Polygenic Model Of Inheritance Research Articles

Inheritance analysis of major lignan contents in Schisandra chinensis hybrid progeny

Schisandra chinensis (Turcz.) Baill. has been used in traditional Chinese medicine for more than 2000 years and is classified as a superior herb. To examine the inheritance of lignan content traits, we measured the contents of six lignan constituents in the fruit and stem of 142 individuals from the cross ‘Jinwuwei 1’ × ‘Zaohong’ for three successive years. The optimal genetic model for each trait was screened using a mixed major gene + polygene inheritance model. The lignan contents differed in degree of variation, with the annual average coefficient of variation ranging from 22.31% to 79.80% across the three years. Significant transgressive heterosis was observed for schisandrol B content both in the fruit and stem, whereas negative heterosis was detected for γ-schisandrin content both in the fruit and stem. The optimal genetic models were inconsistent among different lignans in the same organ and between different organs for the same lignan, which may be associated with specific gene expression patterns. The additive effects of the lignan contents were mostly positive, whereas the dominance effects were mainly negative. The results of this study provide a theoretical basis for quantitative trait locus mapping and marker-assisted breeding of lignan contents in S. chinensis.

Genetic analysis of mixed models of fruit sugar-acid fractions in a cross between jujube (Ziziphus jujuba Mill.) and wild jujube (Z. acido jujuba).

Chinese jujube (Ziziphus jujuba Mill.), an economically significant species in the Rhamnaceae family, is a popular fruit tree in Asia. The sugar and acid concentrations in jujube are considerably higher than those in other plants. Due to the low kernel rate, it is extremely difficult to establish hybrid populations. Little is known about jujube evolution and domestication, particularly with regard to the role of the sugar and acid components of jujube. Therefore, we used cover net control as a hybridization technique for the cross-breeding of Ziziphus jujuba Mill and 'JMS2' and (Z. acido jujuba) 'Xing16' to obtain an F1 population (179 hybrid progeny). The sugar and acid levels in the F1 and parent fruit were determined by HPLC. The coefficient of variation ranged from 28.4 to 93.9%. The sucrose and quinic acid levels in the progeny were higher than those in the parents. The population showed continuous distributions with transgressive segregation on both sides. Analysis by the mixed major gene and polygene inheritance model was performed. It was found that glucose is controlled by one additive-dominant major gene and polygenes, malic acid is controlled by two additive-dominant major genes and polygenes, and oxalic acid and quinic acid are controlled by two additive-dominant-epistatic major genes and polygenes. The results of this study provide insights into the genetic predisposition and molecular mechanisms underlying the role of sugar acids in jujube fruit.

Inheritance analysis of fruit-related traits in Chinese cherry [Cerasus pseudocerasus (Lindl.) G.Don] breeding progenies

• Heredity variation and inheritance tendency were analyzed for eighteen fruit-related traits of F 1 population derived from 'Hongfei' × 'Pujianghonghua' of Chinese cherry for two years. • Significant levels of transgressive heterosis were observed for total soluble solid, anthocyanin content and fruit stalk length, whereas negative heterosis detected in fruit weight and size. • The fruit-related traits were most likely controlled by two pairs of major genes, which exerted both additive effects and dominant effects. • The heritability of major gene controlling maturity date and fruit development period was high, while that of major genes controlling fruit quality traits was low. Chinese cherry [ Cerasus pseudocerasus (Lindl.) G.Don] is one of the important stone fruits in China. To explore the heredity variation of fruit-related traits, we investigated 18 fruit-related traits of the F 1 segregating population around 700 individuals derived from 'Hongfei' × 'Pujianghonghua' of Chinese cherry for two years. The mixed major gene and polygene inheritance model method was also evaluated for their fitness in relating to the traits. The results showed that the main fruit traits had different degrees of variation, with the coefficient of variation ranging from 4.76 to 26.71% (72.23% for anthocyanin content) in 2021, and from 4.71 to 21.57% in 2022. Significant levels of transgressive heterosis were observed for fruit stalk length, total soluble solid and anthocyanin content, whereas negative heterosis was detected in fruit weight and size. The most suitable genetic model for fruit maturity date and fruit development period was 2MG-ADI and 2MG-AD, respectively, and the heritability of major gene was greater than 90%. The optimal genetic model for ten fruit size and flavor related traits was 2MG-AD or 2MG-EA, which were controlled by two pairs of major genes with additive-dominant effect or equal-additive effect, with the major gene heritability being less than 45%. The additive effects of the fruit-related traits were mostly positive, while the dominant effects were mainly negative. These results provide a theoretical basis for quantitative trait locus (QTL) mapping and marker-assisted breeding of fruit-related traits in Chinese cherry.

