Composite Likelihood Ratio Test Research Articles

Detection of genomic variations and selection signatures in Wagyu using whole-genome sequencing data.

Wagyu is recognized for producing marbled beef with high nutritional value and flavor. Reportedly, Wagyu has been widely used to improve the meat quality of local breeds around the world. However, studies on the genetic mechanism of meat quality in Wagyu at the whole-genome level are rarely reported. Here, whole-genome sequencing data of 11 Wagyu and 115 other individuals were used to explore the genomic variations and genes under selection pressure in Wagyu. A total of 31 349 non-synonymous variants and 53 102 synonymous variants were identified in Wagyu. The population structure analysis showed that Wagyu had the closest genetic relationship with Mishima-Ushi cattle and was apparently separated from other cattle breeds. Then, composite likelihood ratio (CLR), integrated haplotype score, fixation index and cross-population composite likelihood ratio (XP-CLR) tests were performed to identify the candidate genes under positive selection in Wagyu. In total, 770 regions containing 312 genes were identified by at least three methods. Among them, 97 regions containing 27 genes were detected by all four methods. We specifically illustrate a list of interesting genes, including LRP2BP, GAA, CACNG6, CXADR, GPCPD1, KLF2, KLF13, SOX5, MYBPC1, SLC25A10, ATP8A1 and MYH15, which are associated with lipid metabolism, fat deposition, muscle development, bone development, feed intake and growth traits in Wagyu. This is the first study to explore the genomic variations and selection signatures of Wagyu at the whole-genome level. These results will provide significant help to beef cattle improvement and breeding.

Identification of Selection Signatures and Loci Associated with Important Economic Traits in Yunan Black and Huainan Pigs.

Henan Province is located in central China and rich in domestic pig populations; Huainan (HN) pigs are one of three Henan indigenous breeds with great performance, including early maturation, strong disease resistance and high meat quality. Yunan (YN) black pigs are a typical, newly cultivated breed, synthesized between HN pigs and American Duroc, and are subjected to selection for important traits, such as fast growth and excellent meat quality. However, the genomic differences, selection signatures and loci associated with important economic traits in YN black pigs and HN pigs are still not well understood. In this study, based on high-density SNP chip analysis of 159 samples covering commercial DLY (Duroc × Landrace × Large White) pigs, HN pigs and YN black pigs, we performed a comprehensive analysis of phylogenetic relationships and genetic diversity among the three breeds. Furthermore, we used composite likelihood ratio tests (CLR) and F-statistics (Fst) to identify specific signatures of selection associated with important economic traits and potential candidate genes. We found 147 selected regions (top 1%) harboring 90 genes based on genetic differentiation (Fst) in the YN-DLY group. In the HN-DLY group, 169 selected regions harbored 58 genes. In the YN-HN group, 179 selected regions harbored 77 genes. In addition, the QTLs database with the most overlapping regions was associated with triglyceride level, number of mummified pigs, hemoglobin and loin muscle depth for YN black pigs, litter size and intramuscular fat content for HN pigs, and humerus length, linolenic acid content and feed conversion ratio mainly in DLY pigs. Of note, overlapping 14 tissue-specific promoters' annotation with the top Fst 1% selective regions systematically demonstrated the muscle-specific and hypothalamus-specific regulatory elements in YN black pigs. Taken together, these results contribute to an accurate knowledge of crossbreeding, thus benefitting the evaluation of production performance and improving the genome-assisted breeding of other important indigenous pig in the future.

Genomic signatures of domestication and adaptation during geographical expansions of rice cultivation

Rice (Oryza sativa L.), a global staple food now grown on all inhabited continents, was domesticated from its wild progenitor, O. rufipogon Griff., in tropical and subtropical regions of Asia (Oka, 1988). After domestication, the expansions of rice landraces into the present-day range required a diverse array of adaptations to local environments, which included changes in daylight sensitivity, expanded thermal tolerance (for excess cold and heat), adaptations to water availability (drought and waterlogging), and resistance to biotic stresses (Garris et al., 2005; Glaszmann, 1987).

