-) were the most common phenotypes (44.05% and 84.35%, respectively). In the MNS blood group system, M+N+S-s+ (45.54%) was the most common, whereas M+N-S-s- and M-N+S-s- were not found. The rare Lu (a-b-) and Lu (a+b+) phenotypes were identified in 0.43% and 1.13% of the donors, respectively. Le(a) and Le(b) were seen in 17.92% and 63.03% of donors, respectively. The frequency of Di(a) was 4.75%, which was higher than in the Chinese population in Taiwan region or the Caucasian and Black populations (P<0.0001). This study systematically describes the frequencies of 24 blood group antigens in the Chinese Han population from Mainland China. The data can be helpful in creating a donor database for preparation of indigenous cell panels and providing antigen-negative blood to patients with multiple alloantibodies.

Likelihood Ratio Test for Excess Homozygosity at Marker Loci on X Chromosome.

The assumption of Hardy-Weinberg equilibrium (HWE) is generally required for association analysis using case-control design on autosomes; otherwise, the size may be inflated. There has been an increasing interest of exploring the association between diseases and markers on X chromosome and the effect of the departure from HWE on association analysis on X chromosome. Note that there are two hypotheses of interest regarding the X chromosome: (i) the frequencies of the same allele at a locus in males and females are equal and (ii) the inbreeding coefficient in females is zero (without excess homozygosity). Thus, excess homozygosity and significantly different minor allele frequencies between males and females are used to filter X-linked variants. There are two existing methods to test for (i) and (ii), respectively. However, their size and powers have not been studied yet. Further, there is no existing method to simultaneously detect both hypotheses till now. Therefore, in this article, we propose a novel likelihood ratio test for both (i) and (ii) on X chromosome. To further investigate the underlying reason why the null hypothesis is statistically rejected, we also develop two likelihood ratio tests for detecting (i) and (ii), respectively. Moreover, we explore the effect of population stratification on the proposed tests. From our simulation study, the size of the test for (i) is close to the nominal significance level. However, the size of the excess homozygosity test and the test for both (i) and (ii) is conservative. So, we propose parametric bootstrap techniques to evaluate their validity and performance. Simulation results show that the proposed methods with bootstrap techniques control the size well under the respective null hypothesis. Power comparison demonstrates that the methods with bootstrap techniques are more powerful than those without bootstrap procedure and the existing methods. The application of the proposed methods to a rheumatoid arthritis dataset indicates their utility.