Patterns of integration and modularity in the primate skeleton: a review.

The question of how complex morphologies evolve, given constraints imposed by genetic, developmental and functional factors, has been a topic of inquiry for many decades. In the mid-twentieth century the study of morphological trait covariation, and the implications of this for evolutionary diversification, was developed under the general concept of "morphological integration". Given the polygenic inheritance model underlying quantitative skeletal traits, and the existence of differential pleiotropic effects, it is assumed that variation in the genotype to phenotype map will lead to the emergence of semi-autonomous "modules" that share relatively stronger covariance (integration) among traits within them. Understanding these potential patterns of modularity in the primate skeleton is important for clarifying the seeming inconsistencies presented by "mosaic" morphologies found in fossil taxa, as well as providing hypothetical units of morphological evolution that can be compared across the primate order. A review of the primate skeletal integration and modularity literature was conducted with the aim of assessing (i) the general nature of primate skeletal integration patterns, and (ii) the extent to which any identified modularity patterns are ubiquitous across primates. The vast literature on cranial integration reveals some consistency in suggesting that the face and the neurocranium (and in some cases, the basicranium and vault) form distinct modules, but the intensity of this modular pattern varies across taxa. The much more modest postcranial integration literature suggests that apes show overall reduced covariation among skeletal regions compared with other anthropoid taxa, but the extent to which any identified modularity patterns hold true across primates is still very unclear. While much has been learned about primate skeletal integration in the past two decades, we still need more studies that establish benchmarks as to what constitutes an integrated modular structure, and that empirically test these potential modules across a wider range of primate taxa.

Genetic analysis of leaf trichome density using mixed major gene plus polygene inheritance model in Brassica rapa ssp. chinensis

ABSTRACT Leaf trichome is an important trait for stress-resistance breeding in Brassica crops, but its scientific evaluation and identification are rarely reported. To investigate the inheritance of leaf trichome in non-heading Chinese cabbage, two inbred lines, ‘14XS23W’ (glabrous) and ‘14XS23Y’ (hirsute), were used to generate F1 and F2 populations for joint analysis using a mixed major genes plus polygene inheritance model. The density of adaxial leaf trichomes was controlled by two pairs of additive-dominance-epistasis major genes plus additive-dominance polygenes. The broad-sense heritabilities of the major genes were 93.8% and 85.51%, respectively, for greenhouse and open-field conditions. However, the density of the abaxial leaf trichome was controlled by two pairs of additive-dominance-epistasis major genes plus additive dominance-epistasis polygenes. The broad-sense heritabilities of the major genes were 91.45% and 72.20%, while the polygenes were 0% and 14.5%, respectively, for greenhouse and open field environments. These results indicated that trichome density in non-heading Chinese cabbage was primarily controlled by two pairs of major genes with high heritability, implying that this trait is suitable for rapid selection in early generations.

Susceptibility Genes and Chromosomal Regions Associated With Non-Syndromic Familial Non-Medullary Thyroid Carcinoma: Some Pathogenetic and Diagnostic Keys