Investigating the impact of reference assembly choice on genomic analyses in a cattle breed

BackgroundReference-guided read alignment and variant genotyping are prone to reference allele bias, particularly for samples that are greatly divergent from the reference genome. A Hereford-based assembly is the widely accepted bovine reference genome. Haplotype-resolved genomes that exceed the current bovine reference genome in quality and continuity have been assembled for different breeds of cattle. Using whole genome sequencing data of 161 Brown Swiss cattle, we compared the accuracy of read mapping and sequence variant genotyping as well as downstream genomic analyses between the bovine reference genome (ARS-UCD1.2) and a highly continuous Angus-based assembly (UOA_Angus_1).ResultsRead mapping accuracy did not differ notably between the ARS-UCD1.2 and UOA_Angus_1 assemblies. We discovered 22,744,517 and 22,559,675 high-quality variants from ARS-UCD1.2 and UOA_Angus_1, respectively. The concordance between sequence- and array-called genotypes was high and the number of variants deviating from Hardy-Weinberg proportions was low at segregating sites for both assemblies. More artefactual INDELs were genotyped from UOA_Angus_1 than ARS-UCD1.2 alignments. Using the composite likelihood ratio test, we detected 40 and 33 signatures of selection from ARS-UCD1.2 and UOA_Angus_1, respectively, but the overlap between both assemblies was low. Using the 161 sequenced Brown Swiss cattle as a reference panel, we imputed sequence variant genotypes into a mapping cohort of 30,499 cattle that had microarray-derived genotypes using a two-step imputation approach. The accuracy of imputation (Beagle R2) was very high (0.87) for both assemblies. Genome-wide association studies between imputed sequence variant genotypes and six dairy traits as well as stature produced almost identical results from both assemblies.ConclusionsThe ARS-UCD1.2 and UOA_Angus_1 assemblies are suitable for reference-guided genome analyses in Brown Swiss cattle. Although differences in read mapping and genotyping accuracy between both assemblies are negligible, the choice of the reference genome has a large impact on detecting signatures of selection that already reached fixation using the composite likelihood ratio test. We developed a workflow that can be adapted and reused to compare the impact of reference genomes on genome analyses in various breeds, populations and species.

Large-Scale Genome Scanning within Exonic Regions Revealed the Contributions of Selective Sweep Prone Genes to Host Divergence and Adaptation in Magnaporthe oryzae Species Complex.

Magnaporthe oryzae, one of the most notorious plant pathogens in the agronomic ecosystem, causes a destructive rice blast disease around the world. The blast fungus infects wide arrays of cultivated and non-cultivated plants within the Poaceae. Studies have shown that host speciation exerts selection pressure that drives the evolution and divergence of the M. oryzae population. Population genetic relationship deducted by genome-wide single nucleotide polymorphisms showed that M. oryzae differentiation is highly consistent with the host speciation process. In particular, the rice-infecting population of M. oryzae is distinct from populations from other hosts. However, how genome regions prone to host-mediated selection pressures associated with speciation in M. oryzae, especially at a large-scale population level, has not been extensively characterized. Here, we detected strong evidence of sweep selection throughout the genomes of rice and non-rice pathotypes of M. oryzae population using integrated haplotype score (iHS), cross population extended haplotype homozygosity (XPEHH), and cross population composite likelihood ratio (XPCLR) tests. Functional annotation analyses of the genes associated with host-mediated selection pressure showed that 14 pathogenicity-related genes are under positive selection pressure. Additionally, we showed that 17 candidate effector proteins are under positive and divergent selection among the blast fungus population through sweep selection analysis. Specifically, we find that a divergent selective gene, MGG_13871, is experiencing host-directed mutation in two amino acid residues in rice and non-rice infecting populations. These results provide a crucial insight into the impact of selective sweeping on the differentiation of M. oryzae populations and the dynamic influences of genomic regions in promoting host adaptation and speciation among M. oryzae species.

Family-based exome sequencing combined with linkage analyses identifies rare susceptibility variants of MUC4 for gastric cancer.