Thyroid cancer is the malignant tumor that is increasing most rapidly in the world, mainly at the expense of sporadic papillary thyroid carcinoma. The somatic alterations involved in the pathogenesis of sporadic follicular cell derived tumors are well recognized, while the predisposing alterations implicated in hereditary follicular tumors are less well known. Since the genetic background of syndromic familial non-medullary carcinoma has been well established, here we review the pathogenesis of non-syndromic familial non-medullary carcinoma emphasizing those aspects that may be useful in clinical and pathological diagnosis. Non-syndromic familial non-medullary carcinoma has a complex and heterogeneous genetic basis involving several genes and loci with a monogenic or polygenic inheritance model. Most cases are papillary thyroid carcinoma (classic and follicular variant), usually accompanied by benign thyroid nodules (follicular thyroid adenoma and/or multinodular goiter). The possible diagnostic and prognostic usefulness of the changes in the expression and/or translocation of various proteins secondary to several mutations reported in this setting requires further confirmation. Given that non-syndromic familial non-medullary carcinoma and sporadic non-medullary thyroid carcinoma share the same morphology and somatic mutations, the same targeted therapies could be used at present, if necessary, until more specific targeted treatments become available.

Genetic Analysis and QTL Mapping of Parthenocarpy in <i>Cucumis sativus</i> L

Breeding of cucumber cultivars with high parthenocarpy rate are the prerequisite that ensuring yield and quality under undesirable environment. The mixed major gene plus polygene inheritance model was used to analyze cucumber parthenocarpy trait in the six generations, including P 1 , P 2 , F 1 , BC 1 , BC 2  and F 2 , derived from a cross between the highly parthenocarpic line DDX and low parthenocarpic line ZK. The major-effect quantitative trait locus (QTL) was identified by genome-wide comparison of single nucleotide polymorphisms (SNPs) between high- and low- parthenocarpy rate F 2  pools, and confirmed by traditional QTL mapping with genetic map. Genetic analysis showed that the genetic model E-2, mixed two additive-dominant-epistatic major genes and additive-dominant polygenes, is the best-fitting genetic model for cucumber parthenocarpy phenotype. A major-effect QTL, namely  par2.1 , were identified by the method of Δ(SNP_index).  par2.1  was confirmed by traditional markers based QTL mapping method with least likelihood (LOD) peak score of 12.6, genetic distance of 11.5cM and accounting for 26.6% of the total phenotypic variance.  par2.1  was narrowed down to a 765kb region through comparison of markers physical locations on chromosome 2. The major-effect QTL,  par2.1  on Chr2, for parthenocarpy identified by this study was not reported previously. Our findings shed light on the genetic architecture underlying cucumber parthenocarpy trait, and lay a solid basis for innovation of cucumber parthenocarpy germplasm and breed of new cucumber varieties with high parthenocarpy.

Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories

Rare variants are collectively numerous and may underlie a considerable proportion of complex disease risk. However, identifying genuine rare variant associations is challenging due to small effect sizes, presence of technical artefacts, and heterogeneity in population structure. We hypothesize that rare variant burden over a large number of genes can be combined into a predictive rare variant genetic risk score (RVGRS). We propose a method (RV-EXCALIBER) that leverages summary-level data from a large public exome sequencing database (gnomAD) as controls and robustly calibrates rare variant burden to account for the aforementioned biases. A calibrated RVGRS strongly associates with coronary artery disease (CAD) in European and South Asian populations by capturing the aggregate effect of rare variants through a polygenic model of inheritance. The RVGRS identifies 1.5% of the population with substantial risk of early CAD and confers risk even when adjusting for known Mendelian CAD genes, clinical risk factors, and a common variant genetic risk score.

Germplasm screening and inheritance analysis of resistance to cabbage black rot in a worldwide collection of cabbage (Brassica oleracea var. capitata) resources

Xanthomonas campestris pv. campestris (Xcc) is the causal agent of cabbage (Brassica oleracea var. capitata) black rot (BR) that leads to severe yield losses worldwide. Cultivation and application of resistant cultivars is the most desirable way to control BR. However, due to the lack of BR-resistant germplasm resources and an unclear understanding of the resistance inheritance as well as the controlling gene, the breeding process has been seriously hindered. To identify new BR resistance sources to Xcc race 1, 162 cabbage accessions collected worldwide were evaluated using the spray inoculation method. In total, 64.2% of them were susceptible, and only four germplasms were highly resistant, including two inbred lines (‘05-574-323’ and ‘MD219’) and two hybrids (‘Qinglian’ and ‘Dadilv 2’). Further, to define the genetic characteristics of resistance, a mixed major gene plus polygene inheritance model was used to analyze BR resistance in six populations (P1, P2, F1, B1, B2, and F2) derived from the resistant parent ‘05-574-323’ and the susceptible parent ‘02-359’. The results showed that BR resistance was controlled by a pair of additive major genes and additive-dominant multiple genes (D-2 model), and the main gene heritabilities of B1, B2, and F2 were 49.29%, 43.53%, and 50.35%, respectively. The resistant accessions obtained in this study provide new resources for cabbage BR-resistance breeding, and the inheritance analysis opens the gate for further mapping and application of the resistance gene.

Genetic analysis of main flower characteristics in the F1 generation derived from intraspecific hybridization between Plumbago auriculata and Plumbago auriculata f. alba

The ornamental characteristics of Plumbago auriculata are mainly reflected in the floral organ. Exploring the genetic inheritance of flower characteristics is important for breeding new varieties. In this study, F1 segregating populations were obtained by using artificial hybridization (direct cross and reciprocal cross) between P. auriculata and its variant P. auriculata f. alba. A heterosis analysis and mixed major gene plus polygene inheritance model were used to investigate the inheritance of eight flower characteristics in the F1 generation: inflorescence length (IL), inflorescence diameter (ID), number of flowers per inflorescence (NFI), beginning of the blooming period (BBP), inflorescence number (IN), flower diameter (FD), flower length (FL) and corolla color value (CCV). In addition to the CCV, the other flower characteristics showed continuous unimodal and skewed distributions, which indicated that these characteristics were quantitative and controlled by polygenes. Although transgressive heterosis was observed only for BBP in both combinations, transgressive segregation was commonly observed, except for CCV in the F1 generation; these findings could facilitate the selection of beneficial individuals for breeding. Genetic analysis revealed that NFI could be described by a B-3 genetic model via two pairs of additive major genes; BBP could be followed by a B-2 genetic model via two pairs of additive-dominance major genes; both FL and FD could be described by a B-6 genetic model via two pairs of major genes that were equally dominant; IN was best fit by the A-1 model, which was controlled by a pair of additive-dominant-epistatic major genes; and IL and ID were best fit by the A-0 model, indicating that both characteristics were controlled by only polygenes. The heritability of the major genes controlling the NFI, BBP, FD, FL and IN traits were 92.58 %, 94.40 %, 63.42 %, 54.23 % and 65.67 %, respectively, indicating that these five characteristics were less affected by the environment. These results can provide some reference for quantitative trait locus (QTL) mapping and molecular marker-assisted breeding of the main flower characteristics in P. auriculata.

Analysis of Vitamin P Content and Inheritance Models in Eggplant

The eggplant (Solanum melongena L.) is rich in vitamin P (also known as rutin), which is beneficial for humans. In this study, the vitamin P contents of 53 eggplant lines were measured via UV spectrophotometry. The results showed that the vitamin P content differed significantly among the eggplant lines and the actual contents of vitamin P in fresh fruit pulp and fresh peel were 0.18–0.82 mg · g−1 and 0.42–2.32 mg · g−1, respectively. Furthermore, the mixed major gene and polygene inheritance model method was used for the inheritance analysis of the vitamin P content in F2 populations of three hybridization combinations. Inheritance analysis demonstrated that the vitamin P content of these eggplant lines was a quantitative trait. One or two major genes were the contributor, and the genetic effect was an additive-dominance effect. The high vitamin P content trait was regulated by the main gene and followed an additive effect. The heritability of the major genes controlling the high vitamin P content was low, while the heritability of the major gene that controls the low vitamin P content trait was high. These results provide a theoretical basis for the breeding of eggplants with high vitamin P content.