Genome-wide association studies of gastric cancer (GC) cases have revealed common gastric cancer susceptibility loci with low effect size. We investigated rare variants with high effect size via whole-exome sequencing (WES) of subjects with familial clustering of gastric cancer. WES of DNAs from the blood of 19 gastric cancer patients and 36 unaffected family members from 14 families with two or more gastric cancer patients were tested. Linkage analysis combined with association tests were performed using Pedigree Variant Annotation, Analysis, and Search Tool (pVAAST) software. Based on the logarithm of odds (LOD) and permutation-based composite likelihood ratio test (CLRT) from pVAAST, MUC4 was identified as a predisposing gene (LOD P-value = 1.9×10-5; permutation-based P-value of CLRT ≤ 9.9×10-9). In a larger cohort consisting of 597 GC patients and 9,759 healthy controls genotyped with SNP array, we discovered common variants in MUC4 regions (rs148735556, rs11717039, and rs547775645) significantly associated with GC supporting the association of MUC4 with gastric cancer. And the MUC4 variants were found in higher frequency in The Cancer Genome Atlas Study (TCGA) germline samples of patients with multiple cancer types. Immunohistochemistry indicated that MUC4 was downregulated in the noncancerous gastric mucosa of subjects with MUC4 germline missense variants, suggesting that loss of the protective function of MUC4 predisposes an individual to gastric cancer. Rare variants in MUC4 can be novel gastric cancer susceptibility loci in Koreans possessing the familial clustering of gastric cancer.

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

BackgroundAutochthonous cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution.ResultsWe annotated 15,722,811 SNPs and 1,580,878 Indels including 10,738 and 2763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive xanthinuria and albinism. The average nucleotide diversity (1.6  × 10− 3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding derived from runs of homozygosity (ROH) was relatively low (FROH = 0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in OB cattle of more recent generations (FROH = 0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P < 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus.ConclusionsWe provide a comprehensive overview of sequence variation in Swiss OB cattle genomes. With WGS data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds. Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to local environmental conditions. Considering that the population size is low and genomic inbreeding increased in the past generations, the implementation of optimal mating strategies seems warranted to maintain genetic diversity in the Swiss OB cattle population.

Analysis of porcine body size variation using re-sequencing data of miniature and large pigs

BackgroundDomestication has led to substantial phenotypic and genetic variation in domestic animals. In pigs, the size of so called minipigs differs by one order of magnitude compared to breeds of large body size. We used biallelic SNPs identified from re-sequencing data to compare various publicly available wild and domestic populations against two minipig breeds to gain better understanding of the genetic background of the extensive body size variation. We combined two complementary measures, expected heterozygosity and the composite likelihood ratio test implemented in “SweepFinder”, to identify signatures of selection in Minipigs. We intersected these sweep regions with a measure of differentiation, namely FST, to remove regions of low variation across pigs. An extraordinary large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on SNP-array data of F2 individuals from a cross of Goettingen Minipigs and large pigs.ResultsSelective sweep analysis identified putative sweep regions for growth and subsequent gene annotation provided a comprehensive set of putative candidate genes. A long swept haplotype on chromosome X, descending from the Goettingen Minipig founders was associated with a reduction of adult body length by 3% in F2 cross-breds.ConclusionThe resulting set of genes in putative sweep regions implies that the genetic background of body size variation in pigs is polygenic rather than mono- or oligogenic. Identified genes suggest alterations in metabolic functions and a possible insulin resistance to contribute to miniaturization. A size QTL located within the sweep on chromosome X, with an estimated effect of 3% on body length, is comparable to the largest known in pigs or other species. The androgen receptor AR, previously known to influence pig performance and carcass traits, is the most obvious potential candidate gene within this region.

Effects of Dietary Arginine Supplementation in Pregnant Mares on Maternal Metabolism and Foal Birthweight

Withers height is an important economic trait for the American Miniature Horses (AMHs) as the breeders' primary objective is to produce small and proportionate animals. Identification of Quantitative Trait Loci (QTLs) affecting height in this breed will result in a better understanding of the genetic architecture and biological pathways contributing to skeletal development. In earlier work, we genotyped 48 horses from 16 different breeds that represent extremes in body size, using the Equine SNP50 bead chip (Illumina Inc). In this study, we applied a dominant model Genome-wide association study (GWAS), a genome-wide fixation index (FST) estimation, as well as a cross-population composite likelihood ratio (XP-CLR) test between the eight large and eight small breeds from this data set. Our GWAS implicated the marker at ECA1:37,676,322 bp, positioned within an intron of the ANKRD1 gene, was significantly associated with height variation. An XP-CLR scan further supported a role in height for the ECA1:37,676,322 bp locus and the FST analysis supported correlations to IGF2BP2 at ECA19:23,815,750. To confirm our findings, we genotyped the candidate loci in an independent set of 89 AMHs. This set verified that the locus at ANKRD1 gene indeed correlates to height under a dominant mode of inheritance, but not the locus at the IGF2BP2 gene. ANKRD1, a transcription factor involved in myocyte growth and differentiation, may contribute to height by influencing the overall growth of the horses. This marker will be a valuable tool for the selection of breeding stock in breeds with height restrictions for registration.