Evidence for craniofacial enhancer variation underlying nonsyndromic cleft lip and palate

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect for which only ~ 20% of the underlying genetic variation has been identified. Variants in noncoding regions have been increasingly suggested to contribute to the missing heritability. In this study, we investigated whether variation in craniofacial enhancers contributes to NSCLP. Candidate enhancers were identified using VISTA Enhancer Browser and previous publications. Prioritization was based on patterning defects in knockout mice, deletion/duplication of craniofacial genes in animal models and results of whole exome/whole genome sequencing studies. This resulted in 20 craniofacial enhancers to be investigated. Custom amplicon-based sequencing probes were designed and used for sequencing 380 NSCLP probands (from multiplex and simplex families of non-Hispanic white (NHW) and Hispanic ethnicities) using Illumina MiSeq. The frequencies of identified variants were compared to ethnically matched European (CEU) and Los Angeles Mexican (MXL) control genomes and used for association analyses. Variants in mm427/MSX1 and hs1582/SPRY1 showed genome-wide significant association with NSCLP (p ≤ 6.4 × 10-11). In silico analysis showed that these enhancer variants may disrupt important transcription factor binding sites. Haplotypes involving these enhancers and also mm435/ABCA4 were significantly associated with NSCLP, especially in NHW (p ≤ 6.3 × 10-7). Importantly, groupwise burden analysis showed several enhancer combinations significantly over-represented in NSCLP individuals, revealing novel NSCLP pathways and supporting a polygenic inheritance model. Our findings support the role of craniofacial enhancer sequence variation in the etiology of NSCLP.

Heredity Indexes for Estimating Heritability Using Known and Unknown Family Data Based on the Model of Polygenic Inheritance.

Objective To establish a model for estimating genetic risk using known and unknown family data. Methods Four simulated datasets were generated for four paternal and maternal chromosomes. The simulated data for children were generated from the parental data according to the Mendelian law. The correlation coefficient between the children's and paternal data was calculated, and 2R was defined as the heredity index for continuous data (HIC). The simulated continuous data were transformed into binary data according to the gene accumulation threshold (incidence); the incidences of children in the parental no-disease group and the disease onset group were obtained; the correlation coefficient (R) was calculated as expected R (Re). The ratio of observed R (Ro) and Re was defined as the Heredity index for binary data (HIB). Results Different actual pedigree data (lunula and holding a hammer in the right or left hand) were successfully used to verify the accuracy of the model. The genetic risk was estimated according to the incidence in a population using a lookup table. Conclusion Our findings indicate the reliability of the model based on the fact that the multigene effect constitutes the normal distribution. Thus, this model can be used for comprehensive analysis of the influence of genetic and nongenetic factors on the genetic phenotype and to estimate genetic risk using known and unknown family data.

Inheritance and Quantitative Trait Locus Mapping of Fusarium Wilt Resistance in Cucumber.

Fusarium wilt (FW) is a very serious soil-borne disease worldwide, which usually results in huge yield losses in cucumber production. However, the inheritance and molecular mechanism of the response to FW are still unknown in cucumber (Cucumis sativus L.). In this study, two inbred cucumber lines Superina (P1) and Rijiecheng (P2) were used as the sensitive and resistant lines, respectively. A mixed major gene plus polygene inheritance model was used to analyze the resistance to FW in different generations of cucumber, namely, P1, P2, F1 (P1×P2), B1, and B2, obtained by backcrossing F1 plants with Superina (B1) or Rijiecheng (B2), and F2, obtained by self-crossing the F1 plants. After screening 18 genetic models, we chose the E-1 model, which included two pairs of additive-dominance-epistatic major genes and additive-dominance polygenes, as the optimal model for resistance to FW on the basis of fitness tests. The major effect quantitative trait locus (QTL) fw2.1 was detected in a 1.91-Mb-long region of chromosome 2 by bulked-segregant analysis. We used five insertion/deletion markers to fine-map the fw2.1 to a 0.60 Mb interval from 1,248,093 to 1,817,308 bp on chromosome 2 that contained 80 candidate genes. We also used the transcriptome data of Rijiecheng inoculated with Fusarium oxysporum f. sp. cucumerinum (Foc) to screen the candidate genes. Twelve differentially expressed genes were detected in fw2.1, and five of them were significantly induced by FW. The expression levels of the five genes were higher in FW-resistant Rijiecheng inoculated with Foc than in the control inoculated with water. Our results will contribute to a better understanding of the genetic basis of FW resistance in cucumber, which may help in breeding FW-resistant cucumber lines in the future.

Calvarial osteoblast gene expression in patients with craniosynostosis leads to novel polygenic mouse model.