Genome-wide evidence for divergent selection between populations of a major agricultural pathogen.

The genetic and environmental homogeneity in agricultural ecosystems is thought to impose strong and uniform selection pressures. However, the impact of this selection on plant pathogen genomes remains largely unknown. We aimed to identify the proportion of the genome and the specific gene functions under positive selection in populations of the fungal wheat pathogen Zymoseptoria tritici. First, we performed genome scans in four field populations that were sampled from different continents and on distinct wheat cultivars to test which genomic regions are under recent selection. Based on extended haplotype homozygosity and composite likelihood ratio tests, we identified 384 and 81 selective sweeps affecting 4% and 0.5% of the 35 Mb core genome, respectively. We found differences both in the number and the position of selective sweeps across the genome between populations. Using a XtX‐based outlier detection approach, we identified 51 extremely divergent genomic regions between the allopatric populations, suggesting that divergent selection led to locally adapted pathogen populations. We performed an outlier detection analysis between two sympatric populations infecting two different wheat cultivars to identify evidence for host‐driven selection. Selective sweep regions harboured genes that are likely to play a role in successfully establishing host infections. We also identified secondary metabolite gene clusters and an enrichment in genes encoding transporter and protein localization functions. The latter gene functions mediate responses to environmental stress, including interactions with the host. The distinct gene functions under selection indicate that both local host genotypes and abiotic factors contributed to local adaptation.

Detection of Selection Signatures in Chinese Landrace and Yorkshire Pigs Based on Genotyping-by-Sequencing Data.

The domestic pigs have been undergone intense selection pressures for these development of interested traits following domestication and modern breeding. This has altered many traits in most of pig breeds, such as growth rate, body weight, fertility, and immunity. Thus, the objectives of this study were to (1) detect these selection signatures and identify the candidate genes that show evidences of recent artificial selection at the level of whole genome, (2) be beneficial to understand the relationship between genomic structure and phenotypic diversity, and (3) highlight the key roles of these candidate genes in growth and development in the two breeds. The data consisted of total raw number of 345570 single nucleotide polymorphisms (SNPs) in 1200 individuals from the Chinese Landrace pigs (L, n = 600) and Yorkshire pigs (Y, n = 600). Based on these SNPs data, two complementary methods, population differentiation (Fst) and composite likelihood ratio test (CLR), were carried out to detect the selection signatures in this study. A total of 540 potential selection regions (50 kb) which contained 111 candidate genes were detected for Landrace-Yorkshire pair (L-Y) by Fst. In addition, 73 and 125 candidate genes were found for Landrace pigs and Yorkshire pigs by CLR test based on 321 and 628 potential selection regions, respectively. Some candidate genes are associated with important traits and signaling pathways including the ACACA, MECR, COL11A1, GHR, IGF1R, IGF2R, IFNG, and MTOR gene. The ACACA and MECR gene are related to fatty acid biosynthesis. The COL11A1 gene is essential for the development of the normal differentiation. The GHR, IGF1R, and IGF2R gene are significant candidate genes which play major roles in the growth and development in animals. The IFNG gene is associated with some aspects of immune response. The MTOR gene regulates many signaling pathways and signaling transduction pathway.

Analysis of cross-population differentiation between Thoroughbred and Jeju horses.

ObjectiveThis study was intended to identify genes positively selected in Thoroughbred horses (THBs) that potentially contribute to their running performances.MethodsThe genomes of THB and Jeju horses (JH, Korean native horse) were compared to identify genes positively selected in THB. We performed cross-population extended haplotype homozygosity (XP-EHH) and cross-population composite likelihood ratio test (XP-CLR) statistical methods for our analysis using whole genome resequencing data of 14 THB and 6 JH.ResultsWe identified 98 (XP-EHH) and 200 (XP-CLR) genes that are under positive selection in THB. Gene enrichment analysis identified 72 gene ontology biological process (GO BP) terms. The genes and GO BP terms explained some of THB’s characteristics such as immunity, energy metabolism and eye size and function related to running performances. GO BP terms that play key roles in several cell signaling mechanisms, which affected ocular size and visual functions were identified. GO BP term Eye photoreceptor cell differentiation is among the terms annotated presumed to affect eye size.ConclusionOur analysis revealed some positively selected candidate genes in THB related to their racing performances. The genes detected are related to the immunity, ocular size and function, and energy metabolism.