Craniosynostosis is the premature fusion of the sutures of the calvaria and is principally designated as being either syndromic (demonstrating characteristic extracranial malformations) or non-syndromic. While many forms of syndromic craniosynostosis are known to be caused by specific mutations, the genetic etiology of non-syndromic, single-suture craniosynostosis (SSC) is poorly understood. Based on the low recurrence rate (4–7%) and the fact that recurrent mutations have not been identified for most cases of SSC, we propose that some cases of isolated, single suture craniosynostosis may be polygenic. Previous work in our lab identified a disproportionately high number of rare and novel gain-of-function IGF1R variants in patients with SSC as compared to controls. Building upon this result, we used expression array data from calvarial osteoblasts isolated from infants with and without SSC to ascertain correlations between high IGF1 expression and expression of other osteogenic genes of interest. We identified a positive correlation between increased expression of IGF1 and RUNX2, a gene known to cause SSC with increased gene dosage. Subsequent phosphorylation assays revealed that osteoblast cell lines from cases with high IGF1 expression demonstrated inhibition of GSK3β, a serine/threonine kinase known to inhibit RUNX2, thus activating osteogenesis through the IRS1-mediated Akt pathway. With these findings, we have utilized established mouse strains to examine a novel model of polygenic inheritance (a phenotype influenced by more than one gene) of SSC. Compound heterozygous mice with selective disinhibition of RUNX2 and either overexpression of IGF1 or loss of function of GSK3β demonstrated an increase in the frequency and severity of synostosis as compared to mice with the RUNX2 disinhibition alone. These polygenic mouse models reinforce, in-vivo, that the combination of activation of the IGF1 pathway and disinhibition of the RUNX2 pathway leads to an increased risk of developing craniosynostosis and serves as a model of human SSC.

Genetic analysis of tomato internode length via mixed major gene plus polygene inheritance model

Internode length is an important factor influencing tomato cultivation and breeding. To investigate the genetic inheritance of tomato internode length, a multi-generation joint analysis of major genes plus polygene model was employed in this study. Six populations (P1, P2, F1, B1, B2 and F2) were obtained from the Heinz1706 (medium internode) × P502 (long internode) and P1609 (short internode) × P502 crosses, respectively. The data of the 30th day seedlings showed that the internode length of two crosses fitted the D-2 model, followed by the one additive major gene plus additive-dominance polygene genetic model. The highest heritability of the major gene was observed in the F2 population (75.92% and 70.16%). However, the internode length of the 40th day seedlings fitted the E-1 model, namely two additive-dominance-epistasis major genes plus additive-dominance polygene genetic model. The heritabilities of the major genes ranged from 34.33% to 78.16% in B1, B2 and F2 populations, while the heritabilities of the polygene were between 1.92% and 24.50%. These results suggested that the tomato internode length was mainly controlled by major gene and should be selected in early populations. Therefore, our findings may provide important information for plant architecture modification of tomato and may lay the foundation for further QTL mapping.

Whole exome sequencing identifies PLEC, EXO5 and DNAH7 as novel susceptibility genes in testicular cancer.

Testicular germ cell tumors (TGCTs) are a clinically and pathologically heterogeneous disease, and little is known of its genetic basis. Only low susceptibility risk loci have been identified for both sporadic and familial cases. Therefore, we tried to identify new susceptibility genes responsible for familial testicular cancer that may contribute to increasing our knowledge about the genetic basis of the disease. Nineteen Spanish families with at least two affected individuals with TGCT were selected. WES was performed on those individuals using an Illumina Hiseq2000 sequencing platform. Data were analyzed under a monogenic and polygenic model of inheritance, and candidate variants were evaluated in a case-control association study performed on 391 Spanish sporadic cases and 1,170 healthy Spanish controls. Results were replicated in a second series consisting of 101 TGCTs from the Cancer Genome Atlas (TGCA) and 27,000 controls from the Exome Aggregation Consortium (ExAC) database. Logistic regression was carried out to analyze the association strength (risk) of candidate variants obtained among cases and controls in different populations. Despite the sample size, we detected a significant earlier age of onset in familial TGCT (28y) than sporadic cases (33y), using a Mann-Whitney U test. We identified significant variants in the comparative study of TGCT cases (391) versus controls (almost 1,170), and three of them [PLEC (OR = 6.28, p = 6.42 × 10-23 ) (p.Arg2016Trp), EXO5 (OR = 3.37, p = 4.82 × 10-09 ) (p.Arg344AlafsTer10) and DNAH7 (OR = 1.64, p = 0.048)] were replicated as potential candidates that may contribute to explaining the genetic basis of TGCT.