A conditional composite likelihood ratio test with boundary constraints

Summary Composite likelihood has been widely used in applications. The asymptotic distribution of the composite likelihood ratio statistic at the boundary of the parameter space is a complicated mixture of weighted $\chi^2$ distributions. In this paper we propose a conditional test with data-dependent degrees of freedom. We consider a modification of the composite likelihood which satisfies the second-order Bartlett identity. We show that the modified composite likelihood ratio statistic given the number of estimated parameters lying on the boundary converges to a simple $\chi^2$ distribution. This conditional testing procedure is validated through simulation studies.

An integrative approach to assess X-chromosome inactivation using allele-specific expression with applications to epithelial ovarian cancer.

X-chromosome inactivation (XCI) epigenetically silences transcription of an X chromosome in females; patterns of XCI are thought to be aberrant in women's cancers, but are understudied due to statistical challenges. We develop a two-stage statistical framework to assess skewed XCI and evaluate gene-level patterns of XCI for an individual sample by integration of RNA sequence, copy number alteration, and genotype data. Our method relies on allele-specific expression (ASE) to directly measure XCI and does not rely on male samples or paired normal tissue for comparison. We model ASE using a two-component mixture of beta distributions, allowing estimation for a given sample of the degree of skewness (based on a composite likelihood ratio test) and the posterior probability that a given gene escapes XCI (using a Bayesian beta-binomial mixture model). To illustrate the utility of our approach, we applied these methods to data from tumors of ovarian cancer patients. Among 99 patients, 45 tumors were informative for analysis and showed evidence of XCI skewed toward a particular parental chromosome. For 397 X-linked genes, we observed tumor XCI patterns largely consistent with previously identified consensus states based on multiple normal tissue types. However, 37 genes differed in XCI state between ovarian tumors and the consensus state; 17 genes aberrantly escaped XCI in ovarian tumors (including many oncogenes), whereas 20 genes were unexpectedly inactivated in ovarian tumors (including many tumor suppressor genes). These results provide evidence of the importance of XCI in ovarian cancer and demonstrate the utility of our two-stage analysis.

Genome-Wide Scans Reveal a Quantitative Trait Locus for Withers Height in Horses Near the ANKRD1 Gene

Withers height is an important economic trait for the American Miniature Horses (AMHs) as the breeders' primary objective is to produce small and proportionate animals. Identification of Quantitative Trait Loci (QTLs) affecting height in this breed will result in a better understanding of the genetic architecture and biological pathways contributing to skeletal development. In earlier work, we genotyped 48 horses from 16 different breeds that represent extremes in body size, using the Equine SNP50 bead chip (Illumina Inc). In this study, we applied a dominant model Genome-wide association study (GWAS), a genome-wide fixation index (FST) estimation, as well as a cross-population composite likelihood ratio (XP-CLR) test between the eight large and eight small breeds from this data set. Our GWAS implicated the marker at ECA1:37,676,322 bp, positioned within an intron of the ANKRD1 gene, was significantly associated with height variation. An XP-CLR scan further supported a role in height for the ECA1:37,676,322 bp locus and the FST analysis supported correlations to IGF2BP2 at ECA19:23,815,750. To confirm our findings, we genotyped the candidate loci in an independent set of 89 AMHs. This set verified that the locus at ANKRD1 gene indeed correlates to height under a dominant mode of inheritance, but not the locus at the IGF2BP2 gene. ANKRD1, a transcription factor involved in myocyte growth and differentiation, may contribute to height by influencing the overall growth of the horses. This marker will be a valuable tool for the selection of breeding stock in breeds with height restrictions for registration.

Detecting Positive Selection of Korean Native Goat Populations Using Next-Generation Sequencing.

Goats (Capra hircus) are one of the oldest species of domesticated animals. Native Korean goats are a particularly interesting group, as they are indigenous to the area and were raised in the Korean peninsula almost 2,000 years ago. Although they have a small body size and produce low volumes of milk and meat, they are quite resistant to lumbar paralysis. Our study aimed to reveal the distinct genetic features and patterns of selection in native Korean goats by comparing the genomes of native Korean goat and crossbred goat populations. We sequenced the whole genome of 15 native Korean goats and 11 crossbred goats using next-generation sequencing (Illumina platform) to compare the genomes of the two populations. We found decreased nucleotide diversity in the native Korean goats compared to the crossbred goats. Genetic structural analysis demonstrated that the native Korean goat and crossbred goat populations shared a common ancestry, but were clearly distinct. Finally, to reveal the native Korean goat’s selective sweep region, selective sweep signals were identified in the native Korean goat genome using cross-population extended haplotype homozygosity (XP-EHH) and a cross-population composite likelihood ratio test (XP-CLR). As a result, we were able to identify candidate genes for recent selection, such as the CCR3 gene, which is related to lumbar paralysis resistance. Combined with future studies and recent goat genome information, this study will contribute to a thorough understanding of the native Korean goat genome.

Detecting recent selective sweeps while controlling for mutation rate and background selection.

A composite likelihood ratio test implemented in the program sweepfinder is a commonly used method for scanning a genome for recent selective sweeps. sweepfinder uses information on the spatial pattern (along the chromosome) of the site frequency spectrum around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson–Kreitman–Aguadé test, we suggest adding fixed differences relative to an out‐group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled as a local reduction in the effective population size. Using simulations, we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.

Empirical and simulated adjustments of composite likelihood ratio statistics

Composite likelihood inference has gained much popularity thanks to its computational manageability and its theoretical properties. Unfortunately, performing composite likelihood ratio tests is inconvenient because of their awkward asymptotic distribution. There are many proposals for adjusting composite likelihood ratio tests in order to recover an asymptotic chi-square distribution, but they all depend on the sensitivity and variability matrices. The same is true for Wald-type and score-type counterparts. In realistic applications, sensitivity and variability matrices usually need to be estimated, but there are no comparisons of the performance of composite likelihood-based statistics in such an instance. A comparison of the accuracy of inference based on the statistics considering two methods typically employed for estimation of sensitivity and variability matrices, namely an empirical method that exploits independent observations, and Monte Carlo simulation, is performed. The results in two examples involving the pairwise likelihood show that a very large number of independent observations should be available in order to obtain accurate coverages using empirical estimation, while limited simulation from the full model provides accurate results regardless of the availability of independent observations. This suggests the latter as a default choice, whenever simulation from the model is possible.

Adjusted composite likelihood ratio test for spatial Gibbs point processes

We investigate an analogue of the likelihood ratio test for spatial Gibbs point process models fitted by maximum pseudolikelihood or maximum composite likelihood. The test statistic must be adjusted in order to obtain an asymptotic distribution under the null hypothesis. Adjustments developed for composite likelihoods of finite systems of random variables are adapted to the point process setting. Recent results in point process theory are used to estimate the composite information J and sensitivity H from the point pattern data. In a large simulation experiment we find that the proposed test is exact if J and H are known exactly; it is slightly conservative when J and H are estimated from the data.

Prediction of Genes Related to Positive Selection Using Whole-Genome Resequencing in Three Commercial Pig Breeds

Selective sweep can cause genetic differentiation across populations, which allows for the identification of possible causative regions/genes underlying important traits. The pig has experienced a long history of allele frequency changes through artificial selection in the domestication process. We obtained an average of 329,482,871 sequence reads for 24 pigs from three pig breeds: Yorkshire (n = 5), Landrace (n = 13), and Duroc (n = 6). An average read depth of 11.7 was obtained using whole-genome resequencing on an Illumina HiSeq2000 platform. In this study, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio tests were implemented to detect genes experiencing positive selection for the genome-wide resequencing data generated from three commercial pig breeds. In our results, 26, 7, and 14 genes from Yorkshire, Landrace, and Duroc, respectively were detected by two kinds of statistical tests. Significant evidence for positive selection was identified on genes ST6GALNAC2 and EPHX1 in Yorkshire, PARK2 in Landrace, and BMP6, SLA-DQA1, and PRKG1 in Duroc.These genes are reportedly relevant to lactation, reproduction, meat quality, and growth traits. To understand how these single nucleotide polymorphisms (SNPs) related positive selection affect protein function, we analyzed the effect of non-synonymous SNPs. Three SNPs (rs324509622, rs80931851, and rs80937718) in the SLA-DQA1 gene were significant in the enrichment tests, indicating strong evidence for positive selection in Duroc. Our analyses identified genes under positive selection for lactation, reproduction, and meat-quality and growth traits in Yorkshire, Landrace, and Duroc, respectively.