The immunogenetics of neurological disease.

Genes encoding antigen-presenting molecules within the human major histocompatibility complex (MHC) account for the highest component of genetic risk for many neurological diseases, such as multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. Myriad genetic, immunological and environmental factors may contribute to an individual's susceptibility to neurological disease. Here, we review and discuss the decades long research on the influence of genetic variation at the MHC locus and the role of immunogenetic killer cell immunoglobulin-like receptor (KIR) loci in neurological diseases, including multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. The findings of immunogenetic association studies are consistent with a polygenic model of inheritance in the heterogeneous and multifactorial nature of complex traits in various neurological diseases. Future investigation is highly recommended to evaluate both coding and non-coding variation in immunogenetic loci using high-throughput high-resolution next-generation sequencing technologies in diverse ethnic groups to fully appreciate their role in neurological diseases.

Heritability and gene effects for plant architecture traits of crape myrtle using major gene plus polygene inheritance analysis

Plant architecture is important for crape myrtle (Lagerstroemia indica) cultivation and breeding. To investigate the genetic inheritance of plant architecture traits in Lagerstroemia, a mixed major gene plus polygene inheritance model was employed to analyze three traits in six generations (P1, P2, F1, B1, B2 and F2), including plant height (PH), internode length (IL) and primary lateral branch height (PLBH). The three traits showed extensive coefficient of variation and high broad sense heritability (0.60–0.84). Though transgressive segregations were present, transgressive heterosis was not observed in all the generations. The results showed that the IL fitted the D-0 model, which was followed by a one additive-dominance major gene plus additive-dominance-epistasis polygene genetic model. In addition, the PH and PLBH were quantitative traits fitting the E-0 model, namely two additive-dominance-epistasis major genes plus additive-dominance-epistasis polygene genetic model. The highest heritability of the major gene (83.62%) for the IL was observed in F2 population, indicating that the IL trait was mainly controlled by genetic factors with a low effect of environmental factors and should be selected in early generations. However, the highest heritabilities of the major genes for the PH and PLBH were 43.23% and 70.29% in B1 population, indicating that the PH and PLBH should be selected in late generations due to the large effect of environmental factors. Therefore, these findings will provide a theoretical instruction for the QTL mapping and breeding of desirable plant architecture in crape myrtle.

Single Marker Family-Based Association Analysis Not Conditional on Parental Information.

Family-based association analysis unconditional on parental genotypes models the effects of observed genotypes. This approach has been shown to have greater power than conditional methods. In this chapter, we review popular association analysis methods accounting for familial correlations: the marginal model using generalized estimating equations (GEE), the mixed model with a polygenic random component, and genome-wide association analyses. The marginal approach does not explicitly model familial correlations but uses the information to improve the efficiency of parameter estimates. This model, using GEE, is useful when the correlation structure is not of interest; the correlations are treated as nuisance parameters. In the mixed model, familial correlations are modeled as random effects, e.g., the polygenic inheritance model accounts for correlations originating from shared genomic components within a family. These unconditional methods provide a flexible modeling framework for general pedigree data to accommodate traits with various distributions and many types of covariate effects. Genome-wide association studies usually test more than 10,000 SNPs and thus traditional statistical methods accounting for the familial correlations often suffer from a computational burden. Multiple approaches that have been recently proposed to avoid this computational issue are reviewed. The single-marker analysis procedures are demonstrated using the R package gee and the ASSOC program in the S.A.G.E. package, including how to prepare input data, conduct the analysis, and interpret the output. ASSOC allows models to include random components of additional familial correlations that may be not sufficiently explained by a polygenic effect and addresses nonnormality of response variables by transformation methods. With its ease of use, ASSOC provides a useful tool for association analysis of large pedigree data.